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Sample records for basolateral amygdala mediates

  1. GABAA-mediated inhibition of basolateral amygdala blocks reward devaluation in macaques.

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    Wellman, Laurie L; Gale, Karen; Malkova, Ludise

    2005-05-04

    Amygdala ablation disrupts reinforcer "devaluation" in monkeys (Malkova et al., 1997). Here, we tested the hypothesis that transient inactivation of amygdala by the GABA(A) agonist muscimol (MUS), specifically during the period of reward satiation, would have a similar effect. Six pigtail macaques were trained on a visual object discrimination task in which 60 objects were associated with one of two specific food rewards. Subsequently, we evaluated the selective satiation-induced change (devaluation) in object preference in probe sessions. We also examined the effect of the amygdala inactivation during the probe sessions to determine whether the inactivation limited to the testing period (and not during the satiation period) is sufficient to impair the expression of reinforcer devaluation. MUS infusions were aimed at basolateral amygdala (BLA) in a pseudorandomized design; each monkey received MUS or saline either before or after selective satiation with each of the two food rewards (six infusions total). Under the control (saline) condition, the monkeys significantly shifted their preference from objects representing the sated food rewards to those representing the nonsated rewards (30% change). When BLA was inactivated during selective satiation (i.e., MUS infused before satiation), this devaluation effect was blocked. In contrast, MUS infusion after satiation, so that it was present just during the testing period, did not impair the shift in object preference (27% change). Thus, BLA is necessary for the appropriate registration of the change in the reinforcer value but not for the subsequent expression of the devaluation involving its transfer to secondary reinforcers.

  2. Basolateral amygdala CB1 cannabinoid receptors mediate nicotine-induced place preference.

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    Hashemizadeh, Shiva; Sardari, Maryam; Rezayof, Ameneh

    2014-06-03

    In the present study, the effects of bilateral microinjections of cannabinoid CB1 receptor agonist and antagonist into the basolateral amygdala (intra-BLA) on nicotine-induced place preference were examined in rats. A conditioned place preference (CPP) apparatus was used for the assessment of rewarding effects of the drugs in adult male Wistar rats. Subcutaneous (s.c.) administration of nicotine (0.2mg/kg) induced a significant CPP, without any effect on the locomotor activity during the testing phase. Intra-BLA microinjection of a non-selective cannabinoid CB1/CB2 receptor agonist, WIN 55,212-2 (0.1-0.5 μg/rat) with an ineffective dose of nicotine (0.1mg/kg, s.c.) induced a significant place preference. On the other hand, intra-BLA administration of AM251 (20-60 ng/rat), a selective cannabinoid CB1 receptor antagonist inhibited the acquisition of nicotine-induced place preference. It should be considered that the microinjection of the same doses of WIN 55,212-2 or AM251 into the BLA, by itself had no effect on the CPP score. The administration of a higher dose of AM251 (60 ng/rat) during the acquisition decreased the locomotor activity of animals on the testing phase. Interestingly, the microinjection of AM251 (20 and 40 ng/rat), but not WIN55,212-2 (0.1-0.5 μg/rat), into the BLA inhibited the expression of nicotine-induced place preference without any effect on the locomotor activity. Taken together, these findings support the possible role of endogenous cannabinoid system of the BLA in the acquisition and the expression of nicotine-induced place preference. Furthermore, it seems that there is a functional interaction between the BLA cannabinoid receptors and nicotine in producing the rewarding effects.

  3. TRH and TRH receptor system in the basolateral amygdala mediate stress-induced depression-like behaviors.

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    Choi, Juli; Kim, Ji-eun; Kim, Tae-Kyung; Park, Jin-Young; Lee, Jung-Eun; Kim, Hannah; Lee, Eun-Hwa; Han, Pyung-Lim

    2015-10-01

    Chronic stress is a potent risk factor for depression, but the mechanism by which stress causes depression is not fully understood. To investigate the molecular mechanism underlying stress-induced depression, C57BL/6 inbred mice were treated with repeated restraint to induce lasting depressive behavioral changes. Behavioral states of individual animals were evaluated using the forced swim test, which measures psychomotor withdrawals, and the U-field test, which measures sociability. From these behavioral analyses, individual mice that showed depression-like behaviors in both psychomotor withdrawal and sociability tests, and individuals that showed a resiliency to stress-induced depression in both tests were selected. Among the neuropeptides expressed in the amygdala, thyrotropin-releasing hormone (TRH) was identified as being persistently up-regulated in the basolateral amygdala (BLA) in individuals exhibiting severe depressive behaviors in the two behavior tests, but not in individuals displaying a stress resiliency. Activation of TRH receptors by local injection of TRH in the BLA in normal mice produced depressive behaviors, mimicking chronic stress effects, whereas siRNA-mediated suppression of either TRH or TRHR1 in the BLA completely blocked stress-induced depressive symptoms. The TRHR1 agonist, taltirelin, injection in the BLA increased the level of p-ERK, which mimicked the increased p-ERK level in the BLA that was induced by treatment with repeated stress. Stereotaxic injection of U0126, a potent inhibitor of the ERK pathway, within the BLA blocked stress-induced behavioral depression. These results suggest that repeated stress produces lasting depression-like behaviors via the up-regulation of TRH and TRH receptors in the BLA.

  4. The Role of the Basolateral Amygdala in Punishment

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    Dit-Bressel, Philip Jean-Richard; McNally, Gavan P.

    2015-01-01

    Aversive stimuli not only support fear conditioning to their environmental antecedents, they also punish behaviors that cause their occurrence. The amygdala, especially the basolateral nucleus (BLA), has been critically implicated in Pavlovian fear learning but its role in punishment remains poorly understood. Here, we used a within-subjects…

  5. Serotonin-2C receptors in the basolateral nucleus of the amygdala mediate the anxiogenic effect of acute imipramine and fluoxetine administration.

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    Vicente, Maria Adrielle; Zangrossi, Helio

    2012-04-01

    A growing body of evidence indicates that facilitation of serotonin-2C receptor (5-HT2CR)-mediated neurotransmission in the basolateral nucleus of the amygdala (BLA) is involved in anxiety generation. We investigated here whether BLA 5-HT2CRs exert a differential role in the regulation of defensive behaviours related to generalized anxiety (inhibitory avoidance) and panic (escape) disorders. We also evaluated whether activation of BLA 5-HT2CRs accounts for the anxiogenic effect caused by acute systemic administration of the antidepressants imipramine and fluoxetine. Male Wistar rats were tested in the elevated T-maze after intra-BLA injection of the endogenous agonist 5-HT, the 5-HT2CR agonist MK-212 or the 5-HT2CR antagonist SB-242084. This test allows the measurement of inhibitory avoidance acquisition and escape expression. We also investigated whether intra-BLA administration of SB-242084 interferes with the acute anxiogenic effect caused by imipramine and fluoxetine in the Vogel conflict test, and imipramine in the elevated T-maze. While intra-BLA administration of 5-HT and MK-212 facilitated inhibitory avoidance acquisition, suggesting an anxiogenic effect, SB-242084 had the opposite effect. None of these drugs affected escape performance. Intra-BLA injection of a sub-effective dose of SB-242084 fully blocked the anxiogenic effect caused either by the local microinjection of 5-HT or the systemic administration of imipramine and fluoxetine. Our findings indicate that 5-HT2CRs in BLA are selectively involved in the regulation of defensive behaviours associated with generalized anxiety, but not panic. The results also provide the first direct evidence that activation of BLA 5-HT2CRs accounts for the short-term aversive effect of antidepressants.

  6. Moderate alcohol exposure during the rat equivalent to the third trimester of human pregnancy alters dopamine regulation of GABAA receptor-mediated transmission in the basolateral amygdala

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    Marvin Rafael Diaz

    2014-05-01

    Full Text Available Fetal ethanol (EtOH exposure leads to a range of neurobehavioral alterations, including deficits in emotional processing. The basolateral amygdala (BLA plays a critical role in modulating emotional processing, in part, via dopamine (DA regulation of GABA transmission. This BLA modulatory system is acquired during the first two weeks of postnatal life in rodents (equivalent to the 3rd trimester of human pregnancy and we hypothesized that it could be altered by EtOH exposure during this period. We found that exposure of rats to moderate levels of EtOH vapor during the 3rd trimester-equivalent (postnatal days (P 2-12 alters DA modulation of GABAergic transmission in BLA pyramidal neurons during periadolescence. Specifically, D1R-mediated potentiation of spontaneous inhibitory postsynaptic currents (IPSCs was significantly attenuated in EtOH-exposed animals. However, this was associated with a compensatory decrease in D3R-mediated suppression of miniature IPSCs. Western blot analysis revealed that these effects were not a result of altered D1R or D3R levels. BLA samples from EtOH-exposed animals also had significantly lower levels of the DA precursor (L-3,4-dihydroxyphenylalanine but DA levels were not affected. This is likely a consequence of reduced catabolism of DA, as indicated by reduced levels of 3,4-dihydroxyphenylacetic acid and homovanillic acid in the BLA samples. Anxiety-like behavior was not altered in EtOH-exposed animals. This is the first study to demonstrate that the modulatory actions of DA in the BLA are altered by developmental EtOH exposure. Although compensatory adaptations were engaged in our moderate EtOH exposure paradigm, it is possible that these are not able to restore homeostasis and correct anxiety-like behaviors under conditions of heavier EtOH exposure. Therefore, future studies should investigate the potential role of alterations in the modulatory actions of DA in the pathophysiology of fetal alcohol spectrum

  7. Acquisition of contextual Pavlovian fear conditioning is blocked by application of an NMDA receptor antagonist D,L-2-amino-5-phosphonovaleric acid to the basolateral amygdala.

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    Fanselow, M S; Kim, J J

    1994-02-01

    Rats, with chronic cannula placed bilaterally in the amygdala, received infusions of the N-methyl-D-aspartate (NMDA) receptor antagonist D,L-2-amino-5-phosphonovaleric acid (APV) before contextual Pavlovian fear conditioning. Administration of APV to the basolateral nucleus prevented acquisition of fear. Central nucleus infusions had no effect. It is concluded that an NMDA-mediated process near the basolateral region of the amygdala (e.g., lateral or basolateral nucleus) is essential for the learning of fear.

  8. NMDA receptors in the basolateral amygdala and gustatory neophobia.

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    Figueroa-Guzmán, Yazmín; Reilly, Steve

    2008-05-19

    The attenuation of gustatory neophobia occurs during repeated exposures to an initially novel taste solution that is increasingly perceived as safe and familiar. The present study examined whether NMDA receptors in the basolateral region of the amygdala (BLA) are involved in this important behavioral phenomenon. The results, which show that the attenuation, but not initial occurrence, of gustatory neophobia is dependent upon NMDA receptors in the BLA, are discussed with reference to a similar finding involving NMDA receptors in the insular cortex.

  9. Paradoxical facilitation of working memory after basolateral amygdala damage.

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    Barak Morgan

    Full Text Available Working memory is a vital cognitive capacity without which meaningful thinking and logical reasoning would be impossible. Working memory is integrally dependent upon prefrontal cortex and it has been suggested that voluntary control of working memory, enabling sustained emotion inhibition, was the crucial step in the evolution of modern humans. Consistent with this, recent fMRI studies suggest that working memory performance depends upon the capacity of prefrontal cortex to suppress bottom-up amygdala signals during emotional arousal. However fMRI is not well-suited to definitively resolve questions of causality. Moreover, the amygdala is neither structurally or functionally homogenous and fMRI studies do not resolve which amygdala sub-regions interfere with working memory. Lesion studies on the other hand can contribute unique causal evidence on aspects of brain-behaviour phenomena fMRI cannot "see". To address these questions we investigated working memory performance in three adult female subjects with bilateral basolateral amygdala calcification consequent to Urbach-Wiethe Disease and ten healthy controls. Amygdala lesion extent and functionality was determined by structural and functional MRI methods. Working memory performance was assessed using the Wechsler Adult Intelligence Scale-III digit span forward task. State and trait anxiety measures to control for possible emotional differences between patient and control groups were administered. Structural MRI showed bilateral selective basolateral amygdala damage in the three Urbach-Wiethe Disease subjects and fMRI confirmed intact functionality in the remaining amygdala sub-regions. The three Urbach-Wiethe Disease subjects showed significant working memory facilitation relative to controls. Control measures showed no group anxiety differences. Results are provisionally interpreted in terms of a 'cooperation through competition' networks model that may account for the observed paradoxical

  10. Excitatory amino acid receptors in the basolateral amygdala regulate anxiety responses in the social interaction test.

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    Sajdyk, T J; Shekhar, A

    1997-08-01

    Blocking GABA(A) receptors in the basolateral amygdala (BLA) elicits increases in heart rate (HR), blood pressure (BP) and anxiety responses by enhancing a glutamate mediated excitation. The present study was conducted to determine the role of the ionotropic glutamate receptors within the BLA in regulating HR, BP and experimental anxiety. Blocking basal glutamate excitation had no significant effect on HR or BP, but did elicit a significant anxiolytic-like effect.

  11. Short environmental enrichment in adulthood reverses anxiety and basolateral amygdala hypertrophy induced by maternal separation.

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    Koe, A S; Ashokan, A; Mitra, R

    2016-02-02

    Maternal separation during early childhood results in greater sensitivity to stressors later in adult life. This is reflected as greater propensity to develop stress-related disorders in humans and animal models, including anxiety and depression. Environmental enrichment (EE) reverses some of the damaging effects of maternal separation in rodent models when provided during peripubescent life, temporally proximal to the separation. It is presently unknown if EE provided outside this critical window can still rescue separation-induced anxiety and neural plasticity. In this report we use a rat model to demonstrate that a single short episode of EE in adulthood reduced anxiety-like behaviour in maternally separated rats. We further show that maternal separation resulted in hypertrophy of dendrites and increase in spine density of basolateral amygdala neurons in adulthood, long after initial stress treatment. This is congruent with prior observations showing centrality of basolateral amygdala hypertrophy in anxiety induced by stress during adulthood. In line with the ability of the adult enrichment to rescue stress-induced anxiety, we show that enrichment renormalized stress-induced structural expansion of the amygdala neurons. These observations argue that behavioural plasticity induced by early adversity can be rescued by environmental interventions much later in life, likely mediated by ameliorating effects of enrichment on basolateral amygdala plasticity.

  12. Severe stress hormone conditions cause an extended window of excitability in the mouse basolateral amygdala

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    Karst, Henk; Joëls, Marian

    2016-01-01

    Shortly after stress, basolateral amygdala neurons are exposed to sequential yet partly overlapping waves of hormones. We examined how these hormonal waves can change activity of basolateral amygdala neurons such that emotional aspects of stress become so deeply ingrained. To this end, spontaneous g

  13. Alcohol-Seeking Triggered by Discrete Pavlovian Cues is Invigorated by Alcohol Contexts and Mediated by Glutamate Signaling in the Basolateral Amygdala.

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    Sciascia, Joanna M; Reese, Rebecca M; Janak, Patricia H; Chaudhri, Nadia

    2015-11-01

    The environmental context in which a discrete Pavlovian conditioned stimulus (CS) is experienced can profoundly impact conditioned responding elicited by the CS. We hypothesized that alcohol-seeking behavior elicited by a discrete CS that predicted alcohol would be influenced by context and require glutamate signaling in the basolateral amygdala (BLA). Male, Long-Evans rats were allowed to drink 15% ethanol (v/v) until consumption stabilized. Next, rats received Pavlovian conditioning sessions in which a 10 s CS (15 trials/session) was paired with ethanol (0.2 ml/CS). Entries into a port where ethanol was delivered were measured. Pavlovian conditioning occurred in a specific context (alcohol context) and was alternated with sessions in a different context (non-alcohol context) where neither the CS nor ethanol was presented. At test, the CS was presented without ethanol in the alcohol context or the non-alcohol context, following a bilateral microinfusion (0.3 μl/hemisphere) of saline or the AMPA glutamate receptor antagonist NBQX (2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide disodium salt) in the BLA (0, 0.3, or 1.0 μg/0.3 μl). The effect of NBQX (0, 0.3 μg/0.3 μl) in the caudate putamen (CPu) on CS responding in the non-alcohol context was also tested. The discrete alcohol CS triggered more alcohol-seeking behavior in the alcohol context than the non-alcohol context. NBQX in the BLA reduced CS responding in both contexts but had no effect in the CPu. These data indicate that AMPA glutamate receptors in the BLA are critical for alcohol-seeking elicited by a discrete CS and that behavior triggered by the CS is strongly invigorated by an alcohol context.

  14. Variation in mouse basolateral amygdala volume is associated with differences in stress reactivity and fear learning.

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    Yang, Rebecca J; Mozhui, Khyobeni; Karlsson, Rose-Marie; Cameron, Heather A; Williams, Robert W; Holmes, Andrew

    2008-10-01

    A wealth of research identifies the amygdala as a key brain region mediating negative affect, and implicates amygdala dysfunction in the pathophysiology of anxiety disorders. Although there is a strong genetic component to anxiety disorders such as posttraumatic stress disorder (PTSD) there remains debate about whether abnormalities in amygdala function predispose to these disorders. In the present study, groups of C57BL/6 x DBA/2 (B x D) recombinant inbred strains of mice were selected for differences in volume of the basolateral amygdala complex (BLA). Strains with relatively small, medium, or large BLA volumes were compared for Pavlovian fear learning and memory, anxiety-related behaviors, depression-related behavior, and glucocorticoid responses to stress. Strains with relatively small BLA exhibited stronger conditioned fear responses to both auditory tone and contextual stimuli, as compared to groups with larger BLA. The small BLA group also showed significantly greater corticosterone responses to stress than the larger BLA groups. BLA volume did not predict clear differences in measures of anxiety-like behavior or depression-related behavior, other than greater locomotor inhibition to novelty in strains with smaller BLA. Neither striatal, hippocampal nor cerebellar volumes correlated significantly with any behavioral measure. The present data demonstrate a phenotype of enhanced fear conditioning and exaggerated glucocorticoid responses to stress associated with small BLA volume. This profile is reminiscent of the increased fear processing and stress reactivity that is associated with amygdala excitability and reduced amygdala volume in humans carrying loss of function polymorphisms in the serotonin transporter and monoamine oxidase A genes. Our study provides a unique example of how natural variation in amygdala volume associates with specific fear- and stress-related phenotypes in rodents, and further supports the role of amygdala dysfunction in anxiety

  15. The basolateral amygdala in reward learning and addiction.

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    Wassum, Kate M; Izquierdo, Alicia

    2015-10-01

    Sophisticated behavioral paradigms partnered with the emergence of increasingly selective techniques to target the basolateral amygdala (BLA) have resulted in an enhanced understanding of the role of this nucleus in learning and using reward information. Due to the wide variety of behavioral approaches many questions remain on the circumscribed role of BLA in appetitive behavior. In this review, we integrate conclusions of BLA function in reward-related behavior using traditional interference techniques (lesion, pharmacological inactivation) with those using newer methodological approaches in experimental animals that allow in vivo manipulation of cell type-specific populations and neural recordings. Secondly, from a review of appetitive behavioral tasks in rodents and monkeys and recent computational models of reward procurement, we derive evidence for BLA as a neural integrator of reward value, history, and cost parameters. Taken together, BLA codes specific and temporally dynamic outcome representations in a distributed network to orchestrate adaptive responses. We provide evidence that experiences with opiates and psychostimulants alter these outcome representations in BLA, resulting in long-term modified action.

  16. The basolateral amygdala in reward learning and addiction

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    Wassum, Kate M.; Izquierdo, Alicia

    2015-01-01

    Sophisticated behavioral paradigms partnered with the emergence of increasingly selective techniques to target the basolateral amygdala (BLA) have resulted in an enhanced understanding of the role of this nucleus in learning and using reward information. Due to the wide variety of behavioral approaches many questions remain on the circumscribed role of BLA in appetitive behavior. In this review, we integrate conclusions of BLA function in reward-related behavior using traditional interference techniques (lesion, pharmacological inactivation) with those using newer methodological approaches in experimental animals that allow in vivo manipulation of cell type-specific populations and neural recordings. Secondly, from a review of appetitive behavioral tasks in rodents and monkeys and recent computational models of reward procurement, we derive evidence for BLA as a neural integrator of reward value, history, and cost parameters. Taken together, BLA codes specific and temporally dynamic outcome representations in a distributed network to orchestrate adaptive responses. We provide evidence that experiences with opiates and psychostimulants alter these outcome representations in BLA, resulting in long-term modified action. PMID:26341938

  17. Impact of basal forebrain cholinergic inputs on basolateral amygdala neurons.

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    Unal, Cagri T; Pare, Denis; Zaborszky, Laszlo

    2015-01-14

    In addition to innervating the cerebral cortex, basal forebrain cholinergic (BFc) neurons send a dense projection to the basolateral nucleus of the amygdala (BLA). In this study, we investigated the effect of near physiological acetylcholine release on BLA neurons using optogenetic tools and in vitro patch-clamp recordings. Adult transgenic mice expressing cre-recombinase under the choline acetyltransferase promoter were used to selectively transduce BFc neurons with channelrhodopsin-2 and a reporter through the injection of an adeno-associated virus. Light-induced stimulation of BFc axons produced different effects depending on the BLA cell type. In late-firing interneurons, BFc inputs elicited fast nicotinic EPSPs. In contrast, no response could be detected in fast-spiking interneurons. In principal BLA neurons, two different effects were elicited depending on their activity level. When principal BLA neurons were quiescent or made to fire at low rates by depolarizing current injection, light-induced activation of BFc axons elicited muscarinic IPSPs. In contrast, with stronger depolarizing currents, eliciting firing above ∼ 6-8 Hz, these muscarinic IPSPs lost their efficacy because stimulation of BFc inputs prolonged current-evoked afterdepolarizations. All the effects observed in principal neurons were dependent on muscarinic receptors type 1, engaging different intracellular mechanisms in a state-dependent manner. Overall, our results suggest that acetylcholine enhances the signal-to-noise ratio in principal BLA neurons. Moreover, the cholinergic engagement of afterdepolarizations may contribute to the formation of stimulus associations during fear-conditioning tasks where the timing of conditioned and unconditioned stimuli is not optimal for the induction of synaptic plasticity.

  18. Neuropeptide S interacts with the basolateral amygdala noradrenergic system in facilitating object recognition memory consolidation.

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    Han, Ren-Wen; Xu, Hong-Jiao; Zhang, Rui-San; Wang, Pei; Chang, Min; Peng, Ya-Li; Deng, Ke-Yu; Wang, Rui

    2014-01-01

    The noradrenergic activity in the basolateral amygdala (BLA) was reported to be involved in the regulation of object recognition memory. As the BLA expresses high density of receptors for Neuropeptide S (NPS), we investigated whether the BLA is involved in mediating NPS's effects on object recognition memory consolidation and whether such effects require noradrenergic activity. Intracerebroventricular infusion of NPS (1nmol) post training facilitated 24-h memory in a mouse novel object recognition task. The memory-enhancing effect of NPS could be blocked by the β-adrenoceptor antagonist propranolol. Furthermore, post-training intra-BLA infusions of NPS (0.5nmol/side) improved 24-h memory for objects, which was impaired by co-administration of propranolol (0.5μg/side). Taken together, these results indicate that NPS interacts with the BLA noradrenergic system in improving object recognition memory during consolidation.

  19. Glutamate Receptor Antagonist Infusions into the Basolateral and Medial Amygdala Reveal Differential Contributions to Olfactory vs. Context Fear Conditioning and Expression

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    Walker, David L.; Paschall, Gayla Y.; Davis, Michael

    2005-01-01

    The basolateral amygdala's involvement in fear acquisition and expression to visual and auditory stimuli is well known. The involvement of the basolateral and other amygdala areas in fear acquisition and expression to stimuli of other modalities is less certain. We evaluated the contribution of the basolateral and medial amygdala to olfactory and…

  20. Multiple anxiogenic drugs recruit a parvalbumin-containing subpopulation of GABAergic interneurons in the basolateral amygdala.

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    Hale, Matthew W; Johnson, Philip L; Westerman, Alex M; Abrams, Jolane K; Shekhar, Anantha; Lowry, Christopher A

    2010-10-01

    The basolateral amygdala is a nodal structure within a distributed and interconnected network that regulates anxiety states and anxiety-related behavior. Administration of multiple anxiogenic drugs increases cellular responses (i.e., increases c-Fos expression) in a subregion of the basolateral amygdala, but the neurochemical phenotypes of these cells are not known. The basolateral amygdala contains glutamatergic projection neurons and several populations of γ-aminobutyric acid-synthesizing (GABAergic) interneurons, including a population of parvalbumin (PV)-expressing GABAergic interneurons that co-express the excitatory 5-HT(2A) receptor. The role for these PV-expressing GABAergic interneurons in anxiety-states is unclear. In this experiment we examined the effects of multiple anxiogenic drugs including the 5-HT(2C/2A) receptor agonist m-chlorophenyl piperazine (mCPP), the adenosine receptor antagonist caffeine, the α(2)-adrenoreceptor antagonist yohimbine and the partial inverse agonist at the benzodiazepine allosteric site on the GABA(A) receptor, N-methyl-beta-carboline-3-carboxamide (FG-7142), on c-Fos expression in PV-immunoreactive (PV-ir) interneurons in subdivisions of the basolateral amygdala. All drugs with the exception of mCPP increased c-Fos expression in PV-ir neurons in the basolateral amygdaloid nucleus, anterior part (BLA). The numbers of c-Fos-immunoreactive (c-Fos-ir)/PV-ir GABAergic interneurons in the BLA were positively correlated with the numbers of c-Fos-ir serotonergic neurons in the mid-rostrocaudal dorsal raphe nucleus (DR) and with a measure of anxiety-related behavior. All four drugs increased c-Fos expression in non-PV-ir cells in most of the subdivisions of the basolateral amygdala that were sampled, compared with vehicle-injected controls. Together, these data suggest that the PV/5-HT(2A) receptor expressing GABAergic interneurons in the basolateral amygdala are part of a DR-basolateral amygdala neuronal circuit modulating

  1. Endocannabinoids in the rat basolateral amygdala enhance memory consolidation and enable glucocorticoid modulation of memory

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    Campolongo, Patrizia; Roozendaal, Benno; Trezza, Viviana; Hauer, Daniela; Schelling, Gustav; McGaugh, James L.; Cuomo, Vincenzo

    2009-01-01

    Extensive evidence indicates that the basolateral complex of the amygdala (BLA) modulates the consolidation of memories for emotionally arousing experiences, an effect that involves the activation of the glucocorticoid system. Because the BLA expresses high densities of cannabinoid CB1 receptors, th

  2. Progressively Disrupted Intrinsic Functional Connectivity of Basolateral Amygdala in Very Early Alzheimer’s Disease

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    Marion Ortner

    2016-09-01

    Full Text Available Abstract:Very early Alzheimer’s disease (AD - i.e., AD at stages of mild cognitive impairment (MCI and mild dementia - is characterized by progressive structural and neuropathologic changes such as atrophy or tangle deposition in medial temporal lobes, including hippocampus and entorhinal cortex but also adjacent amygdala. While progressively disrupted intrinsic connectivity of hippocampus with other brain areas has been demonstrated by many studies, amygdala connectivity was rarely investigated in AD, notwithstanding its known relevance for emotion processing and mood disturbances, which are both important in early AD. Intrinsic functional connectivity (iFC patterns of hippocampus and amygdala overlap in healthy persons. Thus, we hypothesized that increased alteration of iFC patterns along AD is not limited to the hippocampus but also concerns the amygdala, independent from atrophy. To address this hypothesis, we applied structural and functional resting-state MRI in healthy controls (CON, n=33 and patients with AD in the stages of MCI (AD-MCI, n=38 and mild dementia (AD-D, n=36. Outcome measures were voxel-based morphometry (VBM values and region of interest-based intrinsic functional connectivity maps (iFC of basolateral amygdala, which has extended cortical connectivity. Amygdala VBM values were progressively reduced in patients (CON > AD-MCI and AD-D. Amygdala iFC was progressively reduced along impairment severity (CON > AD-MCI > AD-D, particularly for hippocampus, temporal lobes, and fronto-parietal areas. Notably, decreased iFC was independent of amygdala atrophy. Results demonstrate progressively impaired amygdala intrinsic connectivity in temporal and fronto-parietal lobes independent from increasing amygdala atrophy in very early AD. Data suggest that early AD disrupts intrinsic connectivity of medial temporal lobe key regions including that of amygdala.

  3. Post-training depletions of basolateral amygdala serotonin fail to disrupt discrimination, retention, or reversal learning

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    G. Jesus eOchoa; Alexandra eStolyarova; Amandeep eKaur; Evan eHart; Amador eBugarin; Alicia eIzquierdo

    2015-01-01

    In goal-directed pursuits, the basolateral amygdala (BLA) is critical in learning about changes in the value of rewards. BLA-lesioned rats show enhanced reversal learning, a task employed to measure the flexibility of response to changes in reward. Similarly, there is a trend for enhanced discrimination learning, suggesting that BLA may modulate formation of stimulus-reward associations. There is a parallel literature on the importance of serotonin (5HT) in new stimulus-reward and reversal le...

  4. Involvement of basolateral amygdala GABAA receptors in the effect of dexamethasone on memory in rats

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    Lotfollah KHAJEHPOUR; Acieh ALIZADEH-MAKVANDI; Mahnaz KESMATI; Hooman ESHAGH-HAROONI

    2011-01-01

    In this study we investigated whether GABAA receptors of the basolateral amygdala (BLA) interact with the effect of dexamethasone on the retrieval stage of memory.Adult male Wistar rats were bilaterally cannulated in the BLA by stereotaxic surgery.The animals were trained in step-through apparatus by induction of electric shock (1.5 mA,3 s) and were tested for memory retrieval after 1 d.The time of latency for entering the dark compartment of the instrument and the time spent by rats in this chamber were recorded for evaluation of the animals' retrieval in passive avoidance memory.Administration of dexamethasone (0.3 and 0.9 mg/kg,subcutaneously (s.c.)),immediately after training,enhanced memory retrieval.This effect was reduced by intra-BLA microinjection of muscimol (0.125,0.250 and 0.500 μg/rat),when administered before 0.9 mg/kg of dexamethasone.Microinjection of bicuculline (0.75 μg/rat,intra-BLA) with an ineffective dose of dexamethasone (0.1 mg/kg,s.c.) increased memory retrieval.However,the same doses of muscimol and bicuculline without dexamethasone did not affect memory processes.Our data support reports that dexamethasone enhances memory retrieval.It seems that GABAA receptors of the BLA mediate the effect of dexamethasone on memory retrieval in rats.

  5. Endocannabinoid Signaling within the Basolateral Amygdala Integrates Multiple Stress Hormone Effects on Memory Consolidation

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    Atsak, Piray; Hauer, Daniela; Campolongo, Patrizia; Schelling, Gustav; Fornari, Raquel V; Roozendaal, Benno

    2015-01-01

    Glucocorticoid hormones are known to act synergistically with other stress-activated neuromodulatory systems, such as norepinephrine and corticotropin-releasing factor (CRF), within the basolateral complex of the amygdala (BLA) to induce optimal strengthening of the consolidation of long-term memory of emotionally arousing experiences. However, as the onset of these glucocorticoid actions appear often too rapid to be explained by genomic regulation, the neurobiological mechanism of how glucocorticoids could modify the memory-enhancing properties of norepinephrine and CRF remained elusive. Here, we show that the endocannabinoid system, a rapidly activated retrograde messenger system, is a primary route mediating the actions of glucocorticoids, via a glucocorticoid receptor on the cell surface, on BLA neural plasticity and memory consolidation. Furthermore, glucocorticoids recruit downstream endocannabinoid activity within the BLA to interact with both the norepinephrine and CRF systems in enhancing memory consolidation. These findings have important implications for understanding the fine-tuned crosstalk between multiple stress hormone systems in the coordination of (mal)adaptive stress and emotional arousal effects on neural plasticity and memory consolidation. PMID:25547713

  6. Histamine in the basolateral amygdala promotes inhibitory avoidance learning independently of hippocampus.

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    Benetti, Fernando; Furini, Cristiane Regina Guerino; de Carvalho Myskiw, Jociane; Provensi, Gustavo; Passani, Maria Beatrice; Baldi, Elisabetta; Bucherelli, Corrado; Munari, Leonardo; Izquierdo, Ivan; Blandina, Patrizio

    2015-05-12

    Recent discoveries demonstrated that recruitment of alternative brain circuits permits compensation of memory impairments following damage to brain regions specialized in integrating and/or storing specific memories, including both dorsal hippocampus and basolateral amygdala (BLA). Here, we first report that the integrity of the brain histaminergic system is necessary for long-term, but not for short-term memory of step-down inhibitory avoidance (IA). Second, we found that phosphorylation of cyclic adenosine monophosphate (cAMP) responsive-element-binding protein, a crucial mediator in long-term memory formation, correlated anatomically and temporally with histamine-induced memory retrieval, showing the active involvement of histamine function in CA1 and BLA in different phases of memory consolidation. Third, we found that exogenous application of histamine in either hippocampal CA1 or BLA of brain histamine-depleted rats, hence amnesic, restored long-term memory; however, the time frame of memory rescue was different for the two brain structures, short lived (immediately posttraining) for BLA, long lasting (up to 6 h) for the CA1. Moreover, long-term memory was formed immediately after training restoring of histamine transmission only in the BLA. These findings reveal the essential role of histaminergic neurotransmission to provide the brain with the plasticity necessary to ensure memorization of emotionally salient events, through recruitment of alternative circuits. Hence, our findings indicate that the histaminergic system comprises parallel, coordinated pathways that provide compensatory plasticity when one brain structure is compromised.

  7. Histamine in the basolateral amygdala promotes inhibitory avoidance learning independently of hippocampus

    Science.gov (United States)

    Benetti, Fernando; Furini, Cristiane Regina Guerino; de Carvalho Myskiw, Jociane; Provensi, Gustavo; Passani, Maria Beatrice; Baldi, Elisabetta; Bucherelli, Corrado; Munari, Leonardo; Izquierdo, Ivan; Blandina, Patrizio

    2015-01-01

    Recent discoveries demonstrated that recruitment of alternative brain circuits permits compensation of memory impairments following damage to brain regions specialized in integrating and/or storing specific memories, including both dorsal hippocampus and basolateral amygdala (BLA). Here, we first report that the integrity of the brain histaminergic system is necessary for long-term, but not for short-term memory of step-down inhibitory avoidance (IA). Second, we found that phosphorylation of cyclic adenosine monophosphate (cAMP) responsive-element-binding protein, a crucial mediator in long-term memory formation, correlated anatomically and temporally with histamine-induced memory retrieval, showing the active involvement of histamine function in CA1 and BLA in different phases of memory consolidation. Third, we found that exogenous application of histamine in either hippocampal CA1 or BLA of brain histamine-depleted rats, hence amnesic, restored long-term memory; however, the time frame of memory rescue was different for the two brain structures, short lived (immediately posttraining) for BLA, long lasting (up to 6 h) for the CA1. Moreover, long-term memory was formed immediately after training restoring of histamine transmission only in the BLA. These findings reveal the essential role of histaminergic neurotransmission to provide the brain with the plasticity necessary to ensure memorization of emotionally salient events, through recruitment of alternative circuits. Hence, our findings indicate that the histaminergic system comprises parallel, coordinated pathways that provide compensatory plasticity when one brain structure is compromised. PMID:25918368

  8. Basolateral amygdala lesion inhibits the development of pain chronicity in neuropathic pain rats.

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    Zheng Li

    Full Text Available BACKGROUND: Chronicity of pain is one of the most interesting questions in chronic pain study. Clinical and experimental data suggest that supraspinal areas responsible for negative emotions such as depression and anxiety contribute to the chronicity of pain. The amygdala is suspected to be a potential structure for the pain chronicity due to its critical role in processing negative emotions and pain information. OBJECTIVE: This study aimed to investigate whether amygdala or its subregions, the basolateral amygdala (BLA and the central medial amygdala (CeA, contributes to the pain chronicity in the spared nerve injury (SNI-induced neuropathic pain model of rats. METHODOLOGY/PRINCIPAL FINDINGS: (1 Before the establishment of the SNI-induced neuropathic pain model of rats, lesion of the amygdaloid complex with stereotaxic injection of ibotenic acid (IBO alleviated mechanical allodynia significantly at days 7 and 14, even no mechanical allodynia at day 28 after SNI; Lesion of the BLA, but not the CeA had similar effects; (2 however, 7 days after SNI when the neuropathic pain model was established, lesion of the amygdala complex or the BLA or the CeA, mechanical allodynia was not affected. CONCLUSION: These results suggest that BLA activities in the early stage after nerve injury might be crucial to the development of pain chronicity, and amygdala-related negative emotions and pain-related memories could promote pain chronicity.

  9. Post-training depletions of basolateral amygdala serotonin fail to disrupt discrimination, retention, or reversal learning.

    Science.gov (United States)

    Ochoa, Jesus G; Stolyarova, Alexandra; Kaur, Amandeep; Hart, Evan E; Bugarin, Amador; Izquierdo, Alicia

    2015-01-01

    In goal-directed pursuits, the basolateral amygdala (BLA) is critical in learning about changes in the value of rewards. BLA-lesioned rats show enhanced reversal learning, a task employed to measure the flexibility of response to changes in reward. Similarly, there is a trend for enhanced discrimination learning, suggesting that BLA may modulate formation of stimulus-reward associations. There is a parallel literature on the importance of serotonin (5HT) in new stimulus-reward and reversal learning. Recent postulations implicate 5HT in learning from punishment. Whereas, dopaminergic involvement is critical in behavioral activation and reinforcement, 5HT may be most critical for aversive processing and behavioral inhibition, complementary cognitive processes. Given these findings, a 5HT-mediated mechanism in BLA may mediate the facilitated learning observed previously. The present study investigated the effects of selective 5HT lesions in BLA using 5,7-dihydroxytryptamine (5,7-DHT) vs. infusions of saline (Sham) on discrimination, retention, and deterministic reversal learning. Rats were required to reach an 85% correct pairwise discrimination and single reversal criterion prior to surgery. Postoperatively, rats were then tested on the (1) retention of the pretreatment discrimination pair, (2) discrimination of a novel pair, and (3) reversal learning performance. We found statistically comparable preoperative learning rates between groups, intact postoperative retention, and unaltered novel discrimination and reversal learning in 5,7-DHT rats. These findings suggest that 5HT in BLA is not required for formation and flexible adjustment of new stimulus-reward associations when the strategy to efficiently solve the task has already been learned. Given the complementary role of orbitofrontal cortex in reward learning and its interconnectivity with BLA, these findings add to the list of dissociable mechanisms for BLA and orbitofrontal cortex in reward learning.

  10. Post-training depletions of basolateral amygdala serotonin fail to disrupt discrimination, retention, or reversal learning

    Directory of Open Access Journals (Sweden)

    G. Jesus eOchoa

    2015-05-01

    Full Text Available In goal-directed pursuits, the basolateral amygdala (BLA is critical in learning about changes in the value of rewards. BLA-lesioned rats show enhanced reversal learning, a task employed to measure the flexibility of response to changes in reward. Similarly, there is a trend for enhanced discrimination learning, suggesting that BLA may modulate formation of stimulus-reward associations. There is a parallel literature on the importance of serotonin (5HT in new stimulus-reward and reversal learning. Recent postulations implicate 5HT in learning from punishment. Whereas dopaminergic involvement is critical in behavioral activation and reinforcement, 5HT may be most critical for aversive processing and behavioral inhibition, complementary cognitive processes. Given these findings, a 5HT-mediated mechanism in BLA may mediate the facilitated learning observed previously. The present study investigated the effects of selective 5HT lesions in BLA using 5,7-dihydroxytryptamine (5,7-DHT versus infusions of saline (Sham on discrimination, retention, and deterministic reversal learning. Rats were required to reach an 85% correct pairwise discrimination and single reversal criterion prior to surgery. Postoperatively, rats were then tested on the 1 retention of the pretreatment discrimination pair 2 discrimination of a novel pair and 3 reversal learning performance. We found statistically comparable preoperative learning rates between groups, intact postoperative retention, and unaltered novel discrimination and reversal learning in 5,7-DHT rats. These findings suggest that 5HT in BLA is not required for formation and flexible adjustment of new stimulus-reward associations when the strategy to efficiently solve the task has already been learned. Given the complementary role of orbitofrontal cortex in reward learning and its interconnectivity with BLA, these findings add to the list of dissociable mechanisms for BLA and orbitofrontal cortex in reward learning.

  11. Stimulus Intensity-dependent Modulations of Hippocampal Long-term Potentiation by Basolateral Amygdala Priming

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    Zexuan eLi

    2012-05-01

    Full Text Available There is growing realization that the relationship between memory and stress/emotionality is complicated, and may include both memory enhancing and memory impairing aspects. It has been suggested that the underlying mechanisms involve amygdalar modulation of hippocampal synaptic plasticity, such as long-term potentiation (LTP. We recently reported that while in CA1 basolateral amygdala (BLA priming impaired theta stimulation induced LTP, it enhanced LTP in the dentate gyrus (DG. However, emotional and stressfull experiences were found to activate synaptic plasticity within the BLA, rasing the possibility that BLA modulation of other brain regions may be altered as well, as it may depend on the way the BLA is activated or is responding. In previous studies BLA priming stimulation was relatively weak (1V, 50 µs pulse duration. In the present study we assessed the effects of two stronger levels of BLA priming stimulation (1V or 2V, 100 µs pulse duration on LTP induction in hippocampal DG and CA1, in anesthetized rats. Results show that 1V-BLA priming stimulation enhanced but 2V-BLA priming stimulation impaired DG LTP; however, both levels of BLA priming stimulation impaired CA1 LTP, suggesting that modulation of hippocampal synaptic plasticity by amygdala is dependent on the degree of amygdala activation. These findings suggest that plasticity induced within the amygdala, by stressful experiences induces a form of metaplasticity that would alter the way the amygdala may modulate memory-related processes in other brain areas, such as the hippocampus.

  12. Involvement of the basolateral complex and central nucleus of amygdala in the omission effects of different magnitudes of reinforcement.

    Science.gov (United States)

    Judice-Daher, Danielle M; Tavares, Tatiane F; Bueno, José Lino O

    2012-07-15

    Evidence from appetitive Pavlovian and instrumental conditioning studies suggest that the amygdala is involved in modulation of responses correlated with motivational states, and therefore, to the modulation of processes probably underlying reinforcement omission effects. The present study aimed to clarify whether or not the mechanisms related to reinforcement omission effects of different magnitudes depend on basolateral complex and central nucleus of amygdala. Rats were trained on a fixed-interval 12s with limited hold 6s signaled schedule in which correct responses were always followed by one of two reinforcement magnitudes. Bilateral lesions of the basolateral complex and central nucleus were made after acquisition of stable performance. After postoperative recovery, the training was changed from 100% to 50% reinforcement schedules. The results showed that lesions of the basolateral complex and central nucleus did not eliminate or reduce, but interfere with reinforcement omission effects. The response from rats of both the basolateral complex and central nucleus lesioned group was higher relative to that of the rats of their respective sham-lesioned groups after reinforcement omission. Thus, the lesioned rats were more sensitive to the omission effect. Moreover, the basolateral complex lesions prevented the magnitude effect on reinforcement omission effects. Basolateral complex lesioned rats showed no differential performance following omission of larger and smaller reinforcement magnitude. Thus, the basolateral complex is involved in incentive processes relative to omission of different reinforcement magnitudes. Therefore, it is possible that reinforcement omission effects are modulated by brain circuitry which involves amygdala.

  13. β-Adrenergic activation enhances NMDA-induced current in pyramidal cells of the basolateral nucleus of amygdala

    Institute of Scientific and Technical Information of China (English)

    LIU Xinqiu; CAO Xiaohua; LI Bao-ming

    2005-01-01

    NMDA receptor (NMDA-R) in the amygdala complex is critical for both long-term potentiation (LTP) and formation of conditioned fear memory. It is reported that activation of β-adrenoceptors (β-AR) in the amygdala facilitates LTP and enhances memory consolidation. The present study examined the regulatory effect of β-AR activation on NMDA-R mediated current in pyramidal cells of the basolateral nucleus of amygdala (BLA), using whole-cell recording technique. Bath application of the β-AR agonist isoproterenol enhanced NMDA-induced current, and this facilitatory effect was blocked by co-administered propranolol, a β-AR antagonist. The facilitatory effect of isoproterenol on NMDA-induced current could not be induced when the protein kinase A (PKA) inhibitor Rp-cAMPs was added in electrode internal solution.The present results suggest that β-AR activation in the BLA could modulate NMDA-R activity directly and positively, probably via PKA.

  14. Development and physiology of GABAergic feedback excitation in parvalbumin expressing interneurons of the mouse basolateral amygdala

    OpenAIRE

    Spampanato, Jay; Sullivan, Robert K. P.; Perumal, Madhusoothanan B.; Sah, Pankaj

    2016-01-01

    Abstract We have previously shown that in the basolateral amygdala (BLA), action potentials in one type of parvalbumin (PV)‐expressing GABAergic interneuron can evoke a disynaptic feedback excitatory postsynaptic potential (fbEPSP) onto the same presynaptic interneuron. Here, using whole‐cell recordings from PV‐expressing interneurons in acute brain slices we expand on this finding to show that this response is first detectable at 2‐week postnatal, and is most prevalent in animals beyond 3 we...

  15. Protein synthesis inhibition in the basolateral nucleus of amygdala facilitates extinction of auditory fear memory

    Institute of Scientific and Technical Information of China (English)

    JIN XinChun; QI XueLian; YANG XiaoFei; LI BaoMing

    2007-01-01

    It is known that consolidation of fear conditioning requires de novo protein synthesis in the amygdala. However, there is controversy about the role of protein synthesis in post-retrieval extinction of fear memory. The present study investigated the effect of protein synthesis inhibition (PSI) in the basolateral nucleus of amygdala (BLA) on post-retrieval extinction of auditory fear memory. Intra-BLA infusion of the protein synthesis inhibitor anisomycin '0' h post-retrieval facilitated the extinction, but was ineffective if the memory was not retrieved. Anisomycin had no effect on the extinction when it was infused 6 h post-retrieval. The present results suggest that there exists a protein-synthesis-dependent mechanism in the BLA that retards extinction of auditory fear memory.

  16. Blockade of glutamatergic transmission in the primate basolateral amygdala suppresses active behavior without altering social interaction.

    Science.gov (United States)

    Forcelli, Patrick A; Wellman, Laurie L; Malkova, Ludise

    2017-04-01

    The amygdala is an integrator of affective processing, and a key component of a network regulating social behavior. While decades of lesion studies in nonhuman primates have shown alterations in social interactions after amygdala damage, acute manipulations of the amygdala in primates have been underexplored. We recently reported (Wellman, Forcelli, Aguilar, & Malkova, 2016) that acute pharmacological inhibition of the basolateral complex of the amygdala (BLA) or the central nucleus of the amygdala increased affiliative social interactions in experimental dyads of macaques; this was achieved through microinjection of a GABA-A receptor agonist. Prior studies in rodents have shown similar effects achieved by blocking NMDA receptors or AMPA receptors within the BLA. Here, we sought to determine the role of these receptor systems in the primate BLA in the context of social behavior. In familiar dyads, we microinjected the NMDA receptor antagonist 2-amino-7-phosphonoheptanoic acid (AP7) or the AMPA receptor antagonist 2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide (NBQX) and observed behaviors and social interactions in the immediate postinjection period. In striking contrast with our prior report using GABA agonists, and in contrast with prior reports in rodents using glutamate antagonists, we found that neither NMDA nor AMPA blockade increase social interaction. Both treatments, however, were associated with decreases in locomotion and manipulation and increases in passive behavior. These data suggest that local blockade of glutamatergic neurotransmission in BLA is not the functional equivalent of local activation of GABAergic signaling, and raise interesting questions regarding the functional microcircuitry of the nonhuman primate amygdala in the context of social behavior. (PsycINFO Database Record

  17. Prefrontal cortex, hippocampus, and basolateral amygdala plasticity in a rat model of autism spectrum.

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    Sosa-Díaz, Nuvia; Bringas, Maria Elena; Atzori, Marco; Flores, Gonzalo

    2014-10-01

    We aimed to investigate the effect of prenatal administration of valproic acid (VPA) (500 mg/kg) at embryonic day 12.5 on the anatomical properties of the prefrontal cortex, hippocampus, and basolateral amygdala, at three different ages: immediately after weaning (postnatal day 21 [PD21]), prepubertal (PD35), and postpubertal (PD70) ages in a rat model of autistic spectrum disorder. Quantitative analysis of the thickness of the prefrontal cortex revealed a reduced size at all study ages in the cingulate 1 area of the prefrontal cortex and CA1 of the dorsal hippocampus in prenatally exposed animals compared to controls. At the level of the basolateral amygdala, a reduction in the size was observed at PD35 and PD70 in the VPA group. In addition, a reduced thickness was observed in the prelimbic region of the prefrontal cortex in VPA animals at PD35. Interestingly, no differences in cortical thickness were observed between control and VPA animals in the infralimbic region of the prefrontal at any age. Our results suggest that prenatal exposure to VPA differentially alters cortical limbic regions anatomical parameters, with implication in the autistic spectrum disorder.

  18. Basolateral Amygdala Projections to Ventral Hippocampus Modulate the Consolidation of Footshock, but Not Contextual, Learning in Rats

    Science.gov (United States)

    Huff, Mary L.; Emmons, Eric B.; Narayanan, Nandakumar S.; LaLumiere, Ryan T.

    2016-01-01

    The basolateral amygdala (BLA) modulates memory consolidation for a variety of types of learning, whereas other brain regions play more selective roles in specific kinds of learning suggesting a role for differential consolidation via distinct BLA pathways. The ventral hippocampus (VH), an efferent target of the BLA, has been suggested to…

  19. Distinct Contributions of the Basolateral Amygdala and the Medial Prefrontal Cortex to Learning and Relearning Extinction of Context Conditioned Fear

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    Laurent, Vincent; Westbrook, R. Frederick

    2008-01-01

    We studied the roles of the basolateral amygdala (BLA) and the medial prefrontal cortex (mPFC) in learning and relearning to inhibit context conditioned fear (freezing) in extinction. In Experiment 1, pre-extinction BLA infusion of the NMDA receptor (NMDAr) antagonist, ifenprodil, impaired the development and retention of inhibition but…

  20. 17beta-Estradiol reduces excitatory postsynaptic potential (EPSP) amplitude in rat basolateral amygdala neurons.

    Science.gov (United States)

    Womble, Mark D; Andrew, James A; Crook, Joseph J

    2002-10-11

    We examined the actions of estrogen on excitatory synaptic transmission in the basolateral amygdala (BLA), a brain region involved in learning, emotions, and the effects of stress. Intracellular recordings of monosynaptic excitatory postsynaptic potentials (EPSPs) were obtained from BLA neurons in a slice preparation. Bath application of 17beta-estradiol (2 micro M) reduced EPSP amplitude by an average of 77%. This reduction was readily reversed by washing with control saline and was not mimicked by the inactive isomer 17 alpha-estradiol. Other passive and active properties of BLA neurons were unaffected by 17beta-estradiol. The observed EPSP reduction is in sharp contrast to the potentiation of EPSPs by estrogen observed in other brain regions.

  1. Low-frequency stimulation of the kindling focus delays basolateral amygdala kindling in immature rats.

    Science.gov (United States)

    Velísek, Libor; Velísková, Jana; Stanton, Patric K

    2002-06-21

    Stimulation of deep brain sites is a new approach for treatment of intractable seizures. In adult rats, low-frequency stimulation (LFS; 1-3 Hz) of the kindling site interferes with the course of kindling epileptogenesis. In this study we determined whether the LFS will be effective against the fast kindling in the basolateral amygdala in immature, 15 day old rats. LFS (15 min of 1 Hz stimulation) was applied after each of the 1 s, 60 Hz kindling stimulus. LFS suppressed afterdischarge duration and seizure stage throughout the course of kindling, which indicates a strong antiepileptogenic potential. As the kindling and LFS stimulation patterns are similar to those used for induction of long-term potentiation and long-term depression (LTD), respectively, LTD or depotentiation may play a role in the mechanism of action.

  2. Intracellular mechanisms of cocaine-memory reconsolidation in the basolateral amygdala and dorsal hippocampus

    Science.gov (United States)

    Wells, Audrey Marie

    The ability of cocaine-associated environmental contexts to promote relapse in abstinent humans and reinstatement of cocaine-seeking behavior in laboratory animals depends on the formation and maintenance of maladaptive context-response-cocaine associative memories, the latter of which can be disrupted by manipulations that interfere with memory reconsolidation. Memory reconsolidation refers to a protein synthesis-dependent phenomenon whereby memory traces are reincorporated back into long-term memory storage following their retrieval and subsequent destabilization. To elucidate the distinctive roles of the basolateral amygdala (BLA) and dorsal hippocampus (DH) in the reconsolidation of context-response-cocaine memories, Experiments 1-3 evaluated novel molecular mechanisms within each structure that control this phenomenon. Experiment 1 tested the hypothesis that activation of the extracellular signal-regulated kinase (ERK) in the BLA and nucleus accumbens core (NACc - a substrate for Pavlovian cocaine-memory reconsolidation) would critically control instrumental cocaine-memory reconsolidation. To determine this, rats were re-exposed to a context that had previously been used for cocaine self-administration (i.e., cocaine memory-reactivation) and immediately thereafter received bilateral intra-BLA or intra-NACc microinfusions of the ERK inhibitor U0126 or vehicle (VEH) and were subsequently tested for drug context-induced cocaine-seeking behavior (non-reinforced lever responding) ~72 h later. Re-exposure to the cocaine-paired context at test fully reinstated cocaine-seeking behavior, relative to responding in an alternate, extinction context, and post-reactivation U0126 treatment in the BLA, but not the NACc, impaired cocaine-seeking behavior, relative to VEH. This effect was associated with a temporary increase in ERK2, but not ERK1, phosphorylation in the BLA and required explicit reactivation of the target memory trace (i.e., did not similarly manifest when U

  3. Differential roles of the basolateral amygdala and nucleus basalis magnocellularis during post-reactivation contextual fear conditioning reconsolidation in rats.

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    Baldi, Elisabetta; Mariottini, Chiara; Bucherelli, Corrado

    2008-11-01

    The roles of the basolateral amygdala and nucleus basalis magnocellularis in fear conditioning reconsolidation were investigated by means of tetrodotoxin bilateral inactivation performed 96 h after conditioning, immediately after reactivation training. Footshocks of 1.2 mA intensity were employed to induce the generalization phenomenon. Basolateral amygdala inactivation disrupts the contextual fear response and its generalization but not acoustic CS trace retention, when measured 72 and 96 h after tetrodotoxin administration. Nucleus basalis magnocellularis functional inactivation does not affect memory post-reactivation phase of any of the three conditioned fear responses. The present findings show a differential role of the two structures in fear memory reconsolidation and can be a starting point for future investigation of the neural circuits subserving generalization.

  4. Inactivation of basolateral amygdala specifically eliminates palatability-related information in cortical sensory responses

    Science.gov (United States)

    Piette, Caitlin E.; Baez-Santiago, Madelyn A.; Reid, Emily E.; Katz, Donald B.; Moran, Anan

    2012-01-01

    Evidence indirectly implicates the amygdala as the primary processor of emotional information used by cortex to drive appropriate behavioral responses to stimuli. Taste provides an ideal system with which to test this hypothesis directly, as neurons in both basolateral amygdala (BLA) and gustatory cortex (GC)—anatomically interconnected nodes of the gustatory system—code the emotional valence of taste stimuli (i.e., palatability), in firing rate responses that progress similarly through “epochs.” The fact that palatability-related firing appears one epoch earlier in BLA than GC is broadly consistent with the hypothesis that such information may propagate from the former to the latter. Here, we provide evidence supporting this hypothesis, assaying taste responses in small GC single-neuron ensembles before, during and after temporarily inactivating BLA (BLAx) in awake rats. BLAx changed responses in 98% of taste-responsive GC neurons, altering the entirety of every taste response in many neurons. Most changes involved reductions in firing rate, but regardless of the direction of change, the effect of BLAx was epoch-specific: while firing rates were changed, the taste-specificity of responses remained stable; information about taste palatability, however, which normally resides in the “Late” epoch, was reduced in magnitude across the entire GC sample and outright eliminated in most neurons. Only in the specific minority of neurons for which BLAx enhanced responses did palatability-specificity survive undiminished. Our data therefore provide direct evidence that BLA is a necessary component of GC gustatory processing, and that cortical palatability processing in particular is, in part, a function of BLA activity. PMID:22815512

  5. Enhancing second-order conditioning with lesions of the basolateral amygdala.

    Science.gov (United States)

    Holland, Peter C

    2016-04-01

    Because the occurrence of primary reinforcers in natural environments is relatively rare, conditioned reinforcement plays an important role in many accounts of behavior, including pathological behaviors such as the abuse of alcohol or drugs. As a result of pairing with natural or drug reinforcers, initially neutral cues acquire the ability to serve as reinforcers for subsequent learning. Accepting a major role for conditioned reinforcement in everyday learning is complicated by the often-evanescent nature of this phenomenon in the laboratory, especially when primary reinforcers are entirely absent from the test situation. Here, I found that under certain conditions, the impact of conditioned reinforcement could be extended by lesions of the basolateral amygdala (BLA). Rats received first-order Pavlovian conditioning pairings of 1 visual conditioned stimulus (CS) with food prior to receiving excitotoxic or sham lesions of the BLA, and first-order pairings of another visual CS with food after that surgery. Finally, each rat received second-order pairings of a different auditory cue with each visual first-order CS. As in prior studies, relative to sham-lesioned control rats, lesioned rats were impaired in their acquisition of second-order conditioning to the auditory cue paired with the first-order CS that was trained after surgery. However, lesioned rats showed enhanced and prolonged second-order conditioning to the auditory cue paired with the first-order CS that was trained before amygdala damage was made. Implications for an enhanced role for conditioned reinforcement by drug-related cues after drug-induced alterations in neural plasticity are discussed. (PsycINFO Database Record

  6. CRF1 receptor activation increases the response of neurons in the basolateral nucleus of the amygdala to afferent stimulation

    Directory of Open Access Journals (Sweden)

    2008-07-01

    Full Text Available The basolateral nucleus (BLA of the amygdala contributes to the consolidation of memories for emotional or stressful events. The nucleus contains a high density of CRF1 receptors that are activated by corticotropin-releasing factor (CRF. Modulation of the excitability of neurons in the BLA by CRF may regulate the immediate response to stressful events and the formation of associated memories. In the present study, CRF was found to increase the amplitude of field potentials recorded in the BLA following excitatory afferent stimulation, in vitro. The increase was mediated by CRF1 receptors, since it could be blocked by the selective, non-peptide antagonists, NBI30775 and NBI35583, but not by the CRF2-selective antagonist, astressin 2B. Furthermore, the CRF2-selective agonist, urocortin II had no effect on field potential amplitude. The increase induced by CRF was long-lasting, could not be reversed by subsequent administration of NBI35583, and required the activation of protein kinase C. This effect of CRF in the BLA may be important for increasing the salience of aversive stimuli under stressful conditions, and for enhancing the consolidation of associated memories. The results provide further justification for studying the efficacy of selective antagonists of the CRF1 receptor to reduce memory formation linked to emotional or traumatic events, and suggest that these compounds might be useful as prophylactic treatment for stress-related illness such as post-traumatic stress disorder.

  7. Inhibition of projections from the basolateral amygdala to the entorhinal cortex disrupts the acquisition of contextual fear

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    Dennis R. Sparta

    2014-05-01

    Full Text Available The development of excessive fear and/or stress responses to environmental cues such as contexts associated with a traumatic event is a hallmark of post-traumatic stress disorder (PTSD. The basolateral amygdala (BLA has been implicated as a key structure mediating contextual fear conditioning. In addition, the hippocampus has an integral role in the encoding and processing of contexts associated with strong, salient stimuli such as fear. Given that both the BLA and hippocampus play an important role in the regulation of contextual fear conditioning, examining the functional connectivity between these two structures may elucidate a role for this pathway in the development of PTSD. Here, we used optogenetic strategies to demonstrate that the BLA sends a strong glutamatergic projection to the hippocampal formation through the entorhinal cortex (EC. Next, we photoinhibited glutamatergic fibers from the BLA terminating in the EC during the acquisition or expression of contextual fear conditioning. In mice that received optical inhibition of the BLA-to-EC pathway during the acquisition session, we observed a significant decrease in freezing behavior in a context re-exposure session. In contrast, we observed no differences in freezing behavior in mice that were only photoinhibited during the context re-exposure session. These data demonstrate an important role for the BLA-to-EC glutamatergic pathway in the acquisition of contextual fear conditioning.

  8. Transient inactivation of basolateral amygdala during selective satiation disrupts reinforcer devaluation in rats.

    Science.gov (United States)

    West, Elizabeth A; Forcelli, Patrick A; Murnen, Alice T; McCue, David L; Gale, Karen; Malkova, Ludise

    2012-08-01

    Basolateral amygdala (BLA) function is critical for flexible, goal-directed behavior, including performance on reinforcer devaluation tasks. Here we tested, in rats, the hypothesis that BLA is critical for conditioned reinforcer devaluation during the period when the primary reinforcer (food) is being devalued (by feeding it to satiety), but not thereafter for guiding behavioral choices. We used a spatially independent task that used two visual cues, each predicting one of two foods. An instrumental action (lever press) was required for reinforcer delivery. After training, rats received BLA or sham lesions, or cannulae implanted in BLA. Under control conditions (sham lesions, saline infusions), devaluation of one food significantly decreased responding to the cue associated with that food, when both cues were presented simultaneously during extinction. BLA lesions impaired this devaluation effect. Transient inactivation of BLA by microinfusion of the γ-aminobutyric acid receptor type A agonist muscimol resulted in an impairment only when BLA was inactivated during satiation. When muscimol was infused after satiation and therefore, BLA was inactivated only during the choice test, rats showed no impairment. Thus, BLA is necessary for registering or updating cues to reflect updated reinforcer values, but not for guiding choices once the value has been updated. Our results are the first to describe the contribution of rat BLA to specific components of reinforcer devaluation and are the first to show impairment in reinforcer devaluation following transient inactivation in the rat.

  9. Breathing is affected by dopamine D2-like receptors in the basolateral amygdala.

    Science.gov (United States)

    Sugita, Toshihisa; Kanamaru, Mitsuko; Iizuka, Makito; Sato, Kanako; Tsukada, Setsuro; Kawamura, Mitsuru; Homma, Ikuo; Izumizaki, Masahiko

    2015-04-01

    The precise mechanisms underlying how emotions change breathing patterns remain unclear, but dopamine is a candidate neurotransmitter in the process of emotion-associated breathing. We investigated whether basal dopamine release occurs in the basolateral amygdala (BLA), where sensory-related inputs are received and lead to fear or anxiety responses, and whether D1- and D2-like receptor antagonists affect breathing patterns and dopamine release in the BLA. Adult male mice (C57BL/6N) were perfused with artificial cerebrospinal fluid, a D1-like receptor antagonist (SCH 23390), or a D2-like receptor antagonist ((S)-(-)-sulpiride) through a microdialysis probe in the BLA. Respiratory variables were measured using a double-chamber plethysmograph. Dopamine release was measured by an HPLC. Perfusion of (S)-(-)-sulpiride in the BLA, not SCH 23390, specifically decreased respiratory rate without changes in local release of dopamine. These results suggest that basal dopamine release in the BLA, at least partially, increases respiratory rates only through post-synaptic D2-like receptors, not autoreceptors, which might be associated with emotional responses.

  10. Leptin receptor expression in the basolateral nucleus of amygdala of conditioned taste aversion rats

    Institute of Scientific and Technical Information of China (English)

    Zhen Han; Jian-Qun Yan; Guo-Gang Luo; Yong Liu; Yi-Li Wang

    2003-01-01

    AIM: To determine whether serum leptin level and the leptin receptor (OB-R) expression in the basolateral amygdala (BLA)change following conditioned taste aversion (CTA) formation.METHODS: The serum leptin concentration was measured by rat leptin RIA kit, long and short forms of leptin receptor (OB-Rb and OB-Ra) mRNA in the brain sections were examined by in situ hybridization (ISH) and the expression of OB-R was assessed by immunohistochemistry ABC method with a highly specific goat anti-OB-R antibody.RESULTS: The level of serum leptin didn't show significant difference between CTA and control group. Comparing with the control group, the CTA group had an increase on count of OB-R immunohistochemistry positive-stained cells in the BLA (127±12 vs 48±9 per 1 mm2). The OB-Rb mRNA expression level enhanced by 11.9 % in the BLA, while OBRa mRNA level increased by 7.4 % on the choroid plexus in CTA group. So BLA was supposed to be a region where interactions between gustatory and vagal signals take place.CONCLUSION: BLA is one of the sites, which are responsible for CTA formation in the brain. Leptin and OB-R maybe involved in neuronal communication for CTA. So leptin and its receptors probably take part in CTA and integration of autonomic and extroceptive information.

  11. Development and physiology of GABAergic feedback excitation in parvalbumin expressing interneurons of the mouse basolateral amygdala.

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    Spampanato, Jay; Sullivan, Robert K P; Perumal, Madhusoothanan B; Sah, Pankaj

    2016-01-01

    We have previously shown that in the basolateral amygdala (BLA), action potentials in one type of parvalbumin (PV)-expressing GABAergic interneuron can evoke a disynaptic feedback excitatory postsynaptic potential (fbEPSP) onto the same presynaptic interneuron. Here, using whole-cell recordings from PV-expressing interneurons in acute brain slices we expand on this finding to show that this response is first detectable at 2-week postnatal, and is most prevalent in animals beyond 3 weeks of age (>P21). This circuit has a very high fidelity, and single action potential evoked fbEPSPs display few failures. Reconstruction of filled neurons, and electron microscopy show that interneurons that receive feedback excitation make symmetrical synapses on both the axon initial segments (AIS), as well as the soma and proximal dendrites of local pyramidal neurons, suggesting fbEPSP interneurons are morphologically distinct from the highly specialized chandelier neurons that selectively target the axon initial segment of pyramidal neurons. Single PV interneurons could trigger very large (~ 1 nA) feedback excitatory postsynaptic currents (fbEPSCs) suggesting that these neurons are heavily reciprocally connected to local glutamatergic principal cells. We conclude that in the BLA, a subpopulation of PV interneurons forms a distinct neural circuit in which a single action potential can recruit multiple pyramidal neurons to discharge near simultaneously and feed back onto the presynaptic interneuron.

  12. Target-specific suppression of GABA release from parvalbumin interneurons in the basolateral amygdala by dopamine.

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    Chu, Hong-Yuan; Ito, Wataru; Li, Jiayang; Morozov, Alexei

    2012-10-17

    Dopamine (DA) in the basolateral amygdala (BLA) promotes fear learning by disinhibiting principal neurons (PNs) and enabling synaptic plasticity in their sensory inputs. While BLA interneurons (INs) are heterogeneous, it is unclear which interneuron subtypes decrease GABAergic input to PNs in the presence of DA. Here, using cell type-selective photostimulation by channelrhodopsin 2 in BLA slices from mouse brain, we examined the role of parvalbumin-positive INs (PV-INs), the major interneuronal subpopulation in BLA, in the disinhibitory effect of DA. We found that DA selectively suppressed GABAergic transmission from PV-INs to PNs by acting on presynaptic D(2) receptors, and this effect was mimicked by Rp-cAMP, an inhibitor of cAMP-dependent signaling. In contrast, DA did not alter GABA release from PV-INs to INs. Furthermore, neither suppressing cAMP-dependent signaling by Rp-cAMP nor enhancing it by forskolin altered GABA release from PV-INs to BLA INs. Overall, DA disinhibits BLA, at least in part, by suppressing GABA release from PV-INs in the target cell-specific manner that results from differential control of this release by cAMP-dependent signaling.

  13. Functional lateralization of the baso-lateral amygdala neural circuits modulating the motivated exploratory behaviour in rats: role of histamine.

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    Alvarez, Edgardo O; Banzan, Arturo M

    2011-03-17

    Functional laterality appears to be present in many brain functions in man and animals. The existence of paired neural circuits which act differentially to modulate a specific behavioural function seems to be an evolutionary successful strategy in animal evolution. In spite of many examples described in mammals, birds and other vertebrates and invertebrates, still its intrinsic mechanism is not completely understood. In this work the participation of the baso-lateral amygdala (BLA) on lateralized motivated exploratory behaviour and the possible influence of histamine neurons in these mechanisms were studied in rats. Different groups of animals under xylacine-ketamine anesthesia were implanted with microinjection guide cannulae into the right or left BLA. 72 h after implantation, animals were tested in hole-board cage (OVM) with a novelty object positioned in the center of the arena, as a model of exploration of a non-conflictive environment, and 24h later they were tested in the Elevated Asymmetric Plus Maze (APM) as a model of conflictive exploration. In the day of the experiment, lidocaine was applied into the left, or right BLA in order to block the electrical activity of BLA neurons. Saline in the contralateral BLA was considered control. Results showed that exploratory activity in the OVM was significantly inhibited when lidocaine was microinjected into the left BLA, and no changes were observed when lidocaine was applied into the right BLA. When histamine was microinjected into the right BLA and lidocaine into the contralateral BLA, head-dipping, rearing, and focalized exploration behaviour were significantly inhibited. In the APM, lidocaine treatment increased equally the exploration of the "single wall" and "high and low walls" arms of the labyrinth, independently if blocking of electrical activity of the BLA neurons was performed in the left or right amygdala. Histamine treatment inhibited significantly exploration of the lesser fear-inducing arms of the

  14. Histamine acting on the basolateral amygdala reverts the impairment of aversive memory of rats submitted to neonatal maternal deprivation.

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    Benetti, Fernando; da Silveira, Clarice Kras Borges; Rosa, Jessica; Izquierdo, Ivan

    2015-02-01

    Recent findings suggest a role of brain histamine in the regulation of memory consolidation, particularly in one-trial inhibitory avoidance (IA) learning and that disruption in the mother infant relationship i.e. maternal deprivation induces cognitive deficits. We investigate whether histamine itself, and histaminergic compounds given into the basolateral amygdala (BLA) immediately post-training can affect retention (24 h after training) of one-trial (IA) in rats submitted to early postnatal maternal deprivation. In all cases, deprived (Dep) animals had lower retention scores than non-deprived controls (N-dep). Histamine induced memory enhancement on its own in N-dep animals and was able to overcome the deleterious effect of Dep. The effects by SKF-91488 is similar to histamine. The H3 agonist, imetit mimetized the enhancing effects of histamine; neither agonist H1 pyridylethylamine nor the H2 dimaprit had any effect. Ranitidine and thioperamide (50 nmol) co-infused with histamine (10 nmol) fully blocked the restorative effect of histamine on retention in Dep animals. Thioperamide, in addition, blocked the enhancing effect of histamine on memory of the N-dep animals as well. None of the drugs used given into BLA had any effect on open-field or elevated plus-maze behavior in N-dep or Dep rats. Our results are limited to experimental design in rats. Extrapolation i.e. in humans requires further experimentations. The present results suggest that the memory deficit induced by early postnatal maternal deprivation in rats may at least in part be due to an impairment of histamine H3 receptor-mediated mediated mechanisms in the BLA.

  15. Interactions between ethanol and the endocannabinoid system at GABAergic synapses on basolateral amygdala principal neurons.

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    Talani, Giuseppe; Lovinger, David M

    2015-12-01

    The basolateral amygdala (BLA) plays crucial roles in stimulus value coding, as well as drug and alcohol dependence. Ethanol alters synaptic transmission in the BLA, while endocannabinoids (eCBs) produce presynaptic depression at BLA synapses. Recent studies suggest interactions between ethanol and eCBs that have important consequences for alcohol drinking behavior. To determine how ethanol and eCBs interact in the BLA, we examined the physiology and pharmacology of GABAergic synapses onto BLA pyramidal neurons in neurons from young rats. Application of ethanol at concentrations relevant to intoxication increased, in both young and adult animals, the frequency of spontaneous and miniature GABAergic inhibitory postsynaptic currents, indicating a presynaptic site of ethanol action. Ethanol did not potentiate sIPSCs during inhibition of adenylyl cyclase while still exerting its effect during inhibition of protein kinase A. Activation of type 1 cannabinoid receptors (CB1) in the BLA inhibited GABAergic transmission via an apparent presynaptic mechanism, and prevented ethanol potentiation. Surprisingly, ethanol potentiation was also prevented by CB1 antagonists/inverse agonists. Brief depolarization of BLA pyramidal neurons suppressed GABAergic transmission (depolarization-induced suppression of inhibition [DSI]), an effect previously shown to be mediated by postsynaptic eCB release and presynaptic CB1 activation. A CB1-mediated suppression of GABAergic transmission was also produced by combined afferent stimulation at 0.1 Hz (LFS), and postsynaptic loading with the eCB arachidonoyl ethanolamide (AEA). Both DSI and LFS-induced synaptic depression were prevented by ethanol. Our findings indicate antagonistic interactions between ethanol and eCB/CB1 modulation at GABAergic BLA synapses that may contribute to eCB roles in ethanol seeking and drinking.

  16. Pharmacological depletion of serotonin in the basolateral amygdala complex reduces anxiety and disrupts fear conditioning.

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    Johnson, Philip L; Molosh, Andrei; Fitz, Stephanie D; Arendt, Dave; Deehan, Gerald A; Federici, Lauren M; Bernabe, Cristian; Engleman, Eric A; Rodd, Zachary A; Lowry, Christopher A; Shekhar, Anantha

    2015-11-01

    The basolateral and lateral amygdala nuclei complex (BLC) is implicated in a number of emotional responses including conditioned fear and social anxiety. Based on previous studies demonstrating that enhanced serotonin release in the BLC leads to increased anxiety and fear responses, we hypothesized that pharmacologically depleting serotonin in the BLC using 5,7-dihydroxytryptamine (5,7-DHT) injections would lead to diminished anxiety and disrupted fear conditioning. To test this hypothesis, 5,7-DHT(a serotonin-depleting agent) was bilaterally injected into the BLC. Desipramine (a norepinephrine reuptake inhibitor) was systemically administered to prevent non-selective effects on norepinephrine. After 5days, 5-7-DHT-treated rats showed increases in the duration of social interaction (SI) time, suggestive of reduced anxiety-like behavior. We then used a cue-induced fear conditioning protocol with shock as the unconditioned stimulus and tone as the conditioned stimulus for rats pretreated with bilateral 5,7-DHT, or vehicle, injections into the BLC. Compared to vehicle-treated rats, 5,7-DHT rats had reduced acquisition of fear during conditioning (measured by freezing time during tone), also had reduced fear retrieval/recall on subsequent testing days. Ex vivo analyses revealed that 5,7-DHT reduced local 5-HT concentrations in the BLC by ~40% without altering local norepinephrine or dopamine concentrations. These data provide additional support for 5-HT playing a critical role in modulating anxiety-like behavior and fear-associated memories through its actions within the BLC.

  17. The role of basolateral amygdala adrenergic receptors in hippocampus dependent spatial memory in rat

    Directory of Open Access Journals (Sweden)

    Vafaei A.L.

    2008-03-01

    Full Text Available Background and the purpose of the study: There are extensive evidences indicating that the noradrenergic system of the basolateral nucleus of the amygdala (BLA is involved in memory processes. The present study investigated the role of the BLA adrenergic receptors (ARs in hippocampus dependent spatial memory in place avoidance task in male rat. Material and Methods: Long Evans rats (n=150 were trained to avoid footshock in a 60° segment while foraging for scattered food on a circular (80-cm diameter arena. The rats were injected bilaterally in the BLA specific ARS (Adrenergic receptors agonist norepinephrine (NE, 0.5 and 1 µg/µl and specific β-ARs antagonist propranolol (PRO, 0.5 and 1 µg/µl before acquisition, after training or before retrieval of the place avoidance task. Control rats received vehicle at the same volume. The learning in a single 30-min session was assessed 24h later by a 30-min extinction trial in which the time to first entrance and the number of entrances to the shocked area measured the avoidance memory. Results: Acquisition and consolidation were enhanced and impaired significantly by NE and PRO when the drugs were injected 10 min before or immediately after training, respectively. In contrast, neither NE nor PRO influenced animal performances when injected before retention testing. Conclusion: Findings of this study indicates that adrenergic system of the BLA plays an important role in regulation of memory storage and show further evidences for the opinion that the BLA plays an important role in integrating hormonal and neurotransmitter influences on memory storage.

  18. 5-HT1A and benzodiazepine receptors in the basolateral amygdala modulate anxiety in the social interaction test, but not in the elevated plus-maze.

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    Gonzalez, L E; Andrews, N; File, S E

    1996-09-01

    In order to investigate the role of the 5-HT1A receptors of the amygdala in modulating anxiety, rats were implanted with bilateral cannulae aimed at the basolateral nucleus of the amygdala complex and infused with either artificial cerebrospinal fluid (aCSF) or the selective 5-HT1A receptor agonist 8-OH-DPAT (50-200 ng) and tested in two animal models of anxiety. In the elevated plus-maze test, no significant effects were detected in this dose range. In contrast, 8-OH-DPAT caused an overall reduction in levels of social investigation, thus indicating anxiogenic actions in the social interaction test. At 50 ng, 8-OH-DPAT had a selective action on anxiety, while at 200 ng there was a concomitant reduction in locomotor activity and, in some animals, signs of the 5-HT1A syndrome. Evidence that the anxiogenic effect of 8-OH-DPAT (50 ng) was due to activation of 5-HT1A receptors came from the finding that (-)-tertatolol, a 5-HT1A receptor antagonist, reversed this effect at a dose (1.5 micrograms) which was silent when given alone. The benzodiazepine receptor agonist, midazolam (1 and 2 micrograms) was bilaterally administered into the basolateral nucleus of the amygdala and evoked clear-cut anxiolytic effects in the social interaction test. These data indicate that the agonist activation of post-synaptic 5-HT1A receptors in the basolateral nucleus of the amygdala may produce anxiogenic effects, while agonist activation of BDZ receptors in the same areas evokes anxiolytic effects. Our results from the social interaction test are similar to those previously reported from tests of anxiety using punished paradigms, but contrast with those found in the elevated plus-maze. Thus, it is concluded that either the two tests have different sensitivities to midazolam and 8-OH-DPAT or more intriguingly, the tests are evoking fundamentally different states of anxiety, with that evoked by the plus-maze being mediated via brain areas or receptors different from those studied here.

  19. Basolateral amygdala response to food cues in the absence of hunger is associated with weight gain susceptibility.

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    Sun, Xue; Kroemer, Nils B; Veldhuizen, Maria G; Babbs, Amanda E; de Araujo, Ivan E; Gitelman, Darren R; Sherwin, Robert S; Sinha, Rajita; Small, Dana M

    2015-05-20

    In rodents, food-predictive cues elicit eating in the absence of hunger (Weingarten, 1983). This behavior is disrupted by the disconnection of amygdala pathways to the lateral hypothalamus (Petrovich et al., 2002). Whether this circuit contributes to long-term weight gain is unknown. Using fMRI in 32 healthy individuals, we demonstrate here that the amygdala response to the taste of a milkshake when sated but not hungry positively predicts weight change. This effect is independent of sex, initial BMI, and total circulating ghrelin levels, but it is only present in individuals who do not carry a copy of the A1 allele of the Taq1A polymorphism. In contrast, A1 allele carriers, who have decreased D2 receptor density (Blum et al., 1996), show a positive association between caudate response and weight change. Regardless of genotype, however, dynamic causal modeling supports unidirectional gustatory input from basolateral amygdala (BLA) to hypothalamus in sated subjects. This finding suggests that, as in rodents, external cues gain access to the homeostatic control circuits of the human hypothalamus via the amygdala. In contrast, during hunger, gustatory inputs enter the hypothalamus and drive bidirectional connectivity with the amygdala. These findings implicate the BLA-hypothalamic circuit in long-term weight change related to nonhomeostatic eating and provide compelling evidence that distinct brain mechanisms confer susceptibility to weight gain depending upon individual differences in dopamine signaling.

  20. β1-adrenoceptor activation is required for ethanol enhancement of lateral paracapsular GABAergic synapses in the rat basolateral amygdala.

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    Silberman, Yuval; Ariwodola, Olusegun J; Weiner, Jeff L

    2012-11-01

    Ethanol (EtOH) potentiation of GABAergic neurotransmission in the basolateral amygdala (BLA) may contribute to the acute anxiolytic effects of this drug. Previous studies have shown that BLA pyramidal neurons receive GABAergic input from two distinct sources: local interneurons and a cluster of GABAergic cells termed lateral paracapsular (LPCS) interneurons. It is noteworthy that whereas EtOH enhances local GABAergic synapses via a presynaptic increase in GABA release, EtOH potentiation of LPCS inhibition is mediated via a distinct mechanism that requires adrenoceptor (AR) activation. Here, we sought to further characterize the interaction between the AR system and EtOH enhancement of LPCS GABAergic synapses by using in vitro electrophysiology techniques in male Sprague-Dawley rats. Exogenous norepinephrine (NE) enhanced LPCS-evoked inhibitory postsynaptic currents (eIPSCs) via the activation of β-ARs, because this effect was blocked by propranolol. EtOH potentiation of LPCS eIPSCs was also blocked by propranolol and significantly reduced by NE pretreatment, suggesting that NE and EtOH may enhance LPCS inhibition via a common mechanism. EtOH enhancement of LPCS eIPSCs was significantly reduced by a selective β1-, but not β2- or β3-, AR antagonist, and both EtOH and NE potentiation of LPCS IPSCs was blocked by postsynaptic disruption of cAMP signaling. These data suggest that EtOH enhances LPCS synapses via a postsynaptic β1-AR, cAMP-dependent cascade. Because enhancement of LPCS inhibition can reduce anxiety-like behaviors, these findings shed light on a novel mechanism that may play a role in some of the anxiolytic effects of EtOH that are thought to contribute to the development and progression of alcoholism.

  1. Differential role of muscarinic transmission within the entorhinal cortex and basolateral amygdala in the processing of irrelevant stimuli.

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    Barak, Segev; Weiner, Ina

    2010-04-01

    Cholinergic projections to the entorhinal cortex (EC) and basolateral amygdala (BLA) mediate distinct cognitive processes through muscarinic acetylcholine receptors (mAChRs). In this study, we sought to further differentiate the role of muscarinic transmission in these regions in cognition, using the latent inhibition (LI) phenomenon. LI is a cross-species phenomenon manifested as poorer conditioning to a stimulus experienced as irrelevant during an earlier stage of repeated non-reinforced pre-exposure to that stimulus, and is considered to index the ability to ignore, or to in-attend to, irrelevant stimuli. Given our recent findings that systemic administration of the mAChR antagonist scopolamine can produce two contrasting LI abnormalities in rats, ie, abolish LI under conditions yielding LI in non-treated controls, or produce abnormally persistent LI under conditions preventing its expression in non-treated controls, we tested whether mAChR blockade in the EC and BLA would induce LI abolition and persistence, respectively. We found that intra-EC scopolamine infusion (1, 10 mug per hemisphere) abolished LI when infused in pre-exposure or both pre-exposure and conditioning, but not in conditioning alone, whereas intra-BLA scopolamine infusion led to persistent LI when infused in conditioning or both stages, but not in pre-exposure alone. Although cholinergic innervation of the EC and BLA has long been implicated in attention to novel stimuli and in processing of motivationally significant stimuli, respectively, our results provide evidence that EC mAChRs also have a role in the development of inattention to stimuli, whereas BLA mAChRs have a role in re-attending to previously irrelevant stimuli that became motivationally relevant.

  2. Involvement of BDNF signaling transmission from basolateral amygdala to infralimbic prefrontal cortex in conditioned taste aversion extinction.

    Science.gov (United States)

    Xin, Jian; Ma, Ling; Zhang, Tian-Yi; Yu, Hui; Wang, Yue; Kong, Liang; Chen, Zhe-Yu

    2014-05-21

    Brain-derived neurotrophic factor (BDNF) and its receptor, tropomyosin-related kinase receptor B (TrkB), play a critical role in memory extinction. However, the detailed role of BDNF in memory extinction on the basis of neural circuit has not been fully understood. Here, we aim to investigate the role of BDNF signaling circuit in mediating conditioned taste aversion (CTA) memory extinction of the rats. We found region-specific changes in BDNF gene expression during CTA extinction. CTA extinction led to increased BDNF gene expression in the basolateral amygdala (BLA) and infralimbic prefrontal cortex (IL) but not in the central amygdaloid nucleus (CeA) and hippocampus (HIP). Moreover, blocking BDNF signaling or exogenous microinjection of BDNF into the BLA or IL could disrupt or enhance CTA extinction, which suggested that BDNF signaling in the BLA and IL is necessary and sufficient for CTA extinction. Interestingly, we found that microinjection of BDNF-neutralizing antibody into the BLA could abolish the extinction training-induced BDNF mRNA level increase in the IL, but not vice versa, demonstrating that BDNF signaling is transmitted from the BLA to IL during extinction. Finally, the accelerated extinction learning by infusion of exogenous BDNF in the BLA could also be blocked by IL infusion of BDNF-neutralizing antibody rather than vice versa, indicating that the IL, but not BLA, is the primary action site of BDNF in CTA extinction. Together, these data suggest that BLA-IL circuit regulates CTA memory extinction by identifying BDNF as a key regulator.

  3. Third trimester-equivalent ethanol exposure increases anxiety-like behavior and glutamatergic transmission in the basolateral amygdala.

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    Baculis, Brian C; Diaz, Marvin R; Valenzuela, C Fernando

    2015-10-01

    Ethanol consumption during pregnancy produces a wide range of morphological and behavioral alterations known as fetal alcohol spectrum disorder (FASD). Among the behavioral deficits associated with FASD is an increased probability of developing anxiety disorders. Studies with animal models of FASD have demonstrated that ethanol exposure during the equivalent to the 1(st) and 2(nd) trimesters of human pregnancy increases anxiety-like behavior. Here, we examined the impact on this type of behavior of exposure to high doses of ethanol in vapor inhalation chambers during the rat equivalent to the human 3rd trimester of pregnancy (i.e., neonatal period in these animals). We evaluated anxiety-like behavior with the elevated plus maze. Using whole-cell patch-clamp electrophysiological techniques in brain slices, we also characterized glutamatergic and GABAergic synaptic transmission in the basolateral amygdala, a brain region that has been implicated to play a role in emotional behavior. We found that ethanol-exposed adolescent offspring preferred the closed arms over the open arms in the elevated plus maze and displayed lower head dipping activity than controls. Electrophysiological measurements showed an increase in the frequency of spontaneous and miniature excitatory postsynaptic currents in pyramidal neurons from the ethanol group. These findings suggest that high-dose ethanol exposure during the equivalent to the last trimester of human pregnancy can persistently increase excitatory synaptic inputs to principal neurons in the basolateral amygdala, leading to an increase in anxiety-like behaviors.

  4. Development of neurons and fibers containing calcium binding proteins in the pallial amygdala of mouse, with special emphasis on those of the basolateral amygdalar complex.

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    Legaz, Isabel; Olmos, Luis; Real, M Angeles; Guirado, Salvador; Dávila, José Carlos; Medina, Loreta

    2005-08-08

    We studied the development of neurons and fibers containing calbindin, calretinin, and parvalbumin in the mouse pallial amygdala, with special emphasis on those of the basolateral amygdalar complex. Numerous calbindin-immunoreactive (CB+) cells were observed in the incipient basolateral amygdalar complex and cortical amygdalar area from E13.5. At E16.5, CB+ cells became more abundant in the lateral and basolateral nuclei than in the basomedial nucleus, showing a pattern very similar to that of gamma-aminobutyric acid (GABA)ergic neurons. Many CB+ cells observed in the pallial amygdala appeared to originate in the anterior entopeduncular area/ganglionic eminences of the subpallium. The density of CB+ cells gradually increased in the pallial amygdala until the first postnatal week and appeared to decrease later, coinciding with the postnatal appearance of parvalbumin cells and raising the possibility of a partial phenotypic shift. Calretinin (CR) immunoreactivity could be observed in a few cells and fibers in the pallial amygdala at E14.5, and by E16.5 it became a good marker of the different nuclei of the basolateral amygdalar complex. Numerous CB+ and CR+ varicosities, part of which have an intrinsic origin, were observed in the basolateral amygdalar complex from E16.5, and some surrounded unstained perikarya and/or processes before birth, indicating an early formation of inhibitory networks. Each calcium binding protein showed a distinct spatiotemporal expression pattern of development in the mouse pallial amygdala. Any alteration in the development of neurons and fibers containing calcium binding proteins of the pallial amygdala may result in important disorders of emotional and social behavior.

  5. Infusions of AP5 into the basolateral amygdala impair the formation, but not the expression, of step-down inhibitory avoidance

    Directory of Open Access Journals (Sweden)

    Roesler R.

    2000-01-01

    Full Text Available We evaluated the effects of infusions of the NMDA receptor antagonist D,L-2-amino-5-phosphonopentanoic acid (AP5 into the basolateral nucleus of the amygdala (BLA on the formation and expression of memory for inhibitory avoidance. Adult male Wistar rats (215-300 g were implanted under thionembutal anesthesia (30 mg/kg, ip with 9.0-mm guide cannulae aimed 1.0 mm above the BLA. Bilateral infusions of AP5 (5.0 µg were given 10 min prior to training, immediately after training, or 10 min prior to testing in a step-down inhibitory avoidance task (0.3 mA footshock, 24-h interval between training and the retention test session. Both pre- and post-training infusions of AP5 blocked retention test performance. When given prior to the test, AP5 did not affect retention. AP5 did not affect training performance, and a control experiment showed that the impairing effects were not due to alterations in footshock sensitivity. The results suggest that NMDA receptor activation in the BLA is involved in the formation, but not the expression, of memory for inhibitory avoidance in rats. However, the results do not necessarily imply that the role of NMDA receptors in the BLA is to mediate long-term storage of fear-motivated memory within the amygdala.

  6. Proteolytic Cleavage of ProBDNF into Mature BDNF in the Basolateral Amygdala Is Necessary for Defeat-Induced Social Avoidance

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    Dulka, Brooke N.; Ford, Ellen C.; Lee, Melissa A.; Donnell, Nathaniel J.; Goode, Travis D.; Prosser, Rebecca; Cooper, Matthew A.

    2016-01-01

    Brain-derived neurotrophic factor (BDNF) is essential for memory processes. The present study tested whether proteolytic cleavage of proBDNF into mature BDNF (mBDNF) within the basolateral amygdala (BLA) regulates the consolidation of defeat-related memories. We found that acute social defeat increases the expression of mBDNF, but not proBDNF, in…

  7. Oxytocin Signaling in Basolateral and Central Amygdala Nuclei Differentially Regulates the Acquisition, Expression, and Extinction of Context-Conditioned Fear in Rats

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    Campbell-Smith, Emma J.; Holmes, Nathan M.; Lingawi, Nura W.; Panayi, Marios C.; Westbrook, R. Frederick

    2015-01-01

    The present study investigated how oxytocin (OT) signaling in the central (CeA) and basolateral (BLA) amygdala affects acquisition, expression, and extinction of context-conditioned fear (freezing) in rats. In the first set of experiments, acquisition of fear to a shocked context was impaired by a preconditioning infusion of synthetic OT into the…

  8. Interaction between the Basolateral Amygdala and Dorsal Hippocampus Is Critical for Cocaine Memory Reconsolidation and Subsequent Drug Context-Induced Cocaine-Seeking Behaviorin Rats

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    Wells, Audrey M.; Lasseter, Heather C.; Xie, Xiaohu; Cowhey, Kate E.; Reittinger, Andrew M.; Fuchs, Rita A.

    2011-01-01

    Contextual stimulus control over instrumental drug-seeking behavior relies on the reconsolidation of context-response-drug associative memories into long-term memory storage following retrieval-induced destabilization. According to previous studies, the basolateral amygdala (BLA) and dorsal hippocampus (DH) regulate cocaine-related memory…

  9. Cooperative interaction between the basolateral amygdala and ventral tegmental area modulates the consolidation of inhibitory avoidance memory.

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    Nazari-Serenjeh, Farzaneh; Rezayof, Ameneh

    2013-01-10

    The aim of the current study was to examine the existence of a cooperative interaction between the basolateral nucleus of amygdala (BLA) and the ventral tegmental area (VTA) in inhibitory avoidance task. The BLA and the VTA regions of adult male Wistar rats were simultaneously cannulated and memory consolidation was measured in a step-through type inhibitory avoidance apparatus. Post-training microinjection of muscimol, a potent GABA-A receptor agonist (0.01-0.02 μg/rat), into the VTA impaired memory in a dose-dependent manner. Post-training intra-BLA microinjection of NMDA (0.02-0.04 μg/rat), 5 min before the intra-VTA injection of muscimol (0.02 μg/rat), attenuated muscimol-induced memory impairment. Microinjection of a NMDA receptor antagonist, D-AP5 (0.02-0.06 μg/rat) into the BLA inhibited NMDA effect on the memory impairment induced by intra-VTA microinjection of muscimol. On the other hand, post-training intra-BLA microinjection of muscimol (0.02-0.04 μg/rat) dose-dependently decreased step-through latency, indicating an impairing effect on memory. This impairing effect was however significantly attenuated by intra-VTA microinjection of NMDA (0.01-0.03 μg/rat). Intra-VTA microinjection of D-AP5 (0.02-0.08 μg/rat), 5 min prior to NMDA injection, inhibited NMDA response on the impairing effect induced by intra-BLA microinjection of muscimol. It should be considered that post-training microinjection of the same doses of NMDA or D-AP5 into the BLA or the VTA alone had no effect on memory consolidation. The data suggest that the relationship between the BLA and the VTA in mediating memory consolidation in inhibitory avoidance learning may be dependent on a cooperative interaction between the glutamatergic and GABAergic systems via NMDA and GABA-A receptors.

  10. Injections of urocortin 1 into the basolateral amygdala induce anxiety-like behavior and c-Fos expression in brainstem serotonergic neurons.

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    Spiga, F; Lightman, S L; Shekhar, A; Lowry, C A

    2006-01-01

    The amygdala plays a key role in emotional processing and anxiety-related physiological and behavioral responses. Previous studies have shown that injections of the anxiety-related neuropeptide corticotropin-releasing factor or the related neuropeptide urocortin 1 into the region of the basolateral amygdaloid nucleus induce anxiety-like behavior in several behavioral paradigms. Brainstem serotonergic systems in the dorsal raphe nucleus and median raphe nucleus may be part of a distributed neural system that, together with the basolateral amygdala, regulates acute and chronic anxiety states. We therefore investigated the effect of an acute bilateral injection of urocortin 1 into the basolateral amygdala on behavior in the social interaction test and on c-Fos expression within serotonergic neurons in the dorsal raphe nucleus and median raphe nucleus. Male rats were implanted with bilateral cannulae directed at the region of the basolateral amygdala; 72 h after surgery, rats were injected with urocortin 1 (50 fmol/100 nl) or vehicle (100 nl of 1% bovine serum albumin in distilled water). Thirty minutes after injection, a subgroup of rats from each experimental group was exposed to the social interaction test; remaining animals were left in the home cage. Two hours after injection rats were perfused with paraformaldehyde and brains were removed and processed for immunohistochemistry. Acute injection of urocortin 1 had anxiogenic effects in the social interaction test, reducing total interaction time without affecting locomotor activity or exploratory behavior. These behavioral effects were associated with increases in c-Fos expression within brainstem serotonergic neurons. In home cage rats and rats exposed to the social interaction test, urocortin 1 treatment increased the number of c-Fos-immunoreactive serotonergic neurons within subdivisions of both the dorsal raphe nucleus and median raphe nucleus. These results are consistent with the hypothesis that the

  11. Long-term memory for pavlovian fear conditioning requires dopamine in the nucleus accumbens and basolateral amygdala.

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    Jonathan P Fadok

    Full Text Available The neurotransmitter dopamine (DA is essential for learning in a pavlovian fear conditioning paradigm known as fear-potentiated startle (FPS. Mice lacking the ability to synthesize DA fail to learn the association between the conditioned stimulus and the fear-inducing footshock. Previously, we demonstrated that restoration of DA synthesis to neurons of the ventral tegmental area (VTA was sufficient to restore FPS. Here, we used a target-selective viral restoration approach to determine which mesocorticolimbic brain regions receiving DA signaling from the VTA require DA for FPS. We demonstrate that restoration of DA synthesis to both the basolateral amygdala (BLA and nucleus accumbens (NAc is required for long-term memory of FPS. These data provide crucial insight into the dopamine-dependent circuitry involved in the formation of fear-related memory.

  12. Dorsal Periaqueductal gray simultaneously modulates ventral Subiculum induced-plasticity in the Basolateral Amygdala and the Nucleus Accumbens

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    Omer eHorovitz

    2015-03-01

    Full Text Available The ventral subiculum of the hippocampus projects both to the basolateral amygdala, which is typically, associated with a response to aversive stimuli, as well as to the nucleus accumbens, which is typically associated with a response to appetitive stimuli. Traditionally, studies of the responses to emotional events focus on either negative or positive affect-related processes, however, emotional experiences often affect both. The ability of high-level processing brain regions (e.g. medial prefrontal cortex to modulate the balance between negative and positive affect-related regions was examined extensively. In contrast, the ability of low-level processing areas (e.g. periaqueductal grey - PAG to do so, has not been sufficiently studied. To address whether midbrain structures have the ability to modulate limbic regions, we first examined the ventral subiculum stimulation’s (vSub ability to induce plasticity in the basolateral amygdala (BLA and nucleus accumbens (NAcc simultaneously in rats. Further, dorsal PAG (dPAG priming ability to differentially modulate vSub stimulation induced plasticity in the BLA and the NAcc was subsequently examined. vSub stimulation resulted in plasticity in both the BLA and the NAcc simultaneously. Moreover, depending on stimulus intensity, differential dPAG priming effects on LTP in these two regions were observed. The results demonstrate that negative and positive affect-related processes may be simultaneously modulated. Furthermore, under some conditions lower-level processing areas, such as the dPAG, may differentially modulate plasticity in these regions and thus affect the long-term emotional outcome of the experience.

  13. Differential expression of Kv3.1b and Kv3.2 potassium channel subunits in interneurons of the basolateral amygdala.

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    McDonald, A J; Mascagni, F

    2006-01-01

    The expression of Kv3.1 and Kv3.2 voltage-gated potassium channel subunits appears to be critical for high-frequency firing of many neuronal populations. In the cortex these subunits are mainly associated with fast-firing GABAergic interneurons containing parvalbumin or somatostatin. Since the basolateral nuclear complex of the amygdala contains similar interneurons, it is of interest to determine if these potassium channel subunits are expressed in these same interneuronal subpopulations. To investigate this issue, peroxidase and dual-labeling fluorescence immunohistochemistry combined with confocal laser scanning microscopy was used to determine which interneuronal subpopulations in the basolateral nuclear complex of the rat amygdala express Kv3.1b and Kv3.2 subunits. Antibodies to parvalbumin, somatostatin, calretinin, and cholecystokinin were used to label separate subsets of basolateral amygdalar interneurons. Examination of immunoperoxidase preparations suggested that the expression of both channels was restricted to nonpyramidal interneurons in the basolateral amygdala. Somata and proximal dendrites were intensely-stained, and axon terminals arising from presumptive basket cells and chandelier cells were lightly stained. Immunofluorescence observations revealed that parvalbumin+ neurons were the main interneuronal subpopulation expressing the Kv3.1b potassium channel subunit in the basolateral amygdala. More than 92-96% of parvalbumin+ neurons were Kv3.1b+, depending on the nucleus. These parvalbumin+/Kv3.1b+ double-labeled cells constituted 90-99% of all Kv3.1b+ neurons. Parvalbumin+ neurons were also the main interneuronal subpopulation expressing the Kv3.2 potassium channel subunit. More than 67-78% of parvalbumin+ neurons were Kv3.2+, depending on the nucleus. However, these parvalbumin+/Kv3.2+ double-labeled cells constituted only 71-81% of all Kv3.2+ neurons. Most of the remaining neurons with significant levels of the Kv3.2 subunit were somatostatin

  14. Angiotensin II’s role in sodium lactate-induced panic-like responses in rats with repeated urocortin 1 injections into the basolateral amygdala

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    Johnson, Philip L.; Sajdyk, Tammy J.; Fitz, Stephanie D; Hale, Mathew W.; Lowry, Christopher A.; Hay-Schmidt, Anders; Shekhar, Anantha

    2013-01-01

    Rats treated with three daily urocortin 1 (UCN) injections into the basolateral amygdala (BLA; i.e., UCN/BLA-primed rats) develop prolonged anxiety-associated behavior and vulnerability to panic-like physiological responses (i.e., tachycardia, hypertension and tachypnea) following intravenous infusions of 0.5 M sodium lactate (NaLac, an ordinarily mild interoceptive stressor). In these UCN-primed rats, the osmosensitive subfornical organ (SFO) may be a potential site that detects increases in...

  15. Incentive memory: evidence the basolateral amygdala encodes and the insular cortex retrieves outcome values to guide choice between goal-directed actions.

    Science.gov (United States)

    Parkes, Shauna L; Balleine, Bernard W

    2013-05-15

    Choice between goal-directed actions is determined by the relative value of their consequences. Such values are encoded during incentive learning and later retrieved to guide performance. Although the basolateral amygdala (BLA) and the gustatory region of insular cortex (IC) have been implicated in these processes, their relative contribution is still a matter of debate. Here we assessed whether these structures interact during incentive learning and retrieval to guide choice. In these experiments, rats were trained on two actions for distinct outcomes after which one of the two outcomes was devalued by specific satiety immediately before a choice extinction test. We first confirmed that, relative to appropriate controls, outcome devaluation recruited both the BLA and IC based on activation of the immediate early gene Arc; however, we found that infusion of the NMDAr antagonist ifenprodil into the BLA only abolished outcome devaluation when given before devaluation. In contrast, ifenprodil infusion into the IC was effective whether made before devaluation or test. We hypothesized that the BLA encodes and the IC retrieves incentive value for choice and, to test this, developed a novel sequential disconnection procedure. Blocking NMDAr activation unilaterally in the BLA before devaluation and then contralaterally in the IC before test abolished selective devaluation. In contrast, reversing the order of these infusions left devaluation intact. These results confirm that the BLA and IC form a circuit mediating the encoding and retrieval of outcome values, with the BLA encoding and the IC retrieving such values to guide choice.

  16. Infusion of methylphenidate into the basolateral nucleus of amygdala or anterior cingulate cortex enhances fear memory consolidation in rats

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    The psychostimulant methylphenidate (MPD; also called Ritalin) is a blocker of dopamine and norepi-nephrine transporter. It has been clinically used for treatment of Attention Deficit and Hyperactivity Disorder (ADHD). There have been inconsistent reports regarding the effects of systemically adminis-tered MPD on learning and memory, either in animals or humans. In the present study, we investigated the effect of direct infusion of MPD into the basolateral nucleus of amygdala (BLA) or the anterior cin-gulate cortex (ACC) on conditioned fear memory. Rats were trained on a one-trial step-through inhibi-tory avoidance task. MPD was infused bilaterally into the BLA or the ACC, either at ‘0’ or 6 h post-training. Saline was administered as control. Memory retention was tested 48 h post-training. In-tra-BLA or intra-ACC infusion of MPD ‘0’ h but not 6 h post-training significantly improved 48-h memory retention: the MPD-treated rats had significant longer step-through latency than controls. The present results indicate that action of MPD in the BLA or the ACC produces a beneficial effect on the consoli-dation of inhibitory avoidance memory.

  17. Chronic cerebrolysin administration attenuates neuronal abnormalities in the basolateral amygdala induced by neonatal ventral hippocampus lesion in the rat.

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    Vázquez-Roque, Rubén Antonio; Ubhi, Kiren; Masliah, Eliezer; Flores, Gonzalo

    2014-01-01

    The neonatal ventral hippocampal lesion (nVHL) has emerged as a model of schizophrenia-related behavior in the rat. Our previous report demonstrated that cerebrolysin (Cbl), a neuropeptide preparation which mimics the action of endogenous neurotrophic factors on brain protection and repair, promoted recovery of dendritic and neuronal damage of the prefrontal cortex and nucleus accumbens and behavioral improvements in postpubertal nVHL rats. We recently demonstrated that nVHL animals exhibit dendritic atrophy and spine loss in the basolateral amygdala (BLA). This study aimed to determine whether Cbl treatment was capable of reducing BLA neuronal alterations observed in nVHL rats. The morphological evaluation included examination of dendrites using the Golgi-Cox procedure and stereology to quantify the total cell number in BLA. Golgi-Cox staining revealed that nVHL induced dendritic retraction and spine loss in BLA pyramidal neurons. Stereological analysis demonstrated nVHL also produced a reduction in cells in BLA. Interestingly, repeated Cbl treatment ameliorated dendritic pathology and neuronal loss in the BLA of the nVHL rats. Our data show that Cbl may foster recovery of BLA damage in postpubertal nVHL rats and suggests that the use of neurotrophic agents for the management of some schizophrenia-related symptoms may present an alternative therapeutic pathway in these disorders.

  18. Basolateral amygdala lesions attenuate safe taste memory-related c-fos expression in the rat perirhinal cortex.

    Science.gov (United States)

    Gómez-Chacón, Beatriz; Gámiz, Fernando; Gallo, Milagros

    2012-05-01

    Previous results indicated that damage and pharmacological inactivation of the basolateral amygdala (BLA) interfere with the attenuation of taste neophobia. A similar disruption of safe taste memories formation induced by the inhibition of protein synthesis in the perirhinal cortex (PRh) has been reported. Thus, we have assessed the effect of bilateral BLA neurotoxic lesions on PRh activity after novel and familiar taste exposure. Wistar male rats with NMDA lesions of the BLA and SHAM-operated received two consecutive exposures to a 3% cider vinegar solution. Fos-like immunoreactivity (FLI) was examined as a marker of neuronal activity in PRh. As expected the BLA lesioned group showed no evidence of neophobia attenuation. A similar number of PRh Fos-positive cells were found in SHAM and BLA groups exposed to the novel taste solution. However, the BLA-lesioned group exhibited a lower number of Fos stained cells than the SHAM-lesioned group after being exposed to the familiar taste solution. This supports the notion of BLA and PRh as components of a neural circuit involved in safe taste recognition memory and suggests a role of PRh in various forms of recognition memory.

  19. The basolateral amygdala is critical to the expression of pavlovian and instrumental outcome-specific reinforcer devaluation effects.

    Science.gov (United States)

    Johnson, Alexander W; Gallagher, Michela; Holland, Peter C

    2009-01-21

    Considerable evidence implicates the basolateral amygdala (BLA) in the formation of outcome representations that link cues to the incentive properties of reinforcers. Animals with BLA damage show impaired performance in reinforcer devaluation tasks, in which the value of the food reinforcer is reduced by satiation or food-toxin pairings after the completion of cue or response training. Although intact animals spontaneously reduce their conditioned responding after such reinforcer devaluation procedures, animals with BLA lesions made before training typically do not, as evidenced across a range of species, training contingencies, and devaluation procedures. In contrast, the role of the BLA in devaluation task performance once such outcome representations are established is unclear. Whereas Pickens et al. (2003) found normal devaluation performance in rats when BLA lesions were made after pavlovian light-food pairings but before devaluation by food-toxin pairings, Ostlund and Balleine (2008) found impaired devaluation performance when BLA lesions were made after instrumental training with multiple instrumental responses and food reinforcers but before devaluation of one reinforcer by selective satiation. Those studies differed in their use of pavlovian or operant training contingencies, single or multiple reinforcers, and associative or motivational devaluation procedures. Here we found that, when multiple reinforcers were used, posttraining BLA lesions disrupted the expression of devaluation performance in rats, using either pavlovian or instrumental training procedures and either conditioned taste aversion or satiation devaluation procedures. Thus, BLA apparently plays a critical role in maintaining or using sensory associations of reinforcer value when multiple outcomes must be coded but not under single-outcome conditions.

  20. Dissociable roles for the basolateral amygdala and orbitofrontal cortex in decision-making under risk of punishment.

    Science.gov (United States)

    Orsini, Caitlin A; Trotta, Rose T; Bizon, Jennifer L; Setlow, Barry

    2015-01-28

    Several neuropsychiatric disorders are associated with abnormal decision-making involving risk of punishment, but the neural basis of this association remains poorly understood. Altered activity in brain systems including the basolateral amygdala (BLA) and orbitofrontal cortex (OFC) can accompany these same disorders, and these structures are implicated in some forms of decision-making. The current study investigated the role of the BLA and OFC in decision-making under risk of explicit punishment. Rats were trained in the risky decision-making task (RDT), in which they chose between two levers, one that delivered a small safe reward, and the other that delivered a large reward accompanied by varying risks of footshock punishment. Following training, they received sham or neurotoxic lesions of BLA or OFC, followed by RDT retesting. BLA lesions increased choice of the large risky reward (greater risk-taking) compared to both prelesion performance and sham controls. When reward magnitudes were equated, both BLA lesion and control groups shifted their choice to the safe (no shock) reward lever, indicating that the lesions did not impair punishment sensitivity. In contrast to BLA lesions, OFC lesions significantly decreased risk-taking compared with sham controls, but did not impair discrimination between different reward magnitudes or alter baseline levels of anxiety. Finally, neither lesion significantly affected food-motivated lever pressing under various fixed ratio schedules, indicating that lesion-induced alterations in risk-taking were not secondary to changes in appetitive motivation. Together, these findings indicate distinct roles for the BLA and OFC in decision-making under risk of explicit punishment.

  1. Unilateral inactivation of the basolateral amygdala attenuates context-induced renewal of Pavlovian-conditioned alcohol-seeking.

    Science.gov (United States)

    Chaudhri, N; Woods, C A; Sahuque, L L; Gill, T M; Janak, P H

    2013-09-01

    Environmental contexts associated with drug use promote craving in humans and drug-seeking in animals. We hypothesized that the basolateral amygdala (BLA) itself as well as serial connectivity between the BLA and nucleus accumbens core (NAC core) were required for context-induced renewal of Pavlovian-conditioned alcohol-seeking. Male Long-Evans rats were trained to discriminate between two conditioned stimuli (CS): a CS+ that was paired with ethanol (EtOH, 20%, v/v) delivery into a fluid port (0.2 mL/CS+, 3.2 mL per session) and a CS- that was not. Entries into the port during each CS were measured. Next, rats received extinction in a different context where both cues were presented without EtOH. At test, responding to the CS+ and CS- without EtOH was evaluated in the prior training context. Control subjects showed a selective increase in CS+ responding relative to extinction, indicative of renewal. This effect was blocked by pre-test, bilateral inactivation of the BLA using a solution of GABA receptor agonists (0.1 mm muscimol and 1.0 mm baclofen; M/B; 0.3 μL per side). Renewal was also attenuated following unilateral injections of M/B into the BLA, combined with either M/B, the dopamine D1 receptor antagonist SCH 23390 (0.6 μg per side) or saline infusion in the contralateral NAC core. Hence, unilateral BLA inactivation was sufficient to disrupt renewal, highlighting a critical role for functional activity in the BLA in enabling the reinstatement of alcohol-seeking driven by an alcohol context.

  2. Noradrenergic Activation of the Basolateral Amygdala Enhances Object Recognition Memory and Induces Chromatin Remodeling in the Insular Cortex

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    Hassiba eBeldjoud

    2015-04-01

    Full Text Available It is well established that arousal-induced memory enhancement requires noradrenergic activation of the basolateral complex of the amygdala (BLA and modulatory influences on information storage processes in its many target regions. While this concept is well accepted, the molecular basis of such BLA effects on neural plasticity changes within other brain regions remains to be elucidated. The present study investigated whether noradrenergic activation of the BLA after object recognition training induces chromatin remodeling through histone post-translational modifications in the insular cortex (IC, a brain region that is importantly involved in object recognition memory. Male Sprague–Dawley rats were trained on an object recognition task, followed immediately by bilateral microinfusions of norepinephrine (1.0 µg or saline administered into the BLA. Saline-treated control rats exhibited poor 24-h retention, whereas norepinephrine treatment induced robust 24-h object recognition memory. Most importantly, this memory-enhancing dose of norepinephrine induced a global reduction in the acetylation levels of histone H3 at lysine 14, H2B and H4 in the IC 1 h later, whereas it had no effect on the phosphorylation of histone H3 at serine 10 or tri-methylation of histone H3 at lysine 27. Norepinephrine administered into the BLA of non-trained control rats did not induce any changes in the histone marks investigated in this study. These findings indicate that noradrenergic activation of the BLA induces training-specific effects on chromatin remodeling mechanisms, and presumably gene transcription, in its target regions, which may contribute to the understanding of the molecular mechanisms of stress and emotional arousal effects on memory consolidation.

  3. Localization of the CB1 type cannabinoid receptor in the rat basolateral amygdala: high concentrations in a subpopulation of cholecystokinin-containing interneurons.

    Science.gov (United States)

    McDonald, A J; Mascagni, F

    2001-01-01

    The neuronal localization of the CB1 cannabinoid receptor in the rat basolateral amygdala was studied using peroxidase and fluorescence immunohistochemical techniques. All nuclei of the basolateral amygdala contained a large number of lightly stained pyramidal neurons and a small number of more intensely stained non-pyramidal neurons. Most of the latter cells had medium-sized to large multipolar somata and three to four aspiny dendrites, but some exhibited smaller oval somata. The axon initial segments of some of these non-pyramidal neurons exhibited large swollen varicosities in colchicine-injected animals, suggesting that much of the CB1 receptor protein is transported down the axons of these cells. Double-labeling studies using immunofluorescence histochemistry combined with confocal laser scanning microscopy revealed that the great majority of non-pyramidal neurons with CB1 receptor immunoreactivity belonged to a cholecystokinin-containing subpopulation. Whereas none of the other subpopulations of non-pyramidal neurons (exhibiting immunoreactivity for calretinin, parvalbumin, or somatostatin) expressed high levels of CB1 receptor immunoreactivity, a small percentage of these cells exhibited low levels of immunoreactivity. The results indicate that cannabinoids may modulate the activity of pyramidal projection neurons as well as a subpopulation of cholecystokinin-containing non-pyramidal neurons in the basolateral amygdala. Previous studies indicate that most of the latter are inhibitory interneurons that utilize GABA as a neurotransmitter. The intense staining of the cholecystokinin-containing interneurons and the evidence that large amounts of CB1 receptor protein are transported down the axons of these cells suggests that, as in the hippocampus, cannabinoids may inhibit the release of GABA from the axon terminals of these neurons.

  4. Ketamine prevents lidocaine-caused neurotoxicity in the CA3 hippocampal and basolateral amygdala regions of the brain in adult rats.

    Science.gov (United States)

    Lopez-Galindo, Gabriel Eduardo; Cano-Europa, Edgar; Ortiz-Butron, Rocio

    2008-01-01

    Our objective was to prove whether blocking the action of glutamate on N-methyl-D: -aspartate (NMDA) receptors could prevent the neuronal damage caused by the acute administration of lidocaine. Twenty male 2-month-old Wistar rats were randomly assigned to the following groups (n = 5 in each group): groups I and II received 0.9% saline i.p., and groups III and IV received 100 mg x kg(-1) of ketamine i.p. Thirty minutes later, groups I and III were again dosed with 0.9% saline i.p., and groups II and IV received 60 mg x kg(-1) of lidocaine i.p. During treatment, the rectal temperature of the animals was monitored and maintained at 37.5 +/- 0.5 degrees C. Ten days after administration of the agents, all rats were transcardially perfused, under pentobarbital anesthesia, with 10% formaldehyde. Their brains were removed and were embedded in paraffin. Coronal cuts of 7 microm were obtained from -2.3 to -3.8 mm from the bregma. Each brain section was stained with cresyl violet-eosin. The number of normal and abnormal pyramidal neurons in the CA3 hippocampal region and the number of large and medium neurons in the basolateral amygdala within an area of 10 000 microm2 were evaluated. We found that lidocaine significantly reduced the number of normal neurons in both the CA3 hippocampal region (F (3,16) = 225.8; P lidocaine-induced damage in the CA3 hippocampal region and the basolateral amygdala. These results demonstrate the participation of NMDA-receptor activation by lidocaine in the CA3 hippocampal and basolateral amygdala regions as a neurotoxic mechanism.

  5. Low dose prenatal ethanol exposure induces anxiety-like behaviour and alters dendritic morphology in the basolateral amygdala of rat offspring.

    Directory of Open Access Journals (Sweden)

    Carlie L Cullen

    Full Text Available Prenatal exposure to high levels of alcohol is strongly associated with poor cognitive outcomes particularly in relation to learning and memory. It is also becoming more evident that anxiety disorders and anxiety-like behaviour can be associated with prenatal alcohol exposure. This study used a rat model to determine if prenatal exposure to a relatively small amount of alcohol would result in anxiety-like behaviour and to determine if this was associated with morphological changes in the basolateral amygdala. Pregnant Sprague Dawley rats were fed a liquid diet containing either no alcohol (Control or 6% (vol/vol ethanol (EtOH throughout gestation. Male and Female offspring underwent behavioural testing at 8 months (Adult or 15 months (Aged of age. Rats were perfusion fixed and brains were collected at the end of behavioural testing for morphological analysis of pyramidal neuron number and dendritic morphology within the basolateral amygdala. EtOH exposed offspring displayed anxiety-like behaviour in the elevated plus maze, holeboard and emergence tests. Although sexually dimorphic behaviour was apparent, sex did not impact anxiety-like behaviour induced by prenatal alcohol exposure. This increase in anxiety - like behaviour could not be attributed to a change in pyramidal cell number within the BLA but rather was associated with an increase in dendritic spines along the apical dendrite which is indicative of an increase in synaptic connectivity and activity within these neurons. This study is the first to link increases in anxiety like behaviour to structural changes within the basolateral amygdala in a model of prenatal ethanol exposure. In addition, this study has shown that exposure to even a relatively small amount of alcohol during development leads to long term alterations in anxiety-like behaviour.

  6. Lateral/Basolateral Amygdala Serotonin Type-2 Receptors Modulate Operant Self-administration of a Sweetened Ethanol Solution via Inhibition of Principal Neuron Activity

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    Brian eMccool

    2014-01-01

    Full Text Available The lateral/basolateral amygdala (BLA forms an integral part of the neural circuitry controlling innate anxiety and learned fear. More recently, BLA dependent modulation of self-administration behaviors suggests a much broader role in the regulation of reward evaluation. To test this, we employed a self-administration paradigm that procedurally segregates ‘seeking’ (exemplified as lever-press behaviors from consumption (drinking directed at a sweetened ethanol solution. Microinjection of the nonselective serotonin type-2 receptor agonist, alpha-methyl-5-hydroxytryptamine (-m5HT into the BLA reduced lever pressing behaviors in a dose-dependent fashion. This was associated with a significant reduction in the number of response-bouts expressed during non-reinforced sessions without altering the size of a bout or the rate of responding. Conversely, intra-BLA -m5HT only modestly effected consumption-related behaviors; the highest dose reduced the total time spent consuming a sweetened ethanol solution but did not inhibit the total number of licks, number of lick bouts, or amount of solution consumed during a session. In vitro neurophysiological characterization of BLA synaptic responses showed that -m5HT significantly reduced extracellular field potentials. This was blocked by the 5-HT2A/C antagonist ketanserin suggesting that 5-HT2-like receptors mediate the behavioral effect of -m5HT. During whole-cell patch current-clamp recordings, we subsequently found that -m5HT increased action potential threshold and hyperpolarized the resting membrane potential of BLA pyramidal neurons. Together, our findings show that the activation of BLA 5-HT2A/C receptors inhibits behaviors related to reward-seeking by suppressing BLA principal neuron activity. These data are consistent with the hypothesis that the BLA modulates reward-related behaviors and provides specific insight into BLA contributions during operant self-administration of a

  7. The inactivation of the basolateral nucleus of the rat amygdala has an anxiolytic effect in the elevated T-maze and light/dark transition tests

    Directory of Open Access Journals (Sweden)

    Bueno C.H.

    2005-01-01

    Full Text Available Pharmacological evidence indicates that the basolateral nucleus of the amygdala (BLA is involved in the mediation of inhibitory avoidance but not of escape behavior in the elevated T-maze test. These defensive responses have been associated with generalized anxiety disorder (GAD and panic disorder, respectively. In the present study, we determined whether the BLA plays a differential role in the control of inhibitory avoidance and escape responses in the elevated T-maze. Male Wistar rats (250-280 g, N = 9-10 in each treatment group were pre-exposed to one of the open arms of the maze for 30 min and 24 h later tested in the model after inactivation of the BLA by a local injection of the GABA A receptor agonist muscimol (8 nmol in 0.2 µL. It has been shown that a prior forced exposure to one of the open arms of the maze, by shortening latencies to withdrawal from the open arm during the test, improves the escape task as a behavioral index of panic. The effects of muscimol in the elevated T-maze were compared to those caused by this GABA agonist in the avoidance reaction generated in the light/dark transition test. This defensive behavior has also been associated with GAD. In the elevated T-maze, intra-BLA injection of muscimol impaired inhibitory avoidance (control: 187.70 ± 14.90 s, muscimol: 37.10 ± 2.63 s, indicating an anxiolytic effect, without interfering with escape performance. The drug also showed an anxiolytic effect in the light/dark transition test as indicated by the increase in the time spent in the lighted compartment (control: 23.50 ± 2.45 s, muscimol: 47.30 ± 4.48 s. The present findings point to involvement of the BLA in the modulation of defensive responses that have been associated with GAD.

  8. Activation of exchange protein activated by cAMP in the rat basolateral amygdala impairs reconsolidation of a memory associated with self-administered cocaine.

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    Xun Wan

    Full Text Available The intracellular mechanisms underlying memory reconsolidation critically involve cAMP signaling. These events were originally attributed to PKA activation by cAMP, but the identification of Exchange Protein Activated by cAMP (Epac, as a distinct mediator of cAMP signaling, suggests that cAMP-regulated processes that subserve memory reconsolidation are more complex. Here we investigated how activation of Epac with 8-pCPT-cAMP (8-CPT impacts reconsolidation of a memory that had been associated with cocaine self-administration. Rats were trained to lever press for cocaine on an FR-1 schedule, in which each cocaine delivery was paired with a tone+light cue. Lever pressing was then extinguished in the absence of cue presentations and cocaine delivery. Following the last day of extinction, rats were put in a novel context, in which the conditioned cue was presented to reactivate the cocaine-associated memory. Immediate bilateral infusions of 8-CPT into the basolateral amygdala (BLA following reactivation disrupted subsequent cue-induced reinstatement in a dose-dependent manner, and modestly reduced responding for conditioned reinforcement. When 8-CPT infusions were delayed for 3 hours after the cue reactivation session or were given after a cue extinction session, no effect on cue-induced reinstatement was observed. Co-administration of 8-CPT and the PKA activator 6-Bnz-cAMP (10 nmol/side rescued memory reconsolidation while 6-Bnz alone had no effect, suggesting an antagonizing interaction between the two cAMP signaling substrates. Taken together, these studies suggest that activation of Epac represents a parallel cAMP-dependent pathway that can inhibit reconsolidation of cocaine-cue memories and reduce the ability of the cue to produce reinstatement of cocaine-seeking behavior.

  9. Presynaptic facilitation of glutamate release in the basolateral amygdala: a mechanism for the anxiogenic and seizurogenic function of GluK1 receptors.

    Science.gov (United States)

    Aroniadou-Anderjaska, V; Pidoplichko, V I; Figueiredo, T H; Almeida-Suhett, C P; Prager, E M; Braga, M F M

    2012-09-27

    Kainate receptors containing the GluK1 subunit (GluK1Rs; previously known as GluR5 kainate receptors) are concentrated in certain brain regions, where they play a prominent role in the regulation of neuronal excitability, by modulating GABAergic and/or glutamatergic synaptic transmission. In the basolateral nucleus of the amygdala (BLA), which plays a central role in anxiety as well as in seizure generation, GluK1Rs modulate GABAergic inhibition via postsynaptic and presynaptic mechanisms. However, the role of these receptors in the regulation of glutamate release, and the net effect of their activation on the excitability of the BLA network are not well understood. Here, we show that in amygdala slices from 35- to 50-day-old rats, the GluK1 agonist (RS)-2-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl) propanoic acid (ATPA) (300 nM) increased the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) and miniature EPSCs (mEPSCs) recorded from BLA principal neurons, and decreased the rate of failures of evoked EPSCs. The GluK1 antagonist (S)-1-(2-amino-2-carboxyethyl)-3-(2-carboxybenzyl) pyrimidine-2,4-dione (UBP302) (25 or 30 μM) decreased the frequency of mEPSCs, reduced evoked field potentials, and increased the "paired-pulse ratio" of the field potential amplitudes. Taken together, these results suggest that GluK1Rs in the rat BLA are present on presynaptic terminals of principal neurons, where they mediate facilitation of glutamate release. In vivo bilateral microinjections of ATPA (250 pmol) into the rat BLA increased anxiety-like behavior in the open field test, while 2 nmol ATPA induced seizures. Similar intra-BLA injections of UBP302 (20 nmol) had anxiolytic effects in the open field and the acoustic startle response tests, without affecting pre-pulse inhibition. These results suggest that although GluK1Rs in the rat BLA facilitate both GABA and glutamate release, the facilitation of glutamate release prevails, and these receptors can have an

  10. Activation of the basolateral amygdala induces long-term enhancement of specific memory representations in the cerebral cortex.

    Science.gov (United States)

    Chavez, Candice M; McGaugh, James L; Weinberger, Norman M

    2013-03-01

    The basolateral amygdala (BLA) modulates memory, particularly for arousing or emotional events, during post-training periods of consolidation. It strengthens memories whose substrates in part or whole are stored remotely, in structures such as the hippocampus, striatum and cerebral cortex. However, the mechanisms by which the BLA influences distant memory traces are unknown, largely because of the need for identifiable target mnemonic representations. Associative tuning plasticity in the primary auditory cortex (A1) constitutes a well-characterized candidate specific memory substrate that is ubiquitous across species, tasks and motivational states. When tone predicts reinforcement, the tuning of cells in A1 shifts toward or to the signal frequency within its tonotopic map, producing an over-representation of behaviorally important sounds. Tuning shifts have the cardinal attributes of forms of memory, including associativity, specificity, rapid induction, consolidation and long-term retention and are therefore likely memory representations. We hypothesized that the BLA strengthens memories by increasing their cortical representations. We recorded multiple unit activity from A1 of rats that received a single discrimination training session in which two tones (2.0 s) separated by 1.25 octaves were either paired with brief electrical stimulation (400 ms) of the BLA (CS+) or not (CS-). Frequency response areas generated by presenting a matrix of test tones (0.5-53.82 kHz, 0-70 dB) were obtained before training and daily for 3 weeks post-training. Tuning both at threshold and above threshold shifted predominantly toward the CS+ beginning on day 1. Tuning shifts were maintained for the entire 3 weeks. Absolute threshold and bandwidth decreased, producing less enduring increases in sensitivity and selectivity. BLA-induced tuning shifts were associative, highly specific and long-lasting. We propose that the BLA strengthens memory for important experiences by increasing the

  11. Activation of ERK2 in basolateral amygdala underlies the promoting influence of stress on fear memory and anxiety: influence of midazolam pretreatment.

    Science.gov (United States)

    Maldonado, N M; Espejo, P J; Martijena, I D; Molina, V A

    2014-02-01

    Exposure to emotionally arousing experiences elicits a robust and persistent memory and enhances anxiety. The amygdala complex plays a key role in stress-induced emotional processing and in the fear memory formation. It is well known that ERK activation in the amygdala is a prerequisite for fear memory consolidation. Moreover, stress elevates p-ERK2 levels in several areas of the brain stress circuitry. Therefore, given that the ERK1/2 cascade is activated following stress and that the role of this cascade is critical in the formation of fear memory, the present study investigated the potential involvement of p-ERK2 in amygdala subnuclei in the promoting influence of stress on fear memory formation and on anxiety-like behavior. A robust and persistent ERK2 activation was noted in the Basolateral amygdala (BLA), which was evident at 5min after restraint and lasted at least one day after the stressful experience. Midazolam, a short-acting benzodiazepine ligand, administered prior to stress prevented the increase in the p-ERK2 level in the BLA. Pretreatment with intra-BLA infusion of U0126 (MEK inhibitor), but not into the adjacent central nucleus of the amygdala, attenuated the stress-induced promoting influence on fear memory formation. Finally, U0126 intra-BLA infusion prevented the enhancement of anxiety-like behavior in stressed animals. These findings suggest that the selective ERK2 activation in BLA following stress exposure is an important mechanism for the occurrence of the promoting influence of stress on fear memory and on anxiety-like behavior.

  12. Anxiolytic effects of kindling role of anatomical location of the kindling electrode in response to kindling of the right basolateral amygdala.

    Science.gov (United States)

    Adamec, Robert; Blundell, Jacqueline; Burton, Paul

    2004-10-22

    Study of effects of kindling on affect has been complicated by the fact that anxiogenic, anxiolytic or no effects may be observed following kindling of the amygdala. Factors affecting behavioral outcome include strain of rat, hemisphere kindled, amygdala nucleus kindled and location of the kindling electrodes within particular AP planes of a given nucleus. Previous work has suggested that kindling of the right basolateral amygdala (BLA) is predominantly anxiogenic. This conclusion was based on kindling of anterior or posterior parts of the BLA. The present study sought to clarify this conclusion by examining behavioral effects of right BLA kindling in a mid-range of AP planes not yet studied. A variety of measures of rodent anxiety-like behavior were examined, including behavior in the hole board, elevated plus maze, light/dark box, social interaction test and unconditioned acoustic startle. Anhedonic effects of kindling were assessed by a sucrose preference test with controls for fluid consumption and taste sensitivities. All effects were assessed shortly after kindling (1-2 days) and at a longer time interval (7-8 days). Kindling to four stage 5 seizures in the mid-right BLA altered behavior at all time points after kindling in all tests except the hole board and light/dark box tests. The effect of kindling was anxiolytic like in the plus maze, social interaction and startle tests. Kindling in mid-BLA also increased sucrose consumption. Effects on sucrose consumption are consistent with previous studies showing no depressive-like effects of amygdala kindling in rodents. It is hypothesized that the focal nature of the behavioral consequences of amygdala kindling are best understood in the context of the circuitry in which the cells stimulated are imbedded and the impact of kindling on functioning of those circuits.

  13. Capsaicin-induced changes in LTP in the lateral amygdala are mediated by TRPV1.

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    Carsten Zschenderlein

    Full Text Available The transient receptor potential vanilloid type 1 (TRPV1 channel is a well recognized polymodal signal detector that is activated by painful stimuli such as capsaicin. Here, we show that TRPV1 is expressed in the lateral nucleus of the amygdala (LA. Despite the fact that the central amygdala displays the highest neuronal density, the highest density of TRPV1 labeled neurons was found within the nuclei of the basolateral complex of the amygdala. Capsaicin specifically changed the magnitude of long-term potentiation (LTP in the LA in brain slices of mice depending on the anesthetic (ether, isoflurane used before euthanasia. After ether anesthesia, capsaicin had a suppressive effect on LA-LTP both in patch clamp and in extracellular recordings. The capsaicin-induced reduction of LTP was completely blocked by the nitric oxide synthase (NOS inhibitor L-NAME and was absent in neuronal NOS as well as in TRPV1 deficient mice. The specific antagonist of cannabinoid receptor type 1 (CB1, AM 251, was also able to reduce the inhibitory effect of capsaicin on LA-LTP, suggesting that stimulation of TRPV1 provokes the generation of anandamide in the brain which seems to inhibit NO synthesis. After isoflurane anesthesia before euthanasia capsaicin caused a TRPV1-mediated increase in the magnitude of LA-LTP. Therefore, our results also indicate that the appropriate choice of the anesthetics used is an important consideration when brain plasticity and the action of endovanilloids will be evaluated. In summary, our results demonstrate that TRPV1 may be involved in the amygdala control of learning mechanisms.

  14. Distinctive roles of 5-Aza-2′-deoxycytidine in Anterior Agranular Insular and Basolateral Amygdala in Reconsolidation of aversive memory associated with Morphine in Rats

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    Peng eLiu

    2016-03-01

    Full Text Available 5-aza-2-deoxycytidine (5-aza, an inhibitor of DNA methyltransferases (DNMTs, has been implicated in aversive memory and the function of brain region which processing affect. However, little is known about the role of 5-aza in the reconsolidation of opiate withdrawal memory. In the present study, using the morphine-naloxone induced conditioned place aversion (CPA model in rats, we injected 5-aza into agranular insular (AI, granular insular (GI, basolateral amygdala (BLA and central amygdala (CeA immediately after the memory retrieval and tested the behavioral consequences at 24hours, 7 days and 14days after retrieval test. We found that 5-aza injection into AI disrupted the reconsolidation of morphine-associated withdrawal memory, but 5-aza injection into GI had no impact on the reconsolidation. Meanwhile, 5-aza injection into BLA but not CeA attenuated the withdrawal memory trace 14 days later. However, 5-aza administration to rats, in the absence of memory reactivation, had no effect on morphine-associated withdrawal memory. These findings suggest that 5-aza interfere with the reconsolidation of opiate withdrawal memory, and the roles of insular and amygdala in reconsolidation are distinctive.

  15. DBS in the baso-lateral amygdala improves symptoms of autism and related self-injurious behaviourA case report and hypothesis on the pathogenesis of the disorder

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    Volker eSturm

    2013-01-01

    Full Text Available We treated a thirteen year old boy for life-threatening self-injurious behavior (SIB and severe Kanner’s autism with Deep Brain Stimulation (DBS in the amygdaloid complex as well as in the supra-amygdaloid projection system. Two DBS-electrodes were placed in both structures of each hemisphere. The stimulation contacts targeted the paralaminar, the basolateral, the central amygdala as well as the supra-amygdaloid projection system. DBS was applied to each of these structures, but only stimulation of the baso-lateral part proved effective in improving SIB and core symptoms of the autism spectrum in the emotional, social and even cognitive domains over a follow up of now 24 months. These results, which have been gained for the first time in a patient, support hypotheses, according to which the amygdala may be pivotal in the pathogeneses of autism and point to the special relevance of the baso-lateral part.

  16. A Different Recruitment of the Lateral and Basolateral Amygdala Promotes Contextual or Elemental Conditioned Association in Pavlovian Fear Conditioning

    Science.gov (United States)

    Calandreau, Ludovic; Desmedt, Aline; Decorte, Laurence; Jaffard, Robert

    2005-01-01

    Convergent data suggest dissociated roles for the lateral (LA) and basolateral (BLA) amygdaloid nuclei in fear conditioning, depending on whether a discrete conditioned stimulus (CS)-unconditional stimulus (US) or context-US association is considered. Here, we show that pretraining inactivation of the BLA selectively impaired conditioning to…

  17. CaMKIIα knockdown decreases anxiety in the open field and low serotonin-induced upregulation of GluA1 in the basolateral amygdala.

    Science.gov (United States)

    Tran, Lee; Keele, N Bradley

    2016-04-15

    Hyperactivation of the amygdala is implicated in anxiety and mood disorders, but the precise underlying mechanisms are unclear. We previously reported that depletion of serotonin (5-hydroxytryptamine, 5-HT) in the basolateral nucleus of the amygdala (BLA) using the serotonergic neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) potentiated learned fear and increased glutamate receptor (Glu) expression in BLA. Here we investigated the hypothesis that CaMKII facilitates anxiety-like behavior and increased Glu/AMPA receptor subunit A1 (GluA1) expression following depletion of 5-HT in the BLA. Infusion of 5,7-DHT into the BLA resulted in anxiety-like behavior in the open field test (OFT) and increased the phosphorylation of CaMKIIα (Thr-286) in the BLA. Knockdown of the CaMKIIα subunit using adeno-associated virus (AAV)-delivered shRNAi concomitantly attenuated anxiety-like behavior in the OFT and decreased GluA1 expression in the BLA. Our results suggest that the CaMKII signaling plays a key role in low 5-HT-induced anxiety and mood disturbances, potentially through regulation of GluA1 expression in the BLA.

  18. Estrogen receptor GPR30 exerts anxiolytic effects by maintaining the balance between GABAergic and glutamatergic transmission in the basolateral amygdala of ovariectomized mice after stress.

    Science.gov (United States)

    Tian, Zhen; Wang, Yu; Zhang, Nan; Guo, Yan-Yan; Feng, Bin; Liu, Shui-Bing; Zhao, Ming-Gao

    2013-10-01

    G-protein-coupled receptor 30 (GPR30)/G-protein-coupled estrogen receptor is a novel estrogen membrane receptor that localizes to the cell membrane and endoplasmic reticulum. GPR30 is widely distributed and has numerous physiological functions in the central nervous system. We found that GPR30 is highly expressed in the basolateral amygdala (BLA). Additionally, GPR30 expression in the amygdala of ovariectomized (OVX) mice significantly increased after acute stress and was accompanied by anxiety-like behaviors. These effects, however, were reversed by local infusion of the GPR30 agonist (G1) in the BLA. Protein assessments revealed that G1 attenuated the up-regulation of the GluR1 subunit of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor and NR2A-containing N-methyl-d-aspartate receptors (NMDARs) in the BLA of OVX mice using an acute stress paradigm. In the same model, we found that the agonist also blocked the down-regulation of γ-aminobutyric acid A (GABAA) receptors and NR2B-containing NMDARs. Electrophysiological recording showed that the activation of GPR30 increased the inhibitory synaptic transmission in the BLA. Overall, our results indicate that estradiol reduces anxiety-like behaviors induced by acute stress at least partially through GPR30 signaling, maintaining the balance between GABAergic and glutamatergic transmission in the BLA of OVX-stressed mice.

  19. Optogenetic dissection of amygdala functioning

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    Ryan eLalumiere

    2014-03-01

    Full Text Available Studies of amygdala functioning have occupied a significant place in the history of understanding how the brain controls behavior and cognition. Early work on the amygdala placed this small structure as a key component in the regulation of emotion and affective behavior. Over time, our understanding of its role in brain processes has expanded, as we have uncovered amygdala influences on memory, reward behavior, and overall functioning in many other brain regions. Studies have indicated that the amygdala has widespread connections with a variety of brain structures, from the prefrontal cortex to regions of the brainstem, that explain its powerful influence on other parts of the brain and behaviors mediated by those regions. Thus, many optogenetic studies have focused on harnessing the powers of this technique to elucidate the functioning of the amygdala in relation to motivation, fear, and memory as well as to determine how the amygdala regulates activity in other structures. For example, studies using optogenetics have examined how specific circuits within amygdala nuclei regulate anxiety. Other work has provided insight into how the basolateral and central amygdala nuclei regulate memory processing underlying aversive learning. Many experiments have taken advantage of optogenetics’ ability to target either genetically distinct subpopulations of neurons or the specific projections from the amygdala to other brain regions. Findings from such studies have provided evidence that particular patterns of activity in basolateral amygdala glutamatergic neurons are related to memory consolidation processes, while other work has indicated the critical nature of amygdala inputs to the prefrontal cortex and nucleus accumbens in regulating behavior dependent on those downstream structures. This review will examine the recent discoveries on amygdala functioning made through experiments using optogenetics, placing these findings in the context of the major

  20. Drug seeking under a second-order schedule of reinforcement depends on dopamine D3 receptors in the basolateral amygdala.

    Science.gov (United States)

    Di Ciano, Patricia

    2008-02-01

    Drug seeking under the control of drug-associated stimuli and its reinstatement after extinction can be decreased by systemic administration of dopamine D3 receptor antagonists. It is demonstrated that responding by rats on the active lever for cocaine under a 2nd-order schedule of reinforcement, under which responding is maintained by response-contingent cocaine-paired conditioned reinforcers, is markedly attenuated by infusion of the dopamine D3 receptor antagonist SB-277011-A into the amygdala (2 and 4 microg/0.3 microl). By contrast, infusions of SB-277011-A into the shell subregion of the nucleus accumbens and also into the dorsal striatum were without effect. These results show that the control over drug seeking by conditioned reinforcers depends on D3 receptor-dependent dopamine transmission in the amygdala.

  1. Topiramate reduces excitability in the basolateral amygdala by selectively inhibiting GluK1 (GluR5) kainate receptors on interneurons and positively modulating GABAA receptors on principal neurons.

    Science.gov (United States)

    Braga, Maria F M; Aroniadou-Anderjaska, Vassiliki; Li, He; Rogawski, Michael A

    2009-08-01

    Topiramate [2,3:4,5-bis-O-(1-methylethylidene)-beta-D-fructopyranose sulfamate] is a structurally novel antiepileptic drug that has broad efficacy in epilepsy, but the mechanisms underlying its therapeutic activity are not fully understood. We have found that topiramate selectively inhibits GluK1 (GluR5) kainate receptor-mediated excitatory postsynaptic responses in rat basolateral amygdala (BLA) principal neurons and protects against seizures induced by the GluK1 kainate receptor agonist (R,S)-2-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl)propanoic acid (ATPA). Here, we demonstrate that topiramate also modulates inhibitory function in the BLA. Using whole-cell recordings in rat amygdala slices, we found that 0.3 to 10 microM topiramate 1) inhibited ATPA-evoked postsynaptic currents recorded from BLA interneurons; 2) suppressed ATPA-induced enhancement of spontaneous inhibitory postsynaptic currents (IPSCs) recorded from BLA pyramidal cells; and 3) blocked ATPA-induced suppression of evoked IPSCs, which is mediated by presynaptic GluK1 kainate receptors present on BLA interneurons. Topiramate (10 microM) had no effect on the AMPA [(R,S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid]-induced enhancement of spontaneous activity of BLA neurons. Thus, although topiramate inhibits GluK1 kainate receptor-mediated enhancement of interneuron firing, it promotes evoked GABA release, leading to a net inhibition of circuit excitability. In addition, we found that topiramate (0.3-10 microM) increased the amplitude of evoked, spontaneous, and miniature IPSCs in BLA pyramidal neurons, indicating an enhancement of postsynaptic GABA(A) receptor responses. Taken together with our previous findings, we conclude that topiramate protects against hyperexcitability in the BLA by suppressing the GluK1 kainate receptor-mediated excitation of principal neurons by glutamatergic afferents, blocking the suppression of GABA release from interneurons mediated by presynaptic GluK1

  2. Cue-Induced Food Seeking After Punishment Is Associated With Increased Fos Expression in the Lateral Hypothalamus and Basolateral and Medial Amygdala.

    Science.gov (United States)

    Campbell, Erin J; Barker, David J; Nasser, Helen M; Kaganovsky, Konstantin; Dayas, Christopher V; Marchant, Nathan J

    2017-02-20

    In humans, relapse to unhealthy eating habits following dieting is a significant impediment to obesity treatment. Food-associated cues are one of the main triggers of relapse to unhealthy eating during self-imposed abstinence. Here we report a behavioral method examining cue-induced relapse to food seeking following punishment-induced suppression of food taking. We trained male rats to lever press for food pellets that were delivered after a 10-s conditional stimulus (CS) (appetitive). Following training, 25% of reinforced lever presses resulted in the presentation of a compound stimulus consisting of a novel CS (aversive) and the appetitive CS followed by a pellet and footshock. After punishment-imposed abstinence, we tested the rats in an extinction test where lever pressing resulted in the presentation of either the appetitive or aversive CS. We then compared activity of lateral hypothalamus (LH) and associated extrahypothalamic regions following this test. We also assessed Fos expression in LH orexin and GABA neurons. We found that cue-induced relapse of food seeking on test was higher in rats tested with the appetitive CS compared to the aversive CS. Relapse induced by the appetitive CS was associated with increased Fos expression in LH, caudal basolateral amygdala (BLA), and medial amygdala (MeA). This relapse was also associated with increased Fos expression in LH orexin and VGAT-expressing neurons. These data show that relapse to food seeking can be induced by food-associated cues after punishment-imposed abstinence, and this relapse is associated with increased activity in LH, caudal BLA, and MeA. (PsycINFO Database Record

  3. Lesions of basolateral amygdala impair extinction of CS motivational value, but not of explicit conditioned responses, in Pavlovian appetitive second-order conditioning.

    Science.gov (United States)

    Lindgren, John L; Gallagher, Michela; Holland, Peter C

    2003-01-01

    The basolateral amygdala (BLA) is important for the modification of the motivational significance of events through associative learning. In previous work, we found that BLA was critical for the acquisition of conditioned reinforcement value to a visual conditioned stimulus (CS) paired with food. Unlike normal rats, rats with neurotoxic lesions of the BLA failed to acquire Pavlovian second-order conditioning to an auditory stimulus paired with the first-order visual CS in the absence of food. In this experiment, we examined the role of BLA in the extinction of the previously acquired conditioned reinforcement value of a Pavlovian CS. Rats received first-order visual CS-food pairings prior to either BLA- or sham-lesions. Subsequent CS-alone extinction training reduced the ability of the visual CS to reinforce second-order conditioning of an auditory stimulus in the sham-lesioned rats, but not in the BLA-lesioned rats. Despite this persistence of the conditioned reinforcement value of the visual first-order CS in the BLA-lesioned rats, no effects of the lesions were observed on extinction of the explicit behavioural conditioned responses elicited by that CS.

  4. Post-training Activation of Rac1 in the Basolateral Amygdala Is Required for the Formation of both Short-term and Long-term Auditory Fear Memory

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    Qinqin eGao

    2015-11-01

    Full Text Available Rac1, a member of the Rho family of small GTPases, is crucial for morphological changes of the mature neuronal synapse including spine formation and activity-dependent spine enlargement, while its role in the formation of associated memories, such as conditioned fear memory, is not clear. Here we report that selective deletion of Rac1 in excitatory neurons, but not in parvalbumin inhibitory neurons, impaired short- and long-term memories (STM and LTM of fear conditioning. Conditional knockout of Rac1 before associative fear training in the basolateral amygdala (BLA, a key area for fear memory acquisition and storage, impaired fear memory. The expression of dominant-negative mutant of Rac1, or infusion of Rac1 inhibitor NSC23766 into BLA blocked both STM and LTM of fear conditioning. Furthermore, selective inhibition of Rac1 activation in BLA immediately following fear conditioning impaired STM, demonstrating that fear conditioning-induced Rac1 activation in BLA plays a critical role in the formation of both STM and LTM of conditioned fear.

  5. Ex vivo dissection of optogenetically activated mPFC and hippocampal inputs to neurons in the basolateral amygdala: implications for fear and emotional memory

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    Cora eHübner

    2014-03-01

    Full Text Available Many lines of evidence suggest that a reciprocally interconnected network comprising the amygdala, ventral hippocampus (vHC, and medial prefrontal cortex (mPFC participates in different aspects of the acquisition and extinction of conditioned fear responses and fear behavior. This could at least in part be mediated by direct connections from mPFC or vHC to amygdala to control amygdala activity and output. However, currently the interactions between mPFC and vHC afferents and their specific targets in the amygdala are still poorly understood. Here, we use an ex-vivo optogenetic approach to dissect synaptic properties of inputs from mPFC and vHC to defined neuronal populations in the basal amygdala (BA, the area that we identify as a major target of these projections. We find that BA principal neurons (PNs and local BA interneurons (INs receive monosynaptic excitatory inputs from mPFC and vHC. In addition, both these inputs also recruit GABAergic feedforward inhibition in a substantial fraction of PNs, in some neurons this also comprises a slow GABAB-component. Amongst the innervated PNs we identify neurons that project back to subregions of the mPFC, indicating a loop between neurons in mPFC and BA, and a pathway from vHC to mPFC via BA. Interestingly, mPFC inputs also recruit feedforward inhibition in a fraction of INs, suggesting that these inputs can activate dis-inhibitory circuits in the BA. A general feature of both mPFC and vHC inputs to local INs is that excitatory inputs display faster rise and decay kinetics than in PNs, which would enable temporally precise signaling. However, mPFC and vHC inputs to both PNs and INs differ in their presynaptic release properties, in that vHC inputs are more depressing. In summary, our data describe novel wiring, and features of synaptic connections from mPFC and vHC to amygdala that could help to interpret functions of these interconnected brain areas at the network level.

  6. Infusion of methylphenidate into the basolateral nucleus of amygdala or anterior cingulate cortex enhances fear memory consolidation in rats

    Institute of Scientific and Technical Information of China (English)

    ZHENG XinLing; LIU Fang; WU XingWen; LI BaoMing

    2008-01-01

    The psychostimulant methylphenidate (MPD; also called Ritalin) is a blocker of dopamine and norepi-nephrine transporter. It has been clinically used for treatment of Attention Deficit and Hyperactivity Disorder (ADHD). There have been inconsistent reports regarding the effects of systemically adminis-tered MPD on learning and memory, either in animals or humans. In the present study, we investigated the effect of direct infusion of MPD into the basolaterel nucleus of amygdala (BLA) or the anterior cin-gulate cortex (ACC) on conditioned fear memory. Rats were trained on a one-trial step-through inhibi-tory avoidance task. MPD was infused bilaterally into the BLA or the ACC, either at '0' or 6 h post-treining. Saline was administered as control. Memory retention was tested 48 h poet-training. In-tra-BLA or intra-ACC infusion of MPD '0' h but not 6 h post-training significantly improved 48-h memory retention: the MPD-treated rats had significant longer step-through latency than controls. The present results indicate that action of MPD in the BLA or the ACC produces a beneficial effect on the consoli-dation of inhibitory avoidance memory.

  7. Behavioral and neurophysiological evidence that lateral paracapsular GABAergic synapses in the basolateral amygdala contribute to the acquisition and extinction of fear learning.

    Science.gov (United States)

    Skelly, M J; Chappell, A M; Ariwodola, O J; Weiner, J L

    2016-01-01

    The lateral/basolateral amygdala (BLA) is crucial to the acquisition and extinction of Pavlovian fear conditioning, and synaptic plasticity in this region is considered to be a neural correlate of learned fear. We recently reported that activation of BLA β3-adrenoreceptors (β3-ARs) selectively enhances lateral paracapsular (LPC) feed-forward GABAergic inhibition onto BLA pyramidal neurons, and that intra-BLA infusion of a β3-AR agonist reduces measures of unconditioned anxiety-like behavior. Here, we utilized a combination of behavioral and electrophysiological approaches to characterize the role of BLA LPCs in the acquisition of fear and extinction learning in adult male Long-Evans rats. We report that intra-BLA microinjection of β3-AR agonists (BRL37344 or SR58611A, 1μg/0.5μL/side) prior to training fear conditioning or extinction blocks the expression of these behaviors 24h later. Furthermore,ex vivo low-frequency stimulation of the external capsule (LFS; 1Hz, 15min), which engages LPC synapses, induces LTP of BLA fEPSPs, while application of a β3-AR agonist (SR58611A, 5μM) induces LTD of fEPSPs when combined with LFS. Interestingly, fEPSP LTP is not observed in recordings from fear conditioned animals, suggesting that fear learning may engage the same mechanisms that induce synaptic plasticity at this input. In support of this, we find that LFS produces LTD of inhibitory postsynaptic currents (iLTD) at LPC GABAergic synapses, and that this effect is also absent following fear conditioning. Taken together, these data provide preliminary evidence that modulation of LPC GABAergic synapses can influence the acquisition and extinction of fear learning and related synaptic plasticity in the BLA.

  8. Delta-subunit containing GABAA-receptors mediate tonic inhibition in paracapsular cells of the mouse amygdala

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    Anne eMarowsky

    2014-03-01

    Full Text Available The intercalated paracapsular cells (pcs are small GABAergic interneurons that form densely populated clusters surrounding the basolateral (BLA complex of the amygdala. Their main task in the amygdala circuitry appears to be the control of information flow, as they act as an inhibitory interface between input and output nuclei. Modulation of their activity is thus thought to affect amygdala output and the generation of fear and anxiety. Recent evidence indicates that pcs express benzodiazepine (BZ-sensitive GABAA receptor (GABAAR variants containing the α2- and α3-subunit for transmission of postsynaptic currents, yet little is known about the expression of extrasynaptic GABAARs, mediating tonic inhibition and regulating neuronal excitability. Here, we show that pcs from the lateral and medial intercalated cell cluster (l- and mITC, respectively express a tonic GABAergic conductance that could be significantly increased in a concentration-dependent manner by the δ-preferring GABAAR agonist THIP (0.5-10 µM, but not by the BZ diazepam (1 µM. The neurosteroid THDOC (300 nM also increased tonic currents in pcs significantly, but only in the presence of additional GABA (5 µM. Immunohistochemical stainings revealed that both the δ-GABAAR and the α4-GABAAR subunit are expressed throughout all ITCs, while no staining for the α5-GABAAR subunit could be detected. Moreover, 1 µM THIP dampened excitability in pcs most likely by increasing shunting inhibition. In line with this, THIP significantly decreased lITC-generated inhibition in target cells residing in the BLA nucleus by 30%. Taken together these results demonstrate for the first time that pcs express a tonic inhibitory conductance mediated most likely by α4/δ-containing GABAARs. This data also suggest that δ-GABAAR targeting compounds might possibly interfere with pcs-related neuronal processes such as fear extinction.

  9. Accumbens Shell AMPA Receptors Mediate Expression of Extinguished Reward Seeking through Interactions with Basolateral Amygdala

    Science.gov (United States)

    Millan, E. Zayra; McNally, Gavan P.

    2011-01-01

    Extinction is the reduction in drug seeking when the contingency between drug seeking behavior and the delivery of drug reward is broken. Here, we investigated a role for the nucleus accumbens shell (AcbSh). Rats were trained to respond for 4% (v/v) alcoholic beer in one context (Context A) followed by extinction in a second context (Context B).…

  10. 5-HT2C receptors in the basolateral amygdala and dorsal striatum are a novel target for the anxiolytic and antidepressant effects of exercise.

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    Benjamin N Greenwood

    Full Text Available Physical activity reduces the incidence and severity of psychiatric disorders such as anxiety and depression. Similarly, voluntary wheel running produces anxiolytic- and antidepressant-like effects in rodent models. The specific neurobiological mechanisms underlying the beneficial properties of exercise, however, remain unclear. One relevant pharmacological target in the treatment of psychiatric disorders is the 5-HT(2C receptor (5-HT(2CR. Consistent with data demonstrating the anxiogenic consequences of 5-HT(2CR activation in humans and rodents, we have previously reported that site-specific administration of the selective 5-HT(2CR agonist CP-809101 in the lateral/basolateral amygdala (BLA increases shock-elicited fear while administration of CP-809101 in the dorsal striatum (DS interferes with shuttle box escape learning. These findings suggest that activation of 5-HT(2CR in discrete brain regions contributes to specific anxiety- and depression-like behaviors and may indicate potential brain sites involved in the anxiolytic and antidepressant effects of exercise. The current studies tested the hypothesis that voluntary wheel running reduces the behavioral consequences of 5-HT(2CR activation in the BLA and DS, specifically enhanced shock-elicited fear and interference with shuttle box escape learning. After 6 weeks of voluntary wheel running or sedentary conditions, the selective 5-HT(2CR agonist CP-809101 was microinjected into either the BLA or the DS of adult Fischer 344 rats, and shock-elicited fear and shuttle box escape learning was assessed. Additionally, in-situ hybridization was used to determine if 6 weeks of voluntary exercise changed levels of 5-HT(2CR mRNA. We found that voluntary wheel running reduced the behavioral effects of CP-809101 and reduced levels of 5-HT(2CR mRNA in both the BLA and the DS. The current data indicate that expression of 5-HT(2CR mRNA in discrete brain sites is sensitive to physical activity status of the

  11. Anxiolytic and anxiogenic effects of kindling--role of baseline anxiety and anatomical location of the kindling electrode in response to kindling of the right and left basolateral amygdala.

    Science.gov (United States)

    Adamec, Robert; Shallow, Tanya; Burton, Paul

    2005-04-15

    Effects of kindling of right and left basolateral amygdala (BLA) on plus maze anxiety was studied. Using a validated retest paradigm, it was possible to retest rats in the plus maze without increasing anxiety on retest. This permitted determining prekindling baseline levels of plus maze anxiety. Right BLA kindling of high baseline anxiety rats was anxiolytic one week after kindling. Right BLA kindling of low baseline anxiety rats was anxiogenic. In addition, left BLA kindling was either anxiogenic or without effect on plus maze anxiety, depending on baseline anxiety. Effects in left BLA differ from previous work showing anxiolytic effects of left BLA kindling. The discrepancy could be explained in part by prekindling baseline anxiety. These findings require modification of the previous conclusion that left hemisphere (left BLA) kindling is anxiolytic and right BLA kindling is anxiogenic in the plus maze. Rather the hemisphere difference may be due to an interaction between baseline anxiety level and kindling. If true, anxious disposition in rodents may interact with amygdala kindling to change amygdala function differently. Kindling and baseline anxiety effects on other behaviors (such as risk assessment and resistance to capture) are also described. Present data in the light of past studies suggest both premorbid anxiety state and location of the kindling electrode contribute to the effects of kindling on behavior.

  12. Endocannabinoids in amygdala and nucleus accumbens mediate social play reward in adolescent rats.

    Science.gov (United States)

    Trezza, Viviana; Damsteegt, Ruth; Manduca, Antonia; Petrosino, Stefania; Van Kerkhof, Linda W M; Pasterkamp, R Jeroen; Zhou, Yeping; Campolongo, Patrizia; Cuomo, Vincenzo; Di Marzo, Vincenzo; Vanderschuren, Louk J M J

    2012-10-24

    The brain endocannabinoid system plays a crucial role in emotional processes. We have previously identified an important role for endocannabinoids in social play behavior, a highly rewarding form of social interaction in adolescent rats. Here, we tested the hypothesis that endocannabinoid modulation of social play behavior occurs in brain regions implicated in emotion and motivation. Social play increased levels of the endocannabinoid anandamide in the amygdala and nucleus accumbens (NAc), but not in prefrontal cortex or hippocampus of 4- to 5-week-old male Wistar rats. Furthermore, social play increased phosphorylation of CB1 cannabinoid receptors in the amygdala. Systemic administration of the anandamide hydrolysis inhibitor URB597 increased social play behavior, and augmented the associated elevation in anandamide levels in the amygdala, but not the NAc. Infusion of URB597 into the basolateral amygdala (BLA) increased social play behavior, and blockade of BLA CB1 cannabinoid receptors with the antagonist/inverse agonist SR141716A prevented the play-enhancing effects of systemic administration of URB597. Infusion of URB597 into the NAc also increased social play, but blockade of NAc CB1 cannabinoid receptors did not antagonize the play-enhancing effects of systemic URB597 treatment. Last, SR141716A did not affect social play after infusion into the core and shell subregions of the NAc, while it reduced social play when infused into the BLA. These data show that increased anandamide signaling in the amygdala and NAc augments social play, and identify the BLA as a prominent site of action for endocannabinoids to modulate the rewarding properties of social interactions in adolescent rats.

  13. Basolateral P2X receptors mediate inhibition of NaCl transport in mouse medullary thick ascending limb (mTAL)

    DEFF Research Database (Denmark)

    Marques, Rita D; de Bruijn, Pauline I.A.; Sørensen, Mads Vaarby;

    2012-01-01

    Extracellular nucleotides regulate epithelial transport via luminal and basolateral P2 receptors. Renal epithelia express multiple P2 receptors, which mediate significant inhibition of solute absorption. Recently, we identified several P2 receptors in the medullary thick ascending limb (m......TAL) including luminal and basolateral P2Y(2) receptors. In addition, we found evidence for a basolateral P2X receptor. Here we investigate the effect of basolateral ATP on NaCl absorption in isolated, perfused mouse mTALs using the electrical measurement of equivalent short circuit current (I'(sc)). Non...... receptor antagonist suramin blocked the effect. P2Y receptors were found not to be involved in this effect. The P2X receptor agonist 2MeSATP mimicked the ATP effect and the P2X receptor antagonist oATP blocked it. In P2X(7)(-/-) mice the ATP effect remained unaltered. In contrast, in P2X(4)(-/-) mice...

  14. Dopamine in the medial amygdala network mediates human bonding

    Science.gov (United States)

    Touroutoglou, Alexandra; Rudy, Tali; Salcedo, Stephanie; Feldman, Ruth; Hooker, Jacob M.; Dickerson, Bradford C.; Catana, Ciprian; Barrett, Lisa Feldman

    2017-01-01

    Research in humans and nonhuman animals indicates that social affiliation, and particularly maternal bonding, depends on reward circuitry. Although numerous mechanistic studies in rodents demonstrated that maternal bonding depends on striatal dopamine transmission, the neurochemistry supporting maternal behavior in humans has not been described so far. In this study, we tested the role of central dopamine in human bonding. We applied a combined functional MRI-PET scanner to simultaneously probe mothers’ dopamine responses to their infants and the connectivity between the nucleus accumbens (NAcc), the amygdala, and the medial prefrontal cortex (mPFC), which form an intrinsic network (referred to as the “medial amygdala network”) that supports social functioning. We also measured the mothers’ behavioral synchrony with their infants and plasma oxytocin. The results of this study suggest that synchronous maternal behavior is associated with increased dopamine responses to the mother’s infant and stronger intrinsic connectivity within the medial amygdala network. Moreover, stronger network connectivity is associated with increased dopamine responses within the network and decreased plasma oxytocin. Together, these data indicate that dopamine is involved in human bonding. Compared with other mammals, humans have an unusually complex social life. The complexity of human bonding cannot be fully captured in nonhuman animal models, particularly in pathological bonding, such as that in autistic spectrum disorder or postpartum depression. Thus, investigations of the neurochemistry of social bonding in humans, for which this study provides initial evidence, are warranted. PMID:28193868

  15. Divergent responses of inflammatory mediators within the amygdala and medial prefrontal cortex to acute psychological stress.

    Science.gov (United States)

    Vecchiarelli, Haley A; Gandhi, Chaitanya P; Gray, J Megan; Morena, Maria; Hassan, Kowther I; Hill, Matthew N

    2016-01-01

    There is now a growing body of literature that indicates that stress can initiate inflammatory processes, both in the periphery and brain; however, the spatiotemporal nature of this response is not well characterized. The aim of this study was to examine the effects of an acute psychological stress on changes in mRNA and protein levels of a wide range of inflammatory mediators across a broad temporal range, in key corticolimbic brain regions involved in the regulation of the stress response (amygdala, hippocampus, hypothalamus, medial prefrontal cortex). mRNA levels of inflammatory mediators were analyzed immediately following 30min or 120min of acute restraint stress and protein levels were examined 0h through 24h post-termination of 120min of acute restraint stress using both multiplex and ELISA methods. Our data demonstrate, for the first time, that exposure to acute psychological stress results in an increase in the protein level of several inflammatory mediators in the amygdala while concomitantly producing a decrease in the protein level of multiple inflammatory mediators within the medial prefrontal cortex. This pattern of changes seemed largely restricted to the amygdala and medial prefrontal cortex, with stress producing few changes in the mRNA or protein levels of inflammatory mediators within the hippocampus or hypothalamus. Consistent with previous research, stress resulted in a general elevation in multiple inflammatory mediators within the circulation. These data indicate that neuroinflammatory responses to stress do not appear to be generalized across brain structures and exhibit a high degree of spatiotemporal specificity. Given the impact of inflammatory signaling on neural excitability and emotional behavior, these data may provide a platform with which to explore the importance of inflammatory signaling within the prefrontocortical-amygdala circuit in the regulation of the neurobehavioral responses to stress.

  16. CB1 Cannabinoid Agonist (WIN55,212-2) Within the Basolateral Amygdala Induced Sensitization to Morphine and Increased the Level of μ-Opioid Receptor and c-fos in the Nucleus Accumbens.

    Science.gov (United States)

    Molaei, Marzieh; Fatahi, Zahra; Zaringhalam, Jalal; Haghparast, Abbas

    2016-04-01

    The basolateral amygdala (BLA) is rich of CB1 cannabinoid receptors (CB1R) and has reciprocal connections with the nucleus accumbens (NAc) which is involved in opioid sensitization. In this study, effects of intra-BLA administration of CB1R agonist on sensitization to antinociceptive effect of morphine and changes in the levels of μ-opioid receptor (MOR), p-CREB, and c-fos in the NAc were investigated. Animals received intra-BLA microinjection of CB1R agonist (WIN55,212-2) once daily for 3 days consecutively (sensitization period). After 5 days free of drug, tail-flick test was performed before and after the administration of an ineffective dose of morphine. Afterward, the levels of MOR, p-CREB, and c-fos proteins were measured in the NAc by Western blot analysis. The results indicated that intra-BLA injection of WIN55,212-2 during sensitization period resulted in the induction of antinociceptive responses by ineffective dose of morphine and caused a significant increase in the MOR and c-fos levels but not p-CREB/CREB ratio in the NAc. These finding revealed that CB1 receptor agonist in the BLA induces development of morphine sensitization and increases expression of MOR in the NAc. It seems that c-fos is one of the important factors involved in the induction of sensitization to antinociceptive effect of morphine.

  17. Inhibiton of neurons in the amygdala by dorsal raphe stimulation: mediation through a direct serotonergic pathway.

    Science.gov (United States)

    Wang, R Y; Aghajanian, G K

    1977-01-14

    This study presents data showing that the dorsal raphe nucleus (DRN) has a marked inhibitory influence upon neurons in the amygdala and that this inhibitory effect is mediated by a direct DRN-amygdala serotonergic pathway. The evidence may be briefly summarized as follows:(1) on the same amygdaloid cells, both iontophoresis of serotonin (5-HT) and electrical stimulation of the DRN markedly inhibited spontaneous single unit activities; (2) the latency of DRN-induced inhibition was relatively short and is compatible with the conduction velocities (which were determined by antidromic activation of the 5-HT pathway) of unmyelinated 5-HT fibers; (3) destruction of 5-HT projections by 5,7-dihydroxytryptamine (5,7-DHT) or pharmacological depletion of 5-HT by parachlorophenylalanine (PCPA) prevented the inhibitory responsed to DRN stimulation in the great majority of cells studied; (4) in PCPA-pretreated animals, injection of 5-hydroxytryptophan (5-HTP) reversed the PCPA effect, restoring the responses of amygdaloid cells to DRN stimulation. In the amygdala, the presumptive 5-HT antagonists which we tested did not block the inhibitory effects of 5-HT except that intravenously administered LSD blocked the inhibitory responses produced by submaximal DRN stimulation. The implications of these results for the possible functions of 5-HT in the amygdala is discussed.

  18. Neuropeptide S-mediated facilitation of synaptic transmission enforces subthreshold theta oscillations within the lateral amygdala.

    Directory of Open Access Journals (Sweden)

    Susanne Meis

    Full Text Available The neuropeptide S (NPS receptor system modulates neuronal circuit activity in the amygdala in conjunction with fear, anxiety and the expression and extinction of previously acquired fear memories. Using in vitro brain slice preparations of transgenic GAD67-GFP (Δneo mice, we investigated the effects of NPS on neural activity in the lateral amygdala as a key region for the formation and extinction of fear memories. We are able to demonstrate that NPS augments excitatory glutamatergic synaptic input onto both projection neurons and interneurons of the lateral amygdala, resulting in enhanced spike activity of both types of cells. These effects were at least in part mediated by presynaptic mechanisms. In turn, inhibition of projection neurons by local interneurons was augmented by NPS, and subthreshold oscillations were strengthened, leading to their shift into the theta frequency range. These data suggest that the multifaceted effects of NPS on amygdaloid circuitry may shape behavior-related network activity patterns in the amygdala and reflect the peptide's potent activity in various forms of affective behavior and emotional memory.

  19. The Role of Actin Cytoskeleton in Memory Formation in Amygdala

    Directory of Open Access Journals (Sweden)

    Raphael eLamprecht

    2016-03-01

    Full Text Available The central, lateral and basolateral amygdala nuclei are essential for the formation of long-term memories including emotional and drug-related memories. The study of cellular and molecular mechanisms underpinning memory in amygdala may shed light on the formation of memory and on fear and addiction-related disorders. A challenge is to identify molecules activated by learning that subserve cellular changes needed for memory formation and maintenance in amygdala. Recent studies show that activation of synaptic receptors during fear and drug-related learning leads to alteration in actin cytoskeleton dynamics and structure in amygdala. Such changes in actin cytoskeleton in amygdala are essential for fear and drug-related memories formation. Moreover, the actin cytoskeleton subserves, after learning, changes in neuronal morphogenesis and glutamate receptors trafficking in amygdala. These cellular events are involved in fear and drug-related memories formation. Actin polymerization is also needed for the maintenance of drug-associated memories in amygdala. Thus, the actin cytoskeleton is a key mediator between receptor activation during learning and cellular changes subserving long-term memory in amygdala. The actin cytoskeleton may serve as a target for pharmacological treatment of fear memory associated with fear and anxiety disorders and drug addiction to prevent the debilitating consequences of these diseases.

  20. Eyes wide shut: amygdala mediates eyes-closed effect on emotional experience with music.

    Directory of Open Access Journals (Sweden)

    Yulia Lerner

    Full Text Available The perceived emotional value of stimuli and, as a consequence the subjective emotional experience with them, can be affected by context-dependent styles of processing. Therefore, the investigation of the neural correlates of emotional experience requires accounting for such a variable, a matter of an experimental challenge. Closing the eyes affects the style of attending to auditory stimuli by modifying the perceptual relationship with the environment without changing the stimulus itself. In the current study, we used fMRI to characterize the neural mediators of such modification on the experience of emotionality in music. We assumed that closed eyes position will reveal interplay between different levels of neural processing of emotions. More specifically, we focused on the amygdala as a central node of the limbic system and on its co-activation with the Locus Ceruleus (LC and Ventral Prefrontal Cortex (VPFC; regions involved in processing of, respectively, 'low', visceral-, and 'high', cognitive-related, values of emotional stimuli. Fifteen healthy subjects listened to negative and neutral music excerpts with eyes closed or open. As expected, behavioral results showed that closing the eyes while listening to emotional music resulted in enhanced rating of emotionality, specifically of negative music. In correspondence, fMRI results showed greater activation in the amygdala when subjects listened to the emotional music with eyes closed relative to eyes open. More so, by using voxel-based correlation and a dynamic causal model analyses we demonstrated that increased amygdala activation to negative music with eyes closed led to increased activations in the LC and VPFC. This finding supports a system-based model of perceived emotionality in which the amygdala has a central role in mediating the effect of context-based processing style by recruiting neural operations involved in both visceral (i.e. 'low' and cognitive (i.e. 'high' related processes

  1. Functional disconnection of the orbitofrontal cortex and basolateral amygdala impairs acquisition of a rat gambling task and disrupts animals' ability to alter decision-making behavior after reinforcer devaluation.

    Science.gov (United States)

    Zeeb, Fiona D; Winstanley, Catharine A

    2013-04-10

    An inability to adjust choice preferences in response to changes in reward value may underlie key symptoms of many psychiatric disorders, including chemical and behavioral addictions. We developed the rat gambling task (rGT) to investigate the neurobiology underlying complex decision-making processes. As in the Iowa Gambling task, the optimal strategy is to avoid choosing larger, riskier rewards and to instead favor options associated with smaller rewards but less loss and, ultimately, greater long-term gain. Given the demonstrated importance of the orbitofrontal cortex (OFC) and basolateral amygdala (BLA) in acquisition of the rGT and Iowa Gambling task, we used a contralateral disconnection lesion procedure to assess whether functional connectivity between these regions is necessary for optimal decision-making. Disrupting the OFC-BLA pathway retarded acquisition of the rGT. Devaluing the reinforcer by inducing sensory-specific satiety altered decision-making in control groups. In contrast, disconnected rats did not update their choice preference following reward devaluation, either when the devalued reward was still delivered or when animals needed to rely on stored representations of reward value (i.e., during extinction). However, all rats exhibited decreased premature responding and slower response latencies after satiety manipulations. Hence, disconnecting the OFC and BLA did not affect general behavioral changes caused by reduced motivation, but instead prevented alterations in the value of a specific reward from contributing appropriately to cost-benefit decision-making. These results highlight the role of the OFC-BLA pathway in the decision-making process and suggest that communication between these areas is vital for the appropriate assessment of reward value to influence choice.

  2. Role of amygdala in mediating sexual and emotional behavior via coupled nitric oxide release

    Institute of Scientific and Technical Information of China (English)

    Elliott SALAMON; Tobias ESCH; George B STEFANO

    2005-01-01

    Although the anatomical configuration of the amygdala has been studied a great deal, very little research has been conducted on understanding the precise mechanism by which this emotional regulatory center exerts its control on emotional and sexual behavior. By applying research methodology from the Neuroscience Research Institute, State University of New York, College at Old Westbury, we intended to demonstrate that much of the mediated effects of the amygdala, specifically the regulation of the male and female sexual response cycles, as well as related emotional considerations, exert their effects coupled to nitric oxide (NO) release. Furthermore, by using current anatomical and histological data, we demonstrated that amygdalar tissue rich in endocannabinoid and opiate, as well as catecholamine, receptors could exert its neurochemical effects within an NOmediated paradigm. This paradigm, together with the existence of estrogen and androgen signaling within the amygdala, further lends credence to our theoretical framework. We begin with a brief anatomical and functional review of amygdalar function, and then proceed to demonstrate its relationship with NO.

  3. Basolateral Mg2+ extrusion via CNNM4 mediates transcellular Mg2+ transport across epithelia: a mouse model.

    Directory of Open Access Journals (Sweden)

    Daisuke Yamazaki

    Full Text Available Transcellular Mg(2+ transport across epithelia, involving both apical entry and basolateral extrusion, is essential for magnesium homeostasis, but molecules involved in basolateral extrusion have not yet been identified. Here, we show that CNNM4 is the basolaterally located Mg(2+ extrusion molecule. CNNM4 is strongly expressed in intestinal epithelia and localizes to their basolateral membrane. CNNM4-knockout mice showed hypomagnesemia due to the intestinal malabsorption of magnesium, suggesting its role in Mg(2+ extrusion to the inner parts of body. Imaging analyses revealed that CNNM4 can extrude Mg(2+ by exchanging intracellular Mg(2+ with extracellular Na(+. Furthermore, CNNM4 mutations cause Jalili syndrome, characterized by recessive amelogenesis imperfecta with cone-rod dystrophy. CNNM4-knockout mice showed defective amelogenesis, and CNNM4 again localizes to the basolateral membrane of ameloblasts, the enamel-forming epithelial cells. Missense point mutations associated with the disease abolish the Mg(2+ extrusion activity. These results demonstrate the crucial importance of Mg(2+ extrusion by CNNM4 in organismal and topical regulation of magnesium.

  4. 杏仁核内去甲肾上腺素在应激激素调控记忆保持过程中的作用%Role of amygdala norepinephrine in mediating stress hormone regu-lation of memory storage

    Institute of Scientific and Technical Information of China (English)

    Barbara FERRY; James L McGAUGH

    2000-01-01

    There is extensive evidence indicating that the noradrenergic system of the amygdala, particularly the basolateral nucleus of the amygdala (BLA), is involved in memory consolidation. This article reviews the central hypothesis that stress hormones released during emotionally arousing experiences activate noradrenergic mechanisms in the BLA, resulting in enhanced memory for those events. Findings from expenments using rats have shown that the memory-modulatory effects of the adrenocortical stress hormones epinephrine and glucocorficoids involve activation of β-adrenoceptors in the BLA. In addition, both behavioral and microdialysis studies have shown that the noradrenergic system of the BLA also mediates the influences of other neuromodulatory systems such as opioid peptidergic and GABAergic systems on memory storage. Other findings indicate that this stress hormone-induced activation of noradrenergic mechanisms in the BLA regulates memory storage in other brain regions.

  5. Differential involvement of medial prefrontal cortex and basolateral amygdala extracellular signal-regulated kinase in extinction of conditioned taste aversion is dependent on different intervals of extinction following conditioning.

    Science.gov (United States)

    Lin, P-Y; Wang, S-P; Tai, M-Y; Tsai, Y-F

    2010-11-24

    Extinction reflects a decrease in the conditioned response (CR) following non-reinforcement of a conditioned stimulus. Behavioral evidence indicates that extinction involves an inhibitory learning mechanism in which the extinguished CR reappears with presentation of an unconditioned stimulus. However, recent studies on fear conditioning suggest that extinction erases the original conditioning if the time interval between fear acquisition and extinction is short. The present study examined the effects of different intervals between acquisition and extinction of the original memory in conditioned taste aversion (CTA). Male Long-Evans rats acquired CTA by associating a 0.2% sucrose solution with malaise induced by i.p. injection of 4 ml/kg 0.15 M LiCl. Two different time intervals, 5 and 24 h, between CTA acquisition and extinction were used. Five or 24 h after CTA acquisition, extinction trials were performed, in which a bottle containing 20 ml of a 0.2% sucrose solution was provided for 10 min without subsequent LiCl injection. If sucrose consumption during the extinction trials was greater than the average water consumption, then rats were considered to have reached CTA extinction. Rats subjected to extinction trials lasting 24 h, but not 5 h, after acquisition re-exhibited the extinguished CR following injection of 0.15 M LiCl alone 7 days after acquisition. Extracellular signal-regulated kinase (ERK) in the medial prefrontal cortex (mPFC) and basolateral nucleus of the amygdala (BLA) was examined by Western blot after the first extinction trial. ERK activation in the mPFC was induced after the extinction trial beginning 5 h after acquisition, whereas the extinction trial performed 24 h after acquisition induced ERK activation in the BLA. These data suggest that the original conditioning can be inhibited or retained by CTA extinction depending on the time interval between acquisition and extinction and that the ERK transduction pathway in the mPFC and BLA is

  6. Macula densa Na(+)/H(+) exchange activities mediated by apical NHE2 and basolateral NHE4 isoforms.

    Science.gov (United States)

    Peti-Peterdi, J; Chambrey, R; Bebok, Z; Biemesderfer, D; St John, P L; Abrahamson, D R; Warnock, D G; Bell, P D

    2000-03-01

    Functional and immunohistochemical studies were performed to localize and identify Na(+)/H(+) exchanger (NHE) isoforms in macula densa cells. By using the isolated perfused thick ascending limb with attached glomerulus preparation dissected from rabbit kidney, intracellular pH (pH(i)) was measured with fluorescence microscopy by using 2',7'-bis-(2-carboxyethyl)-5-(and -6) carboxyfluorescein. NHE activity was assayed by measuring the initial rate of Na(+)-dependent pH(i) recovery from an acid load imposed by prior lumen and bath Na(+) removal. Removal of Na(+) from the bath resulted in a significant, DIDS-insensitive, ethylisopropyl amiloride (EIPA)-inhibitable decrease in pH(i). This basolateral transporter showed very low affinity for EIPA and Hoechst 694 (IC(50) = 9.0 and 247 microM, respectively, consistent with NHE4). The recently reported apical NHE was more sensitive to inhibition by these drugs (IC(50) = 0.86 and 7.6 microM, respectively, consistent with NHE2). Increasing osmolality, a known activator of NHE4, greatly stimulated basolateral NHE. Immunohistochemical studies using antibodies against NHE1-4 peptides demonstrated expression of NHE2 along the apical and NHE4 along the basolateral, membrane, whereas NHE1 and NHE3 were not detected. These results suggest that macula densa cells functionally and immunologically express NHE2 at the apical membrane and NHE4 at the basolateral membrane. These two isoforms likely participate in Na(+) transport, pH(i), and cell volume regulation and may be involved in tubuloglomerular feedback signaling by these cells.

  7. Exposure to an open-field arena increases c-Fos expression in a distributed anxiety-related system projecting to the basolateral amygdaloid complex

    DEFF Research Database (Denmark)

    Hale, M.W.; Hay-Schmidt, A.; Mikkelsen, J.D.;

    2008-01-01

    Anxiety states and anxiety-related behaviors appear to be regulated by a distributed and highly interconnected system of brain structures including the basolateral amygdala. Our previous studies demonstrate that exposure of rats to an open-field in high- and low-light conditions results in a marked...... of specific afferent input to this region of the amygdala. In order to identify candidate brain regions mediating anxiety-induced activation of the basolateral amygdaloid complex in rats, we used cholera toxin B subunit (CTb) as a retrograde tracer to identify neurons with direct afferent projections...... amygdaloid complex. Rats were housed individually for 11 days after CTb injections and handled (HA) for 2 min each day. On the test day rats were either, 1) exposed to an open-field in low-light conditions (8-13 lux) for 15 min (OF); 2) briefly HA or 3) left undisturbed (control). We report that dual...

  8. Pain-related increase of excitatory transmission and decrease of inhibitory transmission in the central nucleus of the amygdala are mediated by mGluR1

    Directory of Open Access Journals (Sweden)

    Neugebauer Volker

    2010-12-01

    Full Text Available Abstract Neuroplasticity in the central nucleus of the amygdala (CeA, particularly its latero-capsular division (CeLC, is an important contributor to the emotional-affective aspects of pain. Previous studies showed synaptic plasticity of excitatory transmission to the CeLC in different pain models, but pain-related changes of inhibitory transmission remain to be determined. The CeLC receives convergent excitatory inputs from the parabrachial nucleus in the brainstem and from the basolateral amygdala (BLA. In addition, feedforward inhibition of CeA neurons is driven by glutamatergic projections from the BLA area to a cluster of GABAergic neurons in the intercalated cell masses (ITC. Using patch-clamp in rat brain slices we measured monosynaptic excitatory postsynaptic currents (EPSCs and polysynaptic inhibitory currents (IPSCs that were evoked by electrical stimulation in the BLA. In brain slices from arthritic rats, input-output functions of excitatory synaptic transmission were enhanced whereas inhibitory synaptic transmission was decreased compared to control slices from normal untreated rats. A non-NMDA receptor antagonist (NBQX blocked the EPSCs and reduced the IPSCs, suggesting that non-NMDA receptors mediate excitatory transmission and also contribute to glutamate-driven feed-forward inhibition of CeLC neurons. IPSCs were blocked by a GABAA receptor antagonist (bicuculline. Bicuculline increased EPSCs under normal conditions but not in slices from arthritic rats, which indicates a loss of GABAergic control of excitatory transmission. A metabotropic glutamate receptor subtype 1 (mGluR1 antagonist (LY367385 reversed both the increase of excitatory transmission and the decrease of inhibitory transmission in the arthritis pain model but had no effect on basal synaptic transmission in control slices from normal rats. The inhibitory effect of LY367385 on excitatory transmission was blocked by bicuculline suggesting the involvement of a GABAergic

  9. The densities of calbindin and parvalbumin, but not calretinin neurons, are sexually dimorphic in the amygdala of the guinea pig.

    Science.gov (United States)

    Równiak, Maciej; Bogus-Nowakowska, Krystyna; Robak, Anna

    2015-04-16

    In the amygdala, the calcium-binding proteins (calbindin, parvalbumin or calretinin) are useful markers of specific subpopulations of γ-aminobutyric acid (GABA) containing neurons. In the rat and monkey they together mark the vast majority of GABA-containing neurons in this brain region. As GABA involvement in the control of various behaviors in a sex-specific manner and sexual dimorphism of the GABAergic system itself were recently proven, the question is how much dimorphic may be various subpopulations of this system. Thus, the present study investigates for the first time the presence/absence of sexual dimorphism among neurons expressing calbindin (CB), parvalbumin (PV) and calretinin (CR) which form in the amygdala main subsets of GABAergic system. The results show that in the amygdala of the guinea pig the densities of CB and/or PV expressing neurons are sexually dimorphic with the female>male pattern of sex differences in the basolateral amygdala. In the medial and cortical amygdala respectively CB and PV values are also sexually dimorphic, favoring males. The densities of CR expressing neurons are in the amygdala of the guinea pig sexually isomorphic. In conclusion, the results of the present study provide an evidence that in the amygdala of the guinea pig the densities of neurons expressing CB and/or PV are sexually dimorphic what supports the idea that GABA participates in the mediation of sexually dimorphic functions, controlled by this brain area.

  10. The role of the amygdala in the extinction of conditioned fear.

    Science.gov (United States)

    Barad, Mark; Gean, Po-Wu; Lutz, Beat

    2006-08-15

    The amygdala has long been known to play a central role in the acquisition and expression of fear. More recently, convergent evidence has implicated the amygdala in the extinction of fear as well. In rodents, some of this evidence comes from the infusion of drugs directly into the amygdala and, in particular, into the basolateral complex of the amygdala, during or after extinction learning. In vivo electrophysiology has identified cellular correlates of extinction learning and memory in the lateral nucleus of that structure. Human imaging experiments also indicate that amygdaloid activity correlates with extinction training. In addition, some studies have directly identified changes in molecular constituents of the basolateral amygdala. Together these experiments strongly indicate that the basolateral amygdala plays a crucial role in extinction learning. Interpreted in the light of these findings, several recent in vitro electrophysiology studies in amygdala-containing brain slices are suggestive of potential synaptic and circuit bases of extinction learning.

  11. Amygdala perfusion is predicted by its functional connectivity with the ventromedial prefrontal cortex and negative affect.

    Directory of Open Access Journals (Sweden)

    Garth Coombs

    Full Text Available BACKGROUND: Previous studies have shown that the activity of the amygdala is elevated in people experiencing clinical and subclinical levels of anxiety and depression (negative affect. It has been proposed that a reduction in inhibitory input to the amygdala from the prefrontal cortex and resultant over-activity of the amygdala underlies this association. Prior studies have found relationships between negative affect and 1 amygdala over-activity and 2 reduced amygdala-prefrontal connectivity. However, it is not known whether elevated amygdala activity is associated with decreased amygdala-prefrontal connectivity during negative affect states. METHODS: Here we used resting-state arterial spin labeling (ASL and blood oxygenation level dependent (BOLD functional magnetic resonance imaging (fMRI in combination to test this model, measuring the activity (regional cerebral blood flow, rCBF and functional connectivity (correlated fluctuations in the BOLD signal of one subregion of the amygdala with strong connections with the prefrontal cortex, the basolateral nucleus (BLA, and subsyndromal anxiety levels in 38 healthy subjects. RESULTS: BLA rCBF was strongly correlated with anxiety levels. Moreover, both BLA rCBF and anxiety were inversely correlated with the strength of the functional coupling of the BLA with the caudal ventromedial prefrontal cortex. Lastly, BLA perfusion was found to be a mediator of the relationship between BLA-prefrontal connectivity and anxiety. CONCLUSIONS: These results show that both perfusion of the BLA and a measure of its functional coupling with the prefrontal cortex directly index anxiety levels in healthy subjects, and that low BLA-prefrontal connectivity may lead to increased BLA activity and resulting anxiety. Thus, these data provide key evidence for an often-cited circuitry model of negative affect, using a novel, multi-modal imaging approach.

  12. Unilateral block of NMDA receptors in the amygdala prevents predator stress-induced lasting increases in anxiety-like behavior and unconditioned startle--effective hemisphere depends on the behavior.

    Science.gov (United States)

    Adamec, R E; Burton, P; Shallow, T; Budgell, J

    Lasting increases in anxiety-like behavior (ALB) in the elevated plus-maze are produced by a single 5-min exposure of a rat to a cat. Rats become more anxious in the plus-maze for up to 3 weeks after the exposure. The first study in this series demonstrated that blockade of NMDA receptors in rats with MK-801, AP7, or CPP, given systemically 30 min prior to exposure to a cat prevents the increase in ALB assessed 1 week later in the elevated plus-maze. To localize the site of action of systemic MK-801, MK-801 was injected in the amygdala 30 min prior to predator stress. Injections were given either unilaterally in either hemisphere, or bilaterally in both hemispheres. The target of the injection was the basolateral amygdala. The effects of injection depended on both the type of behavior and the hemisphere of injection. Injections of MK-801 in a variety of sites in the basolateral amygdala had no effect on the suppression of open-arm exploration produced by predator stress. Other amygdala nuclei or other limbic sites likely mediate the effects of systemically administered MK-801 on this behavior. In contrast, NMDA receptors in the left lateral amygdala mediate lasting suppression of risk assessment. MK-801, in a variety of sites in the left but not right lateral amygdala, blocked the effects of predator stress on risk assessment. This is clear evidence of separability of neural mechanisms controlling open-arm exploration and risk assessment. Different NMDA-dependent amygdala circuitry mediated effects of predator stress on unconditioned acoustic startle 1 week after cat exposure. The data indicate that integrity of the left lateral amygdala is necessary for potentiation of startle amplitude by predator stress, though NMDA receptors are not involved in this function. Nevertheless, NMDA receptors in the right, but not the left lateral amygdala, mediate initiation of changes in startle. The data also suggest that the right amygdala action is "downstream" from the left

  13. Lansoprazole Exacerbates Pemetrexed-Mediated Hematologic Toxicity by Competitive Inhibition of Renal Basolateral Human Organic Anion Transporter 3.

    Science.gov (United States)

    Ikemura, Kenji; Hamada, Yugo; Kaya, Chinatsu; Enokiya, Tomoyuki; Muraki, Yuichi; Nakahara, Hiroki; Fujimoto, Hajime; Kobayashi, Tetsu; Iwamoto, Takuya; Okuda, Masahiro

    2016-10-01

    Pemetrexed, a multitargeted antifolate, is eliminated by tubular secretion via human organic anion transporter 3 (hOAT3). Although proton pump inhibitors (PPIs) are frequently used in cancer patients, the drug interaction between PPIs and pemetrexed remains to be clarified. In this study, we examined the drug interaction between pemetrexed and PPIs in hOAT3-expressing cultured cells, and retrospectively analyzed the impact of PPIs on the development of hematologic toxicity in 108 patients who received pemetrexed and carboplatin treatment of nonsquamous non-small cell lung cancer for the first time between January 2011 and June 2015. We established that pemetrexed was transported via hOAT3 (Km = 68.3 ± 11.1 µM). Lansoprazole, rabeprazole, pantoprazole, esomeprazole, omeprazole, and vonoprazan inhibited hOAT3-mediated uptake of pemetrexed in a concentration-dependent manner. The inhibitory effect of lansoprazole was much greater than those of other PPIs and the apparent IC50 value of lansoprazole against pemetrexed transport via hOAT3 was 0.57 ± 0.17 µM. The inhibitory type of lansoprazole was competitive. In a retrospective study, multivariate analysis revealed that coadministration of lansoprazole, but not other PPIs, with pemetrexed and carboplatin was an independent risk factor significantly contributing to the development of hematologic toxicity (odds ratio: 10.004, P = 0.005). These findings demonstrated that coadministration of lansoprazole could exacerbate the hematologic toxicity associated with pemetrexed, at least in part, by competitive inhibition of hOAT3. Our results would aid clinicians to make decisions of coadministration drugs to avoid drug interaction-induced side effects for achievement of safe and appropriate chemotherapy with pemetrexed.

  14. Basomedial amygdala mediates top-down control of anxiety and fear.

    Science.gov (United States)

    Adhikari, Avishek; Lerner, Talia N; Finkelstein, Joel; Pak, Sally; Jennings, Joshua H; Davidson, Thomas J; Ferenczi, Emily; Gunaydin, Lisa A; Mirzabekov, Julie J; Ye, Li; Kim, Sung-Yon; Lei, Anna; Deisseroth, Karl

    2015-11-12

    Anxiety-related conditions are among the most difficult neuropsychiatric diseases to treat pharmacologically, but respond to cognitive therapies. There has therefore been interest in identifying relevant top-down pathways from cognitive control regions in medial prefrontal cortex (mPFC). Identification of such pathways could contribute to our understanding of the cognitive regulation of affect, and provide pathways for intervention. Previous studies have suggested that dorsal and ventral mPFC subregions exert opposing effects on fear, as do subregions of other structures. However, precise causal targets for top-down connections among these diverse possibilities have not been established. Here we show that the basomedial amygdala (BMA) represents the major target of ventral mPFC in amygdala in mice. Moreover, BMA neurons differentiate safe and aversive environments, and BMA activation decreases fear-related freezing and high-anxiety states. Lastly, we show that the ventral mPFC-BMA projection implements top-down control of anxiety state and learned freezing, both at baseline and in stress-induced anxiety, defining a broadly relevant new top-down behavioural regulation pathway.

  15. Cortical inputs innervate calbindin-immunoreactive interneurons of the rat basolateral amygdaloid complex.

    Science.gov (United States)

    Unal, Gunes; Paré, Jean-Francois; Smith, Yoland; Paré, Denis

    2014-06-01

    The present study was undertaken to shed light on the synaptic organization of the rat basolateral amygdala (BLA). The BLA contains multiple types of GABAergic interneurons that are differentially connected with extrinsic afferents and other BLA cells. Previously, it was reported that parvalbumin immunoreactive (PV(+) ) interneurons receive strong excitatory inputs from principal BLA cells but very few cortical inputs, implying a prevalent role in feedback inhibition. However, because prior physiological studies indicate that cortical afferents do trigger feedforward inhibition in principal cells, the present study aimed to determine whether a numerically important subtype of interneurons, expressing calbindin (CB(+) ), receives cortical inputs. Rats received injections of the anterograde tracer Phaseolus vulgaris-leucoagglutinin (PHAL) in the perirhinal cortex or adjacent temporal neocortex. Light and electron microscopic observations of the relations between cortical inputs and BLA neurons were performed in the lateral (LA) and basolateral (BL) nuclei. Irrespective of the injection site (perirhinal or temporal neocortex) and target nucleus (LA or BL), ~90% of cortical axon terminals formed asymmetric synapses with dendritic spines of principal BLA neurons, while 10% contacted the dendritic shafts of presumed interneurons, half of which were CB(+) . Given the previously reported pattern of CB coexpression among GABAergic interneurons of the BLA, these results suggest that a subset of PV-immunonegative cells that express CB, most likely the somatostatin-positive interneurons, are important mediators of cortically evoked feedforward inhibition in the BLA.

  16. Fragile X syndrome and the amygdala.

    Science.gov (United States)

    Suvrathan, Aparna; Chattarji, Sumantra

    2011-06-01

    Fragile X syndrome (FXS) is the most commonly inherited form of mental impairment and autism. Current understanding of the molecular and cellular mechanisms underlying FXS symptoms is derived mainly from studies on the hippocampus and cortex. However, FXS is also associated with strong emotional symptoms, which are likely to involve changes in the amygdala. Unfortunately, the synaptic basis of amygdalar dysfunction in FXS remains largely unexplored. Here we describe recent findings from mouse models of FXS that have identified synaptic defects in the basolateral amygdala that are in many respects distinct from those reported earlier in the hippocampus. Long-term potentiation and surface expression of AMPA-receptors are impaired. Further, presynaptic defects are seen at both excitatory and inhibitory synapses. Remarkably, some of these synaptic defects in the amygdala are also amenable to pharmacological rescue. These results also underscore the need to modify the current hippocampus-centric framework to better explain FXS-related synaptic dysfunction in the amygdala.

  17. High-mobility group box 1 inhibits HCO3- absorption in the medullary thick ascending limb through RAGE-Rho-ROCK-mediated inhibition of basolateral Na+/H+ exchange.

    Science.gov (United States)

    Watts, Bruns A; George, Thampi; Badalamenti, Andrew; Good, David W

    2016-09-01

    High-mobility group box 1 (HMGB1) is a nuclear protein released extracellularly in response to infection or injury, where it activates immune responses and contributes to the pathogenesis of kidney dysfunction in sepsis and sterile inflammatory disorders. Recently, we demonstrated that HMGB1 inhibits HCO3 (-) absorption in perfused rat medullary thick ascending limbs (MTAL) through a basolateral receptor for advanced glycation end products (RAGE)-dependent pathway that is additive to Toll-like receptor 4 (TLR4)-ERK-mediated inhibition by LPS (Good DW, George T, Watts BA III. Am J Physiol Renal Physiol 309: F720-F730, 2015). Here, we examined signaling and transport mechanisms that mediate inhibition by HMGB1. Inhibition of HCO3 (-) absorption by HMGB1 was eliminated by the Rho-associated kinase (ROCK) inhibitor Y27632 and by a specific inhibitor of Rho, the major upstream activator of ROCK. HMGB1 increased RhoA and ROCK1 activity. HMGB1-induced ROCK1 activation was eliminated by the RAGE antagonist FPS-ZM1 and by inhibition of Rho. The Rho and ROCK inhibitors had no effect on inhibition of HCO3 (-) absorption by bath LPS. Inhibition of HCO3 (-) absorption by HMGB1 was eliminated by bath amiloride, 0 Na(+) bath, and the F-actin stabilizer jasplakinolide, three conditions that selectively prevent inhibition of MTAL HCO3 (-) absorption mediated through NHE1. HMGB1 decreased basolateral Na(+)/H(+) exchange activity through activation of ROCK. We conclude that HMGB1 inhibits HCO3 (-) absorption in the MTAL through a RAGE-RhoA-ROCK1 signaling pathway coupled to inhibition of NHE1. The HMGB1-RAGE-RhoA-ROCK1 pathway thus represents a potential target to attenuate MTAL dysfunction during sepsis and other inflammatory disorders. HMGB1 and LPS inhibit HCO3 (-) absorption through different receptor signaling and transport mechanisms, which enables these pathogenic mediators to act directly and independently to impair MTAL function.

  18. Differential Effects of Cannabinoid Receptor Agonist on Social Discrimination and Contextual Fear in Amygdala and Hippocampus

    Science.gov (United States)

    Segev, Amir; Akirav, Irit

    2011-01-01

    We examined whether the cannabinoid receptor agonist WIN55,212-2 (WIN; 5 [mu]g/side) microinjected into the hippocampus or the amygdala would differentially affect memory processes in a neutral vs. an aversive task. In the aversive contextual fear task, WIN into the basolateral amygdala impaired fear acquisition/consolidation, but not retrieval.…

  19. The Amygdala Is Not Necessary for Unconditioned Stimulus Inflation after Pavlovian Fear Conditioning in Rats

    Science.gov (United States)

    Rabinak, Christine A.; Orsini, Caitlin A.; Zimmerman, Joshua M.; Maren, Stephen

    2009-01-01

    The basolateral complex (BLA) and central nucleus (CEA) of the amygdala play critical roles in associative learning, including Pavlovian conditioning. However, the precise role for these structures in Pavlovian conditioning is not clear. Recent work in appetitive conditioning paradigms suggests that the amygdala, particularly the BLA, has an…

  20. Post-Training Unilateral Amygdala Lesions Selectively Impair Contextual Fear Memories

    Science.gov (United States)

    Flavell, Charlotte R.; Lee, Jonathan L. C.

    2012-01-01

    The basolateral amygdala (BLA) and the dorsal hippocampus (dHPC) are both structures with key roles in contextual fear conditioning. During fear conditioning, it is postulated that contextual representations of the environment are formed in the hippocampus, which are then associated with foot shock in the amygdala. However, it is not known to what…

  1. Anxiolytic-like effects after vector-mediated overexpression of neuropeptide Y in the amygdala and hippocampus of mice

    DEFF Research Database (Denmark)

    Christiansen, Søren Hofman Oliveira; Olesen, Mikkel Vestergaard; Gøtzsche, Casper René;

    2014-01-01

    . Using a recombinant adeno-associated viral (rAAV) vector, we addressed this idea by testing effects on anxiolytic- and depression-like behaviours in adult mice after overexpression of NPY transgene in the amygdala and/or hippocampus, two brain regions implicated in emotional behaviours. In the amygdala......, injections of rAAV-NPY caused significant anxiolytic-like effect in the open field, elevated plus maze, and light-dark transition tests. In the hippocampus, rAAV-NPY treatment was associated with anxiolytic-like effect only in the elevated plus maze. No additive effect was observed after combined r......AAV-NPY injection into both the amygdala and hippocampus where anxiolytic-like effect was found in the elevated plus maze and light-dark transition tests. Antidepressant-like effects were not detected in any of the rAAV-NPY injected groups. Immobility was even increased in the tail suspension and forced swim tests...

  2. COMT Val158Met polymorphism influences the susceptibility to framing in decision-making: OFC-amygdala functional connectivity as a mediator.

    Science.gov (United States)

    Gao, Xiaoxue; Gong, Pingyuan; Liu, Jinting; Hu, Jie; Li, Yue; Yu, Hongbo; Gong, Xiaoliang; Xiang, Yang; Jiang, Changjun; Zhou, Xiaolin

    2016-05-01

    Individuals tend to avoid risk in a gain frame, in which options are presented in a positive way, but seek risk in a loss frame, in which the same options are presented negatively. Previous studies suggest that emotional responses play a critical role in this "framing effect." Given that the Met allele of COMT Val158Met polymorphism (rs4680) is associated with the negativity bias during emotional processing, this study investigated whether this polymorphism is associated with individual susceptibility to framing and which brain areas mediate this gene-behavior association. Participants were genotyped, scanned in resting state, and completed a monetary gambling task with options (sure vs risky) presented as potential gains or losses. The Met allele carriers showed a greater framing effect than the Val/Val homozygotes as the former gambled more than the latter in the loss frame. Moreover, the gene-behavior association was mediated by resting-state functional connectivity (RSFC) between orbitofrontal cortex (OFC) and bilateral amygdala. Met allele carriers showed decreased RSFC, thereby demonstrating higher susceptibility to framing than Val allele carriers. These findings demonstrate the involvement of COMT Val158Met polymorphism in the framing effect in decision-making and suggest RSFC between OFC and amygdala as a neural mediator underlying this gene-behavior association. Hum Brain Mapp 37:1880-1892, 2016. © 2016 Wiley Periodicals, Inc.

  3. 大鼠杏仁体基底外侧核中小白蛋白反应阳性神经元受抑制性神经网络支配%PARVALBUMIN-IMMUNOREACTIVE INTERNEURONS ARE CONTROLLED BY AN INHIBITORY NEURONAL NETWORK IN BASOLATERAL NUCLEUS OF THE RAT AMYGDALA

    Institute of Scientific and Technical Information of China (English)

    李瑞锡; 彭裕文; 大谷 修; 西条 寿夫; 王劼; 丁忠良; 高璐; 沈馨亚

    2004-01-01

    As the elements of local neuronal circuits, parvalbumin (PV)-containing interneurons in the basolateral nucleus (BL) of the amygdala play an important role in the amygdaloid functions of emotion, learning and memory. In order to investigate how the PV-containing interneurons in the BL are controlled, the synapses established on PV- containing interneurons in the BL of the rat amygdala were examined under immunoelectron microscopy using the double labeling methods with anti-PV and anti-dopamine (DA) antibodies for a reference of dopaminergic axon terminals. The results show that the PV immunoreactive (IR) neurons formed the synapses mainly on the dendritic structures from shafts of the dendrites to median and small dendritic branches. 68% of the synapses on the PV-IR profiles were formed by unlabeled axon terminals, and 32 % of them were formed by DA- (21 % ) and PV- (11 % )IR axon terminals. Majority of the synapses on the PV-IR neurons formed by unlabeled axon terminals were symmetric type, and only a small a mount of them were asymmetric that were observed between the PV-IR spines and unlabeled axon terminals and in the serial synapses in which an unlabeled axon terminal symmetrically contacted to another unlabeled axon terminal that, in turn, synapsed asymmetrically to the PV-IR dendritic profiles. The synapses formed between the PV-IR profiles and DA- or PV-IR axon terminals were exclusively symmetric. The present results suggest that the PV-containing interneurons in the BL of the rat amygdala were controlled by an inhibitory network formed by the symmetric synapses around them, among which the DA system was included.%小白蛋白(PV)神经元作为杏仁核簇基底外侧核(BL)中局部神经环路成分,对杏仁核的情绪、学习和记忆过程等机能发挥重要作用.为探讨BL中PV中间神经元的突触形成状态,本研究用抗PV抗体标示PV神经元,以抗多巴胺(DA)抗体标示多巴胺能轴突及末梢作为传入纤维的标志,对

  4. Increased Serotonin Transporter Expression Reduces Fear and Recruitment of Parvalbumin Interneurons of the Amygdala.

    Science.gov (United States)

    Bocchio, Marco; Fucsina, Giulia; Oikonomidis, Lydia; McHugh, Stephen B; Bannerman, David M; Sharp, Trevor; Capogna, Marco

    2015-12-01

    Genetic association studies suggest that variations in the 5-hydroxytryptamine (5-HT; serotonin) transporter (5-HTT) gene are associated with susceptibility to psychiatric disorders such as anxiety or posttraumatic stress disorder. Individuals carrying high 5-HTT-expressing gene variants display low amygdala reactivity to fearful stimuli. Mice overexpressing the 5-HTT (5-HTTOE), an animal model of this human variation, show impaired fear, together with reduced fear-evoked theta oscillations in the basolateral amygdala (BLA). However, it is unclear how variation in 5-HTT gene expression impacts on the microcircuitry of the BLA to change behavior. We addressed this issue by investigating the activity of parvalbumin (PV)-expressing interneurons (PVINs), the biggest IN population in the basal amygdala (BA). We found that increased 5-HTT expression impairs the recruitment of PVINs (measured by their c-Fos immunoreactivity) during fear. Ex vivo patch-clamp recordings demonstrated that the depolarizing effect of 5-HT on PVINs was mediated by 5-HT2A receptor. In 5-HTTOE mice, 5-HT-evoked depolarization of PVINs and synaptic inhibition of principal cells, which provide the major output of the BA, were impaired. This deficit was because of reduced 5-HT2A function and not because of increased 5-HT uptake. Collectively, these findings provide novel cellular mechanisms that are likely to contribute to differences in emotional behaviors linked with genetic variations of the 5-HTT.

  5. Divergent Routing of Positive and Negative Information from the Amygdala during Memory Retrieval.

    Science.gov (United States)

    Beyeler, Anna; Namburi, Praneeth; Glober, Gordon F; Simonnet, Clémence; Calhoon, Gwendolyn G; Conyers, Garrett F; Luck, Robert; Wildes, Craig P; Tye, Kay M

    2016-04-20

    Although the basolateral amygdala (BLA) is known to play a critical role in the formation of memories of both positive and negative valence, the coding and routing of valence-related information is poorly understood. Here, we recorded BLA neurons during the retrieval of associative memories and used optogenetic-mediated phototagging to identify populations of neurons that synapse in the nucleus accumbens (NAc), the central amygdala (CeA), or ventral hippocampus (vHPC). We found that despite heterogeneous neural responses within each population, the proportions of BLA-NAc neurons excited by reward predictive cues and of BLA-CeA neurons excited by aversion predictive cues were higher than within the entire BLA. Although the BLA-vHPC projection is known to drive behaviors of innate negative valence, these neurons did not preferentially code for learned negative valence. Together, these findings suggest that valence encoding in the BLA is at least partially mediated via divergent activity of anatomically defined neural populations.

  6. NPY Y1 receptors differentially modulate GABAA and NMDA receptors via divergent signal-transduction pathways to reduce excitability of amygdala neurons.

    Science.gov (United States)

    Molosh, Andrei I; Sajdyk, Tammy J; Truitt, William A; Zhu, Weiguo; Oxford, Gerry S; Shekhar, Anantha

    2013-06-01

    Neuropeptide Y (NPY) administration into the basolateral amygdala (BLA) decreases anxiety-like behavior, mediated in part through the Y1 receptor (Y1R) isoform. Activation of Y1Rs results in G-protein-mediated reduction of cAMP levels, which results in reduced excitability of amygdala projection neurons. Understanding the mechanisms linking decreased cAMP levels to reduced excitability in amygdala neurons is important for identifying novel anxiolytic targets. We studied the intracellular mechanisms of activation of Y1Rs on synaptic transmission in the BLA. Activating Y1Rs by [Leu(31),Pro(34)]-NPY (L-P NPY) reduced the amplitude of evoked NMDA-mediated excitatory postsynaptic currents (eEPSCs), without affecting AMPA-mediated eEPSCs, but conversely increased the amplitude of GABAA-mediated evoked inhibitory postsynaptic currents (eIPSCs). Both effects were abolished by the Y1R antagonist, PD160170. Intracellular GDP-β-S, or pre-treatment with either forskolin or 8Br-cAMP, eliminated the effects of L-P NPY on both NMDA- and GABAA-mediated currents. Thus, both the NMDA and GABAA effects of Y1R activation in the BLA are G-protein-mediated and cAMP-dependent. Pipette inclusion of protein kinase A (PKA) catalytic subunit blocked the effect of L-P NPY on GABAA-mediated eIPSCs, but not on NMDA-mediated eEPSCs. Conversely, activating the exchange protein activated by cAMP (Epac) with 8CPT-2Me-cAMP blocked the effect of L-P NPY on NMDA-mediated eEPSCs, but not on GABAA-mediated eIPSCs. Thus, NPY regulates amygdala excitability via two signal-transduction events, with reduced PKA activity enhancing GABAA-mediated eIPSCs and Epac deactivation reducing NMDA-mediated eEPSCs. This multipathway regulation of NMDA- and GABAA-mediated currents may be important for NPY plasticity and stress resilience in the amygdala.

  7. State-dependent modulation of amygdala inputs by dopamine-induced enhancement of sodium currents in layer V entorhinal cortex.

    Science.gov (United States)

    Rosenkranz, J Amiel; Johnston, Daniel

    2007-06-27

    Interaction between the entorhinal cortex (EC) and basolateral amygdala (BLA) may be a fundamental component in the consolidation of many forms of affective memory, such as inhibitory avoidance. Dopamine (DA) in the EC is necessary for, and may facilitate, this form of learning. This effect of DA on affective behaviors may be accomplished in part through modulation of amygdala inputs. Although it is known that DA can modulate neuronal activity in the EC, it is not known whether DA modulates inputs from the BLA. In this study, we used in vitro patch-clamp recordings and Ca2+ imaging of layer V neurons in the rat lateral EC to determine whether DA modulates the integration of inputs from the BLA and the mechanism for this modulation. We found that DA exerted actions that depended on the neuronal state. Near resting membrane potentials, DA suppressed integration of inputs, whereas at depolarized potentials, DA enhanced integration. DA enhanced the integration by a D2-mediated enhancement of Na+ currents, via phospholipase C. These experiments demonstrate that DA can exert actions in the EC that depend on the membrane voltage. This effect of DA may affect a wide range of inputs. Functionally, by enhancement of amygdala inputs that arrive in concert with other inputs, or during depolarized states, DA can facilitate the impact of affect on memory in a subset of conditions.

  8. Enhanced group II mGluR-mediated inhibition of pain-related synaptic plasticity in the amygdala

    Directory of Open Access Journals (Sweden)

    Bird Gary C

    2006-05-01

    Full Text Available Abstract Background The latero-capsular part of the central nucleus of the amygdala (CeLC is the target of the spino-parabrachio-amygdaloid pain pathway. Our previous studies showed that CeLC neurons develop synaptic plasticity and increased neuronal excitability in the kaolin/carrageenan model of arthritic pain. These pain-related changes involve presynaptic group I metabotropic glutamate receptors (mGluRs and postsynaptic NMDA and calcitonin gene-related peptide (CGRP1 receptors. Here we address the role of group II mGluRs. Results Whole-cell current- and voltage-clamp recordings were made from CeLC neurons in brain slices from control rats and arthritic rats (>6 h postinjection of kaolin/carrageenan into the knee. Monosynaptic excitatory postsynaptic currents (EPSCs were evoked by electrical stimulation of afferents from the pontine parabrachial (PB area. A selective group II mGluR agonist (LY354740 decreased the amplitude of EPSCs more potently in CeLC neurons from arthritic rats (IC50 = 0.59 nM than in control animals (IC50 = 15.0 nM. The inhibitory effect of LY354740 was reversed by a group II mGluR antagonist (EGLU but not a GABAA receptor antagonist (bicuculline. LY354740 decreased frequency, but not amplitude, of miniature EPSCs in the presence of TTX. No significant changes of neuronal excitability measures (membrane slope conductance and action potential firing rate were detected. Conclusion Our data suggest that group II mGluRs act presynaptically to modulate synaptic plasticity in the amygdala in a model of arthritic pain.

  9. Amygdala-based intrinsic functional connectivity and anxiety disorders in adolescents and young adults.

    Science.gov (United States)

    Toazza, Rudineia; Franco, Alexandre Rosa; Buchweitz, Augusto; Molle, Roberta Dalle; Rodrigues, Danitsa Marcos; Reis, Roberta Sena; Mucellini, Amanda Brondani; Esper, Nathalia Bianchini; Aguzzoli, Cristiano; Silveira, Patrícia Pelufo; Salum, Giovanni Abrahão; Manfro, Gisele Gus

    2016-11-30

    Anxiety disorders (AD) are the most prevalent group of psychiatric disorders in adolescents and young adults. Nevertheless, the pathophysiology of anxiety disorders is still poorly understood. This study investigated differences in the functional connectivity of intrinsic amygdala-based networks of participants with and without AD. Resting state fMRI data were obtained from 18 participants with an AD and 19 healthy comparison individuals. Psychiatric diagnosis was assessed using standardized structured interviews. The comparison between groups was carried out using functional connectivity maps from six seed regions defined using probabilistic maps bilaterally within the amygdala (basolateral, superficial and centromedial amygdala). We found significant between-group differences in five clusters, which showed aberrant functional connectivity with the left basolateral amygdala: right precentral gyrus, right cingulate gyrus, bilateral precuneus, and right superior frontal gyrus in subjects with AD as compared with the comparison subjects. For the comparison subjects, the correlations between the amygdala and the five clusters were either non-significant, or negative. The present study suggests there is an intrinsic disruption in the communication between left basolateral amygdala and a network of brain regions involved with emotion regulation, and with the default mode network in adolescents and young adults with anxiety disorders.

  10. The amygdala: securing pleasure and avoiding pain

    Science.gov (United States)

    Fernando, Anushka B. P.; Murray, Jennifer E.; Milton, Amy L.

    2013-01-01

    The amygdala has traditionally been associated with fear, mediating the impact of negative emotions on memory. However, this view does not fully encapsulate the function of the amygdala, nor the impact that processing in this structure has on the motivational limbic corticostriatal circuitry of which it is an important structure. Here we discuss the interactions between different amygdala nuclei with cortical and striatal regions involved in motivation; interconnections and parallel circuitries that have become increasingly understood in recent years. We review the evidence that the amygdala stores memories that allow initially motivationally neutral stimuli to become associated through pavlovian conditioning with motivationally relevant outcomes which, importantly, can be either appetitive (e.g. food) or aversive (e.g. electric shock). We also consider how different psychological processes supported by the amygdala such as conditioned reinforcement and punishment, conditioned motivation and suppression, and conditioned approach and avoidance behavior, are not only psychologically but also neurobiologically dissociable, being mediated by distinct yet overlapping neural circuits within the limbic corticostriatal circuitry. Clearly the role of the amygdala goes beyond encoding aversive stimuli to also encode the appetitive, requiring an appreciation of the amygdala's mediation of both appetitive and fearful behavior through diverse psychological processes. PMID:24367307

  11. Alpha-lipoic acid-mediated activation of muscarinic receptors improves hippocampus- and amygdala-dependent memory.

    Science.gov (United States)

    Mahboob, Aamra; Farhat, Syeda Mehpara; Iqbal, Ghazala; Babar, Mustafeez Mujtaba; Zaidi, Najam-us-Sahar Sadaf; Nabavi, Seyed Mohammad; Ahmed, Touqeer

    2016-04-01

    Aluminum (Al) is a neurotoxic agent which readily crosses the blood-brain-barrier (BBB) and accumulates in the brain leading to neurodegenerative disorders, characterised by cognitive impairment. Alpha-lipoic acid (ALA) is an antioxidant and has a potential to improve cognitive functions. This study aimed to evaluate the neuroprotective effect of ALA in AlCl3-induced neurotoxicity mouse model. Effect of ALA (25mg/kg/day) was evaluated in the AlCl3-induced neurotoxicity (AlCl3 150 mg/kg/day) mouse model on learning and memory using behaviour tests and on the expression of muscarinic receptor genes (using RT-PCR), in hippocampus and amygdala. Following ALA treatment, the expression of muscarinic receptor genes M1, M2 and choline acetyltransferase (ChaT) were significantly improved (pnovelty preference (p<0.001) comparative to the AlCl3-treated group. Fear extinction memory was remarkably restored (p<0.001) in ALA-treated group demonstrated by reduced freezing response as compared to the AlCl3-treated group which showed higher freezing. In-silico analysis showed that racemic mixture of ALA has higher binding affinity for M1 and M2 compared to acetylcholine. These novel findings highlight the potential role of ALA in cognitive functions and cholinergic system enhancement thus presenting it an enviable therapeutic candidate for the treatment of neurodegenerative disorders.

  12. Differential Involvement of Amygdala and Cortical NMDA Receptors Activation upon Encoding in Odor Fear Memory

    Science.gov (United States)

    Hegoburu, Chloé; Parrot, Sandrine; Ferreira, Guilaume; Mouly, Anne-Marie

    2014-01-01

    Although the basolateral amygdala (BLA) plays a crucial role for the acquisition of fear memories, sensory cortices are involved in their long-term storage in rats. However, the time course of their respective involvement has received little investigation. Here we assessed the role of the glutamatergic N-methyl-D-aspartate (NMDA) receptors in the…

  13. Human amygdala reactivity is diminished by the beta-noradrenergic antagonist propranolol

    NARCIS (Netherlands)

    Hurlemann, R.; Walter, H.; Rehme, A. K.; Kukolja, J.; Santoro, S. C.; Schmidt, C.; Schnell, K.; Musshoff, F.; Keysers, C.; Maier, W.; Kendrick, K. M.; Onur, O. A.

    2010-01-01

    Background. Animal models of anxiety disorders emphasize the crucial role of locus ceruleus-noradrenergic (norepinephrine, NE) signaling, the basolateral amygdala (BLA) and their interactions in the expression of anxiety-like behavioral responses to stress. Despite clinical evidence for the efficacy

  14. Back to basics: Making predictions in the orbitofrontal-amygdala circuit.

    Science.gov (United States)

    Sharpe, Melissa J; Schoenbaum, Geoffrey

    2016-05-01

    Underlying many complex behaviors are simple learned associations that allow humans and animals to anticipate the consequences of their actions. The orbitofrontal cortex and basolateral amygdala are two regions which are crucial to this process. In this review, we go back to basics and discuss the literature implicating both these regions in simple paradigms requiring the development of associations between stimuli and the motivationally-significant outcomes they predict. Much of the functional research surrounding this ability has suggested that the orbitofrontal cortex and basolateral amygdala play very similar roles in making these predictions. However, electrophysiological data demonstrates critical differences in the way neurons in these regions respond to predictive cues, revealing a difference in their functional role. On the basis of these data and theories that have come before, we propose that the basolateral amygdala is integral to updating information about cue-outcome contingencies whereas the orbitofrontal cortex is critical to forming a wider network of past and present associations that are called upon by the basolateral amygdala to benefit future learning episodes. The tendency for orbitofrontal neurons to encode past and present contingencies in distinct neuronal populations may facilitate its role in the formation of complex, high-dimensional state-specific associations.

  15. Is the Medial Amygdala Part of the Neural Circuit Modulating Conditioned Defeat in Syrian Hamsters?

    Science.gov (United States)

    Markham, Chris M.; Huhman, Kim L.

    2008-01-01

    Conditioned defeat is a model wherein hamsters that have previously experienced a single social defeat subsequently exhibit heightened levels of avoidance and submission in response to a smaller, non-aggressive intruder. While we have previously demonstrated the critical involvement of the basolateral and central nuclei of the amygdala in the…

  16. Differential Activation of Amygdala Arc Expression By Positive and Negatively Valenced Emotional Learning Conditions

    Directory of Open Access Journals (Sweden)

    Erica eYoung

    2013-12-01

    Full Text Available Norepinephrine is released in the amygdala following negatively arousing learning conditions. This event initiates a cascade of changes including the transcription of activity-regulated cytoskeleton-associated protein (Arc expression, an early-immediate gene associated with memory encoding. Recent evidence suggests that the valence of emotionally laden encounters may generate lateralized, as opposed to symmetric release of this transmitter in the right or left amygdala. It is currently not clear if valence-induced patterns of selective norepinephrine output across hemispheres are also reproduced in downstream pathways of cellular signaling necessary for memory formation. This question was addressed by determining if Arc expression is differentially distributed across the right and left amygdala following exposure to positively or negatively valenced learning conditions respectively. Male Sprague Dawley rats were randomly assigned to groups exposed to the Homecage only, 5 auditory tones only, or 5 auditory tones paired with footshock (0.35mA during Pavlovian fear conditioning. Western blot analysis revealed that Arc expression in the right amygdala was elevated significantly above that observed in the left amygdala 60 and 90 minutes following fear conditioning. Similarly, subjects exposed to a a negatively valenced outcome consisting of an unexpected reduction in food rewards showed a greater level of Arc expression in only the right, but not left basolateral amygdala. Presenting a positively valenced event involving an unexpected increase in food reward magnitude following bar pressing, resulted in significantly greater Arc expression in the left, but not right basolateral amygdala (p

  17. Dynamic patterns of colocalization of calbindin, parvalbumin and GABA in subpopulations of mouse basolateral amygdalar cells during development.

    Science.gov (United States)

    Dávila, José Carlos; Olmos, Luis; Legaz, Isabel; Medina, Loreta; Guirado, Salvador; Real, Maria Angeles

    2008-01-01

    Calbindin cells represent a major interneuron subtype of the cortical/pallial regions, such as the basolateral amygdala, which are often analyzed in studies of tangential migration of interneurons from the subpallial ganglionic eminences to the pallium/cortex. However, previous evidence suggests that during development the calbindin cells may include more than one of the interneuron subtypes found in the adult pallium/cortex. Furthermore, in the adult basolateral amygdala, calbindin cells include a subpopulation of non-GABAergic (non-interneuron) cells. To better characterize these cells throughout development, in the present study we investigated the colocalization of calbindin, parvalbumin and GABA in cells of the mouse basolateral amygdala during late embryonic (E16.5) and several postnatal ages from birth until 4 weeks after birth (P0, P10 and P28). Our results indicate that CB, PV and GABA show a dynamic pattern of colocalization in cells of the mouse basolateral amygdalar nucleus throughout development. From E16.5 through P28, the majority of CB+ neurons and virtually all PV+ neurons are GABAergic. However, after P10, the percentage of GABAergic CB+ cells decline from 96% to 70%. Furthermore, while only 9% of CB+ neurons are PV+ at P10, this percentage raises to 42% at P28. At all postnatal ages studied, the majority of the PV+ cells are CB+, suggesting that PV+ interneurons develop postnatally mainly as a subpopulation within the CB+ cells of the basolateral amygdalar nucleus. These results are important for interpreting data from interneuron migration.

  18. Amygdala Dopamine Receptors Are Required for the Destabilization of a Reconsolidating Appetitive Memory(1,2).

    Science.gov (United States)

    Merlo, Emiliano; Ratano, Patrizia; Ilioi, Elena C; Robbins, Miranda A L S; Everitt, Barry J; Milton, Amy L

    2015-01-01

    Disrupting maladaptive memories may provide a novel form of treatment for neuropsychiatric disorders, but little is known about the neurochemical mechanisms underlying the induction of lability, or destabilization, of a retrieved consolidated memory. Destabilization has been theoretically linked to the violation of expectations during memory retrieval, which, in turn, has been suggested to correlate with prediction error (PE). It is well-established that PE correlates with dopaminergic signaling in limbic forebrain structures that are critical for emotional learning. The basolateral amygdala is a key neural substrate for the reconsolidation of pavlovian reward-related memories, but the involvement of dopaminergic mechanisms in inducing lability of amygdala-dependent memories has not been investigated. Therefore, we tested the hypothesis that dopaminergic signaling within the basolateral amygdala is required for the destabilization of appetitive pavlovian memories by investigating the effects dopaminergic and protein synthesis manipulations on appetitive memory reconsolidation in rats. Intra-amygdala administration of either the D1-selective dopamine receptor antagonist SCH23390 or the D2-selective dopamine receptor antagonist raclopride prevented memory destabilization at retrieval, thereby protecting the memory from the effects of an amnestic agent, the protein synthesis inhibitor anisomycin. These data show that dopaminergic transmission within the basolateral amygdala is required for memory labilization during appetitive memory reconsolidation.

  19. Hippocampus and amygdala morphology in attention-deficit/hyperactivity disorder

    DEFF Research Database (Denmark)

    Plessen, Kerstin J; Bansal, Ravi; Zhu, Hongtu;

    2006-01-01

    of the hippocampus and amygdala in children with ADHD. DESIGN: A cross-sectional case-control study of the hippocampus and amygdala using anatomical magnetic resonance imaging. SETTINGS: University research institute. PATIENTS: One hundred fourteen individuals aged 6 to 18 years, 51 with combined-type ADHD and 63...... healthy controls. MAIN OUTCOME MEASURES: Volumes and measures of surface morphology for the hippocampus and amygdala. RESULTS: The hippocampus was larger bilaterally in the ADHD group than in the control group (t = 3.35; P hippocampus further localized...... these differences to an enlarged head of the hippocampus in the ADHD group. Although conventional measures did not detect significant differences in amygdalar volumes, surface analyses indicated the presence of reduced size bilaterally over the area of the basolateral complex. Correlations with prefrontal measures...

  20. Amygdala-gustatory insular cortex connections and taste neophobia.

    Science.gov (United States)

    Lin, Jian-You; Reilly, Steve

    2012-12-01

    To examine whether communication between the amygdala and gustatory insular cortex (GC) is required for normal performance of taste neophobia, three experiments were conducted. In Experiment 1, rats with asymmetric unilateral lesions of the basolateral amygdala (BLA) and the GC displayed elevated intake of a novel saccharin solution relative to control subjects. However, an attenuation of neophobia was not found following asymmetric unilateral lesions of the GC and medial amygdala (MeA; Experiment 2) or of the MeA and BLA (Experiment 3). This pattern of results indicates that the BLA and GC functionally interact during expression of taste neophobia and that the MeA functionally interacts with neither the BLA nor the GC. Research is needed to further characterize the nature of the involvement of the MeA in taste neophobia and to determine the function of the BLA-GC interaction during exposure to a new taste.

  1. The amygdala: securing pleasure and avoiding pain

    Directory of Open Access Journals (Sweden)

    Anushka B P Fernando

    2013-12-01

    Full Text Available The amygdala has traditionally been associated with fear, mediating the impact of negative emotions on memory. However, this view does not fully encapsulate the function of the amygdala, nor the impact that processing in this structure has on the motivational limbic corticostriatal circuitry of which it is an important structure. Here we discuss the interactions between different amygdala nuclei with cortical and striatal regions involved in motivation; interconnections and parallel circuitries that have become increasingly understood in recent years. We review the evidence that the amygdala stores memories that allow initially motivationally neutral stimuli to become associated through pavlovian conditioning with motivationally relevant outcomes which, importantly, can be either appetitive (e.g. food or aversive (e.g. electric shock. We also consider how different psychological processes supported by the amygdala such as conditioned reinforcement and punishment, conditioned motivation and suppression, and conditioned approach and avoidance behavior, are not only psychologically but also neurobiologically dissociable, being mediated by distinct yet overlapping neural circuits within the limbic corticostriatal circuitry. Clearly the role of the amygdala goes beyond encoding aversive stimuli to also encode the appetitive, requiring an appreciation of the amygdala’s mediation of both appetitive and fearful behavior through diverse psychological processes.

  2. Stress Leads to Contrasting Effects on the Levels of Brain Derived Neurotrophic Factor in the Hippocampus and Amygdala

    OpenAIRE

    Harini Lakshminarasimhan; Sumantra Chattarji

    2012-01-01

    Recent findings on stress induced structural plasticity in rodents have identified important differences between the hippocampus and amygdala. The same chronic immobilization stress (CIS, 2 h/day) causes growth of dendrites and spines in the basolateral amygdala (BLA), but dendritic atrophy in hippocampal area CA3. CIS induced morphological changes also differ in their temporal longevity--BLA hypertrophy, unlike CA3 atrophy, persists even after 21 days of stress-free recovery. Furthermore, a ...

  3. Amygdala and hippocampus enlargement during adolescence in autism.

    NARCIS (Netherlands)

    Groen, W.B.; Teluij, M.; Buitelaar, J.K.; Tendolkar, I.

    2010-01-01

    OBJECTIVE: The amygdala and hippocampus are key components of the neural system mediating emotion perception and regulation and are thought to be involved in the pathophysiology of autism. Although some studies in children with autism suggest that there is an enlargement of amygdala and hippocampal

  4. Intra-Amygdala Injections of CREB Antisense Impair Inhibitory Avoidance Memory: Role of Norepinephrine and Acetylcholine

    Science.gov (United States)

    Canal, Clinton E.; Chang, Qing; Gold, Paul E.

    2008-01-01

    Infusions of CREB antisense into the amygdala prior to training impair memory for aversive tasks, suggesting that the antisense may interfere with CRE-mediated gene transcription and protein synthesis important for the formation of new memories within the amygdala. However, the amygdala also appears to modulate memory formation in distributed…

  5. Stress reduction correlates with structural changes in the amygdala.

    Science.gov (United States)

    Hölzel, Britta K; Carmody, James; Evans, Karleyton C; Hoge, Elizabeth A; Dusek, Jeffery A; Morgan, Lucas; Pitman, Roger K; Lazar, Sara W

    2010-03-01

    Stress has significant adverse effects on health and is a risk factor for many illnesses. Neurobiological studies have implicated the amygdala as a brain structure crucial in stress responses. Whereas hyperactive amygdala function is often observed during stress conditions, cross-sectional reports of differences in gray matter structure have been less consistent. We conducted a longitudinal MRI study to investigate the relationship between changes in perceived stress with changes in amygdala gray matter density following a stress-reduction intervention. Stressed but otherwise healthy individuals (N = 26) participated in an 8-week mindfulness-based stress reduction intervention. Perceived stress was rated on the perceived stress scale (PSS) and anatomical MR images were acquired pre- and post-intervention. PSS change was used as the predictive regressor for changes in gray matter density within the bilateral amygdalae. Following the intervention, participants reported significantly reduced perceived stress. Reductions in perceived stress correlated positively with decreases in right basolateral amygdala gray matter density. Whereas prior studies found gray matter modifications resulting from acquisition of abstract information, motor and language skills, this study demonstrates that neuroplastic changes are associated with improvements in a psychological state variable.

  6. Childhood Cumulative Risk Exposure and Adult Amygdala Volume and Function.

    Science.gov (United States)

    Evans, Gary W; Swain, James E; King, Anthony P; Wang, Xin; Javanbakht, Arash; Ho, S Shaun; Angstadt, Michael; Phan, K Luan; Xie, Hong; Liberzon, Israel

    2016-06-01

    Considerable work indicates that early cumulative risk exposure is aversive to human development, but very little research has examined the neurological underpinnings of these robust findings. This study investigates amygdala volume and reactivity to facial stimuli among adults (mean 23.7 years of age, n = 54) as a function of cumulative risk exposure during childhood (9 and 13 years of age). In addition, we test to determine whether expected cumulative risk elevations in amygdala volume would mediate functional reactivity of the amygdala during socioemotional processing. Risks included substandard housing quality, noise, crowding, family turmoil, child separation from family, and violence. Total and left hemisphere adult amygdala volumes were positively related to cumulative risk exposure during childhood. The links between childhood cumulative risk exposure and elevated amygdala responses to emotionally neutral facial stimuli in adulthood were mediated by the corresponding amygdala volumes. Cumulative risk exposure in later adolescence (17 years of age), however, was unrelated to subsequent adult amygdala volume or function. Physical and socioemotional risk exposures early in life appear to alter amygdala development, rendering adults more reactive to ambiguous stimuli such as neutral faces. These stress-related differences in childhood amygdala development might contribute to the well-documented psychological distress as a function of early risk exposure.

  7. Serotonin, amygdala and fear: assembling the puzzle

    Directory of Open Access Journals (Sweden)

    Marco eBocchio

    2016-04-01

    Full Text Available The fear circuitry orchestrates defense mechanisms in response to environmental threats. This circuitry is evolutionarily crucial for survival, but its dysregulation is thought to play a major role in the pathophysiology of psychiatric conditions in humans. The amygdala is a key player in the processing of fear. This brain area is prominently modulated by the neurotransmitter serotonin (5-hydroxytryptamine, 5-HT. The 5-HT input to the amygdala has drawn particular interest because genetic and pharmacological alterations of the 5-HT transporter (5-HTT affect amygdala activation in response to emotional stimuli. Nonetheless, the impact of 5-HT on fear processing remains poorly understood.The aim of this review is to elucidate the physiological role of 5-HT in fear learning via its action on the neuronal circuits of the amygdala. Since 5-HT release increases in the BLA during both fear memory acquisition and expression, we examine whether and how 5-HT neurons encode aversive stimuli and aversive cues. Next, we describe pharmacological and genetic alterations of 5-HT neurotransmission that, in both rodents and humans, lead to altered fear learning.To explore the mechanisms through which 5-HT could modulate conditioned fear, we focus on the rodent basolateral amygdala (BLA. We propose that a circuit-based approach taking into account the localization of specific 5-HT receptors on neurochemically-defined neurons in the BLA may be essential to decipher the role of 5-HT in emotional behavior. In keeping with a 5-HT control of fear learning, we review electrophysiological data suggesting that 5-HT regulates synaptic plasticity, spike synchrony and theta oscillations in the BLA via actions on different subcellular compartments of principal neurons and distinct GABAergic interneuron populations. Finally, we discuss how recently developed optogenetic tools combined with electrophysiological recordings and behavior could progress the knowledge of the

  8. Entorhinal cortex stimulation modulates amygdala and piriform cortex responses to olfactory bulb inputs in the rat.

    Science.gov (United States)

    Mouly, A-M; Di Scala, G

    2006-01-01

    The rodent olfactory bulb sends direct projections to the piriform cortex and to two structures intimately implicated in memory processes, the entorhinal cortex and the amygdala. The piriform cortex has monosynaptic projections with the amygdala and the piriform cortex and is therefore in a position to modulate olfactory input either directly in the piriform cortex, or via the amygdala. In order to investigate this hypothesis, field potential signals induced in anesthetized rats by electrical stimulation of the olfactory bulb or the entorhinal cortex were recorded simultaneously in the piriform cortex (anterior part and posterior part) and the amygdala (basolateral nucleus and cortical nucleus). Single-site paired-pulse stimulation was used to assess the time courses of short-term inhibition and facilitation in each recording site in response to electrical stimulation of the olfactory bulb and entorhinal cortex. Paired-pulse stimulation of the olfactory bulb induced homosynaptic inhibition for short interpulse interpulse intervals (20-30 ms) in all the recording sites, with a significantly lower degree of inhibition in the anterior piriform cortex than in the other structures. At longer intervals (40-80 ms), paired-pulse facilitation was observed in all the structures. Paired-pulse stimulation of the entorhinal cortex mainly resulted in inhibition for the shortest interval duration (20 ms) in anterior piriform cortex, posterior piriform cortex and amygdala basolateral but not cortical nucleus. Double-site paired-pulse stimulation was then applied to determine if stimulation of the entorhinal cortex can modulate responses to olfactory bulb stimulation. For short interpulse intervals (20 ms) heterosynaptic inhibition was observed in anterior piriform cortex, posterior piriform cortex and amygdala basolateral but not cortical nucleus. The level of inhibition was greater in the basolateral nucleus than in the other structures. Taken together these data suggest that the

  9. Disruption of Memory Reconsolidation Erases a Fear Memory Trace in the Human Amygdala: An 18-Month Follow-Up.

    Directory of Open Access Journals (Sweden)

    Johannes Björkstrand

    Full Text Available Fear memories can be attenuated by reactivation followed by disrupted reconsolidation. Using functional magnetic resonance imaging we recently showed that reactivation and reconsolidation of a conditioned fear memory trace in the basolateral amygdala predicts subsequent fear expression over two days, while reactivation followed by disrupted reconsolidation abolishes the memory trace and suppresses fear. In this follow-up study we demonstrate that the behavioral effect persists over 18 months reflected in superior reacquisition after undisrupted, as compared to disrupted reconsolidation, and that neural activity in the basolateral amygdala representing the initial fear memory predicts return of fear. We conclude that disrupting reconsolidation have long lasting behavioral effects and may permanently erase the fear component of an amygdala-dependent memory.

  10. Effects of early-life abuse differ across development: infant social behavior deficits are followed by adolescent depressive-like behaviors mediated by the amygdala.

    Science.gov (United States)

    Raineki, Charlis; Cortés, Millie Rincón; Belnoue, Laure; Sullivan, Regina M

    2012-05-30

    Abuse during early life, especially from the caregiver, increases vulnerability to develop later-life psychopathologies such as depression. Although signs of depression are typically not expressed until later life, signs of dysfunctional social behavior have been found earlier. How infant abuse alters the trajectory of brain development to produce pathways to pathology is not completely understood. Here we address this question using two different but complementary rat models of early-life abuse from postnatal day 8 (P8) to P12: a naturalistic paradigm, where the mother is provided with insufficient bedding for nest building; and a more controlled paradigm, where infants undergo olfactory classical conditioning. Amygdala neural assessment (c-Fos), as well as social behavior and forced swim tests were performed at preweaning (P20) and adolescence (P45). Our results show that both models of early-life abuse induce deficits in social behavior, even during the preweaning period; however, depressive-like behaviors were observed only during adolescence. Adolescent depressive-like behavior corresponds with an increase in amygdala neural activity in response to forced swim test. A causal relationship between the amygdala and depressive-like behavior was suggested through amygdala temporary deactivation (muscimol infusions), which rescued the depressive-like behavior in the forced swim test. Our results indicate that social behavior deficits in infancy could serve as an early marker for later psychopathology. Moreover, the implication of the amygdala in the ontogeny of depressive-like behaviors in infant abused animals is an important step toward understanding the underlying mechanisms of later-life mental disease associated with early-life abuse.

  11. Role of NMDA receptors in the lateralized potentiation of amygdala afferent and efferent neural transmission produced by predator stress.

    Science.gov (United States)

    Adamec, Robert; Blundell, Jacqueline; Burton, Paul

    2005-09-15

    The present study investigated the role of NMDA receptors in behavioral and neuroplastic changes in amygdala efferent (central amygdala to periaqueductal gray-ACE-PAG) and amygdala afferent (ventral angular bundle to basolateral amygdala-VAB-BLA) pathways in response to predator stress. Effects on brain and behavioral response to predator stress of competitive block of NMDA receptors with a dose of 10 mg/kg of CPP (3-(2-carboxypiperazin4-yl)propyl-l-phosphonic acid) were studied. Behavioral response to stress was tested with hole board, elevated plus maze, light/dark box, social interaction and acoustic startle tests. CPP was administered i.p. 30 min prior to predator stress and blocked the effects of predator on some but not all behaviors measured 8-9 days later. Effects of predator stress and CPP on potentials evoked in the PAG by single pulse stimulation of the ACE and in the BLA by single pulse stimulation of VAB were assessed 10-11 days after predator stress. Predator stress potentiated ACE-PAG evoked potentials in the right but not the left hemisphere, replicating previous work. Predator stress potentiated VAB-BLA transmission in both hemispheres 10-11 days after predator stress. Right hemisphere VAB-BLA potentiation replicated and extended past studies showing right hemisphere potentiation at 1 and 9 days after stress. Left VAB-BLA potentiation effects differed from the long term depression seen in VAB-BLA at 1 and 9 days after stress in previous studies. CPP blocked predator stress-induced potentiation of ACE-PAG and VAB-BLA evoked potentials in the right hemisphere. CPP did not block left VAB-BLA potentiation, rather CPP amplified it. Left hemisphere effects of CPP were interpreted as reflecting block of NMDA dependent long term depression, which unmasked a non-NMDA dependent potentiation. Taken together, the findings add to a body of evidence suggesting that a syndrome of behavioral changes follows predator stress. Components of this syndrome likely

  12. Glutamatergic mechanisms associated with stress-induced amygdala excitability and anxiety-related behavior.

    Science.gov (United States)

    Masneuf, Sophie; Lowery-Gionta, Emily; Colacicco, Giovanni; Pleil, Kristen E; Li, Chia; Crowley, Nicole; Flynn, Shaun; Holmes, Andrew; Kash, Thomas

    2014-10-01

    The neural factors underlying individual differences in susceptibility to chronic stress remain poorly understood. Preclinical studies demonstrate that mouse strains vary greatly in anxiety-related responses to chronic stress in a manner paralleled by differential stress-induced changes in glutamatergic signaling in the basolateral amygdala (BLA). Previous work has also shown that alterations in the amygdala gene expression of the GluN1 NMDA and the GluK1 kainate receptors are associated with stress-induced alterations in anxiety-like behavior in the C57BL/6J mouse strain. Using in vivo behavioral pharmacological and ex vivo physiological approaches, the aim of the current study was to further elucidate changes in glutamate neurotransmission in the BLA caused by stress and to test the functional roles of GluN1 and GluK1 in mediating stress-related changes in behavior. Results showed that stress-induced alterations in anxiety-like behavior (light/dark exploration test) were absent following bilateral infusion of the GluK1 agonist ATPA into the BLA. Intra-BLA infusion of the competitive NMDA antagonist AP5 produced a generalized behavioral disinhibition/locomotor hyperactivity, irrespective of stress. Slice electrophysiological recordings showed that ATPA augmented BLA GABAergic neurotransmission and that stress increased the amplitude of network-dependent spontaneous excitatory postsynaptic currents and amplitude of GABAergic miniature inhibitory postsynaptic currents in BLA. These findings could indicate stress-induced BLA glutamatergic neuronal network hyperexcitability and a compensatory increase in GABAergic neurotransmission, suggesting that GluK1 agonism augmented GABAergic inhibition to prevent behavioral sequelae of stress. Current data could have implications for developing novel therapeutic approaches, including GluK1 agonists, for stress-related anxiety disorders.

  13. Effect of gabapentin on anxiety-like behaviors induced by neuropathic pain and NR2B expression in basolateral nucleus of the amygdala of rats%加巴喷丁对神经病理性疼痛大鼠焦虑样行为和杏仁体基底外侧核NR2B表达的影响

    Institute of Scientific and Technical Information of China (English)

    尹玉洁; 于剑锋

    2015-01-01

    目的 观察加巴喷丁对神经病理性疼痛(neuropathic pain,NP)诱发的大鼠焦虑样行为和杏仁体基底外侧核(basolateral nucleus of the amygdale,BLA) N-甲基-D-天门冬氨酸(N-Methyl-D-Aspartate,NMDA)受体2B亚基(NR2B)表达的影响.方法 选择30只健康的3月龄雄性Wistar大鼠,体重250~280 g,随机均分为假手术组(S组)、神经病理性疼痛模型组(NP组)、加巴喷丁组(G组).神经病理性疼痛模型采用右侧坐骨神经慢性压迫损伤(chronic constriction injury,CCI)的方法制备.G组于CCI后3d开始腹腔注射加巴喷丁100 mg/kg,每天一次.分别于术后3、7、10和14 d测右侧后爪机械缩足阈值(mechanical withdrawal threshold,MWT)和热缩足潜伏期(thermal with-drawal latency,TWL).术后第14天,通过高架十字迷宫测试神经病理性疼痛对大鼠情绪的影响,计算开放臂进入次数百分比和开放臂停留时间百分比,然后取大鼠BLA组织用RT-PCR、Western blot和免疫荧光方法检测NR2B mRNA和蛋白表达.结果 与术前1d比较,术后各时点NP组MWT明显减少、TWL明显缩短(P<0.05),而术后3dG组MWT明显减少、TWL明显缩短(P<0.05).与NP组比较,术后7、10和14dG组MWT明显增加、TWL明显延长(P<0.05),术后第14天S组和G组的开放臂进入次数百分比和开放臂停留时间百分比明显升高(P<0.05),术后第14天BLA区S组和G组NR2B mRNA相对吸光度明显减少、NR2B蛋白表达明显降低(P<0.05),而S组和G组平均相对荧光密度值明显下降(P<0.05).结论 加巴喷丁具有治疗神经病理性疼痛作用可反转其导致的焦虑样反应并使杏仁体的NR2B表达下调.

  14. Evolution of the amygdala: new insights from studies in amphibians.

    Science.gov (United States)

    Laberge, Frédéric; Mühlenbrock-Lenter, Sabine; Grunwald, Wolfgang; Roth, Gerhard

    2006-01-01

    The histology of amphibian brains gives an impression of relative simplicity when compared with that of reptiles or mammals. The amphibian telencephalon is small and contains comparatively few and large neurons, which in most parts constitute a dense periventricular cellular layer. However, the view emerging from the last decade is that the brains of all tetrapods, including amphibians, share a general bauplan resulting from common ancestry and the need to perform similar vital functions. To what extent this common organization also applies to higher brain functions is unknown due to a limited knowledge of the neurobiology of early vertebrates. The amygdala is widely recognized as a brain center critical for basic forms of emotional learning (e.g., fear conditioning) and its structure in amphibians could suggest how this capacity evolved. A functional systems approach is used here to synthesize the results of our anatomical investigations of the amphibian amygdala. It is proposed that the connectivity of the amphibian telencephalon portends a capacity for multi-modal association in a limbic system largely similar to that of amniote vertebrates. One remarkable exception is the presence of new sensory-associative regions of the amygdala in amniotes: the posterior dorsal ventricular ridge plus lateral nuclei in reptiles and the basolateral complex in mammals. These presumably homologous regions apparently are capable of modulating the phylogenetically older central amygdala and allow more complex forms of emotional learning.

  15. Interactions between chemical and electrical kindling of the rat amygdala.

    Science.gov (United States)

    Wasterlain, C G; Morin, A M; Jonec, V

    1982-09-16

    Holtzman rats were implanted with a chemitrode into the left basolateral amygdala, which could then be stimulated electrically (400 microA, 1 s, AC) or chemically by injection of carbachol (1 microliter, 2.7 nmoles, sterile, isotonic). Group A received a daily injection of carbachol and developed kindled seizures. Group B received carbachol mixed with equimolar atropine, which blocked seizures and kindling. After 20 injections, both groups were stimulated electrically once a day and kindled at similar rates. Two additional groups received electrical or sham stimulation, followed by carbachol kindling. No transfer effects were observed. Four additional groups received 27 nmoles of atropine through the chemitrode, followed 15 min later by electrical stimulation, sham stimulation, carbachol injection or saline injection, respectively. Atropine completely blocked carbachol kindling but did not alter the rate of electrical kindling. No different in the number of QNB binding sites was observed in the amygdala of rats sacrificed two weeks after full electrical kindling. The lack of interaction between electrical and carbachol kindling and the failure of atropine to block electrical kindling of the amygdala suggest that the activation of local muscarinic synapses, while essential for carbachol kindling, is not required for electrical kindling of the rat amygdala.

  16. Effect of Protein Malnutrition on Efferent Projections of Amygdala to the Hippocampus

    Directory of Open Access Journals (Sweden)

    Gholamreza Hassanzadeh

    2010-11-01

    Full Text Available ABSTRACTIntroduction: Previous investigations have shown that protein malnutrition can alters the structure and function of some areas of hippocampal formation. We investigated the effect of protein malnutrition on amygdaloid projections to the CA1 hippocampal area. In this study we investigated level and pattern of distribution of efferent projections from amygdala to hippocampus in the rat by Horseradish Peroxidas (HRP neural tract tracing in 2 groups; Control group fed with regular diet (% 18 proteinsand case group fed with low protein diet (%8. We used SPSS 11.0 (T test & mann-withney Software for data analysis.Methods: Following injection of HRP to CA1 region of hippocampus in the control group Rats, Labelled neurons showed more density in the Basolateral, Cortical and Medial nuclear Groups. Having done the analysis and examining the relations between the case data and those of the control groups, we found that number of labelled neurons in the Basolateral, Cortical & medial nuclei were decreased in the case group(p<0.05. Our findings showed that different nuclei of amygdala (Basolateral, Cortical and Medial send projections to CA1 region of hippocampus; Among, them basolateral nuclei group send the most projections . Discussion: This results may be caused by decrease of activity of neural cells after protein malnutrition, that can results in impairment in growth and development of nervous system. Also it is possible that axoplasmic transfer rate maybe decreased in this condition.

  17. Cyto- and chemoarchitecture of the amygdala of a monotreme, Tachyglossus aculeatus (the short-beaked echidna).

    Science.gov (United States)

    Ashwell, Ken W S; Hardman, Craig D; Paxinos, George

    2005-10-01

    We have examined the cyto- and chemoarchitecture of the temporal and extended amygdala in the brain of a monotreme (the short-beaked echidna Tachyglossus aculeatus) using Nissl and myelin staining, enzyme histochemistry for acetylcholine esterase and NADPH diaphorase, immunohistochemistry for calcium binding proteins (parvalbumin, calbindin and calretinin) and tyrosine hydroxylase. While the broad subdivisions of the eutherian temporal amygdala were present in the echidna brain, there were some noticeable differences. No immunoreactivity for parvalbumin or calretinin for somata was found in the temporal amygdala of the echidna. The nucleus of the lateral olfactory tract could not be definitively identified and the medial nucleus of amygdala appeared to be very small in the echidna. Calbindin immunoreactive neurons were most frequently found in the ventrolateral part of the lateral nucleus, intraamygdaloid parts of the bed nucleus of the stria terminalis and the lateral part of the central nucleus. Neurons strongly reactive for NADPH diaphorase with filling of the dendritic tree were found mainly scattered through the cortical, central and lateral subnuclei, while neurons showing only somata reactivity for NADPH diaphorase were concentrated in the basomedial and basolateral subnuclei. Most of the components of the extended amygdala of eutherians could also be identified in the echidna. Volumetric analysis indicated that the temporal amygdala in both the platypus and echidna is small compared to the same structure in both insectivores and primates, with the central and medial components of the temporal amygdala being particularly small.

  18. Perturbed connectivity of the amygdala and its subregions with the central executive and default mode networks in chronic pain.

    Science.gov (United States)

    Jiang, Ying; Oathes, Desmond; Hush, Julia; Darnall, Beth; Charvat, Mylea; Mackey, Sean; Etkin, Amit

    2016-09-01

    Maladaptive responses to pain-related distress, such as pain catastrophizing, amplify the impairments associated with chronic pain. Many of these aspects of chronic pain are similar to affective distress in clinical anxiety disorders. In light of the role of the amygdala in pain and affective distress, disruption of amygdalar functional connectivity in anxiety states, and its implication in the response to noxious stimuli, we investigated amygdala functional connectivity in 17 patients with chronic low back pain and 17 healthy comparison subjects, with respect to normal targets of amygdala subregions (basolateral vs centromedial nuclei), and connectivity to large-scale cognitive-emotional networks, including the default mode network, central executive network, and salience network. We found that patients with chronic pain had exaggerated and abnormal amygdala connectivity with central executive network, which was most exaggerated in patients with the greatest pain catastrophizing. We also found that the normally basolateral-predominant amygdala connectivity to the default mode network was blunted in patients with chronic pain. Our results therefore highlight the importance of the amygdala and its network-level interaction with large-scale cognitive/affective cortical networks in chronic pain, and help link the neurobiological mechanisms of cognitive theories for pain with other clinical states of affective distress.

  19. Cortisol-sensitive urea transport across the gill basolateral membrane of the gulf toadfish (Opsanus beta).

    Science.gov (United States)

    Rodela, Tamara M; Gilmour, Kathleen M; Walsh, Patrick J; McDonald, M Danielle

    2009-08-01

    Gulf toadfish (Opsanus beta) use a unique pulsatile urea excretion mechanism that allows urea to be voided in large pulses via the periodic insertion or activation of a branchial urea transporter. The precise cellular and subcellular location of the facilitated diffusion mechanism(s) remains unclear. An in vitro basolateral membrane vesicle (BLMV) preparation was used to test the hypothesis that urea movement across the gill basolateral membrane occurs through a cortisol-sensitive carrier-mediated mechanism. Toadfish BLMVs demonstrated two components of urea uptake: a linear element at high external urea concentrations, and a phloretin-sensitive saturable constituent (K(m) = 0.24 mmol/l; V(max) = 6.95 micromol x mg protein(-1) x h(-1)) at low urea concentrations ( 2, further suggestive of carrier-mediated processes. Our data provide evidence that a basolateral urea facilitated transporter accelerates the movement of urea between the plasma and gills to enable the pulsatile excretion of urea. Furthermore, in vivo infusion of cortisol caused a significant 4.3-fold reduction in BLMV urea transport capacity in lab-crowded fish, suggesting that cortisol inhibits the recruitment of urea transporters to the basolateral membrane, which may ultimately affect the size of the urea pulse event in gulf toadfish.

  20. Basolateral potassium channels of rabbit colon epithelium: role in sodium absorption and chloride secretion.

    Science.gov (United States)

    Turnheim, Klaus; Plass, Herbert; Wyskovsky, Wolfgang

    2002-02-18

    different types of K(+) channels mediate basolateral K(+) exit during transepithelial Na(+) and Cl(-) transport.

  1. Increased N-Ethylmaleimide-Sensitive Factor Expression in Amygdala and Perirhinal Cortex during Habituation of Taste Neophobia

    Science.gov (United States)

    Gómez-Chacón, Beatriz; Gámiz, Fernando; Foster, Thomas C.

    2016-01-01

    Interactions between GluR2 and N-ethylmaleimide-sensitive factor (NSF) mediate AMPA receptors trafficking. This might be linked with molecular mechanisms related with memory formation. Previous research has shown basolateral amygdala (BLA) dependent activity changes in the perirhinal cortex (PRh) during the formation of taste memory. In the present experiments we investigate both the behavioral performance and the expression profile of NSF and GluR2 genes in several brain areas, including PRh, BLA, and hippocampus. Twenty-one naïve male Wistar rats were exposed to a saccharin solution (0.4%) during the first (novel), the second (Familiar I), and the sixth presentation (Familiar II). Total RNA was extracted and gene expression was measured by quantitative PCR (qPCR) using TaqMan gene expression assays. In addition the expression of the synaptic plasticity related immediate early genes, Homer 1 and Narp, was also assessed. We have found increased expression of NSF gene in BLA and PRh in Group Familiar I in comparison with Familiar II. No changes in the expression of GluR2, Homer 1, and Narp genes were found. The results suggest the relevance of a potential network in the temporal lobe for taste recognition memory and open new possibilities for understanding the molecular mechanisms mediating the impact of sensory experience on brain circuit function. PMID:26839712

  2. Increased N-Ethylmaleimide-Sensitive Factor Expression in Amygdala and Perirhinal Cortex during Habituation of Taste Neophobia

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    Beatriz Gómez-Chacón

    2016-01-01

    Full Text Available Interactions between GluR2 and N-ethylmaleimide-sensitive factor (NSF mediate AMPA receptors trafficking. This might be linked with molecular mechanisms related with memory formation. Previous research has shown basolateral amygdala (BLA dependent activity changes in the perirhinal cortex (PRh during the formation of taste memory. In the present experiments we investigate both the behavioral performance and the expression profile of NSF and GluR2 genes in several brain areas, including PRh, BLA, and hippocampus. Twenty-one naïve male Wistar rats were exposed to a saccharin solution (0.4% during the first (novel, the second (Familiar I, and the sixth presentation (Familiar II. Total RNA was extracted and gene expression was measured by quantitative PCR (qPCR using TaqMan gene expression assays. In addition the expression of the synaptic plasticity related immediate early genes, Homer 1 and Narp, was also assessed. We have found increased expression of NSF gene in BLA and PRh in Group Familiar I in comparison with Familiar II. No changes in the expression of GluR2, Homer 1, and Narp genes were found. The results suggest the relevance of a potential network in the temporal lobe for taste recognition memory and open new possibilities for understanding the molecular mechanisms mediating the impact of sensory experience on brain circuit function.

  3. Increased N-Ethylmaleimide-Sensitive Factor Expression in Amygdala and Perirhinal Cortex during Habituation of Taste Neophobia.

    Science.gov (United States)

    Gómez-Chacón, Beatriz; Gámiz, Fernando; Foster, Thomas C; Gallo, Milagros

    2016-01-01

    Interactions between GluR2 and N-ethylmaleimide-sensitive factor (NSF) mediate AMPA receptors trafficking. This might be linked with molecular mechanisms related with memory formation. Previous research has shown basolateral amygdala (BLA) dependent activity changes in the perirhinal cortex (PRh) during the formation of taste memory. In the present experiments we investigate both the behavioral performance and the expression profile of NSF and GluR2 genes in several brain areas, including PRh, BLA, and hippocampus. Twenty-one naïve male Wistar rats were exposed to a saccharin solution (0.4%) during the first (novel), the second (Familiar I), and the sixth presentation (Familiar II). Total RNA was extracted and gene expression was measured by quantitative PCR (qPCR) using TaqMan gene expression assays. In addition the expression of the synaptic plasticity related immediate early genes, Homer 1 and Narp, was also assessed. We have found increased expression of NSF gene in BLA and PRh in Group Familiar I in comparison with Familiar II. No changes in the expression of GluR2, Homer 1, and Narp genes were found. The results suggest the relevance of a potential network in the temporal lobe for taste recognition memory and open new possibilities for understanding the molecular mechanisms mediating the impact of sensory experience on brain circuit function.

  4. State-dependent amygdala stimulation-induced cardiovascular effects in rats.

    Science.gov (United States)

    Chiou, Ruei-Jen; Kuo, Chung-Chih; Liang, Keng-Chen; Yen, Chen-Tung

    2009-12-31

    Stimulation of the amygdala is known to produce pressor, depressor, or has no effects. The present study was performed to test whether amygdala cardiovascular effects are influenced by consciousness states and by different types of anesthetics. Adult rats were set up for stimulation amygdala and measurement of blood pressure in a chronic preparation. After recovery, same sites of the amygdala were stimulated electrically for several trials with the rat under conscious or anesthetic states induced by pentobarbital, urethane, ketamine, alpha-chloralose and urethane plus alpha-chloralose, respectively. The interval between any two stimulation trials was at least 2 days. The stimulation was an 80-Hz, 0.5-ms, 100-micro A square wave pulse train lasting for 15 s. Cardiovascular responsive sites were found in the central, medial, and basolateral nuclei of the amygdala. In stimulating these responsive sites, significantly different cardiovascular effects were induced under a conscious state and an anesthetized state of the animal, yet no significant differences were found among the various anesthetic agents. We conclude, that the cardiovascular influence of the amygdala is state-dependent in the rat.

  5. Bidirectional synaptic plasticity in intercalated amygdala neurons and the extinction of conditioned fear responses.

    Science.gov (United States)

    Royer, S; Paré, D

    2002-01-01

    Classical fear conditioning is believed to result from potentiation of conditioned synaptic inputs in the basolateral amygdala. That is, the conditioned stimulus would excite more neurons in the central nucleus and, via their projections to the brainstem and hypothalamus, evoke fear responses. However, much data suggests that extinction of fear responses does not depend on the reversal of these changes but on a parallel NMDA-dependent learning that competes with the first one. Because they control impulse traffic from the basolateral amygdala to the central nucleus, GABAergic neurons of the intercalated cell masses are ideally located to implement this second learning. Consistent with this hypothesis, the present study shows that low- and high-frequency stimulation of basolateral afferents respectively induce long-term depression (LTD) and potentiation (LTP) of responses in intercalated cells. Moreover, induction of LTP and LTD is prevented by application of an NMDA antagonist. To determine how these activity-dependent changes are expressed, we tested whether LTD and LTP induction are associated with modifications in paired-pulse facilitation, an index of transmitter release probability. Only LTP induction was associated with a change in paired-pulse facilitation. Depotentiation of previously potentiated synapses did not revert the modification in paired pulse facilitation, suggesting that LTP is associated with presynaptic alterations, but that LTD and depotentiation depend on postsynaptic changes. Taken together, our results suggest that basolateral synapses onto intercalated neurons can express NMDA-dependent LTP and LTD, consistent with the possibility that intercalated neurons are a critical locus of plasticity for the extinction of conditioned fear responses. Ultimately, these plastic events may prevent conditioned amygdala responses from exciting neurons of the central nucleus, and thus from evoking conditioned fear responses.

  6. Regulation of the fear network by mediators of stress: Norepinephrine alters the balance between Cortical and Subcortical afferent excitation of the Lateral Amygdala

    Directory of Open Access Journals (Sweden)

    Luke R Johnson

    2011-05-01

    Full Text Available Pavlovian auditory fear conditioning crucially involves the integration of information about and acoustic conditioned stimulus (CS and an aversive unconditioned stimulus (US in the lateral nucleus of the amygdala (LA. The auditory CS reaches the LA subcortically via a direct connection from the auditory thalamus and also from the auditory association cortex itself. How neural modulators, especially those activated during stress, such as norepinephrine (NE, regulate synaptic transmission and plasticity in this network is poorly understood. Here we show that NE inhibits synaptic transmission in both the subcortical and cortical input pathway but that sensory processing is biased towards the subcortical pathway. In addition binding of NE to β-adrenergic receptors further dissociates sensory processing in the LA. These findings suggest a network mechanism that shifts sensory balance towards the faster but more primitive subcortical input.

  7. Neurons in the amygdala play an important role in the neuronal network mediating a clonic form of audiogenic seizures both before and after audiogenic kindling.

    Science.gov (United States)

    Raisinghani, Manish; Faingold, Carl L

    2005-01-25

    Previous studies showed that neuronal network nuclei for behaviorally different forms of audiogenic seizure (AGS) exhibit similarities and important differences. The amygdala is involved differentially in tonic AGS as compared to clonic AGS networks. The role of the lateral amygdala (LAMG) undergoes major changes after AGS repetition (AGS kindling) in tonic forms of AGS. The present study examined the role of LAMG in a clonic form of AGS [genetically epilepsy-prone rats (GEPR-3s)] before and after AGS kindling using bilateral microinjection and chronic neuronal recordings. AGS kindling in GEPR-3s results in facial and forelimb (F&F) clonus, and this behavior could be blocked following bilateral microinjection of a NMDA antagonist (2-amino-7-phosphonoheptanoate) without affecting generalized clonus. Higher AP7 doses blocked both generalized clonus and F&F clonus. LAMG neurons in GEPR-3s exhibited only onset type neuronal responses both before and after AGS kindling, unlike LAMG neurons in normal rats and a tonic form of AGS. A significantly greater LAMG neuronal firing rate occurred after AGS kindling at high acoustic intensities. The latency of LAMG neuronal firing increased significantly after AGS kindling. Burst firing occurred during wild running and generalized clonic behaviors before and after AGS kindling. Burst firing also occurred during F&F clonus after AGS kindling. These findings indicate that LAMG neurons play a critical role in the neuronal network for generalized clonus as well as F&F clonus in GEPR-3s, both before and after AGS kindling, which contrasts markedly with the role of LAMG in tonic AGS.

  8. Enhancement of basolateral amygdaloid neuronal dendritic arborization following Bacopa monniera extract treatment in adult rats

    Directory of Open Access Journals (Sweden)

    Venkata Ramana Vollala

    2011-01-01

    Full Text Available OBJECTIVE: In the ancient Indian system of medicine, Ayurveda, Bacopa monniera is classified as Medhya rasayana, which includes medicinal plants that rejuvenate intellect and memory. Here, we investigated the effect of a standardized extract of Bacopa monniera on the dendritic morphology of neurons in the basolateral amygdala, a region that is concerned with learning and memory. METHODS: The present study was conducted on 2¹/2-month-old Wistar rats. The rats were divided into 2-, 4- and 6-week treatment groups. Rats in each of these groups were further divided into 20 mg/kg, 40 mg/kg and 80 mg/kg dose groups (n = 8 for each dose. After the treatment period, treated rats and age-matched control rats were subjected to spatial learning (T-maze and passive avoidance tests. Subsequently, these rats were killed by decapitation, the brains were removed, and the amygdaloid neurons were impregnated with silver nitrate (Golgi staining. Basolateral amygdaloid neurons were traced using camera lucida, and dendritic branching points (a measure of dendritic arborization and dendritic intersections (a measure of dendritic length were quantified. These data were compared with the data from the age-matched control rats. RESULTS: The results showed an improvement in spatial learning performance and enhanced memory retention in rats treated with Bacopa monniera extract. Furthermore, a significant increase in dendritic length and the number of dendritic branching points was observed along the length of the dendrites of the basolateral amygdaloid neurons of rats treated with 40 mg/kg and 80 mg/kg of Bacopa monniera (BM for longer periods of time (i.e., 4 and 6 weeks. CONCLUSION: We conclude that constituents present in Bacopa monniera extract have neuronal dendritic growth-stimulating properties.

  9. Amygdala neurons differentially encode motivation and reinforcement.

    Science.gov (United States)

    Tye, Kay M; Janak, Patricia H

    2007-04-11

    Lesion studies demonstrate that the basolateral amygdala complex (BLA) is important for assigning motivational significance to sensory stimuli, but little is known about how this information is encoded. We used in vivo electrophysiology procedures to investigate how the amygdala encodes motivating and reinforcing properties of cues that induce reinstatement of reward-seeking behavior. Two groups of rats were trained to respond to a sucrose reward. The "paired" group was trained with a reward-predictive cue, whereas the "unpaired" group was trained with a randomly presented cue. Both groups underwent identical extinction and reinstatement procedures during which the reward was withheld. The proportion of neurons that were phasically cue responsive during reinstatement was significantly higher in the paired group (46 of 100) than in the unpaired group (8 of 112). Cues that induce reward-seeking behavior can do so by acting as incentives or reinforcers. Distinct populations of neurons responded to the cue in trials in which the cue acted as an incentive, triggering a motivated reward-seeking state, or as a reinforcer, supporting continued instrumental responding. The incentive motivation-encoding population of neurons (34 of 46 cue-responsive neurons; 74%) extinguished in temporal agreement with a decrease in the rate of instrumental responding. The conditioned reinforcement-encoding population of neurons (12 of 46 cue-responsive neurons; 26%) maintained their response for the duration of cue-reinforced instrumental responding. These data demonstrate that separate populations of cue-responsive neurons in the BLA encode the motivating or reinforcing properties of a cue previously associated with a reward.

  10. Modulation of Long-Term Potentiation of Cortico-Amygdala Synaptic Responses and Auditory Fear Memory by Dietary Polyunsaturated Fatty Acid

    Science.gov (United States)

    Yamada, Daisuke; Wada, Keiji; Sekiguchi, Masayuki

    2016-01-01

    Converging evidence suggests that an imbalance of ω3 to ω6 polyunsaturated fatty acid (PUFA) in the brain is involved in mental illnesses such as anxiety disorders. However, the underlying mechanism is unknown. We previously reported that the dietary ratio of ω3 to ω6 PUFA alters this ratio in the brain, and influences contextual fear memory. In addition to behavioral change, enhancement of cannabinoid CB1 receptor-mediated short-term synaptic plasticity and facilitation of the agonist sensitivity of CB1 receptors have been observed in excitatory synaptic responses in the basolateral nucleus of the amygdala (BLA). However, it is not known whether long-term synaptic plasticity in the amygdala is influenced by the dietary ratio of ω3 to ω6 PUFA. In the present study, we examined long-term potentiation (LTP) of optogenetically-evoked excitatory synaptic responses in synapses between the terminal of the projection from the auditory cortex (ACx) and the pyramidal cells in the lateral nucleus of the amygdala. We found that LTP in this pathway was attenuated in mice fed with a high ω3 to ω6 PUFA ratio diet (0.97), compared with mice fed with a low ω3 to ω6 PUFA ratio diet (0.14). Furthermore, mice in the former condition showed reduced fear responses in an auditory fear conditioning test, compared with mice in the latter condition. In both electrophysiological and behavioral experiments, the effect of a diet with a high ω3 to ω6 PUFA diet ratio was completely blocked by treatment with a CB1 receptor antagonist. Furthermore, a significant reduction was observed in cholesterol content, but not in the level of an endogenous CB1 receptor agonist, 2-arachidonoylglycerol (2-AG), in brain samples containing the amygdala. These results suggest that the balance of ω3 to ω6 PUFA has an impact on fear memory and cortico-amygdala synaptic plasticity, both in a CB1 receptor–dependent manner. PMID:27601985

  11. Molecular evidence for BDNF- and GABA-related dysfunctions in the amygdala of female subjects with Major Depression

    OpenAIRE

    Guilloux, Jean-Philippe; Douillard-Guilloux, Gaelle; Kota, Rama; Wang, Xingbin; Gardier, Alain; Martinowich, Keri; Tseng, George C.; David A Lewis; Sibille, Etienne

    2011-01-01

    Women are twice as likely as men to develop major depressive disorder (MDD) and are more prone to recurring episodes. Hence, we tested the hypothesis that the illness may associate with robust molecular changes in female subjects, and investigated large-scale gene expression in the postmortem brain of MDD subjects paired with matched controls (n=21 pairs). We focused on the lateral/basolateral/basomedian (LBNC) complex of the amygdala as a neural hub of mood regulation affected in MDD. Among ...

  12. Serotonergic innervation and serotonin receptor expression of NPY-producing neurons in the rat lateral and basolateral amygdaloid nuclei.

    Science.gov (United States)

    Bonn, M; Schmitt, A; Lesch, K-P; Van Bockstaele, E J; Asan, E

    2013-03-01

    Pharmacobehavioral studies in experimental animals, and imaging studies in humans, indicate that serotonergic transmission in the amygdala plays a key role in emotional processing, especially for anxiety-related stimuli. The lateral and basolateral amygdaloid nuclei receive a dense serotonergic innervation in all species studied to date. We investigated interrelations between serotonergic afferents and neuropeptide Y (NPY)-producing neurons, which are a subpopulation of inhibitory interneurons in the rat lateral and basolateral nuclei with particularly strong anxiolytic properties. Dual light microscopic immunolabeling showed numerous appositions of serotonergic afferents on NPY-immunoreactive somata. Using electron microscopy, direct membrane appositions and synaptic contacts between serotonin-containing axon terminals and NPY-immunoreactive cellular profiles were unequivocally established. Double in situ hybridization documented that more than 50 %, and about 30-40 % of NPY mRNA-producing neurons, co-expressed inhibitory 5-HT1A and excitatory 5-HT2C mRNA receptor subtype mRNA, respectively, in both nuclei with no gender differences. Triple in situ hybridization showed that individual NPY mRNA-producing interneurons co-express both 5-HT1A and 5-HT2C mRNAs. Co-expression of NPY and 5-HT3 mRNA was not observed. The results demonstrate that serotonergic afferents provide substantial innervation of NPY-producing neurons in the rat lateral and basolateral amygdaloid nuclei. Studies of serotonin receptor subtype co-expression indicate a differential impact of the serotonergic innervation on this small, but important, population of anxiolytic interneurons, and provide the basis for future studies of the circuitry underlying serotonergic modulation of emotional stimulus processing in the amygdala.

  13. Glucocorticoids Enhance Taste Aversion Memory via Actions in the Insular Cortex and Basolateral Amygdala

    Science.gov (United States)

    Miranda, Maria Isabel; Quirarte, Gina L.; Rodriguez-Garcia, Gabriela; McGaugh, James L.; Roozendaal, Benno

    2008-01-01

    It is well established that glucocorticoid hormones strengthen the consolidation of hippocampus-dependent spatial and contextual memory. The present experiments investigated glucocorticoid effects on the long-term formation of conditioned taste aversion (CTA), an associative learning task that does not depend critically on hippocampal function.…

  14. Recurrent hypoglycemia increases anxiety and amygdala norepinephrine release during subsequent hypoglycemia

    Directory of Open Access Journals (Sweden)

    Ewan eMcNay

    2015-11-01

    Full Text Available Recurrent hypoglycemia (RH is a common and debilitating side effect of therapy in patients with both type 1 and, increasingly, type 2 diabetes. Previous studies in rats have shown marked effects of RH on subsequent hippocampal behavioral, metabolic, and synaptic processes. In addition to impaired memory, patients experiencing RH report alterations in cognitive processes that include mood and anxiety, suggesting that RH may also affect amygdala function. We tested the impact of RH on amygdala function using an elevated plus-maze test of anxiety together with in vivo amygdala microdialysis for norepinephrine (NEp, a widely used marker of basolateral amygdala cognitive processes. In contrast to findings in the hippocampus and pre-frontal cortex, neither RH nor acute hypoglycemia alone significantly affected plus-maze performance or NEp release. However, animals tested when hypoglycemic who had previously experienced RH had elevated amygdala NEp during plus-maze testing, accompanied by increased anxiety (i.e. less time spent in the open arms of the plus-maze. The results show that RH has widespread effects on subsequent brain function, which vary by neural system.

  15. Running exercise delays neurodegeneration in amygdala and hippocampus of Alzheimer's disease (APP/PS1) transgenic mice.

    Science.gov (United States)

    Lin, Tzu-Wei; Shih, Yao-Hsiang; Chen, Shean-Jen; Lien, Chi-Hsiang; Chang, Chia-Yuan; Huang, Tung-Yi; Chen, Shun-Hua; Jen, Chauying J; Kuo, Yu-Min

    2015-02-01

    Alzheimer's disease (AD) is an age-related neurodegenerative disease. Post-mortem examination and brain imaging studies indicate that neurodegeneration is evident in the hippocampus and amygdala of very early stage AD patients. Exercise training is known to enhance hippocampus- and amygdala-associated neuronal function. Here, we investigated the effects of exercise (running) on the neuronal structure and function of the hippocampus and amygdala in APP/PS1 transgenic (Tg) mice. At 4-months-old, an age before amyloid deposition, the amygdala-associated, but not the hippocampus-associated, long-term memory was impaired in the Tg mice. The dendritic complexities of the amygdalar basolateral neurons, but not those in the hippocampal CA1 and CA3 neurons, were reduced. Furthermore, the levels of BDNF/TrkB signaling molecules (i.e. p-TrkB, p-Akt and p-PKC) were reduced in the amygdala, but not in the hippocampus of the 4-month-old Tg mice. The concentrations of Aβ40 and Aβ42 in the amygdala were higher than those in the hippocampus. Ten weeks of treadmill training (from 1.5- to 4-month-old) increased the hippocampus-associated memory and dendritic arbor of the CA1 and CA3 neurons, and also restored the amygdala-associated memory and the dendritic arbor of amygdalar basolateral neurons in the Tg mice. Similarly, exercise training also increased the levels of p-TrkB, p-AKT and p-PKC in the hippocampus and amygdala. Furthermore, exercise training reduced the levels of soluble Aβ in the amygdala and hippocampus. Exercise training did not change the levels of APP or RAGE, but significantly increased the levels of LRP-1 in both brain regions of the Tg mice. In conclusion, our results suggest that tests of amygdala function should be incorporated into subject selection for early prevention trials. Long-term exercise protects neurons in the amygdala and hippocampus against AD-related degeneration, probably via enhancements of BDNF signaling pathways and Aβ clearance. Physical

  16. Mesolimbic dopaminergic supersensitivity following electrical kindling of the amygdala

    Energy Technology Data Exchange (ETDEWEB)

    Csernansky, J.G.; Mellentin, J.; Beauclair, L.; Lombrozo, L.

    1988-02-01

    Limbic seizures developed in rats following daily electrical stimulation of the basolateral nucleus of the amygdala. Animals were designated as kindled after five complete (stage 5) behavioral seizures were observed. A subgroup, designated as superkindled, received three additional weeks of electrical stimulations. Kindled rats were significantly subsensitive to the stereotypy-inducing effects of apomorphine, a direct dopamine agonist, compared to controls. Superkindled rats were supersensitive to the effects of apomorphine. However, both kindled and superkindled rats demonstrated an increase in /sup 3/H-spiperone Bmax values, reflecting dopamine D2-receptor densities, in the nucleus accumbens ipsilateral to the stimulating electrode. The number of interictal spikes recorded from the stimulating amygdaloid electrode during the last week of kindling was correlated with changes in apomorphine sensitivity in individual animals.

  17. Ethanol and corticotropin releasing factor receptor modulation of central amygdala neurocircuitry: An update and future directions.

    Science.gov (United States)

    Silberman, Yuval; Winder, Danny G

    2015-05-01

    The central amygdala is a critical brain region for many aspects of alcohol dependence. Much of the work examining the mechanisms by which the central amygdala mediates the development of alcohol dependence has focused on the interaction of acute and chronic ethanol with central amygdala corticotropin releasing factor signaling. This work has led to a great deal of success in furthering the general understanding of central amygdala neurocircuitry and its role in alcohol dependence. Much of this work has primarily focused on the hypothesis that ethanol utilizes endogenous corticotropin releasing factor signaling to upregulate inhibitory GABAergic transmission in the central amygdala. Work that is more recent suggests that corticotropin releasing factor also plays an important role in mediating anxiety-like behaviors via the enhancement of central amygdala glutamatergic transmission, implying that ethanol/corticotropin releasing factor interactions may modulate excitatory neurotransmission in this brain region. In addition, a number of studies utilizing optogenetic strategies or transgenic mouse lines have begun to examine specific central amygdala neurocircuit dynamics and neuronal subpopulations to better understand overall central amygdala neurocircuitry and the role of neuronal subtypes in mediating anxiety-like behaviors. This review will provide a brief update on this literature and describe some potential future directions that may be important for the development of better treatments for alcohol addiction.

  18. Electrical amygdala kindling.

    Science.gov (United States)

    Dürmüller, N; Porsolt, R D

    2003-11-01

    This unit describes a method of electrical amygdala kindling in the rat. This procedure requires mastery of stereotaxic electrode implantation which is not covered in the current unit. Also, the investigator must have a sound knowledge of electronics and computing. The text gives instructions on how to render rats epileptic, how to determine the effects of compounds in kindled rats, and how to analyze the data. Results with three reference substances are illustrated. These substances are used in the clinic and give robust results in kindling.

  19. Fasting induces basolateral uptake transporters of the SLC family in the liver via HNF4alpha and PGC1alpha.

    Science.gov (United States)

    Dietrich, Christoph G; Martin, Ina V; Porn, Anne C; Voigt, Sebastian; Gartung, Carsten; Trautwein, Christian; Geier, Andreas

    2007-09-01

    Fasting induces numerous adaptive changes in metabolism by several central signaling pathways, the most important represented by the HNF4alpha/PGC-1alpha-pathway. Because HNF4alpha has been identified as central regulator of basolateral bile acid transporters and a previous study reports increased basolateral bile acid uptake into the liver during fasting, we hypothesized that HNF4alpha is involved in fasting-induced bile acid uptake via upregulation of basolateral bile acid transporters. In rats, mRNA of Ntcp, Oatp1, and Oatp2 were significantly increased after 48 h of fasting. Protein expression as determined by Western blot showed significant increases for all three transporters 72 h after the onset of fasting. Whereas binding activity of HNF1alpha in electrophoretic mobility shift assays remained unchanged, HNF4alpha binding activity to the Ntcp promoter was increased significantly. In line with this result, we found significantly increased mRNA expression of HNF4alpha and PGC-1alpha. Functional studies in HepG2 cells revealed an increased endogenous NTCP mRNA expression upon cotransfection with either HNF4alpha, PGC-1alpha, or a combination of both. We conclude that upregulation of the basolateral bile acid transporters Ntcp, Oatp1, and Oatp2 in fasted rats is mediated via the HNF4alpha/PGC-1alpha pathway.

  20. Pituitary Adenylate Cyclase-Activating Peptide in the Central Amygdala Causes Anorexia and Body Weight Loss via the Melanocortin and the TrkB Systems.

    Science.gov (United States)

    Iemolo, Attilio; Ferragud, Antonio; Cottone, Pietro; Sabino, Valentina

    2015-07-01

    Growing evidence suggests that the pituitary adenylate cyclase-activating polypeptide (PACAP)/PAC1 receptor system represents one of the main regulators of the behavioral, endocrine, and autonomic responses to stress. Although induction of anorexia is a well-documented effect of PACAP, the central sites underlying this phenomenon are poorly understood. The present studies addressed this question by examining the neuroanatomical, behavioral, and pharmacological mechanisms mediating the anorexia produced by PACAP in the central nucleus of the amygdala (CeA), a limbic structure implicated in the emotional components of ingestive behavior. Male rats were microinfused with PACAP (0-1 μg per rat) into the CeA and home-cage food intake, body weight change, microstructural analysis of food intake, and locomotor activity were assessed. Intra-CeA (but not intra-basolateral amygdala) PACAP dose-dependently induced anorexia and body weight loss without affecting locomotor activity. PACAP-treated rats ate smaller meals of normal duration, revealing that PACAP slowed feeding within meals by decreasing the regularity and maintenance of feeding from pellet-to-pellet; postprandial satiety was unaffected. Intra-CeA PACAP-induced anorexia was blocked by coinfusion of either the melanocortin receptor 3/4 antagonist SHU 9119 or the tyrosine kinase B (TrKB) inhibitor k-252a, but not the CRF receptor antagonist D-Phe-CRF(12-41). These results indicate that the CeA is one of the brain areas through which the PACAP system promotes anorexia and that PACAP preferentially lessens the maintenance of feeding in rats, effects opposite to those of palatable food. We also demonstrate that PACAP in the CeA exerts its anorectic effects via local melanocortin and the TrKB systems, and independently from CRF.

  1. Chronic stress exacerbates neuropathic pain via the integration of stress-affect-related information with nociceptive information in the central nucleus of the amygdala.

    Science.gov (United States)

    Li, Ming-Jia; Liu, Ling-Yu; Chen, Lin; Cai, Jie; Wan, You; Xing, Guo-Gang

    2017-04-01

    Exacerbation of pain by chronic stress and comorbidity of pain with stress-related psychiatric disorders, including anxiety and depression, represent significant clinical challenges. However, the underlying mechanisms still remain unclear. Here, we investigated whether chronic forced swim stress (CFSS)-induced exacerbation of neuropathic pain is mediated by the integration of stress-affect-related information with nociceptive information in the central nucleus of the amygdala (CeA). We first demonstrated that CFSS indeed produces both depressive-like behaviors and exacerbation of spared nerve injury (SNI)-induced mechanical allodynia in rats. Moreover, we revealed that CFSS induces both sensitization of basolateral amygdala (BLA) neurons and augmentation of long-term potentiation (LTP) at the BLA-CeA synapse and meanwhile, exaggerates both SNI-induced sensitization of CeA neurons and LTP at the parabrachial (PB)-CeA synapse. In addition, we discovered that CFSS elevates SNI-induced functional up-regulation of GluN2B-containing NMDA (GluN2B-NMDA) receptors in the CeA, which is proved to be necessary for CFSS-induced augmentation of LTP at the PB-CeA synapse and exacerbation of pain hypersensitivity in SNI rats. Suppression of CFSS-elicited depressive-like behaviors by antidepressants imipramine or ifenprodil inhibits the CFSS-induced exacerbation of neuropathic pain. Collectively, our findings suggest that CFSS potentiates synaptic efficiency of the BLA-CeA pathway, leading to the activation of GluN2B-NMDA receptors and sensitization of CeA neurons, which subsequently facilitate pain-related synaptic plasticity of the PB-CeA pathway, thereby exacerbating SNI-induced neuropathic pain. We conclude that chronic stress exacerbates neuropathic pain via the integration of stress-affect-related information with nociceptive information in the CeA.

  2. Cannabinoids and traumatic stress modulation of contextual fear extinction and GR expression in the amygdala-hippocampal-prefrontal circuit.

    Science.gov (United States)

    Ganon-Elazar, Eti; Akirav, Irit

    2013-09-01

    Considerable evidence suggests that cannabinoids modulate the behavioral and physiological response to stressful events. We have recently shown that activating the cannabinoid system using the CB1/CB2 receptor agonist WIN55,212-2 (WIN) in proximity to exposure to single-prolonged stress (SPS), a rat model of emotional trauma, prevented the stress-induced enhancement of acoustic startle response, the impairment in avoidance extinction and the enhanced negative feedback on the hypothalamic-pituitary-adrenal (HPA) axis (Ganon-Elazar and Akirav, 2012). Some of the effects were found to be mediated by CB1 receptors in the basolateral amygdala (BLA). Here we examined whether cannabinoid receptor activation in a putative brain circuit that includes the BLA, hippocampus and prefrontal cortex (PFC), could prevent the effects of traumatic stress on contextual fear extinction and alterations in glucocorticoid receptor (GR) protein levels. We found that: (i) SPS impaired contextual fear extinction tested one week after trauma exposure and that WIN prevented the stress-induced impairment of extinction when microinjected immediately after trauma exposure into the BLA or hippocampus (5 μg), but not when microinjected into the PFC, (ii) the ameliorating effects of WIN on contextual extinction were prevented by blocking GRs in the BLA and hippocampus, and (iii) SPS up regulated GRs in the BLA, PFC and hippocampus and systemic WIN administration (0.5 mg/kg) after trauma exposure normalized GR levels in the BLA and hippocampus, but not in the PFC. Cannabinoid receptor activation in the aftermath of trauma exposure may regulate the emotional response to the trauma and prevent stress-induced impairment of extinction and GR up regulation through the mediation of CB1 receptors in the BLA and hippocampus. Taken together, the findings suggest that the interaction between the cannabinoid and glucocorticoid systems is crucial in the modulation of emotional trauma.

  3. Afferent and Efferent Connections of the Cortex-Amygdala Transition Zone in Mice

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    Cádiz-Moretti, Bernardita; Abellán-Álvaro, María; Pardo-Bellver, Cecília; Martínez-García, Fernando; Lanuza, Enrique

    2016-01-01

    The transitional zone between the ventral part of the piriform cortex and the anterior cortical nucleus of the amygdala, named the cortex-amygdala transition zone (CxA), shows two differential features that allow its identification as a particular structure. First, it receives dense cholinergic and dopaminergic innervations as compared to the adjacent piriform cortex and amygdala, and second, it receives projections from the main and accessory olfactory bulbs. In this work we have studied the pattern of afferent and efferent projections of the CxA, which are mainly unknown, by using the retrograde tracer Fluorogold and the anterograde tracer biotinylated dextranamine. The results show that the CxA receives a relatively restricted set of intratelencephalic connections, originated mainly by the olfactory system and basal forebrain, with minor afferents from the amygdala. The only relevant extratelencephalic afference originates in the ventral tegmental area (VTA). The efferent projections of the CxA reciprocate the inputs from the piriform cortex and olfactory amygdala. In addition, the CxA projects densely to the basolateral amygdaloid nucleus and the olfactory tubercle. The extratelencephalic projections of the CxA are very scarce, and target mainly hypothalamic structures. The pattern of connections of the CxA suggests that it is indeed a transitional area between the piriform cortex and the cortical amygdala. Double labeling with choline acetyltransferase indicates that the afferent projection from the basal forebrain is the origin of its distinctive cholinergic innervation, and double labeling with dopamine transporter shows that the projection from the VTA is the source of dopaminergic innervation. These connectivity and neurochemical features, together with the fact that it receives vomeronasal in addition to olfactory information, suggest that the CxA may be involved in processing olfactory information endowed with relevant biological meaning, such as odors

  4. Altered resting-state amygdala functional connectivity after 36 hours of total sleep deprivation.

    Directory of Open Access Journals (Sweden)

    Yongcong Shao

    Full Text Available Recent neuroimaging studies have identified a potentially critical role of the amygdala in disrupted emotion neurocircuitry in individuals after total sleep deprivation (TSD. However, connectivity between the amygdala and cerebral cortex due to TSD remains to be elucidated. In this study, we used resting-state functional MRI (fMRI to investigate the functional connectivity changes of the basolateral amygdala (BLA and centromedial amygdala (CMA in the brain after 36 h of TSD.Fourteen healthy adult men aged 25.9 ± 2.3 years (range, 18-28 years were enrolled in a within-subject crossover study. Using the BLA and CMA as separate seed regions, we examined resting-state functional connectivity with fMRI during rested wakefulness (RW and after 36 h of TSD.TSD resulted in a significant decrease in the functional connectivity between the BLA and several executive control regions (left dorsolateral prefrontal cortex [DLPFC], right dorsal anterior cingulate cortex [ACC], right inferior frontal gyrus [IFG]. Increased functional connectivity was found between the BLA and areas including the left posterior cingulate cortex/precuneus (PCC/PrCu and right parahippocampal gyrus. With regard to CMA, increased functional connectivity was observed with the rostral anterior cingulate cortex (rACC and right precentral gyrus.These findings demonstrate that disturbance in amygdala related circuits may contribute to TSD psychophysiology and suggest that functional connectivity studies of the amygdala during the resting state may be used to discern aberrant patterns of coupling within these circuits after TSD.

  5. Relationship between amygdala volume and emotion recognition in adolescents at ultra-high risk for psychosis.

    Science.gov (United States)

    Bartholomeusz, Cali F; Whittle, Sarah L; Pilioussis, Eleanor; Allott, Kelly; Rice, Simon; Schäfer, Miriam R; Pantelis, Christos; Amminger, G Paul

    2014-12-30

    Amygdala volume has been proposed as a neural risk biomarker for psychotic illness, but findings in the ultra-high risk for psychosis (UHR) population have been somewhat inconsistent, which may be related to underlying social cognitive abilities. The current study investigated whether amygdala volumes were related to emotion-recognition impairments in UHR individuals, and whether volumes differed by sex. Secondary aims were to assess whether (a) emotion-recognition performance was associated with interhemispheric amygdala volume asymmetry and (b) amgydala volume and volume asymmetry acted as a mediator between emotion-recognition and outcome measures. The amygdala was manually delineated from magnetic resonance images for 39 UHR individuals who had also completed facial and prosody emotion-recognition tasks. Partial correlations were conducted to examine associations between amydgala volume/asymmetry and recognition of negative emotions. Mediation analyses were conducted using regression and bootstrapping techniques. Amygdala volume was positively correlated with sadness emotion recognition, in particular prosody, for females only. Left amygdala volume mediated the effect of sadness recognition on depressive symptoms, negative symptoms, overall psychopathology, and global functioning in females. Findings suggest a complex relationship between emotion recognition, the structure of the amygdala and illness outcome, where recognition of sadness appears to be the precipitator of this relationship in UHR females. Further research is needed to determine illness specificity and to confirm our sex- and emotion-specific results.

  6. Elevated emotional contagion in a mouse model of Alzheimer’s disease is associated with increased synchronization in the insula and amygdala

    Science.gov (United States)

    Choi, Jiye; Jeong, Yong

    2017-01-01

    Emotional contagion, a primitive form of empathy, is heightened in patients with Alzheimer’s disease (AD); however, the mechanism underlying this attribute has not been thoroughly elucidated. In this study, observational fear conditioning was performed to measure emotional contagion levels in a mouse model of AD. Simultaneous recording of local field potentials in the bilateral anterior insula, basolateral amygdala, anterior cingulate cortex, and retrosplenial cortex was also conducted to investigate related brain network changes. Consistent with the results obtained with AD patients, 11-month-old AD model mice exhibited significantly higher freezing levels in observational fear conditioning, indicating elevated emotional contagion compared to age-matched wild-type mice. Furthermore, the left anterior insula and right basolateral amygdala of 11-months-old AD model mice indicated sustained increases in synchronization when they observed the suffering of conspecifics. These changes did not appear in other age groups or wild-type controls. Additionally, the amyloid plaque burden within the anterior insula was significantly correlated with the freezing levels in observational fear conditioning. Taken together, this study reveals increased and sustained network synchrony between the anterior insula and basolateral amygdala, which comprise a salience network in humans, as a potential mechanism for elevated emotional contagion in a mouse model of AD. PMID:28387348

  7. The amygdala and basal forebrain as a pathway for motivationally guided attention.

    Science.gov (United States)

    Peck, Christopher J; Salzman, C Daniel

    2014-10-08

    Visual stimuli associated with rewards attract spatial attention. Neurophysiological mechanisms that mediate this process must register both the motivational significance and location of visual stimuli. Recent neurophysiological evidence indicates that the amygdala encodes information about both of these parameters. Furthermore, the firing rate of amygdala neurons predicts the allocation of spatial attention. One neural pathway through which the amygdala might influence attention involves the intimate and bidirectional connections between the amygdala and basal forebrain (BF), a brain area long implicated in attention. Neurons in the rhesus monkey amygdala and BF were therefore recorded simultaneously while subjects performed a detection task in which the stimulus-reward associations of visual stimuli modulated spatial attention. Neurons in BF were spatially selective for reward-predictive stimuli, much like the amygdala. The onset of reward-predictive signals in each brain area suggested different routes of processing for reward-predictive stimuli appearing in the ipsilateral and contralateral fields. Moreover, neurons in the amygdala, but not BF, tracked trial-to-trial fluctuations in spatial attention. These results suggest that the amygdala and BF could play distinct yet inter-related roles in influencing attention elicited by reward-predictive stimuli.

  8. Threat-related amygdala functional connectivity is associated with 5-HTTLPR genotype and neuroticism.

    Science.gov (United States)

    Madsen, Martin Korsbak; Mc Mahon, Brenda; Andersen, Sofie Bech; Siebner, Hartwig Roman; Knudsen, Gitte Moos; Fisher, Patrick MacDonald

    2016-01-01

    Communication between the amygdala and other brain regions critically regulates sensitivity to threat, which has been associated with risk for mood and affective disorders. The extent to which these neural pathways are genetically determined or correlate with risk-related personality measures is not fully understood. Using functional magnetic resonance imaging, we evaluated independent and interactive effects of the 5-HTTLPR genotype and neuroticism on amygdala functional connectivity during an emotional faces paradigm in 76 healthy individuals. Functional connectivity between left amygdala and medial prefrontal cortex (mPFC) and between both amygdalae and a cluster including posterior cingulate cortex, precuneus and visual cortex was significantly increased in 5-HTTLPR S' allele carriers relative to L(A)L(A) individuals. Neuroticism was negatively correlated with functional connectivity between right amygdala and mPFC and visual cortex, and between both amygdalae and left lateral orbitofrontal (lOFC) and ventrolateral prefrontal cortex (vlPFC). Notably, 5-HTTLPR moderated the association between neuroticism and functional connectivity between both amygdalae and left lOFC/vlPFC, such that S' carriers exhibited a more negative association relative to L(A)L(A) individuals. These findings provide novel evidence for both independent and interactive effects of 5-HTTLPR genotype and neuroticism on amygdala communication, which may mediate effects on risk for mood and affective disorders.

  9. Stress-induced structural plasticity of medial amygdala stellate neurons and rapid prevention by a candidate antidepressant

    Science.gov (United States)

    Lau, T.; Bigio, B.; Zelli, D.; McEwen, BS.; Nasca, C.

    2016-01-01

    The adult brain is capable of adapting to internal and external stressors by undergoing structural plasticity, and failure to be resilient and preserve normal structure and function is likely to contribute to depression and anxiety disorders. While the hippocampus has provided the gateway for understanding stress effects on the brain, less is known about the amygdala, a key brain area involved in the neural circuitry of fear and anxiety. Here, in mice more vulnerable to stressors, we demonstrate structural plasticity within the medial and basolateral regions of the amygdala in response to prolonged 21day chronic restraint stress (CRS). Three days before the end of CRS, treatment with the putative, rapidly acting antidepressant, acetyl-L-carnitine (LAC) in the drinking water opposed the direction of these changes. Behaviorally, the LAC treatment during the last part of CRS enhanced resilience, opposing the effects of CRS, as shown by an increased social interaction and reduced passive behavior in a forced swim test. Furthermore, CRS mice treated with LAC show resilience of the CRS-induced structural remodeling of medial amygdala (MeA) stellate neurons. Within the basolateral (BLA) amygdala, LAC did not reduce, but slightly enhanced, the CRS-increased length and number of intersections of pyramidal neurons. No structural changes were observed in MeA bipolar neurons, BLA stellate neurons, or in lateral amygdala (LA) stellate neurons. Our findings identify MeA stellate neurons as an important component in the responses to stress and LAC action and show that LAC can promote structural plasticity of the MeA. This may be useful as a model for increasing resilience to stressors in at risk populations. PMID:27240534

  10. Evidence that limbic neural plasticity in the right hemisphere mediates partial kindling induced lasting increases in anxiety-like behavior: effects of low frequency stimulation (quenching?) on long term potentiation of amygdala efferents and behavior following kindling.

    Science.gov (United States)

    Adamec, R E

    1999-08-21

    Behavioral and physiological effects of partial kindling of the right ventral hippocampus by perforant path (PP) stimulation were investigated in the cat. Partial kindling produced lasting changes in affect (increased defensive response to rats) and predatory attack (decreased pawing and biting attack). Partial kindling also induced long term potentiation (LTP) of amygdala efferent transmission to ventromedial hypothalamus (VMH) and periaqueductal gray (PAG) in left and right hemispheres. LTP of field population spikes evoked in area CA3 by PP stimulation was also observed. LTP was detected using evoked potential methods. These findings parallel previous studies of left PP-CA3 partial kindling. Analysis of covariance removing effects of LTP from behavioral changes suggests that initiation of increased defensiveness at 2 days after completion of partial kindling depended on LTP of left and right amygdalo-VMH and right amygdalo-PAG transmission. From 6 days after kindling onward, increased defensiveness depended on LTP of right amygdalo-PAG transmission. Depotentiation of amygdala efferent LTP by bilateral low frequency amygdala stimulation (LFS) (900 pulses at 1 Hz, once daily for 7 days) selectively reduced LTP in right amygdala efferents. At the same time, defensive, but not predatory attack behavior, was returned to levels seen prior to partial kindling. Both depotentiation and reduction of defensiveness were transient. Defensiveness increased to post-kindling levels by 76 days after LFS. At the same time, LTP was restored in the right amygdalo-PAG pathway. In contrast LTP in the right amygdalo-VMH pathway remained depotentiated. Effects of LFS were not due to damage, as thresholds to evoke amygdala efferent response were unchanged. These findings suggest that lasting change in affect following partial hippocampal kindling depends on LTP of right amygdala efferent transmission to PAG. The findings parallel studies of non-convulsant pharmacological induction of

  11. Arousal modulation of memory and amygdala-parahippocampal connectivity: a PET-psychophysiology study in specific phobia.

    Science.gov (United States)

    Ahs, Fredrik; Palmquist, Asa Michelgård; Pissiota, Anna; Appel, Lieuwe; Frans, Orjan; Liberzon, Israel; Furmark, Tomas; Fredrikson, Mats

    2011-11-01

    Phobic fear is accompanied by intense bodily responses modulated by the amygdala. An amygdala moderated psychophysiological measure related to arousal is electrodermal activity. We evaluated the contributions of electrodermal activity to amygdala-parahippocampal regional cerebral blood flow (rCBF) during phobic memory encoding in subjects with spider or snake phobia. Recognition memory was increased for phobia-related slides and covaried with rCBF in the amygdala and the parahippocampal gyrus. The covariation between parahippocampal rCBF and recognition was related to electrodermal activity suggesting that parahippocampal memory processes were associated with sympathetic activity. Electrodermal activity further mediated the amygdala effect on parahippocampal activity. Memory encoding during phobic fear therefore seems contingent on amygdala's influence on arousal and parahippocampal activity.

  12. Deep prepiriform cortex kindling and amygdala interactions.

    Science.gov (United States)

    Zhao, D Y; Moshé, S L

    1987-03-01

    The deep prepiriform cortex (DPC) has been recently suggested to be a crucial epileptogenic site in the rat brain. We investigated the susceptibility of the DPC to the development of electrical kindling as compared to that of the superficial prepiriform cortex (SPC) and amygdala as well as the transfer interactions between the two prepiriform sites and amygdala. Adult rats with electrodes implanted in the right prepiriform cortex (DPC or SPC) and left amygdala were divided into a DPC-amygdala and SPC-amygdala group while a third group consisted of rats with electrodes implanted in the ipsilateral DPC and amygdala. Within each group the rats were initially kindled from one site selected randomly and then rekindled from the other site. Both DPC and SPC were as sensitive to the development of kindling as the amygdala. The behavioral seizures elicited with DPC or SPC primary kindling were identical to those induced by amygdala kindling. Initial DPC kindling facilitated the development of kindling from either ipsilateral or contralateral amygdala with the ipsilateral transfer being significantly more potent than the contralateral. SPC kindling also facilitated the development of contralateral amygdala kindling but was less effective than DPC kindling. On the other hand, amygdala kindling did not facilitate contralateral SPC or DPC kindling although it transferred to the ipsilateral DPC. These results indicate that the prepiriform cortex can be readily kindled but not faster than the amygdala and that there are unequal kindling transfer interactions between prepiriform cortex and amygdala.

  13. Bile Acids Trigger GLP-1 Release Predominantly by Accessing Basolaterally Located G Protein-Coupled Bile Acid Receptors

    DEFF Research Database (Denmark)

    Brighton, Cheryl A.; Rievaj, Juraj; Kuhre, Rune E.;

    2015-01-01

    Bile acids are well-recognized stimuli of glucagon-like peptide-1 (GLP-1) secretion. This action has been attributed to activation of the G protein-coupled bile acid receptor GPBAR1 (TGR5), although other potential bile acid sensors include the nuclear farnesoid receptor and the apical sodium......-coupled bile acid transporter ASBT. The aim of this study was to identify pathways important for GLP-1 release and to determine whether bile acids target their receptors on GLP-1-secreting L-cells from the apical or basolateral compartment. Using transgenic mice expressing fluorescent sensors specifically in L...... to either TLCA or TDCA. We conclude that the action of bile acids on GLP-1 secretion is predominantly mediated by GPBAR1 located on the basolateral L-cell membrane, suggesting that stimulation of gut hormone secretion may include postabsorptive mechanisms....

  14. Molecular and neuronal plasticity mechanisms in the amygdala-prefrontal cortical circuit: implications for opiate addiction memory formation.

    Science.gov (United States)

    Rosen, Laura G; Sun, Ninglei; Rushlow, Walter; Laviolette, Steven R

    2015-01-01

    The persistence of associative memories linked to the rewarding properties of drugs of abuse is a core underlying feature of the addiction process. Opiate class drugs in particular, possess potent euphorigenic effects which, when linked to environmental cues, can produce drug-related "trigger" memories that may persist for lengthy periods of time, even during abstinence, in both humans, and other animals. Furthermore, the transitional switch from the drug-naïve, non-dependent state to states of dependence and withdrawal, represents a critical boundary between distinct neuronal and molecular substrates associated with opiate-reward memory formation. Identifying the functional molecular and neuronal mechanisms related to the acquisition, consolidation, recall, and extinction phases of opiate-related reward memories is critical for understanding, and potentially reversing, addiction-related memory plasticity characteristic of compulsive drug-seeking behaviors. The mammalian prefrontal cortex (PFC) and basolateral nucleus of the amygdala (BLA) share important functional and anatomical connections that are involved importantly in the processing of associative memories linked to drug reward. In addition, both regions share interconnections with the mesolimbic pathway's ventral tegmental area (VTA) and nucleus accumbens (NAc) and can modulate dopamine (DA) transmission and neuronal activity associated with drug-related DAergic signaling dynamics. In this review, we will summarize research from both human and animal modeling studies highlighting the importance of neuronal and molecular plasticity mechanisms within this circuitry during critical phases of opiate addiction-related learning and memory processing. Specifically, we will focus on two molecular signaling pathways known to be involved in both drug-related neuroadaptations and in memory-related plasticity mechanisms; the extracellular-signal-regulated kinase system (ERK) and the Ca(2+)/calmodulin-dependent protein

  15. Molecular and Neuronal Plasticity Mechanisms in the Amygdala-Prefrontal Cortical Circuit: Implications for Opiate Addiction Memory Formation

    Directory of Open Access Journals (Sweden)

    Laura G Rosen

    2015-11-01

    Full Text Available The persistence of associative memories linked to the rewarding properties of drugs of abuse is a core underlying feature of the addiction process. Opiate class drugs in particular, possess potent euphorigenic effects which, when linked to environmental cues, can produce drug-related ‘trigger’ memories that may persist for lengthy periods of time, even during abstinence, in both humans and other animals. Furthermore, the transitional switch from the drug-naïve, non-dependent state to states of dependence and withdrawal, represents a critical boundary between distinct neuronal and molecular substrates associated with opiate-reward memory formation. Identifying the functional molecular and neuronal mechanisms related to the acquisition, consolidation, recall and extinction phases of opiate-related reward memories is critical for understanding, and potentially reversing, addiction-related memory plasticity characteristic of compulsive drug-seeking behaviors. The mammalian prefrontal cortex (PFC and basolateral nucleus of the amygdala (BLA share important functional and anatomical connections that are involved importantly in the processing of associative memories linked to drug reward. In addition, both regions share interconnections with the mesolimbic pathway’s ventral tegmental area (VTA and nucleus accumbens (NAc and can modulate dopamine (DA transmission and neuronal activity associated with drug-related DAergic signaling dynamics. In this review, we will summarize research from both human and animal modelling studies highlighting the importance of neuronal and molecular plasticity mechanisms within this circuitry during critical phases of opiate addiction-related learning and memory processing. Specifically, we will focus on two molecular signaling pathways known to be involved in both drug-related neuroadaptations and in memory-related plasticity mechanisms; the extracellular-signal-regulated kinase system (ERK and the Ca2+/calmodulin

  16. Trauma exposure relates to heightened stress, altered amygdala morphology and deficient extinction learning: Implications for psychopathology.

    Science.gov (United States)

    Cacciaglia, Raffaele; Nees, Frauke; Grimm, Oliver; Ridder, Stephanie; Pohlack, Sebastian T; Diener, Slawomira J; Liebscher, Claudia; Flor, Herta

    2017-02-01

    Stress exposure causes a structural reorganization in neurons of the amygdala. In particular, animal models have repeatedly shown that both acute and chronic stress induce neuronal hypertrophy and volumetric increase in the lateral and basolateral nuclei of amygdala. These effects are visible on the behavioral level, where stress enhances anxiety behaviors and provokes greater fear learning. We assessed stress and anxiety levels in a group of 18 healthy human trauma-exposed individuals (TR group) compared to 18 non-exposed matched controls (HC group), and related these measurements to amygdala volume. Traumas included unexpected adverse experiences such as vehicle accidents or sudden loss of a loved one. As a measure of aversive learning, we implemented a cued fear conditioning paradigm. Additionally, to provide a biological marker of chronic stress, we measured the sensitivity of the hypothalamus-pituitary-adrenal (HPA) axis using a dexamethasone suppression test. Compared to the HC, the TR group showed significantly higher levels of chronic stress, current stress and trait anxiety, as well as increased volume of the left amygdala. Specifically, we observed a focal enlargement in its lateral portion, in line with previous animal data. Compared to HC, the TR group also showed enhanced late acquisition of conditioned fear and deficient extinction learning, as well as salivary cortisol hypo-suppression to dexamethasone. Left amygdala volumes positively correlated with suppressed morning salivary cortisol. Our results indicate differences in trauma-exposed individuals which resemble those previously reported in animals exposed to stress and in patients with post-traumatic stress disorder and depression. These data provide new insights into the mechanisms through which traumatic stress might prompt vulnerability for psychopathology.

  17. Stimulus-dependent amygdala involvement in affective theory of mind generation.

    Science.gov (United States)

    Schmitgen, Mike M; Walter, Henrik; Drost, Sarah; Rückl, Sarah; Schnell, Knut

    2016-04-01

    Successful social interaction requires knowledge about another person's emotional states, represented in an affective theory of mind (ToM). This information can be acquired either directly or indirectly, i.e., by observing emotional facial expressions (EFE) or indirectly by inferring emotions through cognitive perspective taking. Therefore, it is of great interest how the function of the cortical ToM network and the limbic system in affective ToM depends on the presence of facial expressions. We addressed this question in a functional magnetic resonance imaging (fMRI) study. The experimental paradigm applied a well-established ToM cartoon task to test functional effects of EFE on the activation of the amygdala and the anterior ToM network during affective ToM judgments. During the task, 22 healthy participants had to judge the changes of the emotional state of the stories protagonist in the presence or absence of EFE. After quality control, 21 data sets entered the final analyses. The presence of EFE during affective ToM judgments was associated with shorter reaction times as well as increased activation of the right amygdala, most probably located in the basolateral nucleus (BLA), coincident with reduced activation of ToM-related regions of the prefrontal cortex. Psychophysiological interactions (PPI) revealed EFE-dependent modulation of connectivity between the right BLA and the contralateral ToM network regions. In combination with the functional interaction of EFE and affective ToM in the right amygdala, our data suggest a complementary but parallel organization of EFE processing and affective ToM. In this framework, the amygdala seems to act as an EFE detector when affective ToM judgments are demanded. Additionally, the facts that EFE induced exclusively right-sided amygdala activation and modulated the connectivity with the contralateral ToM network support the idea of a functional lateralization of stimulus driven components of affective ToM.

  18. Amygdala reactivity and negative emotionality: divergent correlates of antisocial personality and psychopathy traits in a community sample.

    Science.gov (United States)

    Hyde, Luke W; Byrd, Amy L; Votruba-Drzal, Elizabeth; Hariri, Ahmad R; Manuck, Stephen B

    2014-02-01

    Previous studies have emphasized that antisocial personality disorder (APD) and psychopathy overlap highly but differ critically in several features, notably negative emotionality (NEM) and possibly amygdala reactivity to social signals of threat and distress. Here we examined whether dimensions of psychopathy and APD correlate differentially with NEM and amygdala reactivity to emotional faces. Testing these relationships among healthy individuals, dimensions of psychopathy and APD were generated by the profile matching technique of Lynam and Widiger (2001), using facet scales of the NEO Personality Inventory-Revised, and amygdala reactivity was measured using a well-established emotional faces task, in a community sample of 103 men and women. Higher psychopathy scores were associated with lower NEM and lower amygdala reactivity, whereas higher APD scores were related to greater NEM and greater amygdala reactivity, but only after overlapping variance in APD and psychopathy was adjusted for in the statistical model. Amygdala reactivity did not mediate the relationship of APD and psychopathy scores to NEM. Supplemental analyses also compared other measures of factors within psychopathy in predicting NEM and amygdala reactivity and found that Factor 2 psychopathy was positively related to NEM and amygdala reactivity across measures of psychopathy. The overall findings replicate seminal observations on NEM in psychopathy by Hicks and Patrick (2006) and extend this work to neuroimaging in a normative population. They also suggest that one critical way in which APD and psychopathy dimensions may differ in their etiology is through their opposing levels of NEM and amygdala reactivity to threat.

  19. Somatostatin-like immunoreactivity in the amygdala of the pig.

    Directory of Open Access Journals (Sweden)

    Agnieszka Bossowska

    2008-06-01

    Full Text Available The distribution and morphology of neurons containing somatostatin (SOM was investigated in the amygdala (CA of the pig. The SOM-immunoreactive (SOM-IR cell bodies and fibres were present in all subdivisions of the porcine CA, however, their number and density varied depending on the nucleus studied. The highest density of SOM-positive somata was observed in the layer III of the cortical nuclei, in the anterior (magnocellular part of the basomedial nucleus and in the caudal (large-celled part of the lateral nucleus. Moderate to high numbers of SOM-IR cells were also observed in the medial and basolateral nuclei. Many labeled neurons were also consistently observed in the lateral part of the central nucleus. In the remaining CA regions, the density of SOM-positive cell bodies varied from moderate to low. In any CA region studied SOM-IR neurons formed heterogeneous population consisting of small, rounded or slightly elongated cell bodies, with a few poorly branched smooth dendrites. In general, morphological features of these cells clearly resembled the non-pyramidal Golgi type II interneurons. The routine double-labeling studies with antisera directed against SOM and neuropeptide Y (NPY demonstrated that a large number of SOM-IR cell bodies and fibers in all studied CA areas contained simultaneously NPY. In contrast, co-localization of SOM and cholecystokinin (CCK or SOM and vasoactive intestinal polypeptide (VIP was never seen in cell bodies and fibres in any of nuclei studied. In conclusion, SOM-IR neurons of the porcine amygdala form large and heterogeneous subpopulation of, most probably, interneurons that often contain additionally NPY. On the other hand, CCK- and/or VIP-IR neurons belonged to another, discrete subpopulations of porcine CA neurons.

  20. Amygdala hyperactivation during symptom provocation in obsessive–compulsive disorder and its modulation by distraction

    Directory of Open Access Journals (Sweden)

    Daniela Simon

    2014-01-01

    Full Text Available Anxiety disorders have been linked to a hyperactivated cortico-amygdalar circuitry. Recent findings highlight the amygdala's role in mediating elevated anxiety in obsessive–compulsive disorder (OCD. However, modulation of amygdala hyperactivation by attentional distraction – an effective emotion regulation strategy in healthy individuals – has not yet been examined. While undergoing functional magnetic resonance imaging twenty-one unmedicated OCD patients and 21 controls performed an evaluation and a distraction task during symptom provocation with individually tailored OCD-relevant pictures. To test the specificity of responses, additional aversive and neutral stimuli were included. Significant group-by-picture type interactions were observed within fronto–striato–limbic circuits including the amygdala. In these regions patients showed increased BOLD responses during processing of OCD triggers relative to healthy controls. Amygdala hyperactivation was present across OCD symptom dimensions indicating that it represents a common neural correlate. During distraction, we observed dampening of patients' amygdala hyperactivity to OCD-relevant stimuli. Augmented amygdala involvement in patients during symptom provocation, present across OCD symptom dimensions, might constitute a correlate of fear expression in OCD linking it to other anxiety disorders. Attentional distraction seemed to dampen emotional processing of disorder-relevant stimuli via amygdala downregulation. The clinical impact of this strategy to manage anxiety in OCD should be further elucidated.

  1. Amygdala kindling elevates plasma vasopressin.

    Science.gov (United States)

    Greenwood, R S; Meeker, R B; Hayward, J N

    1991-01-01

    Acute and chronic effects of epilepsy on endocrine function are known to occur in humans with partial seizures of limbic origin and in animals with limbic kindled seizures. The amygdala, a component of the limbic system, has dense hypothalamic connections and amygdala stimulation in monkeys and cats result in vasopressin release. In the present study we sought to determine if amygdala stimulation in the rats results in an immediate acute release of vasopressin and to determine if acute or chronic changes occur in vasopressin release in the fully kindled animal. Plasma vasopressin, osmolality and hematocrit were measured in blood samples drawn from rats with implanted venous catheters before and after stimulation and at different stages of kindling. Low-frequency (15 Hz) electrical stimulation of the amygdala was followed by an immediate, 3-fold increase in plasma vasopressin concentration. Moreover, although the 60 Hz kindling stimulus did not result in a significant immediate rise in plasma vasopressin prior to kindling, after kindling to stage 5 seizures the 60 Hz kindling stimulus resulted in seizures and a significant immediate rise in plasma vasopressin. In addition, we found that kindling was followed by a significant, though modest, rise in the resting plasma vasopressin without an accompanying change in osmolality or hematocrit. We conclude that kindling results in a persistent alteration in the vasopressinergic neuroendocrine system.

  2. The effects of lesions of the posterior piriform cortex on amygdala kindling in the rat.

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    Wahnschaffe, U; Ebert, U; Löscher, W

    1993-07-01

    The piriform cortex (PC) is thought to be critically involved in the genesis of forebrain (limbic type) seizures, including limbic kindled seizures. More recent studies have shown that the posterior PC is particularly sensitive to kindling stimulation, suggesting that the posterior PC contains specific generating sites which may be important for the stepwise progression of kindling. In the present experiments, we used microinjections of ibotenate to study the effect of selective lesions of the posterior PC on amygdala kindling in rats. Large unilateral lesions of the posterior PC and adjacent endopiriform nucleus markedly decreased the susceptibility of the ipsilateral basolateral amygdala to electrical stimulation, thus indicating that the posterior PC may normally contribute to regulation of physiologic excitability in amygdala. During kindling, rats with large lesions of the PC stayed longer in the initial phase of kindling (stage 1) than sham-lesioned controls, consistent with involvement of the posterior PC in the early stages of seizure propagation during kindling acquisition. However, the PC lesions were not capable of blocking or even severely retarding kindling. Following kindling development, rats with large lesions of the posterior PC had significantly higher focal seizure thresholds than kindled rats without lesion or rats with only small PC lesions, which suggests that the posterior PC is involved in the mechanisms which are responsible for the marked increase in seizure susceptibility induced by kindling. Taken together, the data substantiate that PC structures play a facilitatory role in kindling.

  3. Amygdala Kindling Alters Estrus Cycle and Ovarian Morphology in the Rat.

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    Pan, Juan; Zhang, Lingwu; Wang, Feng; Liu, Dan; Li, P Andy; Sun, Tao

    2013-11-01

    The objective of this study is to explore the effects of amygdala kindling on estrus cycle and ovarian morphology. Thirty-five female rats at the age of 8 weeks were randomly designated to electrode kindled, sham-kindled, and normal controls. Kindled rats were implanted with kindling electrodes in the left basolateral amygdala and kindled by brief suprathreshold stimulations with a bipolar electrode. Estrous cycles were daily monitored through vaginal smears. Electrographic and behavioral seizures were recorded and ovarian morphology was evaluated by light and electron microscopies. Our results showed that the kindled rats lost their ovarian periodicity displayed significant ovarian enlargement. H&E staining revealed increased number of growing follicles and total follicles, as well as polycysts in the ovaries of the kindled animals compared to sham and control animals. Ultrastructural study detected numerous apoptotic granulosa cells in growing follicles and thecal cell hyperplasia with secretary granules in the thecal cells in the kindled rats. The results suggest that amygdala kindling is a risk factor for the development of polycystic ovary syndrome.

  4. Molecular Mechanisms of Stress-Induced Increases in Fear Memory Consolidation Within the Amygdala

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    Antonio Aubry

    2016-10-01

    Full Text Available Stress can significantly impact brain function and increase the risk for developing various psychiatric disorders. Many of the brain regions that are implicated in psychiatric disorders and are vulnerable to the effects of stress are also involved in mediating emotional learning. Emotional learning has been a subject of intense investigation for the past 30 years, with the vast majority of studies focusing on the amygdala and its role in associative fear learning. However, the mechanisms by which stress affects the amygdala and amygdala-dependent fear memories remain unclear. Here we review the literature on the enhancing effects of acute and chronic stress on the acquisition and/or consolidation of a fear memory, as measured by auditory Pavlovian fear conditioning, and discuss potential mechanisms by which these changes occur in the amygdala. We hypothesize that stress-mediated activation of glucocorticoid receptors (GR and norepinephrine release within the amygdala leads to the mobilization of AMPA receptors to the synapse, which underlies stress-induced increases in fear memory. We discuss the implications of this hypothesis for evaluating the effects of stress on extinction and for developing treatments for anxiety disorders. Understanding how stress-induced changes in glucocorticoid and norepinephrine signaling might converge to affect emotional learning by increasing the trafficking of AMPA receptors and enhancing amygdala excitability is a promising area for future research.

  5. Molecular Mechanisms of Stress-Induced Increases in Fear Memory Consolidation within the Amygdala.

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    Aubry, Antonio V; Serrano, Peter A; Burghardt, Nesha S

    2016-01-01

    Stress can significantly impact brain function and increase the risk for developing various psychiatric disorders. Many of the brain regions that are implicated in psychiatric disorders and are vulnerable to the effects of stress are also involved in mediating emotional learning. Emotional learning has been a subject of intense investigation for the past 30 years, with the vast majority of studies focusing on the amygdala and its role in associative fear learning. However, the mechanisms by which stress affects the amygdala and amygdala-dependent fear memories remain unclear. Here we review the literature on the enhancing effects of acute and chronic stress on the acquisition and/or consolidation of a fear memory, as measured by auditory Pavlovian fear conditioning, and discuss potential mechanisms by which these changes occur in the amygdala. We hypothesize that stress-mediated activation of glucocorticoid receptors (GR) and norepinephrine release within the amygdala leads to the mobilization of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors to the synapse, which underlies stress-induced increases in fear memory. We discuss the implications of this hypothesis for evaluating the effects of stress on extinction and for developing treatments for anxiety disorders. Understanding how stress-induced changes in glucocorticoid and norepinephrine signaling might converge to affect emotional learning by increasing the trafficking of AMPA receptors and enhancing amygdala excitability is a promising area for future research.

  6. The interplay between the hippocampus and the amygdala in regulating aberrant hippocampal neurogenesis during protracted abstinence from alcohol dependence

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    Chitra D Mandyam

    2013-06-01

    Full Text Available The development of alcohol dependence involves elevated anxiety, low mood, and increased sensitivity to stress, collectively labeled negative affect. Particularly interesting is the recent accumulating evidence that sensitized extrahypothalamic stress systems (e.g., hyperglutamatergic activity, blunted hypothalamic-pituitary-adrenal [HPA] hormonal levels, altered corticotropin-releasing factor signaling, and altered glucocorticoid receptor signaling in the extended amygdala are evident in withdrawn dependent rats, supporting the hypothesis that pathological neuroadaptations in the extended amygdala contribute to the negative affective state. Notably, hippocampal neurotoxicity observed as aberrant dentate gyrus (DG neurogenesis (neurogenesis is a process where neural stem cells in the adult hippocampal subgranular zone generate DG granule cell neurons and DG neurodegeneration are observed in withdrawn dependent rats. These correlations between withdrawal and aberrant neurogenesis in dependent rats suggest that alterations in the DG could be hypothesized to be due to compromised HPA axis activity and associated hyperglutamatergic activity originating from the basolateral amygdala in withdrawn dependent rats. This review discusses a possible link between the neuroadaptations in the extended amygdala stress systems and the resulting pathological plasticity that could facilitate recruitment of new emotional memory circuits in the hippocampus as a function of aberrant DG neurogenesis.

  7. Systemic or intra-amygdala infusion of an endocannabinoid CB1 receptor antagonist AM251 blocked propofol-induced anterograde amnesia.

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    Ren, Y; Wang, J; Xu, P B; Xu, Y J; Miao, C H

    2015-01-01

    Propofol is well-known for its anterograde amnesic actions. However, a recent experiment showed that propofol can also produce retrograde memory enhancement effects via an interaction with the endocannabinoid CB1 system. Therefore, the authors hypothesized that the regulating effect of propofol on the endocannabinoid CB1 system might also decrease the anterograde amnesic effect of propofol under some conditions, which might be a risk factor for intraoperative awareness. Since, the basolateral amygdala (BLA) has been confirmed to mediate propofol-induced anterograde amnesia and the BLA contains a high concentration of CB1 receptors, the authors investigated whether and how the endocannabinoid system, particularly the CB1 receptor within BLA, influences propofol-induced anterograde amnesia. Male Sprague-Dawley rats trained with inhibitory avoidance (IA) were systematically pre-trained using a memory-impairing dose of propofol (25 mg/kg). Before propofol administration, rats received an intraperitoneal injection of a CB1 receptor antagonist AM251 (1 mg/kg or 2 mg/kg) or a bilateral intra-BLA injection of AM251 (0.6 ng or 6 ng per 0.5 μl). Twenty-four hours after IA training, the IA retention latency was tested. It was found that systemic or intra-BLA injection of a non-regulating dose of AM251 (2 mg/kg or 6 ng per 0.5 μl, respectively) blocked the memory-impairing effect of propofol. These results indicate that the anterograde amnesic effect of propofol is mediated, in part, by activation of the CB1 cannabinoid receptors in the BLA.

  8. Prefrontal Cortical Kappa Opioid Receptors Attenuate Responses to Amygdala Inputs.

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    Tejeda, Hugo A; Hanks, Ashley N; Scott, Liam; Mejias-Aponte, Carlos; Hughes, Zoë A; O'Donnell, Patricio

    2015-12-01

    Kappa opioid receptors (KORs) have been implicated in anxiety and stress, conditions that involve activation of projections from the basolateral amygdala (BLA) to the medial prefrontal cortex (mPFC). Although KORs have been studied in several brain regions, their role on mPFC physiology and on BLA projections to the mPFC remains unclear. Here, we explored whether KORs modify synaptic inputs from the BLA to the mPFC using in vivo electrophysiological recordings with electrical and optogenetic stimulation. Systemic administration of the KOR agonist U69,593 inhibited BLA-evoked synaptic responses in the mPFC without altering hippocampus-evoked responses. Intra-mPFC U69,593 inhibited electrical and optogenetic BLA-evoked synaptic responses, an effect blocked by the KOR antagonist nor-BNI. Bilateral intra-mPFC injection of the KOR antagonist nor-BNI increased center time in the open field test, suggesting an anxiolytic effect. The data demonstrate that mPFC KORs negatively regulate glutamatergic synaptic transmission in the BLA-mPFC pathway and anxiety-like behavior. These findings provide a framework whereby KOR signaling during stress and anxiety can regulate the flow of emotional state information from the BLA to the mPFC.

  9. Different patterns of amygdala priming differentially affect dentate gyrus plasticity and corticosterone, but not CA1 plasticity.

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    Rose-Marie eVouimba

    2013-05-01

    Full Text Available Stress-induced activation of the amygdala is involved in the modulation of memory processes in the hippocampus. However, stress effects on amygdala and memory remain complex. The activation of the basolateral amygdala (BLA was found to modulate plasticity in other brain areas, including the hippocampus. We previously demonstrated a differential effect of BLA priming on LTP in the CA1 and the dentate gyrus (DG. While BLA priming suppressed long term potentiation (LTP in CA1, it was found to enhance it in the DG. However, since the amygdala itself is amenable to experience-induced plasticity it is thus conceivable that when activity within the amygdala is modified this will have impact on the way the amygdala modulates activity and plasticity in other brain areas. In the current study we examined the effects of different patterns of BLA activation on the modulation of LTP in the DG and CA1, as well as on serum corticosterone (CORT. In CA1, BLA priming impaired LTP induction as was reported before. In contrast, in the DG, varying BLA stimulation intensity and frequency resulted in differential effects on LTP, ranging from no effect to strong impairment or enhancement. Varying BLA stimulation patterns resulted in also differential alterations in Serum CORT, leading to higher CORT levels being positively correlated with LTP magnitude in DG but not in CA1.The results support the notion of a differential role for the DG in aspects of memory, and add to this view the possibility that DG-associated aspects of memory will be enhanced under more emotional or stressful conditions. It is interesting to think of BLA patterns of activation and the differential levels of circulating CORT as two arms of the emotional and stress response that attempt to synchronize brain activity to best meet the challenge. It is foreseeable to think of abnormal such synchronization under extreme conditions, which would lead to the development of maladaptive behavior.

  10. Auditory responses in the amygdala to social vocalizations

    Science.gov (United States)

    Gadziola, Marie A.

    The underlying goal of this dissertation is to understand how the amygdala, a brain region involved in establishing the emotional significance of sensory input, contributes to the processing of complex sounds. The general hypothesis is that communication calls of big brown bats (Eptesicus fuscus) transmit relevant information about social context that is reflected in the activity of amygdalar neurons. The first specific aim analyzed social vocalizations emitted under a variety of behavioral contexts, and related vocalizations to an objective measure of internal physiological state by monitoring the heart rate of vocalizing bats. These experiments revealed a complex acoustic communication system among big brown bats in which acoustic cues and call structure signal the emotional state of a sender. The second specific aim characterized the responsiveness of single neurons in the basolateral amygdala to a range of social syllables. Neurons typically respond to the majority of tested syllables, but effectively discriminate among vocalizations by varying the response duration. This novel coding strategy underscores the importance of persistent firing in the general functioning of the amygdala. The third specific aim examined the influence of acoustic context by characterizing both the behavioral and neurophysiological responses to natural vocal sequences. Vocal sequences differentially modify the internal affective state of a listening bat, with lower aggression vocalizations evoking the greatest change in heart rate. Amygdalar neurons employ two different coding strategies: low background neurons respond selectively to very few stimuli, whereas high background neurons respond broadly to stimuli but demonstrate variation in response magnitude and timing. Neurons appear to discriminate the valence of stimuli, with aggression sequences evoking robust population-level responses across all sound levels. Further, vocal sequences show improved discrimination among stimuli

  11. Mesencephalic basolateral domain specification is dependent on Sonic Hedgehog

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    Jesus E. Martinez-Lopez

    2015-02-01

    Full Text Available In the study of central nervous system morphogenesis, the identification of new molecular markers allows us to identify domains along the antero-posterior and dorso-ventral axes. In the past years, the alar and basal plates of the midbrain have been divided into different domains. The precise location of the alar-basal boundary is still under discussion. We have identified Barhl1, Nhlh1 and Six3 as appropriate molecular markers to the adjacent domains of this transition. The description of their expression patterns and the contribution to the different mesencephalic populations corroborated their role in the specification of these domains. We studied the influence of Sonic Hedgehog on these markers and therefore on the specification of these territories. The lack of this morphogen produced severe alterations in the expression pattern of Barhl1 and Nhlh1 with consequent misspecification of the basolateral domain. Six3 expression was apparently unaffected, however its distribution changed leading to altered basal domains. In this study we confirmed the localization of the alar-basal boundary dorsal to the basolateral domain and demonstrated that the development of the basolateral domain highly depends on Shh.

  12. Basolateral Cl- uptake mechanisms in Xenopus laevis lung epithelium.

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    Berger, Jens; Hardt, Martin; Clauss, Wolfgang G; Fronius, Martin

    2010-07-01

    A thin liquid layer covers the lungs of air-breathing vertebrates. Active ion transport processes via the pulmonary epithelial cells regulate the maintenance of this layer. This study focuses on basolateral Cl(-) uptake mechanisms in native lungs of Xenopus laevis and the involvement of the Na(+)/K(+)/2 Cl(-) cotransporter (NKCC) and HCO(3)(-)/Cl(-) anion exchanger (AE), in particular. Western blot analysis and immunofluorescence staining revealed the expression of the NKCC protein in the Xenopus lung. Ussing chamber experiments demonstrated that the NKCC inhibitors (bumetanide and furosemide) were ineffective at blocking the cotransporter under basal conditions, as well as under pharmacologically stimulated Cl(-)-secreting conditions (forskolin and chlorzoxazone application). However, functional evidence for the NKCC was detected by generating a transepithelial Cl(-) gradient. Further, we were interested in the involvement of the HCO(3)(-)/Cl(-) anion exchanger to transepithelial ion transport processes. Basolateral application of DIDS, an inhibitor of the AE, resulted in a significantly decreased the short-circuit current (I(SC)). The effect of DIDS was diminished by acetazolamide and reduced by increased external HCO(3)(-) concentrations. Cl(-) secretion induced by forskolin was decreased by DIDS, but this effect was abolished in the presence of HCO(3)(-). These experiments indicate that the AE at least partially contributes to Cl(-) secretion. Taken together, our data show that in Xenopus lung epithelia, the AE, rather than the NKCC, is involved in basolateral Cl(-) uptake, which contrasts with the common model for Cl(-) secretion in pulmonary epithelia.

  13. Intact electrodermal skin conductance responses after bilateral amygdala damage.

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    Tranel, D; Damasio, H

    1989-01-01

    Several lines of evidence have suggested that the amygdala is a crucial component of the anatomical network that mediates the skin conductance orienting response (SCOR). In this study, the electrodermal activity of a patient whose entire amygdaloid complex had been destroyed bilaterally, and of 7 age- and gender-matched controls, was recorded under the same experimental conditions. The results indicate unequivocally that the subject could generate normal skin conductance and SCORs, in response to stimuli of different sensory modalities and configurations. This suggests that the amygdala is not a necessary component of the neural network underlying SCORs and that there are alternate neural units and pathways that link sensory cortices to autonomic effectors.

  14. Increased training prevents the impairing effect of intra-amygdala infusion of the non-NMDA receptor antagonist CNQX on inhibitory avoidance expression

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    Roesler R.

    1999-01-01

    Full Text Available Intra-amygdala infusion of the non-N-methyl-D-aspartate (NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX prior to testing impairs inhibitory avoidance retention test performance. Increased training attenuates the impairing effects of amygdala lesions and intra-amygdala infusions of CNQX. The objective of the present study was to determine the effects of additional training on the impairing effects of intra-amygdala CNQX on expression of the inhibitory avoidance task. Adult female Wistar rats bilaterally implanted with cannulae into the border between the central and the basolateral nuclei of the amygdala were submitted to a single session or to three training sessions (0.2 mA, 24-h interval between sessions in a step-down inhibitory avoidance task. A retention test session was held 48 h after the last training. Ten minutes prior to the retention test session, the animals received a 0.5-µl infusion of CNQX (0.5 µg or its vehicle (25% dimethylsulfoxide in saline. The CNQX infusion impaired, but did not block, retention test performance in animals submitted to a single training session. Additional training prevented the impairing effect of CNQX. The results suggest that amygdaloid non-NMDA receptors may not be critical for memory expression in animals given increased training.

  15. Fluoxetine Facilitates Fear Extinction Through Amygdala Endocannabinoids.

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    Gunduz-Cinar, Ozge; Flynn, Shaun; Brockway, Emma; Kaugars, Katherine; Baldi, Rita; Ramikie, Teniel S; Cinar, Resat; Kunos, George; Patel, Sachin; Holmes, Andrew

    2016-05-01

    Pharmacologically elevating brain endocannabinoids (eCBs) share anxiolytic and fear extinction-facilitating properties with classical therapeutics, including the selective serotonin reuptake inhibitor, fluoxetine. There are also known functional interactions between the eCB and serotonin systems and preliminary evidence that antidepressants cause alterations in brain eCBs. However, the potential role of eCBs in mediating the facilitatory effects of fluoxetine on fear extinction has not been established. Here, to test for a possible mechanistic contribution of eCBs to fluoxetine's proextinction effects, we integrated biochemical, electrophysiological, pharmacological, and behavioral techniques, using the extinction-impaired 129S1/Sv1mJ mouse strain. Chronic fluoxetine treatment produced a significant and selective increase in levels of anandamide in the BLA, and an associated decrease in activity of the anandamide-catabolizing enzyme, fatty acid amide hydrolase. Slice electrophysiological recordings showed that fluoxetine-induced increases in anandamide were associated with the amplification of eCB-mediated tonic constraint of inhibitory, but not excitatory, transmission in the BLA. Behaviorally, chronic fluoxetine facilitated extinction retrieval in a manner that was prevented by systemic or BLA-specific blockade of CB1 receptors. In contrast to fluoxetine, citalopram treatment did not increase BLA eCBs or facilitate extinction. Taken together, these findings reveal a novel, obligatory role for amygdala eCBs in the proextinction effects of a major pharmacotherapy for trauma- and stressor-related disorders and anxiety disorders.

  16. The link between testosterone and amygdala-orbitofrontal cortex connectivity in adolescent alcohol use.

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    Peters, Sabine; Jolles, Dietsje J; Van Duijvenvoorde, Anna C K; Crone, Eveline A; Peper, Jiska S

    2015-03-01

    Alcohol consumption is one of the most problematic and widespread forms of risk taking in adolescence. It has been hypothesized that sex hormones such as testosterone play an important role in risk taking by influencing the development of brain networks involved in emotion and motivation, particularly the amygdala and its functional connections. Connectivity between the amygdala and the orbitofrontal cortex (OFC) may be specifically related to alcohol use, given the association of this tract with top-down control over behavioral approach tendencies. In line with this, prior studies in adults indicate a link between alcohol use and functional connectivity between the amygdala and the orbitofrontal cortex (OFC), as well as between testosterone and amygdala-OFC connectivity. We consolidated these research lines by investigating the association between alcohol use, testosterone and resting state functional brain connectivity within one large-scale adolescent sample (n=173, aged 12-25 years). Mediation analyses demonstrated an indirect effect of testosterone levels on alcohol use through amygdala-OFC intrinsic functional connectivity, but only in boys. That is, increased testosterone in boys was associated with reduced amygdala-OFC connectivity, which in turn was associated with increased alcohol intake. This study is the first to demonstrate the interplay between adolescent alcohol use, sex hormones and brain mechanisms, thus taking an important step to increase our understanding of the mechanisms behind this form of adolescent risk-taking.

  17. Amygdala functional connectivity as a longitudinal biomarker of symptom changes in generalized anxiety

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    Makovac, Elena; Watson, David R.; Meeten, Frances; Garfinkel, Sarah N.; Cercignani, Mara; Critchley, Hugo D.

    2016-01-01

    Generalized anxiety disorder (GAD) is characterized by excessive worry, autonomic dysregulation and functional amygdala dysconnectivity, yet these illness markers have rarely been considered together, nor their interrelationship tested longitudinally. We hypothesized that an individual’s capacity for emotion regulation predicts longer-term changes in amygdala functional connectivity, supporting the modification of GAD core symptoms. Sixteen patients with GAD (14 women) and individually matched controls were studied at two time points separated by 1 year. Resting-state fMRI data and concurrent measurement of vagally mediated heart rate variability were obtained before and after the induction of perseverative cognition. A greater rise in levels of worry following the induction predicted a stronger reduction in connectivity between right amygdala and ventromedial prefrontal cortex, and enhanced coupling between left amygdala and ventral tegmental area at follow-up. Similarly, amplified physiological responses to the induction predicted increased connectivity between right amygdala and thalamus. Longitudinal shifts in a distinct set of functional connectivity scores were associated with concomitant changes in GAD symptomatology over the course of the year. Results highlight the prognostic value of indices of emotional dysregulation and emphasize the integral role of the amygdala as a critical hub in functional neural circuitry underlying the progression of GAD symptomatology. PMID:27369066

  18. Basal forebrain neurons suppress amygdala kindling via cortical but not hippocampal cholinergic projections in rats.

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    Ferencz, I; Leanza, G; Nanobashvili, A; Kokaia, M; Lindvall, O

    2000-06-01

    Intraventricular administration of the immunotoxin 192 IgG-saporin in rats has been shown to cause a selective loss of cholinergic afferents to the hippocampus and cortical areas, and to facilitate seizure development in hippocampal kindling. Here we demonstrate that this lesion also accelerates seizure progression when kindling is induced by electrical stimulations in the amygdala. However, whereas intraventricular 192 IgG-saporin facilitated the development of the initial stages of hippocampal kindling, the same lesion promoted the late stages of amygdala kindling. To explore the role of various parts of the basal forebrain cholinergic system in amygdala kindling, selective lesions of the cholinergic projections to either hippocampus or cortex were produced by intraparenchymal injections of 192 IgG-saporin into medial septum/vertical limb of the diagonal band or nucleus basalis, respectively. Cholinergic denervation of the cortical regions caused acceleration of amygdala kindling closely resembling that observed after the more widespread lesion induced by intraventricular 192 IgG-saporin. In contrast, removal of the cholinergic input to the hippocampus had no effect on the development of amygdala kindling. These data indicate that basal forebrain cholinergic neurons suppress kindling elicited from amygdala, and that this dampening effect is mediated via cortical but not hippocampal projections.

  19. Role of anxiety in the pathophysiology of irritable bowel syndrome: importance of the amygdala.

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    Myers, Brent; Greenwood-Van Meerveld, Beverley

    2009-01-01

    A common characteristic of irritable bowel syndrome (IBS) is that symptoms, including abdominal pain and abnormal bowel habits, are often triggered or exacerbated during periods of stress and anxiety. However, the impact of anxiety and affective disorders on the gastrointestinal (GI) tract is poorly understood and may in part explain the lack of effective therapeutic approaches to treat IBS. The amygdala is an important structure for regulating anxiety with the central nucleus of the amygdala facilitating the activation of the hypothalamic-pituitary-adrenal axis and the autonomic nervous system in response to stress. Moreover, chronic stress enhances function of the amygdala and promotes neural plasticity throughout the amygdaloid complex. This review outlines the latest findings obtained from human studies and animal models related to the role of the emotional brain in the regulation of enteric function, specifically how increasing the gain of the amygdala to induce anxiety-like behavior using corticosterone or chronic stress increases responsiveness to both visceral and somatic stimuli in rodents. A focus of the review is the relative importance of mineralocorticoid receptor and glucocorticoid receptor-mediated mechanisms within the amygdala in the regulation of anxiety and nociceptive behaviors that are characteristic features of IBS. This review also discusses several outstanding questions important for future research on the role of the amygdala in the generation of abnormal GI function that may lead to potential targets for new therapies to treat functional bowel disorders such as IBS.

  20. Role of anxiety in the pathophysiology of irritable bowel syndrome: importance of the amygdala

    Directory of Open Access Journals (Sweden)

    Brent Myers

    2009-06-01

    Full Text Available A common characteristic of irritable bowel syndrome (IBS is that symptoms, including abdominal pain and abnormal bowel habits, are often triggered or exacerbated during periods of stress and anxiety. However, the impact of anxiety and affective disorders on the gastrointestinal (GI tract is poorly understood and may in part explain the lack of effective therapeutic approaches to treat IBS. The amygdala is an important structure for regulating anxiety with the central nucleus of the amygdala (CeA facilitating the activation of the hypothalamic-pituitary-adrenal (HPA axis and the autonomic nervous system in response to stress. Moreover, chronic stress enhances function of the amygdala and promotes neural plasticity throughout the amygdaloid complex. This review outlines the latest findings obtained from human studies and animal models related to the role of the emotional brain in the regulation of enteric function, specifically how increasing the gain of the amygdala to induce anxiety-like behavior using corticosterone (CORT or chronic stress increases responsiveness to both visceral and somatic stimuli in rodents. A focus of the review is the relative importance of mineralocorticoid receptor (MR and glucocorticoid receptor (GR-mediated mechanisms within the amygdala in the regulation of anxiety and nociceptive behaviors that are characteristic features of IBS. This review also discusses several outstanding questions important for future research on the role of the amygdala in the generation of abnormal GI function that may lead to potential targets for new therapies to treat functional bowel disorders such as IBS.

  1. Pathophysiological Alterations In The Basolateral Amygdala And Neurodegeneration Of Limbic Structures During Epileptogenesis Induced By Status Epilepticus

    Science.gov (United States)

    2009-02-05

    ketamine 60 mg/kg intraperitonally (i.p.), medetomidine 0.5 mg/kg i.p.), using the following coordinates, in mm, after Paxinos and Watson (1998): Two...MicroBrightField, Williston, VT). The BLA was identified on slide-mounted sections and delineated under a 2.5× objective, based on 36 the atlas of Paxinos ...receptors in Xenopus oocytes: An innovative approach to study epilepsy. Proc Natl Acad Sci USA 99:15078–15083. Paxinos G, Watson C (1998) The Rat

  2. Cortico-amygdala-striatal circuits are organized as hierarchical subsystems through the primate amygdala.

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    Cho, Youngsun T; Ernst, Monique; Fudge, Julie L

    2013-08-28

    The prefrontal and insula cortex, amygdala, and striatum are key regions for emotional processing, yet the amygdala's role as an interface between the cortex and striatum is not well understood. In the nonhuman primate (Macaque fascicularis), we analyzed a collection of bidirectional tracer injections in the amygdala to understand how cortical inputs and striatal outputs are organized to form integrated cortico-amygdala-striatal circuits. Overall, diverse prefrontal and insular cortical regions projected to the basal and accessory basal nuclei of the amygdala. In turn, these amygdala regions projected to widespread striatal domains extending well beyond the classic ventral striatum. Analysis of the cases in aggregate revealed a topographic colocalization of cortical inputs and striatal outputs in the amygdala that was additionally distinguished by cortical cytoarchitecture. Specifically, the degree of cortical laminar differentiation of the cortical inputs predicted amygdalostriatal targets, and distinguished three main cortico-amygdala-striatal circuits. These three circuits were categorized as "primitive," "intermediate," and "developed," respectively, to emphasize the relative phylogenetic and ontogenetic features of the cortical inputs. Within the amygdala, these circuits appeared arranged in a pyramidal-like fashion, with the primitive circuit found in all examined subregions, and subsequent circuits hierarchically layered in discrete amygdala subregions. This arrangement suggests a stepwise integration of the functions of these circuits across amygdala subregions, providing a potential mechanism through which internal emotional states are managed with external social and sensory information toward emotionally informed complex behaviors.

  3. The amygdala: an agent of change in adolescent neural networks.

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    Scherf, K Suzanne; Smyth, Joshua M; Delgado, Mauricio R

    2013-07-01

    This article is part of a Special Issue "Puberty and Adolescence". A unique component of adolescent development is the need to master new developmental tasks in which peer interactions become primary (for the purposes of becoming autonomous from parents, forming intimate friendships, and romantic/sexual partnerships). Previously, it has been suggested that the ability to master these tasks requires an important re-organization in the relation between perceptual, motivational, affective, and cognitive systems in a very general and broad way that is fundamentally influenced by the infusion of sex hormones during pubertal development (Scherf et al., 2012). Herein, we extend this argument to suggest that the amygdala, which is vastly connected with cortical and subcortical regions and contains sex hormone receptors, may lie at the heart of this re-organization. We propose that during adolescent development there is a shift in the attribution of relevance to existing stimuli and contexts that is mediated by the amygdala (e.g., heightened relevance of peer faces, reduced relevance of physical distance from parents). As a result, amygdala inputs to existing stable neural networks are re-weighted (increased or decreased), which destabilizes the functional interactions among regions within these networks and allows for a critical restructuring of the network functional organization. This process of network re-organization enables processing of qualitatively new kinds of social information and the emergence of novel behaviors that support mastery of adolescent-specific developmental tasks.

  4. Amygdalar neuropeptide Y Y1 receptors mediate the anxiolytic-like actions of neuropeptide Y in the social interaction test.

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    Sajdyk, T J; Vandergriff, M G; Gehlert, D R

    1999-03-01

    The effects of intra-amygdalar neuropeptide Y infusions were assessed in rats using the social interaction test. Neuropeptide Y administered into the central nucleus of the amygdala did not alter behavior, while injections into the basolateral nucleus of the amygdala produced an increased social interaction time. Furthermore, the anxiolytic-like effect was antagonized by co-administration of the potent neuropeptide Y Y1 receptor antagonist ((R)-N-[[4-(aminocarbonylaminomethyl)-phenyl]methyl]-N2-(diphen ylacetyl)-argininamide trifluoroacetate) 3304, but not with the inactive enantiomer ((R)-N-[[4-(aminocarbonylaminomethyl)-phenyl]methyl]-N2-(diphen ylacetyl)-argininamide trifluoroacetate) 3457. Therefore, neuropeptide Y produces an anxiolytic-like effect in the social interaction test through neuropetide Y Y1 receptors located in the basolateral amygdala.

  5. Framing effect following bilateral amygdala lesion.

    Science.gov (United States)

    Talmi, Deborah; Hurlemann, René; Patin, Alexandra; Dolan, Raymond J

    2010-05-01

    A paradigmatic example of an emotional bias in decision making is the framing effect, where the manner in which a choice is posed--as a potential loss or a potential gain--systematically biases an ensuing decision. Two fMRI studies have shown that the activation in the amygdala is modulated by the framing effect. Here, contrary to an expectation based on these studies, we show that two patients with Urbach-Wiethe (UW) disease, a rare condition associated with congenital, complete bilateral amygdala degeneration, exhibit an intact framing effect. However, choice preference in these patients did show a qualitatively distinct pattern compared to controls evident in an increased propensity to gamble, indicating that loss of amygdala function does exert an overall influence on risk-taking. These findings suggest either that amygdala does contribute to decision making but does not play a causal role in framing, or that UW is not a pure lesion model of amygdala function.

  6. Linkage of functional and structural anomalies in the left amygdala of reactive-aggressive men.

    Science.gov (United States)

    Bobes, María A; Ostrosky, Feggy; Diaz, Karla; Romero, Cesar; Borja, Karina; Santos, Yusniel; Valdés-Sosa, Mitchell

    2013-12-01

    Amygdala structural and functional abnormalities have been associated to reactive aggression in previous studies. However, the possible linkage of these two types of anomalies has not been examined. We hypothesized that they would coincide in the same localizations, would be correlated in intensity and would be mediated by reactive aggression personality traits. Here violent (n = 25) and non-violent (n = 29) men were recruited on the basis of their reactive aggression. Callous-unemotional (CU) traits were also assessed. Gray matter concentration (gmC) and reactivity to fearful and neutral facial expressions were measured in dorsal and ventral amygdala partitions. The difference between responses to fearful and neutral facial expressions was calculated (F/N-difference). Violent individuals exhibited a smaller F/N-difference and gmC in the left dorsal amygdala, where a significant coincidence was found in a conjunction analysis. Moreover, the left amygdala F/N-difference and gmC were correlated to each other, an effect mediated by reactive aggression but not by CU. The F/N-difference was caused by increased reactivity to neutral faces. This suggests that anatomical anomalies within local circuitry (and not only altered input) may underlie the amygdala hyper-reactivity to social signals which is characteristic of reactive aggression.

  7. Distribution of Prestin on Outer Hair Cell Basolateral Surface

    Institute of Scientific and Technical Information of China (English)

    YU Ning; ZHAI Suo-qiang; YANG Shi-ming; HAN Dong-yi; ZHAO Hong-bo

    2008-01-01

    Prestin has been identified as a motor protein responsible for outer hair cell (OHC) electromotility and is expressed on the OHC surface. Previous studies revealed that OHC eleetromotility and its associated nonlinear capacitance were mainly located at the OHC lateral wall and absent at the apical cutieular plate and the basal nucleus region. Immunofluorescent staining for prestin also failed to demonstrate prestin expression at the OHC basal ends in whole-mount preparation of the organ of Corti. However, there lacks a definitive demonstration of the pattern of prestin distribution. The OHC lateral wall has a trilaminate organization and is composed of the plasma membrane, cortical lattice, and subsurface cisternae. In this study, the location of prestin proteins in dissociated OHCs was examined using immunofluorescent staining and confocal microscopy. We found that prestin was uniformly expressed on the basolateral surface, including the basal pole. No staining was seen on the cuticular plate and stereocilia. When co-stained with a membrane marker di-8-ANEPPS, prestin-labeling was found to be in the outer layer of the OHC lateral wall. After separating the plasma membrane from the underlying subsurface eisternae using a hypotonic extracellular solution, prestin-labeling was found to be in the plasma membrane, not the subsurface cisternae. The data show that prestin is expressed in the plasma membrane on the entire OHC basolateral surface.

  8. Hippocampal oscillations in the rodent model of schizophrenia induced by amygdala GABA receptor blockade

    Directory of Open Access Journals (Sweden)

    Tope eLanre-Amos

    2010-09-01

    Full Text Available Brain oscillations are critical for cognitive processes, and their alterations in schizophrenia have been proposed to contribute to cognitive impairments. Network oscillations rely upon GABAergic interneurons, which also show characteristic changes in schizophrenia. The aim of this study was to examine the capability of hippocampal networks to generate oscillations in a rat model previously shown to reproduce the stereotypic structural alterations of the hippocampal interneuron circuit seen in schizophrenic patients. This model uses injection of GABA-A receptor antagonist picrotoxin into the basolateral amygdala which causes cell-type specific disruption of interneuron signaling in the hippocampus. We found that after such treatment, hippocampal theta rhythm was still present during REM sleep, locomotion, and exploration of novel environment and could be elicited under urethane anesthesia. Subtle changes in theta and gamma parameters were observed in both preparations; specifically in the stimulus intensity—theta frequency relationship under urethane and in divergent reactions of oscillations at the two major theta dipoles in freely moving rats. Thus, theta power in the CA1 region was generally enhanced as compared with deep theta dipole which decreased or did not change. The results indicate that pathologic reorganization of interneurons that follows the over-activation of the amygdala-hippocampal pathway, as shown for this model of schizophrenia, does not lead to destruction of the oscillatory circuit but changes the normal balance of rhythmic activity in its various compartments.

  9. The effect of Rosa damascena essential oil on the amygdala electrical kindling seizures in rat.

    Science.gov (United States)

    Ramezani, Roohollah; Moghimi, Ali; Rakhshandeh, Hassan; Ejtehadi, Hamid; Kheirabadi, Masoumeh

    2008-03-01

    We investigated the effect of Rosa damascena Mill, essential oil on the development of induced amygdala kindling seizures. Male Wistar rats were implanted with one tripolar and two monopolar electrodes in right basolateral amygdala and dura surface, respectively. The control group was injected solvent of essential oil and two experimental groups were injected 750 and 1000 mg kg(-1) of essential oil (ip), 30 min before a daily kindling stimulation. The number of stimulations required for the first appearance of seizure stages was significantly larger in two experimental groups than in control group. Mean after discharge duration was significantly different and essential oil reduced the increase of after discharge duration. Mean after discharge amplitude was also shorter in the groups treated with essential oil than in control group. Duration time for 5th stage of seizure at fully-kindled rats was significantly shorter in two experimental groups than control group. These results suggest that Rosa damascena essential oil significantly retarded the development of seizure stages and possesses the ability to counteract kindling acquisition. The flavonoids of Rosa damascena may act via GABAA receptors as previous studies have proposed for flavonoids of other medicinal plants. More detailed studies are recommended to define the effective component(s) of Rosa on different types of epilepsy.

  10. LXR/RXR ligand activation enhances basolateral efflux of beta-sitosterol in CaCo-2 cells.

    Science.gov (United States)

    Field, F Jeffrey; Born, Ella; Mathur, Satya N

    2004-05-01

    To examine whether intestinal ABCA1 was responsible for the differences observed between cholesterol and beta-sitosterol absorption, ABCA1-facilitated beta-sitosterol efflux was investigated in CaCo-2 cells following liver X receptor/retinoid X receptor (LXR/RXR) activation. Both the LXR agonist T0901317 and the natural RXR/LXR agonists 22-hydroxycholesterol and 9-cis retinoic acid enhanced the basolateral efflux of beta-sitosterol without altering apical efflux. LXR-mediated enhanced beta-sitosterol efflux occurred between 6 h and 12 h after activation, suggesting that transcription, protein synthesis, and trafficking was likely necessary prior to facilitating efflux. The transcription inhibitor actinomycin D prevented the increase in beta-sitosterol efflux by T0901317. Glybenclamide, an inhibitor of ABCA1 activity, and arachidonic acid, a fatty acid that interferes with LXR activation, also prevented beta-sitosterol efflux in response to the LXR ligand activation. Influx of beta-sitosterol mass did not alter the basolateral or apical efflux of the plant sterol, nor did it alter ABCA1, ABCG1, ABCG5, or ABCG8 gene expression or ABCA1 mass. Similar to results observed with intestinal ABCA1-facilitated cholesterol efflux, LXR/RXR ligand activation enhanced the basolateral efflux of beta-sitosterol without affecting apical efflux. The results suggest that ABCA1 does not differentiate between cholesterol and beta-sitosterol and thus is not responsible for the selectivity of sterol absorption by the intestine. ABCA1, however, may play a role in beta-sitosterol absorption.

  11. Comparative distribution of relaxin-3 inputs and calcium-binding protein-positive neurons in rat amygdala

    Directory of Open Access Journals (Sweden)

    Fabio N Santos

    2016-04-01

    Full Text Available The neural circuits involved in mediating complex behaviors are being rapidly elucidated using various newly developed and powerful anatomical and molecular techniques, providing insights into the neural basis for anxiety disorders, depression, addiction, and dysfunctional social behaviors. Many of these behaviors and associated physiological processes involve the activation of the amygdala in conjunction with cortical and hippocampal circuits. Ascending subcortical projections provide modulatory inputs to the extended amygdala and its related nodes (or ‘hubs’ within these key circuits. One such input arises from the nucleus incertus (NI in the tegmentum, which sends amino acid- and peptide-containing projections throughout the forebrain. Notably, a distinct population of GABAergic NI neurons expresses the highly-conserved neuropeptide, relaxin-3, and relaxin-3 signaling has been implicated in the modulation of reward/motivation and anxiety- and depressive-like behaviors in rodents via actions within the extended amygdala. Thus, a detailed description of the relaxin-3 innervation of the extended amygdala would provide an anatomical framework for an improved understanding of NI and relaxin-3 modulation of these and other specific amygdala-related functions. Therefore, in this study, we examined the distribution of NI projections and relaxin-3-positive elements (axons/fibers/terminals within the amygdala, relative to the distribution of neurons expressing the calcium-binding proteins, parvalbumin, calretinin and/or calbindin. Anterograde tracer injections into the NI revealed a topographic distribution of NI efferents within the amygdala that was near identical to the distribution of relaxin-3-immunoreactive fibers. Highest densities of anterogradely-labeled elements and relaxin-3-immunoreactive fibers were observed in the medial nucleus of the amygdala, medial divisions of the bed nucleus of the stria terminalis (BST and in the endopiriform

  12. Consequences of amygdala kindling and repeated withdrawal from ethanol on amphetamine-induced behaviours.

    Science.gov (United States)

    Ripley, Tamzin L; Dunworth, Sarah J; Stephens, David N

    2002-09-01

    It has been shown previously that chronic ethanol treatment in mice leads to accelerated behavioural sensitization to psychomotor stimulants [Manley & Little (1997) J. Pharmacol. Exp. Ther., 281, 1330-1339], whilst repeated experience of ethanol withdrawal sensitizes pathways underlying seizure activity (Becker & Hale (1993) Alcohol Clin. Exp. Res., 17, 94-98]. The aim of the current experiment was to investigate the consequences of repeated withdrawal from ethanol on amphetamine-induced behaviours in the rat and compare this with animals with electrical kindling of the amygdala, a procedure that has been shown to enhance alcohol withdrawal seizures [Pinel et al. (1975) Can. J. Neurol. Sci., 2, 467-475]. For the kindling experiments, electrodes were surgically implanted in the left basolateral amygdala and were stimulated daily at the afterdischarge threshold until a criterion of three consecutive stage 5 seizures was reached. Fully kindled rats showed a marginally significant reduction in sensitivity to the locomotor stimulant effects of acute amphetamine compared with sham and partially kindled rats which had experienced subthreshold stimulation of the amygdala. Sham and partially kindled rats sensitized readily to the locomotor activating effects of amphetamine (0.125 mg/kg) following repeated treatments, but the fully kindled rats did not. Fully kindled rats also failed to show place preference conditioning to amphetamine (0.5 mg/kg). Rats, withdrawn three times from chronic ethanol (liquid-diet), kindled more quickly to PTZ (30 mg/kg, i.p.) than rats with the same overall exposure to ethanol (24 days) followed by a single withdrawal or control animals. However, there was no difference in the locomotor stimulating effects of acute amphetamine (0.25-1 mg/kg, i.p.), the rate of sensitization to amphetamine (0.125 mg/kg, i.p.) or amphetamine induced conditioned place preference (1 mg/kg, i.p.). These observations suggest that, in rats, repeated withdrawal from a

  13. The Spatiotemporal Dynamics of Phase Synchronization during Epileptogenesis in Amygdala-Kindling Mice

    Science.gov (United States)

    Gong, Hai-Qing; Liang, Pei-Ji; Zhang, Pu-Ming; Lu, Qin-Chi

    2016-01-01

    The synchronization among the activities of neural populations in functional regions is one of the most important electrophysiological phenomena in epileptic brains. The spatiotemporal dynamics of phase synchronization was investigated to reveal the reciprocal interaction between different functional regions during epileptogenesis. Local field potentials (LFPs) were recorded simultaneously from the basolateral amygdala (BLA), the cornu ammonis 1 of hippocampus (CA1) and the mediodorsal nucleus of thalamus (MDT) in the mouse amygdala-kindling models during the development of epileptic seizures. The synchronization of LFPs was quantified between BLA, CA1 and MDT using phase-locking value (PLV). During amygdala kindling, behavioral changes (from stage 0 to stage 5) of mice were accompanied by after-discharges (ADs) of similar waveforms appearing almost simultaneously in CA1, MDT, as well as BLA. AD durations were positively related to the intensity of seizures. During seizures at stages 1~2, PLVs remained relatively low and increased dramatically shortly after the termination of the seizures; by contrast, for stages 3~5, PLVs remained a relatively low level during the initial period but increased dramatically before the seizure termination. And in the theta band, the degree of PLV enhancement was positively associated with seizure intensity. The results suggested that during epileptogenesis, the functional regions were kept desynchronized rather than hyper-synchronized during either the initial or the entire period of the seizures; so different dynamic patterns of phase synchronization may be involved in different periods of the epileptogenesis, and this might also reflect that during seizures at different stages, the mechanisms underlying the dynamics of phase synchronization were different. PMID:27100891

  14. The Spatiotemporal Dynamics of Phase Synchronization during Epileptogenesis in Amygdala-Kindling Mice.

    Science.gov (United States)

    Li, Jia-Jia; Li, Yong-Hua; Gong, Hai-Qing; Liang, Pei-Ji; Zhang, Pu-Ming; Lu, Qin-Chi

    2016-01-01

    The synchronization among the activities of neural populations in functional regions is one of the most important electrophysiological phenomena in epileptic brains. The spatiotemporal dynamics of phase synchronization was investigated to reveal the reciprocal interaction between different functional regions during epileptogenesis. Local field potentials (LFPs) were recorded simultaneously from the basolateral amygdala (BLA), the cornu ammonis 1 of hippocampus (CA1) and the mediodorsal nucleus of thalamus (MDT) in the mouse amygdala-kindling models during the development of epileptic seizures. The synchronization of LFPs was quantified between BLA, CA1 and MDT using phase-locking value (PLV). During amygdala kindling, behavioral changes (from stage 0 to stage 5) of mice were accompanied by after-discharges (ADs) of similar waveforms appearing almost simultaneously in CA1, MDT, as well as BLA. AD durations were positively related to the intensity of seizures. During seizures at stages 1~2, PLVs remained relatively low and increased dramatically shortly after the termination of the seizures; by contrast, for stages 3~5, PLVs remained a relatively low level during the initial period but increased dramatically before the seizure termination. And in the theta band, the degree of PLV enhancement was positively associated with seizure intensity. The results suggested that during epileptogenesis, the functional regions were kept desynchronized rather than hyper-synchronized during either the initial or the entire period of the seizures; so different dynamic patterns of phase synchronization may be involved in different periods of the epileptogenesis, and this might also reflect that during seizures at different stages, the mechanisms underlying the dynamics of phase synchronization were different.

  15. Relation between Amygdala Structure and Function in Adolescents with Bipolar Disorder

    Science.gov (United States)

    Kalmar, Jessica H.; Wang, Fei; Chepenik, Lara G.; Womer, Fay Y.; Jones, Monique M.; Pittman, Brian; Shah, Maulik P.; Martin, Andres; Constable, R. Todd; Blumberg, Hilary P.

    2009-01-01

    Adolescents with bipolar disorder showed decreased amygdala volume and increased amygdala response to emotional faces. Amygdala volume is inversely related to activation during emotional face processing.

  16. Concurrent and lasting effects of emotion regulation on amygdala response in adolescence and young adulthood.

    Science.gov (United States)

    Silvers, Jennifer A; Shu, Jocelyn; Hubbard, Alexa D; Weber, Jochen; Ochsner, Kevin N

    2015-09-01

    This study used functional MRI (fMRI) to examine a novel aspect of emotion regulation in adolescent development: whether age predicts differences in both the concurrent and lasting effects of emotion regulation on amygdala response. In the first, active regulation, phase of the testing session, fMRI data were collected while 56 healthy individuals (age range: 10.50-22.92 years) reappraised aversive stimuli so as to diminish negative responses to them. After a short delay, the second, re-presentation, phase involved passively viewing the aversive images from the reappraisal task. During active regulation, older individuals showed greater drops in negative affect and inverse rostrolateral prefrontal-amygdala connectivity. During re-presentation, older individuals continued to show lasting reductions in the amygdala response to aversive stimuli they had previously reappraised, an effect mediated by rostrolateral PFC. These data suggest that one source of heightened emotionality in adolescence is a diminished ability to cognitively down-regulate aversive reactions.

  17. Serotonin, Amygdala and Fear: Assembling the Puzzle

    OpenAIRE

    Bocchio, Marco; McHugh, Stephen B.; Bannerman, David M; Sharp, Trevor; Capogna, Marco

    2016-01-01

    The fear circuitry orchestrates defense mechanisms in response to environmental threats. This circuitry is evolutionarily crucial for survival, but its dysregulation is thought to play a major role in the pathophysiology of psychiatric conditions in humans. The amygdala is a key player in the processing of fear. This brain area is prominently modulated by the neurotransmitter serotonin (5-hydroxytryptamine, 5-HT). The 5-HT input to the amygdala has drawn particular interest because genetic an...

  18. Structural Connectivity of the Developing Human Amygdala

    Science.gov (United States)

    Saygin, Zeynep M.; Osher, David E.; Koldewyn, Kami; Martin, Rebecca E.; Finn, Amy; Saxe, Rebecca; Gabrieli, John D.E.; Sheridan, Margaret

    2015-01-01

    A large corpus of research suggests that there are changes in the manner and degree to which the amygdala supports cognitive and emotional function across development. One possible basis for these developmental differences could be the maturation of amygdalar connections with the rest of the brain. Recent functional connectivity studies support this conclusion, but the structural connectivity of the developing amygdala and its different nuclei remains largely unstudied. We examined age related changes in the DWI connectivity fingerprints of the amygdala to the rest of the brain in 166 individuals of ages 5-30. We also developed a model to predict age based on individual-subject amygdala connectivity, and identified the connections that were most predictive of age. Finally, we segmented the amygdala into its four main nucleus groups, and examined the developmental changes in connectivity for each nucleus. We observed that with age, amygdalar connectivity becomes increasingly sparse and localized. Age related changes were largely localized to the subregions of the amygdala that are implicated in social inference and contextual memory (the basal and lateral nuclei). The central nucleus’ connectivity also showed differences with age but these differences affected fewer target regions than the basal and lateral nuclei. The medial nucleus did not exhibit any age related changes. These findings demonstrate increasing specificity in the connectivity patterns of amygdalar nuclei across age. PMID:25875758

  19. Structural connectivity of the developing human amygdala.

    Directory of Open Access Journals (Sweden)

    Zeynep M Saygin

    Full Text Available A large corpus of research suggests that there are changes in the manner and degree to which the amygdala supports cognitive and emotional function across development. One possible basis for these developmental differences could be the maturation of amygdalar connections with the rest of the brain. Recent functional connectivity studies support this conclusion, but the structural connectivity of the developing amygdala and its different nuclei remains largely unstudied. We examined age related changes in the DWI connectivity fingerprints of the amygdala to the rest of the brain in 166 individuals of ages 5-30. We also developed a model to predict age based on individual-subject amygdala connectivity, and identified the connections that were most predictive of age. Finally, we segmented the amygdala into its four main nucleus groups, and examined the developmental changes in connectivity for each nucleus. We observed that with age, amygdalar connectivity becomes increasingly sparse and localized. Age related changes were largely localized to the subregions of the amygdala that are implicated in social inference and contextual memory (the basal and lateral nuclei. The central nucleus' connectivity also showed differences with age but these differences affected fewer target regions than the basal and lateral nuclei. The medial nucleus did not exhibit any age related changes. These findings demonstrate increasing specificity in the connectivity patterns of amygdalar nuclei across age.

  20. Stress leads to contrasting effects on the levels of brain derived neurotrophic factor in the hippocampus and amygdala.

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    Harini Lakshminarasimhan

    Full Text Available Recent findings on stress induced structural plasticity in rodents have identified important differences between the hippocampus and amygdala. The same chronic immobilization stress (CIS, 2 h/day causes growth of dendrites and spines in the basolateral amygdala (BLA, but dendritic atrophy in hippocampal area CA3. CIS induced morphological changes also differ in their temporal longevity--BLA hypertrophy, unlike CA3 atrophy, persists even after 21 days of stress-free recovery. Furthermore, a single session of acute immobilization stress (AIS, 2 h leads to a significant increase in spine density 10 days, but not 1 day, later in the BLA. However, little is known about the molecular correlates of the differential effects of chronic and acute stress. Because BDNF is known to be a key regulator of dendritic architecture and spines, we investigated if the levels of BDNF expression reflect the divergent effects of stress on the hippocampus and amygdala. CIS reduces BDNF in area CA3, while it increases it in the BLA of male Wistar rats. CIS-induced increase in BDNF expression lasts for at least 21 days after the end of CIS in the BLA. But CIS-induced decrease in area CA3 BDNF levels, reverses to normal levels within the same period. Finally, BDNF is up regulated in the BLA 1 day after AIS and this increase persists even 10 days later. In contrast, AIS fails to elicit any significant change in area CA3 at either time points. Together, these findings demonstrate that both acute and chronic stress trigger opposite effects on BDNF levels in the BLA versus area CA3, and these divergent changes also follow distinct temporal profiles. These results point to a role for BDNF in stress-induced structural plasticity across both hippocampus and amygdala, two brain areas that have also been implicated in the cognitive and affective symptoms of stress-related psychiatric disorders.

  1. Stress leads to contrasting effects on the levels of brain derived neurotrophic factor in the hippocampus and amygdala.

    Science.gov (United States)

    Lakshminarasimhan, Harini; Chattarji, Sumantra

    2012-01-01

    Recent findings on stress induced structural plasticity in rodents have identified important differences between the hippocampus and amygdala. The same chronic immobilization stress (CIS, 2 h/day) causes growth of dendrites and spines in the basolateral amygdala (BLA), but dendritic atrophy in hippocampal area CA3. CIS induced morphological changes also differ in their temporal longevity--BLA hypertrophy, unlike CA3 atrophy, persists even after 21 days of stress-free recovery. Furthermore, a single session of acute immobilization stress (AIS, 2 h) leads to a significant increase in spine density 10 days, but not 1 day, later in the BLA. However, little is known about the molecular correlates of the differential effects of chronic and acute stress. Because BDNF is known to be a key regulator of dendritic architecture and spines, we investigated if the levels of BDNF expression reflect the divergent effects of stress on the hippocampus and amygdala. CIS reduces BDNF in area CA3, while it increases it in the BLA of male Wistar rats. CIS-induced increase in BDNF expression lasts for at least 21 days after the end of CIS in the BLA. But CIS-induced decrease in area CA3 BDNF levels, reverses to normal levels within the same period. Finally, BDNF is up regulated in the BLA 1 day after AIS and this increase persists even 10 days later. In contrast, AIS fails to elicit any significant change in area CA3 at either time points. Together, these findings demonstrate that both acute and chronic stress trigger opposite effects on BDNF levels in the BLA versus area CA3, and these divergent changes also follow distinct temporal profiles. These results point to a role for BDNF in stress-induced structural plasticity across both hippocampus and amygdala, two brain areas that have also been implicated in the cognitive and affective symptoms of stress-related psychiatric disorders.

  2. Basolateral Na+/HCO3– cotransport activity is regulated by the dissociable Na+/H+ exchanger regulatory factor

    Science.gov (United States)

    Bernardo, Angelito A.; Kear, Felicidad T.; Santos, Anna V.P.; Ma, Jianfei; Steplock, Debra; Robey, R. Brooks; Weinman, Edward J.

    1999-01-01

    In the renal proximal tubule, the activities of the basolateral Na+/HCO3– cotransporter (NBC) and the apical Na+/H+ exchanger (NHE3) uniformly vary in parallel, suggesting that they are coordinately regulated. PKA-mediated inhibition of NHE3 is mediated by a PDZ motif–containing protein, the Na+/H+ exchanger regulatory factor (NHE-RF). Given the common inhibition of these transporters after protein kinase A (PKA) activation, we sought to determine whether NHE-RF also plays a role in PKA-regulated NBC activity. Renal cortex immunoblot analysis using anti-peptide antibodies directed against rabbit NHE-RF demonstrated the presence of this regulatory factor in both brush-border membranes (BBMs) and basolateral membranes (BLMs). Using a reconstitution assay, we found that limited trypsin digestion of detergent solubilized rabbit renal BLM preparations resulted in NBC activity that was unaffected by PKA activation. Co-reconstitution of these trypsinized preparations with a recombinant protein corresponding to wild-type rabbit NHE-RF restored the inhibitory effect of PKA on NBC activity in a concentration-dependent manner. NBC activity was inhibited 60% by 10–8M NHE-RF; this effect was not observed in the absence of PKA. Reconstitution with heat-denatured NHE-RF also failed to attenuate NBC activity. To establish further a physiologic role for NHE-RF in NBC regulation, the renal epithelial cell line B-SC-1, which lacks detectable endogenous NHE-RF expression, was engineered to express stably an NHE-RF transgene. NHE-RF–expressing B-SC-1 cells (B-SC-RF) exhibited markedly lower basal levels of NBC activity than did wild-type controls. Inhibition of NBC activity in B-SC-RF cells was enhanced after 10 μM of forskolin treatment, consistent with a postulated role for NHE-RF in mediating the inhibition of NBC activity by PKA. These findings not only suggest NHE-RF involvement in PKA-regulated NBC activity, but also provide a unique molecular mechanism whereby

  3. Long-lasting attenuation of amygdala-kindled seizures after convection-enhanced delivery of botulinum neurotoxins a and B into the amygdala in rats.

    Science.gov (United States)

    Gasior, Maciej; Tang, Rebecca; Rogawski, Michael A

    2013-09-01

    Botulinum neurotoxins (BoNTs) are well recognized to cause potent, selective, and long-lasting neuroparalytic actions by blocking cholinergic neurotransmission to muscles and glands. There is evidence that BoNT isoforms can also inhibit neurotransmission in the brain. In this study, we examined whether locally delivered BoNT/A and BoNT/B can attenuate kindling measures in amygdala-kindled rats. Male rats were implanted with a combination infusion cannula-stimulating electrode assembly into the right basolateral amygdala. Fully kindled animals received a single infusion of vehicle or BoNT/A or BoNT/B at doses of 1, 3.2, or 10 ng over a 20-minute period by convection-enhanced delivery. Electrographic (EEG) and behavioral kindling measures were determined at selected times during the 3- to 64-day period after the infusion. BoNT/B produced a dose-dependent elevation in after-discharge threshold and duration and a reduction in the seizure stage and duration of behavioral seizures that lasted for up to 50 days after infusion. BoNT/A had similar effects on EEG measures; behavioral seizure measures were also reduced, but the effect did not reach statistical significance. The effects of both toxins on EEG and behavioral measures progressively resolved during the latter half of the observation period. Animals gained weight normally, maintained normal body temperature, and did not show altered behavior. This study demonstrates for the first time that locally delivered BoNTs can produce prolonged inhibition of brain excitability, indicating that they could be useful for the treatment of brain disorders, including epilepsy, that would benefit from long-lasting suppression of neurotransmission within a circumscribed brain region.

  4. Anterior olfactory organ removal produces anxiety-like behavior and increases spontaneous neuronal firing rate in basal amygdala.

    Science.gov (United States)

    Contreras, Carlos M; Gutiérrez-García, Ana G; Molina-Jiménez, Tania

    2013-09-01

    Some chemical cues may produce signs of anxiety and fear mediated by amygdala nuclei, but unknown is the role of two anterior olfactory epithelial organs, the septal and vomeronasal organs (SO-VNOs). The effects of SO-VNO removal were explored in different groups of Wistar rats using two complementary approaches: (i) the assessment of neuronal firing rate in basal and medial amygdala nuclei and (ii) behavioral testing. Fourteen days after SO-VNO removal, spontaneous activity in basal and medial amygdala nuclei in one group was determined using single-unit extracellular recordings. A separate group of rats was tested in the elevated plus maze, social interaction test, and open field test. Compared with sham-operated and intact control rats, SO-VNO removal produced a higher neuronal firing rate in the basal amygdala but not medial amygdala. In the behavioral tests, SO-VNO removal increased signs of anxiety in the elevated plus maze, did not alter locomotion, and increased self-directed behavior, reflecting anxiety-like behavior. Histological analysis showed neuronal destruction in the accessory olfactory bulb but not anterior olfactory nucleus in the SO-VNO group. The present results suggest the participation of SO-VNO/accessory olfactory bulb/basal amygdala relationships in the regulation of anxiety through a process of disinhibition.

  5. Comparing the anticonvulsant effects of low frequency stimulation of different brain sites on the amygdala kindling acquisition in rats.

    Science.gov (United States)

    Esmaeilpour, Khadijeh; Masoumi-Ardakani, Yaser; Sheibani, Vahid; Shojaei, Amir; Harandi, Shaahin; Mirnajafi-Zadeh, Javad

    2013-01-01

    Low frequency stimulation (LFS) is a potential alternative therapy for epilepsy. However, it seems that the anticonvulsant effects of LFS depend on its target sites in the brain. Thus, the present study was designed to compare the anticonvulsant effects of LFS administered to amygdala, piriform cortex and substantia nigra on amygdala kindling acquisition. In control group, rats were kindled in a chronic manner (one stimulation per 24 h). In other experimental groups, animals received low-frequency stimulation (8 packages at 100 s intervals, each package contained 200 monophasic square-wave pulses, 0.1 ms pulse duration at 1 Hz andAD threshold intensity) in amygdala, piriform cortex or substantia nigra 60 seconds after the kindling stimulation, the AD duration and daily seizure stages were recorded. The obtained results showed that administration of LFS in all three regions reduced electrical and behavioral parameters of the kindling procedure. However LFS has a stronger inhibitory effect on kindling development when applied in substantia nigra compared to the amygdala and piriform cortex which reinforce the view that the substantia nigra mediates a crucial role in amygdala-kindled seizures. LFS had also greater inhibitory effects when applied to the amygdala compared to piriform cortex. Thus, it may be suggested that antiepileptogenic effect of LFS depends on its target site and different brain areas exert different inhibitory effects on kindling acquisition according to the seizure focus.

  6. A Developmental Examination of Amygdala Response to Facial Expressions

    OpenAIRE

    Guyer, Amanda E.; Monk, Christopher S.; McClure-Tone, Erin B.; Nelson, Eric E.; Roberson-Nay, Roxann; Adler, Abby D.; Fromm, Stephen J.; Leibenluft, Ellen; Daniel S Pine; Ernst, Monique

    2008-01-01

    Several lines of evidence implicate the amygdala in face– emotion processing, particularly for fearful facial expressions. Related findings suggest that face–emotion processing engages the amygdala within an interconnected circuitry that can be studied using a functional-connectivity approach. Past work also underscores important functional changes in the amygdala during development. Taken together, prior research on amygdala function and development reveals a need for more work examining dev...

  7. Anxiogenic-like activity of 3,4-methylenedioxy-methamphetamine ("Ecstasy") in the social interaction test is accompanied by an increase of c-fos expression in mice amygdala.

    Science.gov (United States)

    Navarro, José Francisco; Rivera, Alicia; Maldonado, Enrique; Cavas, María; de la Calle, Adelaida

    2004-03-01

    3,4-Methylenedioxymethamphetamine (MDMA) is a synthetic amphetamine popularly known as "Ecstasy." Animal studies examining acute effects of MDMA on anxiety are unclear because although an anxiolytic-like action of MDMA in different animal models of anxiety has been described, there is also substantial evidence supporting an anxiogenic-like effect of this drug. To date, several studies have examined c-fos expression following MDMA administration in rats. However, there is no information about the MDMA-induced c-fos expression in mice previously tested in an animal model of anxiety. In this study, male mice were injected with MDMA (1, 8 and 15 mg/kg ip) and assessed for changes on anxiety and for the expression of the immediate early gene c-fos in the amygdala (central, basolateral and basomedial). Anxiety was evaluated by the "social interaction test." Ten behavioral categories were recorded: body care, digging, nonsocial exploration, exploration from a distance, social investigation, threat, attack, avoidance/flee, defense/submission and immobility. As compared with the control group, mice treated with MDMA (all doses) showed a decrease in mean duration and total time spent in social investigation behaviors, whereas avoidance/flee behaviors were significantly increased after treatment with this compound (8 and 15 mg/kg). Likewise, a significant increase in c-fos expression was found in the basolateral (all doses) and central (15 mg/kg) amygdala after MDMA administration. Overall, these findings indicate that MDMA exhibits an anxiogenic-like profile in the social interaction test in mice, and that central and basolateral amygdala might be involved in these anxiogenic-like effects of the drug.

  8. Murine GRPR and stathmin control in opposite directions both cued fear extinction and neural activities of the amygdala and prefrontal cortex.

    Directory of Open Access Journals (Sweden)

    Guillaume Martel

    Full Text Available Extinction is an integral part of normal healthy fear responses, while it is compromised in several fear-related mental conditions in humans, such as post-traumatic stress disorder (PTSD. Although much research has recently been focused on fear extinction, its molecular and cellular underpinnings are still unclear. The development of animal models for extinction will greatly enhance our approaches to studying its neural circuits and the mechanisms involved. Here, we describe two gene-knockout mouse lines, one with impaired and another with enhanced extinction of learned fear. These mutant mice are based on fear memory-related genes, stathmin and gastrin-releasing peptide receptor (GRPR. Remarkably, both mutant lines showed changes in fear extinction to the cue but not to the context. We performed indirect imaging of neuronal activity on the second day of cued extinction, using immediate-early gene c-Fos. GRPR knockout mice extinguished slower (impaired extinction than wildtype mice, which was accompanied by an increase in c-Fos activity in the basolateral amygdala and a decrease in the prefrontal cortex. By contrast, stathmin knockout mice extinguished faster (enhanced extinction and showed a decrease in c-Fos activity in the basolateral amygdala and an increase in the prefrontal cortex. At the same time, c-Fos activity in the dentate gyrus was increased in both mutant lines. These experiments provide genetic evidence that the balance between neuronal activities of the amygdala and prefrontal cortex defines an impairment or facilitation of extinction to the cue while the hippocampus is involved in the context-specificity of extinction.

  9. Anxiolytic-Like Effects of Increased Ghrelin Receptor Signaling in the Amygdala

    DEFF Research Database (Denmark)

    Jensen, Morten; Ratner, Cecilia; Rudenko, Olga;

    2016-01-01

    BACKGROUND: Besides the well-known effects of ghrelin on adiposity and food intake regulation, the ghrelin system has been shown to regulate aspects of behavior including anxiety and stress. However, the effect of virus-mediated overexpression of the ghrelin receptor in the amygdala has not previ......BACKGROUND: Besides the well-known effects of ghrelin on adiposity and food intake regulation, the ghrelin system has been shown to regulate aspects of behavior including anxiety and stress. However, the effect of virus-mediated overexpression of the ghrelin receptor in the amygdala has...... overexpression on anxiety-related behavior before and after acute stress and measured the modulation of serotonin receptor expression. RESULTS: We found that ghrelin caused an anxiolytic-like effect in both the open field and elevated plus maze tests. Additionally, it attenuated air-puff induced stress...... axis potentially engaging the central serotonin system....

  10. Blocking the mineralocorticoid receptor in humans prevents the stress-induced enhancement of centromedial amygdala connectivity with the dorsal striatum

    NARCIS (Netherlands)

    Vogel, S.; Klumpers, F.; Krugers, H.J.; Fang, Z.; Oplaat, K.T.; Oitzl, M.S.; Joels, M.; Fernandez, G.S.E.

    2015-01-01

    Two research lines argue for rapid stress-induced reallocations of neural network activity involving the amygdala. One focuses on the role of norepinephrine (NE) in mediating a shift towards the salience network and improving vigilance processing, whereas the other focuses on the role of cortisol in

  11. Post-Acquisition Release of Glutamate and Norepinephrine in the Amygdala Is Involved in Taste-Aversion Memory Consolidation

    Science.gov (United States)

    Guzman-Ramos, Kioko; Osorio-Gomez, Daniel; Moreno-Castilla, Perla; Bermudez-Rattoni, Federico

    2012-01-01

    Amygdala activity mediates the acquisition and consolidation of emotional experiences; we have recently shown that post-acquisition reactivation of this structure is necessary for the long-term storage of conditioned taste aversion (CTA). However, the specific neurotransmitters involved in such reactivation are not known. The aim of the present…

  12. Amygdala regulates risk of predation in rats foraging in a dynamic fear environment.

    Science.gov (United States)

    Choi, June-Seek; Kim, Jeansok J

    2010-12-14

    In a natural environment, foragers constantly face the risk of encountering predators. Fear is a defensive mechanism evolved to protect animals from danger by balancing the animals' needs for primary resources with the risk of predation, and the amygdala is implicated in mediating fear responses. However, the functions of fear and amygdala in foraging behavior are not well characterized because of the technical difficulty in quantifying prey-predator interaction with real (unpredictable) predators. Thus, the present study investigated the rat's foraging behavior in a seminaturalistic environment when confronted with a predator-like robot programmed to surge toward the animal seeking food. Rats initially fled into the nest and froze (demonstrating fear) and then cautiously approached and seized the food as a function of decreasing nest-food and increasing food-robot distances. The likelihood of procuring food increased and decreased via lesioning/inactivating and disinhibiting the amygdala, respectively. These results indicate that the amygdala bidirectionally regulates risk behavior in rats foraging in a dynamic fear environment.

  13. Changes on auditory physiology in response to the inactivation of amygdala nuclei in high anxiety rats expressing learned fear.

    Science.gov (United States)

    Nobre, Manoel Jorge

    2013-06-13

    The inferior colliculus (IC) is primarily involved in the processing of acoustic stimuli, including those emitted by prey and predators. The role of the central nucleus of the IC (CIC) in fear and anxiety has been suggested based on electrophysiological, behavioral and immunohistochemical studies. The reactivity of high-anxiety rats (HA) to diverse challenges is different from low-anxiety ones (LA). In humans and laboratory animals, pathological anxiety is often accompanied by heightened vigilance and alertness, hyperactivity of the amygdala (AM), and increased amplitude of the auditory evoked potentials (AEP) from the IC. This study aims to evaluate the influence of the inactivation of the central (CEA) and basolateral (BLA) nuclei of the amygdala, after local infusions of the full GABAA agonist muscimol (1nmol/0.2μl), on the AEP elicited in the CIC of rats tested under a learned fear state. Our results showed that both BLA and CEA inactivation change the expression of conditioned fear, in a paradigm using the context as the conditioned stimulus (CS). These changes are correlated to the innate anxiety levels of the animals. It is supposed that this shortcoming is in addition to the imbalance between the regulatory role of the top-down and bottom-up processes in the control of anxiety.

  14. Reversal of reduced parvalbumin neurons in hippocampus and amygdala of Angelman syndrome model mice by chronic treatment of fluoxetine.

    Science.gov (United States)

    Godavarthi, Swetha K; Sharma, Ankit; Jana, Nihar Ranjan

    2014-08-01

    Angelman syndrome (AS) is a neuropsychiatric disorder characterized by autism, intellectual disability and motor disturbances. The disease is primarily caused by the loss of function of maternally inherited UBE3A. Ube3a maternal-deficient mice recapitulates many essential feature of AS. These AS mice have been shown to be under chronic stress and exhibits anxiety-like behaviour because of defective glucocorticoid receptor signalling. Here, we demonstrate that chronic stress in these mice could lead to down-regulation of parvalbumin-positive interneurons in the hippocampus and basolateral amygdala from early post-natal days. Down-regulation of parvalbumin-positive interneurons number could be because of decrease in the expression of parvalbumin in these neurons. We also find that treatment with fluoxetine, a selective serotonin reuptake inhibitor, results in restoration of impaired glucocorticoid signalling, elevated serum corticosterone level, parvalbumin-positive interneurons and anxiety-like behaviours. Our findings suggest that impaired glucocorticod signalling in hippocampus and amygdala of AS mice is critical for the decrease in parvalbumin interneurons number, emergence of anxiety and other behavioural deficits and highlights the importance of fluoxetine in the recovery of these abnormalities.

  15. Optogenetic stimulation of lateral amygdala input to posterior piriform cortex modulates single-unit and ensemble odor processing

    Directory of Open Access Journals (Sweden)

    Benjamin eSadrian

    2015-12-01

    Full Text Available Olfactory information is synthesized within the olfactory cortex to provide not only an odor percept, but also a contextual significance that supports appropriate behavioral response to specific odor cues. The piriform cortex serves as a communication hub within this circuit by sharing reciprocal connectivity with higher processing regions, such as the lateral entorhinal cortex and amygdala. The functional significance of these descending inputs on piriform cortical processing of odorants is currently not well understood. We have employed optogenetic methods to selectively stimulate lateral and basolateral amygdala (BLA afferent fibers innervating the posterior piriform cortex (pPCX to quantify BLA modulation of pPCX odor-evoked activity. Single unit odor-evoked activity of anaesthetized BLA-infected animals was significantly modulated compared with control animal recordings, with individual cells displaying either enhancement or suppression of odor-driven spiking. In addition, BLA activation induced a decorrelation of odor-evoked pPCX ensemble activity relative to odor alone. Together these results indicate a modulatory role in pPCX odor processing for the BLA complex, which could contribute to learned changes in PCX activity following associative conditioning.

  16. Optogenetic Stimulation of Lateral Amygdala Input to Posterior Piriform Cortex Modulates Single-Unit and Ensemble Odor Processing.

    Science.gov (United States)

    Sadrian, Benjamin; Wilson, Donald A

    2015-01-01

    Olfactory information is synthesized within the olfactory cortex to provide not only an odor percept, but also a contextual significance that supports appropriate behavioral response to specific odor cues. The piriform cortex serves as a communication hub within this circuit by sharing reciprocal connectivity with higher processing regions, such as the lateral entorhinal cortex and amygdala. The functional significance of these descending inputs on piriform cortical processing of odorants is currently not well understood. We have employed optogenetic methods to selectively stimulate lateral and basolateral amygdala (BLA) afferent fibers innervating the posterior piriform cortex (pPCX) to quantify BLA modulation of pPCX odor-evoked activity. Single unit odor-evoked activity of anesthetized BLA-infected animals was significantly modulated compared with control animal recordings, with individual cells displaying either enhancement or suppression of odor-driven spiking. In addition, BLA activation induced a decorrelation of odor-evoked pPCX ensemble activity relative to odor alone. Together these results indicate a modulatory role in pPCX odor processing for the BLA complex. This interaction could contribute to learned changes in PCX activity following associative conditioning, as well as support alternate patterns of odor processing that are state-dependent.

  17. Combined sub-threshold dosages of phenobarbital and low-frequency stimulation effectively reduce seizures in amygdala-kindled rats.

    Science.gov (United States)

    Asgari, Azam; Semnanian, Saeed; Atapour, Nafiseh; Shojaei, Amir; Moradi, Homeira; Mirnajafi-Zadeh, Javad

    2014-08-01

    Low-frequency stimulation (LFS) is a potential therapy utilized in patients who do not achieve satisfactory control of seizures with pharmacological treatments. Here, we investigated the interaction between anticonvulsant effects of LFS and phenobarbital (a commonly used medicine) on amygdala-kindled seizures in rats. Animals were kindled by electrical stimulation of basolateral amygdala in a rapid manner (12 stimulations/day). Fully kindled animals randomly received one of the three treatment choices: phenobarbital (1, 2, 3, 4 and 8 mg/kg; i.p.; 30 min before kindling stimulation), LFS (one or 4 packages contained 100 or 200 monophasic square wave pulses, 0.1-ms pulse duration at 1 Hz, immediately before kindling stimulation) or a combination of both (phenobarbital at 3 mg/kg and LFS). Phenobarbital alone at the doses of 1, 2 and 3 mg/kg had no significant effect on the main seizure parameters. LFS application always produced anticonvulsant effects unless applied with the pattern of one package of 100 pulses, which is considered as non-effective. All the seizure parameters were significantly reduced when phenobarbital (3 mg/kg) was administered prior to the application of the non-effective pattern of LFS. Phenobarbital (3 mg/kg) also increased the anticonvulsant actions of the effective LFS pattern. Our results provide an evidence of a positive cumulative anticonvulsant effect of LFS and phenobarbital, suggesting a potential combination therapy at sub-threshold dosages of phenobarbital and LFS to achieve a satisfactory clinical effect.

  18. The central amygdala nucleus is critical for incubation of methamphetamine craving.

    Science.gov (United States)

    Li, Xuan; Zeric, Tamara; Kambhampati, Sarita; Bossert, Jennifer M; Shaham, Yavin

    2015-04-01

    Cue-induced methamphetamine seeking progressively increases after withdrawal but mechanisms underlying this 'incubation of methamphetamine craving' are unknown. Here we studied the role of central amygdala (CeA), ventral medial prefrontal cortex (vmPFC), and orbitofrontal cortex (OFC), brain regions implicated in incubation of cocaine and heroin craving, in incubation of methamphetamine craving. We also assessed the role of basolateral amygdala (BLA) and dorsal medial prefrontal cortex (dmPFC). We trained rats to self-administer methamphetamine (10 days; 9 h/day, 0.1 mg/kg/infusion) and tested them for cue-induced methamphetamine seeking under extinction conditions during early (2 days) or late (4-5 weeks) withdrawal. We first confirmed that 'incubation of methamphetamine craving' occurs under our experimental conditions. Next, we assessed the effect of reversible inactivation of CeA or BLA by GABAA+GABAB receptor agonists (muscimol+baclofen, 0.03+0.3 nmol) on cue-induced methamphetamine seeking during early and late withdrawal. We also assessed the effect of muscimol+baclofen reversible inactivation of vmPFC, dmPFC, and OFC on 'incubated' cue-induced methamphetamine seeking during late withdrawal. Lever presses in the cue-induced methamphetamine extinction tests were higher during late withdrawal than during early withdrawal (incubation of methamphetamine craving). Muscimol+baclofen injections into CeA but not BLA decreased cue-induced methamphetamine seeking during late but not early withdrawal. Muscimol+baclofen injections into dmPFC, vmPFC, or OFC during late withdrawal had no effect on incubated cue-induced methamphetamine seeking. Together with previous studies, results indicate that the CeA has a critical role in incubation of both drug and non-drug reward craving and demonstrate an unexpected dissociation in mechanisms of incubation of methamphetamine vs cocaine craving.

  19. Interplay between serotonin and cannabinoid function in the amygdala in fear conditioning.

    Science.gov (United States)

    Nasehi, Mohammad; Davoudi, Kamelia; Ebrahimi-Ghiri, Mohaddeseh; Zarrindast, Mohammad-Reza

    2016-04-01

    The possible interactions between the cannabinoid and serotonin systems in the regions of the brain involved in emotional learning and memory formation have been studied by some researchers. In view of the key role of the amygdala in the acquisition and expression of fear memory, we investigated the involvement of basolateral amygdala (BLA) serotonin 5-HT4 receptors in arachidonylcyclopropylamide (ACPA; selective CB1 cannabinoid receptor agonist)-induced fear memory consolidation impairment. In our study, a context and tone fear conditioning apparatus was used for testing fear conditioning in adult male NMRI mice. The results showed that intraperitoneal administration of ACPA 0.5 or 0.05, 0.1 and 0.5mg/kg immediately after training decreased the percentage of freezing time in context or tone fear conditioning respectively, suggesting a context- or tone-dependent fear memory consolidation impairment. Post-training intra-BLA microinjections of RS67333, as 5-HT4 serotonin receptor agonist, at doses of 0.025 and 0.05 µg/mouse also impaired context or tone memory consolidation, while RS23597, as 5-HT4 serotonin receptor antagonist, did not produce a marked difference in both fear memories as compared with the control group. Moreover, a subthreshold dose of RS67333 did not alter ACPA response in both fear conditionings. Interestingly, a subthreshold dose of RS23597 potentiated or reversed ACPA response at the dose of 0.01 or 0.05 respectively. It is concluded that BLA serotonin 5-HT4 receptors are involved in tone-dependent fear memory consolidation impairment induced by CB1 activation using ACPA, suggesting a modulatory role for serotonin 5-HT4 receptor.

  20. Differential efferent projections of the anterior, posteroventral and posterodorsal subdivisions of the medial amygdala in mice

    Directory of Open Access Journals (Sweden)

    Cecília ePardo-Bellver

    2012-08-01

    Full Text Available The medial amygdaloid nucleus (Me is a key structure in the control of sociosexual behaviour in mice. It receives direct projections from the main and accessory olfactory bulbs, as well as an important hormonal input. To better understand its behavioural role, in this work we investigate the structures receiving information from the Me, by analysing the efferent projections from its anterior (MeA, posterodorsal (MePD and posteroventral (MePV subdivisions, using anterograde neuronal tracing with biotinylated and tetrametylrhodamine-conjugated dextranamines.The Me is strongly interconnected with the rest of the chemosensory amygdala, but shows only moderate projections to the central nucleus and light projections to the associative nuclei of the basolateral amygdaloid complex. In addition, the MeA originates a strong feedback projection to the deep mitral cell layer of the accessory olfactory bulb, whereas the MePV projects to its granule cell layer. The medial amygdaloid nucleus (especially the MeA has also moderate projections to different olfactory structures, including the piriform cortex. The densest outputs of the Me target the bed nucleus of the stria terminalis (BST and the hypothalamus. The MeA and MePV project to key structures of the circuit involved in the defensive response against predators (medial posterointermediate BST, anterior hypothalamic area, dorsomedial aspect of the ventromedial hypothalamic nucleus, although less dense projections also innervate reproductive-related nuclei. In contrast, the MePD projects mainly to structures that control reproductive behaviours (medial posteromedial BST, medial preoptic nucleus, and ventrolateral aspect of the ventromedial hypothalamic nucleus, although less dense projections to defensive-related nuclei also exist. These results confirm and extend previous results in other rodents and suggest that the medial amygdala is anatomically and functionally compartmentalized.

  1. Monoarthritis-induced emotional and cognitive impairments in rats are sensitive to low systemic doses or intra-amygdala injections of morphine.

    Science.gov (United States)

    Grégoire, Stéphanie; Wattiez, Anne-Sophie; Etienne, Monique; Marchand, Fabien; Ardid, Denis

    2014-07-15

    Chronic pain is a multidimensional experience that not only includes changes in nociception but also impairments in emotional and cognitive functions, not often taken into account in preclinical research. The present study investigated emotional and cognitive impairments in an animal model of persistent inflammatory pain as well as the involvement of the basolateral complex (BLC) of the amygdala in these components. Monoarthritis was induced by intra-articular injection of complete Freund׳s adjuvant. Mechanical hypersensitivity, anxiety and depressive-like behaviours as well as cognitive capacities were assessed using several tests, such as von Frey, social interaction, open field, saccharin preference, spatial and social recognition memory tests. The effects of morphine administered systemically or into the BLC of the amygdala were also studied. Monoarthritic rats exhibited mechanical hypersensitivity, anxiety and depressive-like behaviours as well as cognitive impairments. Whereas low systemic doses and intra-BLC infusion of morphine failed to reduce mechanical hypersensitivity, they reversed monoarthritis-induced anxiety-like behaviours and cognitive impairments. Our findings further support a crucial role of amygdala in the effect of morphine on emotional/cognitive components of pain and not on mechanical hypersensitivity. Finally, our study highlights the interest of a multi-behavioural approach in the assessment of pain and the analgesic effect of drugs.

  2. Characterization of basolateral chloride/bicarbonate exchange in macula densa cells.

    Science.gov (United States)

    Komlosi, Peter; Frische, Sebastian; Fuson, Amanda L; Fintha, Attila; Zsembery, Akos; Peti-Peterdi, Janos; Bell, P Darwin

    2005-02-01

    Functional and immunohistological studies were performed to identify basolateral chloride/bicarbonate exchange in macula densa cells. Using the isolated, perfused thick ascending limb with attached glomerulus preparation dissected from rabbit kidney, macula densa intracellular pH (pH(i)) was measured with fluorescence microscopy and BCECF. For these experiments, basolateral chloride was reduced, resulting in reversible macula densa cell alkalinization. Anion exchange activity was assessed by measuring the maximal net base efflux on readdition of bath chloride. Anion exchange activity required the presence of bicarbonate, was independent of changes in membrane potential, did not require the presence of sodium, and was inhibited by high concentrations of DIDS. Inhibition of macula densa anion exchange activity by basolateral DIDS increased luminal NaCl concentration-induced elevations in pH(i). Immunohistochemical studies using antibodies against AE2 demonstrated expression of AE2 along the basolateral membrane of macula densa cells of rabbit kidney. These results suggest that macula densa cells functionally and immunologically express a chloride/bicarbonate exchanger at the basolateral membrane. This transporter likely participates in the regulation of pH(i) and might be involved in macula densa signaling.

  3. Basolateral sorting and transcytosis define the Cu+-regulated translocation of ATP7B to the bile canaliculus.

    Science.gov (United States)

    Lalioti, Vasiliki; Peiró, Ramón; Pérez-Berlanga, Manuela; Tsuchiya, Yo; Muñoz, Angeles; Villalba, Teresa; Sanchez, Carlos; Sandoval, Ignacio V

    2016-06-01

    The Cu(+) pump ATP7B plays an irreplaceable role in the elimination of excess Cu(+) by the hepatocyte into the bile. The trafficking and site of action of ATP7B are subjects of controversy. One current proposal is that an increase in intracellular Cu(+) results in the translocation of ATP7B to the lysosomes and excretion of excess Cu(+) through lysosomal-mediated exocytosis at the bile canaliculus. Here, we show that ATP7B is transported from the trans-Golgi network (TGN) to the bile canaliculus by basolateral sorting and endocytosis, and microtubule-mediated transcytosis through the subapical compartment. Trafficking ATP7B is not incorporated into lysosomes, and addition of Cu(+) does not cause relocalization of lysosomes and the appearance of lysosome markers in the bile canaliculus. Our data reveal the pathway of the Cu(+)-mediated transport of ATP7B from the TGN to the bile canaliculus and indicates that the bile canaliculus is the primary site of ATP7B action in the elimination of excess Cu(.)

  4. Hemodynamic responses in amygdala and hippocampus distinguish between aversive and neutral cues during Pavlovian fear conditioning in behaving rats.

    Science.gov (United States)

    McHugh, Stephen B; Marques-Smith, Andre; Li, Jennifer; Rawlins, J N P; Lowry, John; Conway, Michael; Gilmour, Gary; Tricklebank, Mark; Bannerman, David M

    2013-02-01

    Lesion and electrophysiological studies in rodents have identified the amygdala and hippocampus (HPC) as key structures for Pavlovian fear conditioning, but human functional neuroimaging studies have not consistently found activation of these structures. This could be because hemodynamic responses cannot detect the sparse neuronal activity proposed to underlie conditioned fear. Alternatively, differences in experimental design or fear levels could account for the discrepant findings between rodents and humans. To help distinguish between these alternatives, we used tissue oxygen amperometry to record hemodynamic responses from the basolateral amygdala (BLA), dorsal HPC (dHPC) and ventral HPC (vHPC) in freely-moving rats during the acquisition and extinction of conditioned fear. To enable specific comparison with human studies we used a discriminative paradigm, with one auditory cue [conditioned stimulus (CS)+] that was always followed by footshock, and another auditory cue (CS-) that was never followed by footshock. BLA tissue oxygen signals were significantly higher during CS+ than CS- trials during training and early extinction. In contrast, they were lower during CS+ than CS- trials by the end of extinction. dHPC and vHPC tissue oxygen signals were significantly lower during CS+ than CS- trials throughout extinction. Thus, hemodynamic signals in the amygdala and HPC can detect the different patterns of neuronal activity evoked by threatening vs. neutral stimuli during fear conditioning. Discrepant neuroimaging findings may be due to differences in experimental design and/or fear levels evoked in participants. Our methodology offers a way to improve translation between rodent models and human neuroimaging.

  5. Central noradrenergic lesion induced by DSP-4 impairs the acquisition of avoidance reactions and prevents molecular changes in the amygdala.

    Science.gov (United States)

    Radwanska, Kasia; Nikolaev, Evgenij; Kaczmarek, Leszek

    2010-10-01

    The noradrenergic system plays and an important modulatory role in memory consolidation of emotionally arousing tasks. However, the molecular cascades regulated in the brain by norepinephrine and involved in memory formation are still largely unknown. The purpose of the present study was to evaluate the role of the noradrenergic system on the acquisition of a highly emotionally arousing task-two-way active avoidance training-and its molecular and cellular substrates. The selective norepinephrine neurotoxin N-(2-chloroethyl)-N-ethyl-2 bromobenzylamine (DSP-4, 50mg/kg) was used. DSP-4-treated rats were trained in a shuttle box to avoid a footshock signaled by an auditory stimulus. Immunohistochemical mapping of the neuronal plasticity-related molecules c-Fos protein and the activated form of extracellular signal-regulated kinase (phosphorylated ERK [pERK]) was then employed. We found that DSP-4 treatment depleted the expression of the norepinephrine marker dopamine -hydroxylase (DBH) in the locus coeruleus and its projection area, the basolateral nucleus of the amygdala, confirming locus coeruleus noradrenergic lesion in the experimental animals. Furthermore, DSP-4 treatment impaired the acquisition of the avoidance reaction. We also found that acquisition of the active avoidance reaction induced c-Fos expression and ERK activation in the amygdala and piriform cortex. This upregulation was prevented by DSP-4 treatment. Thus, our data suggest that the noradrenergic system is involved in the acquisition of the active avoidance reaction by regulating ERK pathway activity and c-Fos expression in the amygdala and piriform cortex.

  6. The Emotional Gatekeeper: A Computational Model of Attentional Selection and Suppression through the Pathway from the Amygdala to the Inhibitory Thalamic Reticular Nucleus.

    Directory of Open Access Journals (Sweden)

    Yohan J John

    2016-02-01

    Full Text Available In a complex environment that contains both opportunities and threats, it is important for an organism to flexibly direct attention based on current events and prior plans. The amygdala, the hub of the brain's emotional system, is involved in forming and signaling affective associations between stimuli and their consequences. The inhibitory thalamic reticular nucleus (TRN is a hub of the attentional system that gates thalamo-cortical signaling. In the primate brain, a recently discovered pathway from the amygdala sends robust projections to TRN. Here we used computational modeling to demonstrate how the amygdala-TRN pathway, embedded in a wider neural circuit, can mediate selective attention guided by emotions. Our Emotional Gatekeeper model demonstrates how this circuit enables focused top-down, and flexible bottom-up, allocation of attention. The model suggests that the amygdala-TRN projection can serve as a unique mechanism for emotion-guided selection of signals sent to cortex for further processing. This inhibitory selection mechanism can mediate a powerful affective 'framing' effect that may lead to biased decision-making in highly charged emotional situations. The model also supports the idea that the amygdala can serve as a relevance detection system. Further, the model demonstrates how abnormal top-down drive and dysregulated local inhibition in the amygdala and in the cortex can contribute to the attentional symptoms that accompany several neuropsychiatric disorders.

  7. The Emotional Gatekeeper: A Computational Model of Attentional Selection and Suppression through the Pathway from the Amygdala to the Inhibitory Thalamic Reticular Nucleus.

    Science.gov (United States)

    John, Yohan J; Zikopoulos, Basilis; Bullock, Daniel; Barbas, Helen

    2016-02-01

    In a complex environment that contains both opportunities and threats, it is important for an organism to flexibly direct attention based on current events and prior plans. The amygdala, the hub of the brain's emotional system, is involved in forming and signaling affective associations between stimuli and their consequences. The inhibitory thalamic reticular nucleus (TRN) is a hub of the attentional system that gates thalamo-cortical signaling. In the primate brain, a recently discovered pathway from the amygdala sends robust projections to TRN. Here we used computational modeling to demonstrate how the amygdala-TRN pathway, embedded in a wider neural circuit, can mediate selective attention guided by emotions. Our Emotional Gatekeeper model demonstrates how this circuit enables focused top-down, and flexible bottom-up, allocation of attention. The model suggests that the amygdala-TRN projection can serve as a unique mechanism for emotion-guided selection of signals sent to cortex for further processing. This inhibitory selection mechanism can mediate a powerful affective 'framing' effect that may lead to biased decision-making in highly charged emotional situations. The model also supports the idea that the amygdala can serve as a relevance detection system. Further, the model demonstrates how abnormal top-down drive and dysregulated local inhibition in the amygdala and in the cortex can contribute to the attentional symptoms that accompany several neuropsychiatric disorders.

  8. Divergent effects of amygdala glucocorticoid and mineralocorticoid receptors in the regulation of visceral and somatic pain.

    Science.gov (United States)

    Myers, Brent; Greenwood-Van Meerveld, Beverley

    2010-02-01

    Elevated amygdala activity and increased responsiveness of the hypothalamic-pituitary-adrenal axis have been observed in irritable bowel syndrome (IBS) patients. Recently, we demonstrated that corticosterone (Cort) placed on the amygdala induced anxiety-like behavior coupled with decreased thresholds for visceral and somatic pain in rats. Moreover, these studies suggested that the effects of Cort were dependent on both the glucocorticoid receptor (GR) and mineralocorticoid receptor (MR); however, the specific contributions of these receptors to the interaction between corticosteroids and the amygdala are still unclear. In the present study, we sought to define the distinct roles of amygdaloid GR and MR in anxiety-like behavior, visceral sensitivity, and somatic sensitivity through selective pharmacological activation. Male Fischer 344 rats received bilateral implants on the dorsal margin of the central amygdala containing the GR agonist dexamethasone (Dex), the MR agonist aldosterone (Aldo), or cholesterol as a control. Our results showed that GR or MR activation significantly reduced open arm exploration on the elevated plus maze, a measure of anxiety-like behavior. Aldo increased the number of abdominal muscle contractions in response to all levels of colorectal distension (CRD). In contrast, Dex only increased visceral sensitivity at noxious levels of CRD. Furthermore, GR but not MR activation reduced somatic pain thresholds measured by the mechanical force required to elicit hindlimb withdrawal. In summary, GR and MR mediated-mechanisms induce anxiety and visceral hypersensitivity, whereas somatic sensitivity involves only GR, suggesting that corticosteroids may enhance visceral and somatic sensation via divergent processes originating in the amygdala and involving specific steroid receptor mechanisms.

  9. Amygdala kindling disrupts trace and delay fear conditioning with parallel changes in Fos protein expression throughout the limbic brain.

    Science.gov (United States)

    Botterill, J J; Fournier, N M; Guskjolen, A J; Lussier, A L; Marks, W N; Kalynchuk, L E

    2014-04-18

    Amygdala kindling is well known to increase unconditioned fear and anxiety. However, relatively little is known about whether this form of kindling causes functional changes within the neural circuitry that mediates fear learning and the retrieval of fear memories. To address this issue, we examined the effect of short- (i.e., 30 stimulations) and long-term (i.e., 99 stimulations) amygdala kindling in rats on trace and delay fear conditioning, which are aversive learning tasks that rely predominantly on the hippocampus and amygdala, respectively. After memory retrieval, we analyzed the pattern of neural activity with Fos, the protein product of the immediate early gene c-fos. We found that kindling had no effect on acquisition of the trace fear conditioning task but it did selectively impair retrieval of this fear memory. In contrast, kindling disrupted both acquisition and retrieval of fear memory in the delay fear conditioning task. We also found that kindling-induced impairments in memory retrieval were accompanied by decreased Fos expression in several subregions of the hippocampus, parahippocampus, and amygdala. Interestingly, decreased freezing in the trace conditioning task was significantly correlated with dampened Fos expression in hippocampal and parahippocampal regions whereas decreased freezing in the delay conditioning task was significantly correlated with dampened Fos expression in hippocampal, parahippocampal, and amygdaloid circuits. Overall, these results suggest that amygdala kindling promotes functional changes in brain regions involved in specific types of fear learning and memory.

  10. Stimulation site determines the conditioned effects of kindling in rats: anterior neocortex versus amygdala.

    Science.gov (United States)

    Barnes, Steven J; Pinel, John P J; Wig, Gagan S; Stuettgen, Maik C; Hölzel, C Heike

    2003-04-01

    Rats received 53 stimulations to either the left basolateral amygdala (BA) or left anterior neocortex (AN) in one environment (CS+) and 53 sham stimulations (the stimulation lead was attached but no current was delivered) in another environment (CS-), quasirandomly over 54 days. Confirming a previous report [Barnes, S.J., Pinel, J.P., Francis, L.H. & Wig, G.S. (2001) Behav. Neurosci., 115, 1065-1072], as BA kindling progressed, the CS+ began to elicit more defensive behaviours (i.e. less activity, more freezing and avoidance of the CS+) than the CS-, and at the end of the experiment, convulsions elicited in the CS+ were more severe than those elicited in the CS-. Like BA kindling, AN kindling led to less activity in the CS+; but unlike BA kindling, AN kindling led to more wet-dog-shakes and less, rather than more, severe convulsions in the CS+. During AN kindling, the mean number of wet-dog-shakes in the CS+ was negatively correlated with the mean convulsion class, suggesting that wet-dog-shakes contribute to the inherent variability of AN kindling. These findings confirm that inherent conditioned effects influence kindled convulsions and interictal behaviour and establish for the first time that the pattern of these conditioned effects is a function of the kindling site.

  11. Effect of topiramate on interleukin 6 expression in the hippocampus of amygdala-kindled epileptic rats

    Science.gov (United States)

    YE, FEI; CHEN, XU-QIN; BAO, GUAN-SHUI; HUA, YIN; WANG, ZHE-DONG; BAO, YI-CHUAN

    2014-01-01

    The objective of this study was to analyze the changes in expression and the possible functions of interleukin-6 (IL-6) in electrical kindling of the basolateral amygdala (BLA) in epileptic rats. Bipolar electrodes were implanted into the BLA of Sprague-Dawley rats, and the rats were then subjected to chronic electrical stimulation through the electrodes to induce kindling. The seizure characteristics and behavioral changes of the rats were observed, and electroencephalograms were recorded during and following kindling. The IL-6 mRNA expression in the hippocampi of the rats was analyzed using semi-quantitative reverse transcription-polymerase chain reaction, and control and topiramate (TPM)-treated groups were compared. The mean time-period required for kindling was 13.50±3.99 days, and the afterdischarge duration (ADD) measured between 21,450 and 119,720 msec. The expression of IL-6 mRNA was significantly upregulated in the kindled rats. TPM was able to depress the seizures and decrease the IL-6 level in the kindled rats. In conclusion, IL-6 mRNA was upregulated in the hippocampi of epileptic rats, and IL-6 may have participated in the process of kindling. PMID:24348794

  12. Role of the hippocampus and amygdala in the extinction of fear-motivated learning.

    Science.gov (United States)

    Vianna, Monica R; Coitinho, Adriana S; Izquierdo, Ivan

    2004-01-01

    Fear-motivated learning is at the root of phobias, panic, generalized anxiety and the posttraumatic stress disorder. This makes the inhibition of fear-motivated behavior a therapeutic desideratum in these diseases. The simplest way to accomplish this is by extinction, a procedure by which a given association between a conditioned stimulus or context (CS) and a fearsome event is replaced by a new association between the CS and the lack of the fearsome stimulus. This is a new learning for the subject and, in rats, it requires gene expression and protein synthesis both in the hippocampus and the basolateral amygdala, alongside with the activation of various metabolic signaling pathways. These requirements are similar to, but not identical with those for consolidation of the original memory. In addition, some systems uninvolved in original consolidation appear to be involved in extinction, namely, the endocannabinoid system. Extinction can be enhanced by prolonging the exposure to the lack of fearsome stimulation; e.g., in rats, by increasing the time of permanence in the compartment where the animals no longer receive a footshock. Further research into the possibilities of enhancing extinction at the expense of the original fearsome learning is desirable.

  13. A Developmental Examination of Amygdala Response to Facial Expressions

    Science.gov (United States)

    Guyer, Amanda E.; Monk, Christopher S.; McClure-Tone, Erin B.; Nelson, Eric E.; Roberson-Nay, Roxann; Adler, Abby D.; Fromm, Stephen J.; Leibenluft, Ellen; Pine, Daniel S.; Ernst, Monique

    2010-01-01

    Several lines of evidence implicate the amygdala in face– emotion processing, particularly for fearful facial expressions. Related findings suggest that face–emotion processing engages the amygdala within an interconnected circuitry that can be studied using a functional-connectivity approach. Past work also underscores important functional changes in the amygdala during development. Taken together, prior research on amygdala function and development reveals a need for more work examining developmental changes in the amygdala’s response to fearful faces and in amygdala functional connectivity during face processing. The present study used event-related functional magnetic resonance imaging to compare 31 adolescents (9–17 years old) and 30 adults (21–40 years old) on activation to fearful faces in the amygdala and other regions implicated in face processing. Moreover, these data were used to compare patterns of amygdala functional connectivity in adolescents and adults. During passive viewing, adolescents demonstrated greater amygdala and fusiform activation to fearful faces than did adults. Functional connectivity analysis revealed stronger connectivity between the amygdala and the hippocampus in adults than in adolescents. Within each group, variability in age did not correlate with amygdala response, and sex-related developmental differences in amygdala response were not found. Eye movement data collected outside of the magnetic resonance imaging scanner using the same task suggested that developmental differences in amygdala activation were not attributable to differences in eye-gaze patterns. Amygdala hyperactivation in response to fearful faces may explain increased vulnerability to affective disorders in adolescence; stronger amygdala–hippocampus connectivity in adults than adolescents may reflect maturation in learning or habituation to facial expressions. PMID:18345988

  14. Iron repletion relocalizes hephaestin to a proximal basolateral compartment in polarized MDCK and Caco2 cells

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Seung-Min [Department of Biological Sciences, University of Columbia, NY (United States); Department of Nutritional Science and Toxicology, University of California, Berkeley, CA (United States); Attieh, Zouhair K. [Department of Laboratory Science and Technology, American University of Science and Technology, Ashrafieh (Lebanon); Department of Nutritional Science and Toxicology, University of California, Berkeley, CA (United States); Son, Hee Sook [Department of Food Science and Human Nutrition, College of Human Ecology, Chonbuk National University (Korea, Republic of); Department of Nutritional Science and Toxicology, University of California, Berkeley, CA (United States); Chen, Huijun [Medical School, Nanjing University, Nanjing 210008, Jiangsu Province (China); Department of Nutritional Science and Toxicology, University of California, Berkeley, CA (United States); Bacouri-Haidar, Mhenia [Department of Biology, Faculty of Sciences (I), Lebanese University, Hadath (Lebanon); Department of Nutritional Science and Toxicology, University of California, Berkeley, CA (United States); Vulpe, Chris D., E-mail: vulpe@berkeley.edu [Department of Nutritional Science and Toxicology, University of California, Berkeley, CA (United States)

    2012-05-11

    Highlights: Black-Right-Pointing-Pointer Hephaestin localizes in the perinuclear space in non-polarized cells. Black-Right-Pointing-Pointer Hephaestin localizes in the perinuclear space in iron deficient and polarized cells. Black-Right-Pointing-Pointer Hephaestin with apical iron moves near to basolateral membrane of polarized cells. Black-Right-Pointing-Pointer Peri-basolateral location of hephaestin is accessible to the extracellular space. Black-Right-Pointing-Pointer Hephaestin is involved in iron mobilization from the intestine to circulation. -- Abstract: While intestinal cellular iron entry in vertebrates employs multiple routes including heme and non-heme routes, iron egress from these cells is exclusively channeled through the only known transporter, ferroportin. Reduced intestinal iron export in sex-linked anemia mice implicates hephaestin, a ferroxidase, in this process. Polarized cells are exposed to two distinct environments. Enterocytes contact the gut lumen via the apical surface of the cell, and through the basolateral surface, to the body. Previous studies indicate both local and systemic control of iron uptake. We hypothesized that differences in iron availability at the apical and/or basolateral surface may modulate iron uptake via cellular localization of hephaestin. We therefore characterized the localization of hephaestin in two models of polarized epithelial cell lines, MDCK and Caco2, with varying iron availability at the apical and basolateral surfaces. Our results indicate that hephaestin is expressed in a supra-nuclear compartment in non-polarized cells regardless of the iron status of the cells and in iron deficient and polarized cells. In polarized cells, we found that both apical (as FeSO{sub 4}) and basolateral iron (as the ratio of apo-transferrin to holo-transferrin) affect mobilization of hephaestin from the supra-nuclear compartment. We find that the presence of apical iron is essential for relocalization of hephaestin to a

  15. [Emotion, amygdala, and autonomic nervous system].

    Science.gov (United States)

    Ueyama, Takashi

    2012-10-01

    Emotion refers to the dynamic changes of feeling accompanied by the alteration of physical and visceral activities. Autonomic nervous system (sympathetic and parasympathetic) regulates the visceral activities. Therefore, monitoring and analyzing autonomic nervous activity help understand the emotional changes. To this end, the survey of the expression of immediate early genes (IEGs), such as c-Fos in the brain and target organs, and the viral transneuronal labeling method using the pseudorabies virus (PRV) have enabled the visualization of the neurocircuitry of emotion. By comparing c-Fos expression and data from PRV or other neuroanatomical labeling techniques, the central sites that regulate emotional stress-induced autonomic activation can be deduced. Such regions have been identified in the limbic system (e. g., the extended amygdaloid complex; lateral septum; and infralimbic, insular, and ventromedial temporal cortical regions), as well as in several hypothalamic and brainstem nuclei. The amygdala is structurally diverse and comprises several subnuclei, which play a role in emotional process via projections from the cortex and a variety of subcortical structures. All amygdaloid subnuclei receive psychological information from other limbic systems, while the lateral and central subnuclei receive peripheral and sensory information. Output to the hypothalamus and peripheral sympathetic system mainly originates from the medial amygdala. As estrogen receptor α, estrogen receptor β, and androgen receptor are expressed in the medial amygdala, sex steroids may modulate the autonomic nervous activities.

  16. Amygdala upregulation of NCAM polysialylation induced by auditory fear conditioning is not required for memory formation, but plays a role in fear extinction.

    Science.gov (United States)

    Markram, Kamila; Lopez Fernandez, Miguel Angel; Abrous, Djoher Nora; Sandi, Carmen

    2007-05-01

    There is much interest to understand the mechanisms leading to the establishment, maintenance, and extinction of fear memories. The amygdala has been critically involved in the processing of fear memories and a number of molecular changes have been implicated in this brain region in relation to fear learning. Although neural cell adhesion molecules (NCAMs) have been hypothesized to play a role, information available about their contribution to fear memories is scarce. We investigate here whether polysialylated NCAM (PSA-NCAM) contributes to auditory fear conditioning in the amygdala. First, PSA-NCAM expression was evaluated in different amygdala nuclei after auditory fear conditioning at two different shock intensities. Results showed that PSA-NCAM expression was increased 24 h post-training only in animals subjected to the highest shock intensity (1mA). Second, PSA-NCAM was cleaved in the basolateral amygdaloid complex through micro-infusions of the enzyme endoneuraminidase N, and the consequences of such treatment were investigated on the acquisition, consolidation, remote memory expression, and extinction of conditioned fear memories. Intra-amygdaloid cleavage of PSA-NCAM did not affect acquisition, consolidation or expression of remote fear memories. However, intra-amygdaloid PSA-NCAM cleavage enhanced fear extinction processes. These results suggest that upregulation of PSA-NCAM is a correlate of fear conditioning that is not necessary for the establishment of fear memory in the amygdala, but participates in mechanisms precluding fear extinction. These findings point out PSA-NCAM as a potential target for the treatment of psychopathologies that involve impairment in fear extinction.

  17. Dysfunctional amygdala activation and connectivity with the prefrontal cortex in current cocaine users

    NARCIS (Netherlands)

    Crunelle, C.L.; Kaag, A.M.; Munkhof, H.E. van den; Reneman, L.; Homberg, J.R.; Sabbe, B.; Brink, W. van den; Wingen, G. van

    2015-01-01

    OBJECTIVES: Stimulant use is associated with increased anxiety and a single administration of dexamphetamine increases amygdala activation to biologically salient stimuli in healthy individuals. Here, we investigate how current cocaine use affects amygdala activity and amygdala connectivity with the

  18. FAST and SLOW amygdala kindling rat strains: comparison of amygdala, hippocampal, piriform and perirhinal cortex kindling.

    Science.gov (United States)

    McIntyre, D C; Kelly, M E; Dufresne, C

    1999-07-01

    In our companion paper, we selectively bred offspring of a Long Evans Hooded and Wistar rat cross for either fast or slow rates of amygdala kindling (Racine et al., 1999. Development of kindling-prone and kindling resistant rats: Selective breeding and electrophysiological studies, Epilepsy Res. 35, 183-195). Within 10 generations, there was no overlap in the distribution of kindling rates between these newly developed FAST and SLOW kindling strains. In the present report, we compared the local excitability, kindling rates, and convulsion profiles of kindling sites in either the amygdala, dorsal hippocampus, piriform cortex or perirhinal cortex in the two strains. Local excitability, measured as the local afterdischarge (AD) threshold and its duration, showed varied effects between structures and strains. Before kindling, the AD threshold was lower in the FAST than the SLOW rats in the hippocampus, piriform and perirhinal cortices, but not the amygdala (the selection structure). Also, the duration of the AD threshold duration was significantly longer in the FAST than in the SLOW rats in all structures, except the CA1 hippocampus. Most of these differences were maintained after kindling. Kindling itself was significantly faster in the FAST compared with the SLOW rats in all structures; however, the different structural kindling rates showed proportional differences between strains that were about five times different in the amygdala compared with only about two times different in the hippocampus. This suggested a selection bias for the amygdala and its networks. As in other rat strains, the fastest kindling rates were seen in the perirhinal cortex followed by the piriform cortex, amygdala and hippocampus in both FAST and SLOW rats. Other important differences between strains and structures occurred in the stage-5 convulsion profiles, including latency to forelimb clonus, clonus duration and duration of associated local afterdischarges. The differences in kindling

  19. Surface morphology of amygdala is associated with trait anxiety.

    Directory of Open Access Journals (Sweden)

    Shuyu Li

    Full Text Available Previous neuroimaging studies have suggested a role of amygdala in trait anxiety level, in which amygdala was typically treated as a whole. To date, it remains unknown whether the morphology of specific subregions of amygdala are associated with trait anxiety. Here, we employed a shape analysis approach to locate the association between its morphology and trait anxiety on the surface of amygdala. 24 healthy young participants were included. The boundary of amygdala for each subject was first manually outlined using high-resolution magnetic resonance (MR image, followed by 3D surface reconstruction and parameterization using spherical harmonic description. Two point-wise metrics, direct displacement between the individual surface and atlas surface and its normal projection, were used to quantify the surface morphology of amygdala. Statistical analysis revealed significant correlations between the two surface metrics and trait anxiety levels, which were located around the lateral and central nucleus of right amygdala. Our results provided localized information for the association between amygdala and trait anxiety, and suggested a central role of the lateral and central nucleus of right amygdala on trait anxiety.

  20. Impact of family history and depression on amygdala volume.

    LENUS (Irish Health Repository)

    Saleh, Karim

    2012-07-30

    Family history of depression significantly impacts life-long depression risk. Family history could impact the stress and emotion regulation system that involves the amygdala. This study\\'s purpose was to investigate family history\\'s effect on amygdala volumes, and differences in first degree relatives with and without major depressive disorder (MDD). Participants, aged 18-65, were healthy volunteers (N=52) with (n=26) and without (n=26) first degree family history, and patients with MDD (N=48) with (n=27) and without (n=21)first-degree family history recruited for structural magnetic resonance imaging (MRI). Participants underwent clinical assessment followed by manual amygdala tracing. Patients with MDD without family history showed significantly larger right amygdala without a family history of MDD. These effects had larger right amygdala than healthy controls without MDD family history. These effects were pronounced in females. Family history and gender impacted amygdala volumes in all participants, providing a rationale for the inconsistent results in MDD amygdala studies. Higher familial risk in depression seems to be associated with smaller amygdala volumes, whereas depression alone is associated with larger amygdala volumes. Ultimately, these findings highlight consideration of family history and gender in research and treatment strategies.

  1. Impact of family history and depression on amygdala volume.

    Science.gov (United States)

    Saleh, Karim; Carballedo, Angela; Lisiecka, Danutia; Fagan, Andrew J; Connolly, Gerald; Boyle, Gerard; Frodl, Thomas

    2012-07-30

    Family history of depression significantly impacts life-long depression risk. Family history could impact the stress and emotion regulation system that involves the amygdala. This study's purpose was to investigate family history's effect on amygdala volumes, and differences in first degree relatives with and without major depressive disorder (MDD). Participants, aged 18-65, were healthy volunteers (N=52) with (n=26) and without (n=26) first degree family history, and patients with MDD (N=48) with (n=27) and without (n=21)first-degree family history recruited for structural magnetic resonance imaging (MRI). Participants underwent clinical assessment followed by manual amygdala tracing. Patients with MDD without family history showed significantly larger right amygdala compared to patients with a MDD family history.MDD without family history also had larger right amygdala than healthy controls without MDD family history.These effects were pronounced in females. Family history and gender impacted amygdala volumes in all participants providing rationale for the inconsistent results in MDD amygdala studies [corrected]. Higher familial risk in depression seems to be associated with smaller amygdala volumes, whereas depression alone is associated with larger amygdala volumes. Ultimately, these findings highlight consideration of family history and gender in research and treatment strategies.

  2. Transient elevation of amygdala alpha 2 adrenergic receptor binding sites during the early stages of amygdala kindling.

    Science.gov (United States)

    Chen, M J; Vigil, A; Savage, D D; Weiss, G K

    1990-03-01

    Enhanced noradrenergic neurotransmission retards but does not prevent the development of kindling. We previously reported that locus coeruleus (LC) alpha 2 adrenergic receptor binding sites are transiently elevated during the early stages of kindling development. Since the firing activity of LC noradrenergic neurons is partially regulated via an alpha 2 receptor-mediated recurrent inhibition, the transient elevation in LC alpha 2 receptors could decrease LC activity and consequently facilitate the development of kindling. Transient elevation of alpha 2 receptor binding sites during early stages of kindling may also occur on noradrenergic axon terminals projecting to forebrain sites. Using in vitro neurotransmitter autoradiography techniques, we investigated this hypothesis by measuring specific [3H]idazoxan binding in 5 different areas of rat forebrain at 2 different stages of kindling development. After 2 class 1 kindled seizures, specific [3H]idazoxan binding was elevated significantly in the amygdala, but not in other forebrain regions. No differences in specific [3H]idazoxan binding were observed in any of the 5 brain regions in rats kindled to a single class 5 kindled motor seizure. Saturation of binding experiments indicated that the increase in amygdala [3H]idazoxan binding, following 2 class 1 kindled motor seizures, was due to an increase in the total number of alpha 2 receptor binding sites without a change in the affinity of the binding sites for [3H]idazoxan. Thus, the transient increase in alpha 2 receptors that occurs in the LC in the early stages of kindling also occurs in the forebrain region in which the kindled seizure originates.

  3. Inhibitory effect of ketamine on lighting amygdala of rats

    Institute of Scientific and Technical Information of China (English)

    Jiguo Zhang; Bin Yang; Jing Zhang; Feng Zhang; Wang Yue

    2006-01-01

    BACKGROUND: Ketamine is a noncompetitive antagonist of N-methyl-D-aspartic acid receptor. Some researchers suggest that N-methyl-D-aspartic acid (NMDA) receptor is closely related to epileptic attack.OBJECTIVE: To observe inhibitory effect of ketamine on lighting amygdala of rats and analyze pathway of anti-lighting.DESIGN: Randomized controlled animal study.SETTING: Department of Pharmacology and Department of Management, Pharmacological College of Taishan Medical College; Department of Pharmacology, Medical College of Qingdao University.MATERIALS: Sixty adult female Wistar rats, of clean grade, weighing 180-200 g, were provided by Animal Center of Qingdao Institute of Drug Control. Ketamine hydrochloride was provided by the First Pharmacological Factory of the First Biochemical Pharmacology Company of Shanghai, and nicardipine, an antagonist of calcium ions, was provided by Sigma Company.METHODS: The experiment was completed in the Department of Pharmacology, Medical College of Qingdao University from March to November 2004. ① Model establishing: After anesthesia, left and right amygdalas were inserted with double electrodes. The top was separated about 0.25 mm, and the other end was welded with a micro-plug, respectively. Electrode and micro-plug were fixed with dental base acrylic resin powder at the surface of cranium. Two weeks after recovery, right amygdala was stimulated with constant current once a day. According to Racine technique, attacking intensity was divided into 5 grades: grade I:closing eyes, a little tingling of beards and twitching face; grade Ⅱ: nodding, chewing accompanying with twitching face; grade Ⅲ: raising one of a forelimb and clonus; grade Ⅳ: standing accompanying with bilateral forelimbs; grade Ⅴ: standing accompanying with falling down. Rats with grades Ⅳ and Ⅴ were used to establish secondarily generalized epilepsy. If 3 successive attacks of grade Ⅴ were observed, the lighting was to be successful. ② Effect of

  4. The role of technical, biological, and pharmacological factors in the laboratory evaluation of anticonvulsant drugs. V. Lack of seasonal influences on amygdala kindling in rats.

    Science.gov (United States)

    Wlaź, P; Löscher, W

    1993-10-01

    Previous studies have suggested that seizure models may be affected by seasonal rhythms, even under controlled environmental conditions. In the present experiments in rats with chronically implanted electrodes in the basolateral amygdala, kindling was initiated at different seasons of the year over a period of 3 years. In a total of 109 animals, the following parameters were determined: the threshold for induction of amygdaloid afterdischarges prior to kindling (pre-kindling ADT), the number of daily amygdaloid stimulations to fully kindled (stage 5) seizures, and the post-kindling ADT. No seasonal influences were found with respect to rate of kindling development and post-kindling ADT. In contrast, pre-kindling ADTs appeared to be higher in spring than in other seasons, which, however, could not be reproduced in another spring. Thus, the data do not indicate that seasonal rhythms affect the kindling model of epilepsy.

  5. Basolateral Cl- channels in the larval bullfrog skin epithelium

    DEFF Research Database (Denmark)

    Hillyard, Stanley D.; Rios, K.; Larsen, Erik Hviid

    2002-01-01

    The addition of 150 U/ml nystatin to the mucosal surface of isolated skin from larval bullfrogs increases apical membrane permeability and allows a voltage clamp to be applied to the basolateral membrane. With identical Ringer's solutions bathing either side of the tissue the short-circuit curren...

  6. Effects of corticotropin releasing factor on spontaneous burst activity in the piriform-amygdala complex of in vitro brain preparations from newborn rats.

    Science.gov (United States)

    Fujii, Tomoko; Onimaru, Hiroshi; Homma, Ikuo

    2011-10-01

    The amygdala is an important higher regulatory center of the autonomic nervous system, involved in respiratory and cardiovascular control, and it also plays a role in the formation of emotions. Corticotropin-releasing factor (CRF) is a neuropeptide involved in stress responses. We have examined the effects of CRF on the spontaneous burst activity in the piriform-amygdala complex of rat brain preparations in vitro. Limbic-brainstem-spinal cord preparations of 0- to 1-day-old Wistar rats were isolated under deep ether anesthesia, and were superperfused in a modified Krebs solution. Bath application of 50nM CRF substantially increased the frequency of burst activity in the piriform-amygdala complex, whereas this polypeptide exerted only minor effects on C4 inspiratory activity. The excitatory effect of CRF on the amygdala burst was effectively blocked by the CRF1 antagonist, antalarmin, but not the CRF2 antagonist, astressin-2B, suggesting that CRF1 mediated the excitatory effect. The spatio-temporal pattern of the burst activity according to optical recordings was basically identical to the controls; the burst activity initially appeared in the piriform cortex and then propagated to the amygdala. The present experimental model could be useful for the study of role of the limbic system, including the amygdala, in stress responses.

  7. Dendritic morphology changes in neurons from the ventral hippocampus, amygdala and nucleus accumbens in rats with neonatal lesions into the prefrontal cortex.

    Science.gov (United States)

    Lazcano, Zayda; Solis, Oscar; Díaz, Alfonso; Brambila, Eduardo; Aguilar-Alonso, Patricia; Guevara, Jorge; Flores, Gonzalo

    2015-06-01

    Neonatal prefrontal cortex (nPFC) lesions in rats could be a potential animal model to study the early neurodevelopmental abnormalities associated with the behavioral and morphological brain changes observed in schizophrenia. Morphological alterations in pyramidal neurons from the ventral hippocampus (VH) have been observed in post-mortem schizophrenic brains, mainly because of decreased dendritic arbor and spine density. We assessed the effects of nPFC-lesions on the dendritic morphology of neurons from the VH, basolateral-amygdala (BLA) and the nucleus accumbens (NAcc) in rats. nPFC lesions were made on postnatal day 7 (PD7), after dendritic morphology was studied by the Golgi-Cox stain procedure followed by Sholl analysis at PD35 (prepubertal) and PD60 (adult) ages. We also evaluated the effects of PFC-lesions on locomotor activity caused by a novel environment. Adult animals with nPFC lesions showed a decreased spine density in pyramidal neurons from the VH and in medium spiny cells from the NAcc. An increased locomotion was observed in a novel environment for adult animals with a PFC-lesion. Our results indicate that PFC-lesions alter the neuronal dendrite morphology of the NAcc and the VH, suggesting a disconnection between these limbic structures. The locomotion paradigms suggest that dopaminergic transmission is altered in the PFC lesion model. This could help to understand the consequences of an earlier PFC dysfunction in schizophrenia. To evaluate possible dendritic changes in neonatal prefrontal cortex lesions in schizophrenia-related regions including nucleus accumbens, ventral hippocampus and basolateral amygdala, we used the Golgi-Cox stain samples at PD35 and PD70. Our results suggest that neonatal prefrontal cortex damage alters dendritic parameters in limbic regions, and this has potential implications for schizophrenia.

  8. Lifespan anxiety is reflected in human amygdala cortical connectivity

    Science.gov (United States)

    He, Ye; Xu, Ting; Zhang, Wei

    2016-01-01

    Abstract The amygdala plays a pivotal role in processing anxiety and connects to large‐scale brain networks. However, intrinsic functional connectivity (iFC) between amygdala and these networks has rarely been examined in relation to anxiety, especially across the lifespan. We employed resting‐state functional MRI data from 280 healthy adults (18–83.5 yrs) to elucidate the relationship between anxiety and amygdala iFC with common cortical networks including the visual network, somatomotor network, dorsal attention network, ventral attention network, limbic network, frontoparietal network, and default network. Global and network‐specific iFC were separately computed as mean iFC of amygdala with the entire cerebral cortex and each cortical network. We detected negative correlation between global positive amygdala iFC and trait anxiety. Network‐specific associations between amygdala iFC and anxiety were also detectable. Specifically, the higher iFC strength between the left amygdala and the limbic network predicted lower state anxiety. For the trait anxiety, left amygdala anxiety–connectivity correlation was observed in both somatomotor and dorsal attention networks, whereas the right amygdala anxiety–connectivity correlation was primarily distributed in the frontoparietal and ventral attention networks. Ventral attention network exhibited significant anxiety–gender interactions on its iFC with amygdala. Together with findings from additional vertex‐wise analysis, these data clearly indicated that both low‐level sensory networks and high‐level associative networks could contribute to detectable predictions of anxiety behaviors by their iFC profiles with the amygdala. This set of systems neuroscience findings could lead to novel functional network models on neural correlates of human anxiety and provide targets for novel treatment strategies on anxiety disorders. Hum Brain Mapp 37:1178–1193, 2016. © 2015 The Authors Human Brain Mapping

  9. Lifespan anxiety is reflected in human amygdala cortical connectivity.

    Science.gov (United States)

    He, Ye; Xu, Ting; Zhang, Wei; Zuo, Xi-Nian

    2016-03-01

    The amygdala plays a pivotal role in processing anxiety and connects to large-scale brain networks. However, intrinsic functional connectivity (iFC) between amygdala and these networks has rarely been examined in relation to anxiety, especially across the lifespan. We employed resting-state functional MRI data from 280 healthy adults (18-83.5 yrs) to elucidate the relationship between anxiety and amygdala iFC with common cortical networks including the visual network, somatomotor network, dorsal attention network, ventral attention network, limbic network, frontoparietal network, and default network. Global and network-specific iFC were separately computed as mean iFC of amygdala with the entire cerebral cortex and each cortical network. We detected negative correlation between global positive amygdala iFC and trait anxiety. Network-specific associations between amygdala iFC and anxiety were also detectable. Specifically, the higher iFC strength between the left amygdala and the limbic network predicted lower state anxiety. For the trait anxiety, left amygdala anxiety-connectivity correlation was observed in both somatomotor and dorsal attention networks, whereas the right amygdala anxiety-connectivity correlation was primarily distributed in the frontoparietal and ventral attention networks. Ventral attention network exhibited significant anxiety-gender interactions on its iFC with amygdala. Together with findings from additional vertex-wise analysis, these data clearly indicated that both low-level sensory networks and high-level associative networks could contribute to detectable predictions of anxiety behaviors by their iFC profiles with the amygdala. This set of systems neuroscience findings could lead to novel functional network models on neural correlates of human anxiety and provide targets for novel treatment strategies on anxiety disorders.

  10. DNA methylation in the developing hippocampus and amygdala of anxiety-prone versus risk-taking rats.

    Science.gov (United States)

    Simmons, Rebecca K; Howard, Jasmine L; Simpson, Danielle N; Akil, Huda; Clinton, Sarah M

    2012-01-01

    part to parallel our early microarray gene expression work, and because this represents a critical period of brain development, which shapes individuals' lifelong emotional and stress reactivity. We found significant differences in dentate gyrus and CA3 regions of the hippocampus at P7 with no differences seen at P14 or P21. Interestingly, we also found significant bHR-bLR DNMT1 differences at P7 within the lateral, basolateral and medial nuclei of the amygdala, with no difference at P14 and P21, suggesting that the first postnatal week is a critical period for DNA methylation during brain development.

  11. Amygdala temporal dynamics: temperamental differences in the timing of amygdala response to familiar and novel faces

    Directory of Open Access Journals (Sweden)

    Shelton Richard C

    2009-12-01

    Full Text Available Abstract Background Inhibited temperament - the predisposition to respond to new people, places or things with wariness or avoidance behaviors - is associated with increased risk for social anxiety disorder and major depression. Although the magnitude of the amygdala's response to novelty has been identified as a neural substrate of inhibited temperament, there may also be differences in temporal dynamics (latency, duration, and peak. We hypothesized that persons with inhibited temperament would have faster responses to novel relative to familiar neutral faces compared to persons with uninhibited temperament. We used event-related functional magnetic resonance imaging to measure the temporal dynamics of the blood oxygen level dependent (BOLD response to both novel and familiar neutral faces in participants with inhibited or uninhibited temperament. Results Inhibited participants had faster amygdala responses to novel compared with familiar faces, and both longer and greater amygdala response to all faces. There were no differences in peak response. Conclusion Faster amygdala response to novelty may reflect a computational bias that leads to greater neophobic responses and represents a mechanism for the development of social anxiety.

  12. Robust automated amygdala segmentation via multi-atlas diffeomorphic registration

    Directory of Open Access Journals (Sweden)

    Jamie eHanson

    2012-11-01

    Full Text Available Here, we describe a novel method for volumetric segmentation of the amygdala from MRI images collected from 35 human subjects. This approach is adapted from open-source techniques employed previously with the hippocampus (Suh et al., 2011; Wang et al., 2011a; Wang et al., 2011b. Using multi-atlas segmentation and machine learning-based correction, we were able to produce automated amygdala segments with high dice (Mean= 0.918 for the left amygdala; 0.916 for the right amygdala and Jaccard coefficients (Mean= 0.850 for the left; 0.846 for the right compared to rigorously hand-traced volumes. This automated routine also produced amygdala segments with high intra-class (consistency=.830, absolute agreement =.819 for the left; consistency=. 786, absolute agreement =. 783 for the right and bivariate (r =.831 for the left; r =0.797 for the right correlations compared to hand-drawn amygdala. Our results are discussed in relation to results from other cutting-edge segmentation techniques, as well as commonly- available approaches to amygdala segmentation (e.g., Freesurfer. We believe this new technique has broad application to research with large sample sizes for which amygdala quantification might be needed.

  13. Prediction of economic choice by primate amygdala neurons.

    Science.gov (United States)

    Grabenhorst, Fabian; Hernádi, István; Schultz, Wolfram

    2012-11-13

    The amygdala is a key structure of the brain's reward system. Existing theories view its role in decision-making as restricted to an early valuation stage that provides input to decision mechanisms in downstream brain structures. However, the extent to which the amygdala itself codes information about economic choices is unclear. Here, we report that individual neurons in the primate amygdala predict behavioral choices in an economic decision task. We recorded the activity of amygdala neurons while monkeys chose between saving liquid reward with interest and spending the accumulated reward. In addition to known value-related responses, we found that activity in a group of amygdala neurons predicted the monkeys' upcoming save-spend choices with an average accuracy of 78%. This choice-predictive activity occurred early in trials, even before information about specific actions associated with save-spend choices was available. For a substantial number of neurons, choice-differential activity was specific for free, internally generated economic choices and not observed in a control task involving forced imperative choices. A subgroup of choice-predictive neurons did not show relationships to value, movement direction, or visual stimulus features. Choice-predictive activity in some amygdala neurons was preceded by transient periods of value coding, suggesting value-to-choice transitions and resembling decision processes in other brain systems. These findings suggest that the amygdala might play an active role in economic decisions. Current views of amygdala function should be extended to incorporate a role in decision-making beyond valuation.

  14. Long-term aldosterone treatment induces decreased apical but increased basolateral expression of AQP2 in CCD of rat kidney

    DEFF Research Database (Denmark)

    de Seigneux, Sophie; Nielsen, Jakob; Olesen, Emma T B;

    2007-01-01

    of hypokalemia in aldosterone-treated rats, we studied dietary-induced hypokalemia in rats, which also reduced apical AQP2 expression in the CCD but did not induce any increase in basolateral AQP2 expression in the CCD as observed with aldosterone treatment. The aldosterone-induced basolateral AQP2 expression...... in the CCD was thus independent of hypokalemia but was dependent on the presence of sodium and aldosterone. This redistribution was clearly blocked by mineralocorticoid receptor blockade. The increased basolateral expression of AQP2 induced by aldosterone may play a significant role in water metabolism...... in conditions with increased sodium reabsorption in the CCD....

  15. The role of the amygdala in face perception and evaluation.

    Science.gov (United States)

    Todorov, Alexander

    2012-03-01

    Faces are one of the most significant social stimuli and the processes underlying face perception are at the intersection of cognition, affect, and motivation. Vision scientists have had a tremendous success of mapping the regions for perceptual analysis of faces in posterior cortex. Based on evidence from (a) single unit recording studies in monkeys and humans; (b) human functional localizer studies; and (c) meta-analyses of neuroimaging studies, I argue that faces automatically evoke responses not only in these regions but also in the amygdala. I also argue that (a) a key property of faces represented in the amygdala is their typicality; and (b) one of the functions of the amygdala is to bias attention to atypical faces, which are associated with higher uncertainty. This framework is consistent with a number of other amygdala findings not involving faces, suggesting a general account for the role of the amygdala in perception.

  16. Amygdala and Ventral Striatum Make Distinct Contributions to Reinforcement Learning.

    Science.gov (United States)

    Costa, Vincent D; Dal Monte, Olga; Lucas, Daniel R; Murray, Elisabeth A; Averbeck, Bruno B

    2016-10-19

    Reinforcement learning (RL) theories posit that dopaminergic signals are integrated within the striatum to associate choices with outcomes. Often overlooked is that the amygdala also receives dopaminergic input and is involved in Pavlovian processes that influence choice behavior. To determine the relative contributions of the ventral striatum (VS) and amygdala to appetitive RL, we tested rhesus macaques with VS or amygdala lesions on deterministic and stochastic versions of a two-arm bandit reversal learning task. When learning was characterized with an RL model relative to controls, amygdala lesions caused general decreases in learning from positive feedback and choice consistency. By comparison, VS lesions only affected learning in the stochastic task. Moreover, the VS lesions hastened the monkeys' choice reaction times, which emphasized a speed-accuracy trade-off that accounted for errors in deterministic learning. These results update standard accounts of RL by emphasizing distinct contributions of the amygdala and VS to RL.

  17. A unique role for the human amygdala in novelty detection.

    Science.gov (United States)

    Blackford, Jennifer Urbano; Buckholtz, Joshua W; Avery, Suzanne N; Zald, David H

    2010-04-15

    Previous research indicates that the amygdala and hippocampus are sensitive to novelty; however, two types of novelty can be distinguished - stimuli that are ordinary, but novel in the current context, and stimuli that are unusual. Using functional magnetic resonance imaging, we examined blood oxygen dependent level (BOLD) response of the human amygdala and hippocampus to novel, commonly seen objects versus novel unusual objects. When presented with the novel common stimuli, the BOLD signal increased significantly in both the amygdala and hippocampus. However, for the novel unusual stimuli, only the amygdala showed an increased response compared to the novel common stimuli. These findings suggest that the amygdala is distinctly responsive to novel unusual stimuli, making a unique contribution to the novelty detection circuit.

  18. Functional interaction of medial mediodorsal thalamic nucleus but not nucleus accumbens with amygdala and orbital prefrontal cortex is essential for adaptive response selection after reinforcer devaluation.

    Science.gov (United States)

    Izquierdo, Alicia; Murray, Elisabeth A

    2010-01-13

    In nonhuman primates, reward-based decision making may be assessed through choices of objects overlying two different foods, one of which has been devalued by selective satiation. The most adaptive object choices yield the food of higher value. A large body of data identifies the amygdala and orbital prefrontal cortex (PFo) as neural mediators of adaptive responses to reinforcer devaluation. More recent work in nonhuman primates reveals the critical role of the medial, magnocellular portion of the mediodorsal nucleus of the thalamus (MDm) as well. Because both the nucleus accumbens (NA) and the MDm are anatomically related to the amygdala and PFo, and because both regions are implicated in reward processing, we tested whether either region necessarily interacts with the amygdala and PFo to mediate reinforcer devaluation effects. We used a crossed-disconnection design in which monkeys received amygdala and PFo lesions in one hemisphere combined with either NA or MDm lesions in the contralateral hemisphere. Monkeys that sustained NA disconnection, like controls, showed robust shifts in object choices in response to reinforcer devaluation. In contrast, monkeys that sustained MDm disconnection failed to adjust their object choices. Thus, MDm, but not NA, works together with the amygdala and PFo to support reward-based decision making.

  19. The amygdala to periaqueductal gray pathway: plastic changes induced by audiogenic kindling and reversal by gabapentin.

    Science.gov (United States)

    Tupal, S; Faingold, C L

    2012-09-26

    Repeated, periodic induction of AGS (AGS kindling) in GEPR-9s increases seizure duration and induces an additional generalized clonus phase [post-tonic clonus (PTC)], which involves expansion of the localized brainstem AGS network to the amygdala. The pathway between central amygdala (CeA) and ventrolateral periaqueductal gray (vlPAG) is implicated in several disorders, including pain and anxiety. This pathway is also implicated in the network of audiogenic seizures (AGS) in genetically epilepsy-prone rats (GEPR-9s). We examined AGS kindling-induced changes in vlPAG extracellular action potentials evoked by electrical stimuli in CeA in awake, behaving GEPR-9s, using chronically-implanted stimulation electrodes in CeA and microwire recording electrodes in vlPAG. The effect of gabapentin, an anticonvulsant drug that is also effective in pain and anxiety disorders, on the CeA to vlPAG pathway in AGS-kindled GEPR-9s was also evaluated. Electrical stimulation in CeA evoked consistent, short latency and intensity-dependent vlPAG neuronal firing increases. However, in AGS-kindled GEPR-9s these responses showed a precipitous firing increase with increasing stimulus intensity, as compared to non-kindled GEPR-9s. Gabapentin (50mg/kg, i.p.) significantly reduced vlPAG neuronal responses to CeA stimulation to pre-AGS-kindled levels and reversibly blocked PTC in AGS-kindled GEPR-9s. These data suggest that the amygdala to vlPAG pathway may be critical in mediating the emergence of PTC during AGS kindling. The ability of gabapentin to suppress this pathway may be important for its anticonvulsant effects in AGS-kindled GEPR-9s, and this effect may contribute to gabapentin's effectiveness in anxiety and pain in which the amygdala to PAG pathway is also implicated.

  20. Medial amygdala lesions selectively block aversive Pavlovian-instrumental transfer in rats.

    Directory of Open Access Journals (Sweden)

    Margaret Grace McCue

    2014-09-01

    Full Text Available Pavlovian conditioned stimuli (CSs play an important role in the reinforcement and motivation of instrumental active avoidance (AA. Conditioned threats can also invigorate ongoing AA responding (aversive Pavlovian-instrumental transfer or PIT. The neural circuits mediating AA are poorly understood, although lesion studies suggest that lateral, basal and central amygdala nuclei, as well as infralimbic prefrontal cortex, make key, and sometimes opposing, contributions. We recently completed an extensive analysis of brain c-Fos expression in good vs. poor avoiders following an AA test (Martinez et al 2013, Learning and Memory. This analysis identified medial amygdala (MeA as a potentially important region for Pavlovian motivation of instrumental actions. MeA is known to mediate defensive responding to innate threats as well as social behaviors, but its role in mediating aversive Pavlovian-instrumental interactions is unknown. We evaluated the effect of MeA lesions on Pavlovian conditioning, Sidman two-way AA conditioning (shuttling and aversive PIT in rats. Mild footshocks served as the unconditioned stimulus in all conditioning phases. MeA lesions had no effect on AA but blocked the expression of aversive PIT and 22 kHz ultrasonic vocalizations in the AA context. Interestingly, MeA lesions failed to affect Pavlovian freezing to discrete threats but reduced freezing to contextual threats when assessed outside of the AA chamber. These findings differentiate MeA from lateral and central amygdala, as lesions of these nuclei disrupt Pavlovian freezing and aversive PIT, but have opposite effects on AA performance. Taken together, these results suggest that MeA plays a selective role in the motivation of instrumental avoidance by general or uncertain Pavlovian threats.

  1. Differential patterns of amygdala and ventral striatum activation predict gender-specific changes in sexual risk behavior.

    Science.gov (United States)

    Victor, Elizabeth C; Sansosti, Alexandra A; Bowman, Hilary C; Hariri, Ahmad R

    2015-06-10

    Although the initiation of sexual behavior is common among adolescents and young adults, some individuals express this behavior in a manner that significantly increases their risk for negative outcomes including sexually transmitted infections. Based on accumulating evidence, we have hypothesized that increased sexual risk behavior reflects, in part, an imbalance between neural circuits mediating approach and avoidance in particular as manifest by relatively increased ventral striatum (VS) activity and relatively decreased amygdala activity. Here, we test our hypothesis using data from seventy 18- to 22-year-old university students participating in the Duke Neurogenetics Study. We found a significant three-way interaction between amygdala activation, VS activation, and gender predicting changes in the number of sexual partners over time. Although relatively increased VS activation predicted greater increases in sexual partners for both men and women, the effect in men was contingent on the presence of relatively decreased amygdala activation and the effect in women was contingent on the presence of relatively increased amygdala activation. These findings suggest unique gender differences in how complex interactions between neural circuit function contributing to approach and avoidance may be expressed as sexual risk behavior in young adults. As such, our findings have the potential to inform the development of novel, gender-specific strategies that may be more effective at curtailing sexual risk behavior.

  2. Activity dependent protein degradation is critical for the formation and stability of fear memory in the amygdala.

    Directory of Open Access Journals (Sweden)

    Timothy J Jarome

    Full Text Available Protein degradation through the ubiquitin-proteasome system [UPS] plays a critical role in some forms of synaptic plasticity. However, its role in memory formation in the amygdala, a site critical for the formation of fear memories, currently remains unknown. Here we provide the first evidence that protein degradation through the UPS is critically engaged at amygdala synapses during memory formation and retrieval. Fear conditioning results in NMDA-dependent increases in degradation-specific polyubiquitination in the amygdala, targeting proteins involved in translational control and synaptic structure and blocking the degradation of these proteins significantly impairs long-term memory. Furthermore, retrieval of fear memory results in a second wave of NMDA-dependent polyubiquitination that targets proteins involved in translational silencing and synaptic structure and is critical for memory updating following recall. These results indicate that UPS-mediated protein degradation is a major regulator of synaptic plasticity necessary for the formation and stability of long-term memories at amygdala synapses.

  3. Central amygdala lesions inhibit pontine nuclei acoustic reactivity and retard delay eyeblink conditioning acquisition in adult rats.

    Science.gov (United States)

    Pochiro, Joseph M; Lindquist, Derick H

    2016-06-01

    In delay eyeblink conditioning (EBC) a neutral conditioned stimulus (CS; tone) is repeatedly paired with a mildly aversive unconditioned stimulus (US; periorbital electrical shock). Over training, subjects learn to produce an anticipatory eyeblink conditioned response (CR) during the CS, prior to US onset. While cerebellar synaptic plasticity is necessary for successful EBC, the amygdala is proposed to enhance eyeblink CR acquisition. In the current study, adult Long-Evans rats received bilateral sham or neurotoxic lesions of the central nucleus of the amygdala (CEA) followed by 1 or 4 EBC sessions. Fear-evoked freezing behavior, CS-mediated enhancement of the unconditioned response (UR), and eyeblink CR acquisition were all impaired in the CEA lesion rats relative to sham controls. There were also significantly fewer c-Fos immunoreactive cells in the pontine nuclei (PN)-major relays of acoustic information to the cerebellum-following the first and fourth EBC session in lesion rats. In sham rats, freezing behavior decreased from session 1 to 4, commensurate with nucleus-specific reductions in amygdala Fos+ cell counts. Results suggest delay EBC proceeds through three stages: in stage one the amygdala rapidly excites diffuse fear responses and PN acoustic reactivity, facilitating cerebellar synaptic plasticity and the development of eyeblink CRs in stage two, leading, in stage three, to a diminution or stabilization of conditioned fear responding.

  4. Dexmedetomidine Dose-Dependently Attenuates Ropivacaine-Induced Seizures and Negative Emotions Via Inhibiting Phosphorylation of Amygdala Extracellular Signal-Regulated Kinase in Mice.

    Science.gov (United States)

    Zhai, Ming-Zhu; Wu, Huang-Hui; Yin, Jun-Bin; Cui, Yuan-Yuan; Mei, Xiao-Peng; Zhang, Han; Zhu, Xia; Shen, Xue-Feng; Kaye, Alan David; Chen, Guo-Zhong

    2016-05-01

    Ropivacaine (Ropi), one of the newest and safest amino amide local anesthetics, is linked to toxicity, including the potential for seizures, changes in behavior, and even cardiovascular collapse. Dexmedetomidine (Dex), an α2-adrenergic receptor agonist, has been widely used in anesthesia and critical care practice. To date, the underlying mechanisms of the effects of Dex premedication on Ropi-induced toxicity have not been clearly identified. In the current study, we investigated the effects of increasing doses of Dex premedication on 50% convulsive dose (CD50) of Ropi. With increasing doses of intraperitoneal (i.p.) Dex 10 min prior to each i.p. RopiCD50, the latency and duration of seizure activity were recorded. Open-field (OF) and elevated plus maze (EPM) test were used to measure negative behavioral emotions such as depression and anxiety. Immunohistochemistry and Western blot were utilized to investigate phosphorylation-extracellular regulated protein kinases (p-ERK) expression in the basolateral amygdala (BLA) on 2 h and in the central amygdala (CeA) on 24 h after convulsion in mice. The results of our investigation demonstrated that Dex dose-dependently increased RopiCD50, prolonged the latency and shortened the duration of each RopiCD50-induced seizure, improved the negative emotions revealed by both OF and EPM test, and inhibited p-ERK expression in the BLA and the CeA.

  5. Electrophysiological study of transport systems in isolated perfused pancreatic ducts: properties of the basolateral membrane

    DEFF Research Database (Denmark)

    Novak, I; Greger, R

    1988-01-01

    In order to study the mechanism of pancreatic HCO3- transport, a perfused preparation of isolated intra- and interlobular ducts (i.d. 20-40 microns) of rat pancreas was developed. Responses of the epithelium to changes in the bath ionic concentration and to addition of transport inhibitors...... was monitored by electrophysiological techniques. In this report some properties of the basolateral membrane of pancreatic duct cells are described. The transepithelial potential difference (PDte) in ducts bathed in HCO3(-)-free and HCO3(-)-containing solution was -0.8 and -2.6 mV, respectively. The equivalent...... short circuit current (Isc) under similar conditions was 26 and 50 microA . cm-2. The specific transepithelial resistance (Rte) was 88 omega cm2. In control solutions the PD across the basolateral membrane (PDbl) was -63 +/- 1 mV (n = 314). Ouabain (3 mmol/l) depolarized PDbl by 4.8 +/- 1.1 mV (n = 6...

  6. Clathrin and AP1B: Key roles in basolateral trafficking through trans-endosomal routes

    Science.gov (United States)

    Gonzalez, Alfonso; Rodriguez-Boulan, Enrique

    2013-01-01

    Research following introduction of the MDCK model system to study epithelial polarity (1978) led to an initial paradigm that posited independent roles of the trans Golgi network (TGN) and recycling endosomes (RE) in the generation of, respectively, biosynthetic and recycling routes of plasma membrane (PM) proteins to apical and basolateral PM domains. This model dominated the field for 20 years. However, studies over the past decade and the discovery of the involvement of clathrin and clathrin adaptors in protein trafficking to the basolateral PM has led to a new paradigm. TGN and RE are now believed to cooperate closely in both biosynthetic and recycling trafficking routes. Here, we critically review these recent advances and the questions that remain unanswered. PMID:19854182

  7. The prefrontal cortex communicates with the amygdala to impair learning after acute stress in females but not in males.

    Science.gov (United States)

    Maeng, Lisa Y; Waddell, Jaylyn; Shors, Tracey J

    2010-12-01

    Acute stress exposure enhances classical eyeblink conditioning in male rats, whereas exposure to the same event dramatically impairs performance in females (Wood and Shors, 1998; Wood et al., 2001). We hypothesized that stress affects learning differently in males and females because different brain regions and circuits are being activated. In the first experiment, we determined that neuronal activity within the medial prefrontal cortex (mPFC) during the stressful event is necessary to disrupt learning in females. In both males and females, the mPFC was bilaterally inactivated with GABA agonist muscimol before the stressor. Inactivation prevented only the impaired performance in females; it had no consequence for performance in males. However, in the second experiment, excitation of the mPFC alone with GABA antagonist picrotoxin was insufficient to elicit the stress effect that was prevented through the inactivation of this region in females. Therefore, we hypothesized that the mPFC communicates with the basolateral amygdala to disrupt learning in females after the stressor. To test this hypothesis, these structures were disconnected from each other with unilateral excitotoxic (NMDA) lesions on either the same or opposite sides of the brain. Females with contralateral lesions, which disrupt the connections on both sides of the brain, were able to learn after the stressful event, whereas those with ipsilateral lesions, which disrupt only one connection, did not learn after the stressor. Together, these data indicate that the mPFC is critically involved in females during stress to impair subsequent learning and does so via communication with the amygdala.

  8. Molecular evidence for BDNF- and GABA-related dysfunctions in the amygdala of female subjects with major depression.

    Science.gov (United States)

    Guilloux, J-P; Douillard-Guilloux, G; Kota, R; Wang, X; Gardier, A M; Martinowich, K; Tseng, G C; Lewis, D A; Sibille, E

    2012-11-01

    Women are twice as likely as men to develop major depressive disorder (MDD) and are more prone to recurring episodes. Hence, we tested the hypothesis that the illness may associate with robust molecular changes in female subjects, and investigated large-scale gene expression in the post-mortem brain of MDD subjects paired with matched controls (n=21 pairs). We focused on the lateral/basolateral/basomedian complex of the amygdala as a neural hub of mood regulation affected in MDD. Among the most robust findings were downregulated transcripts for genes coding for γ-aminobutyric acid (GABA) interneuron-related peptides, including somatostatin (SST), tachykinin, neuropeptide Y (NPY) and cortistatin, in a pattern reminiscent to that previously reported in mice with low brain-derived neurotrophic factor (BDNF). Changes were confirmed by quantitative PCR and not explained by demographic, technical or known clinical parameters. BDNF itself was significantly downregulated at the RNA and protein levels in MDD subjects. Investigating putative mechanisms, we show that this core MDD-related gene profile (including SST, NPY, TAC1, RGS4 and CORT) is recapitulated by complementary patterns in mice with constitutive (BDNF-heterozygous) or activity-dependent (exon IV knockout) decreases in BDNF function, with a common effect on SST and NPY. Together, these results provide both direct (low RNA/protein) and indirect (low BDNF-dependent gene pattern) evidence for reduced BDNF function in the amygdala of female subjects with MDD. Supporting studies in mutant mice models suggest a complex mechanism of low constitutive and activity-dependent BDNF function in MDD, particularly affecting SST/NPY-related GABA neurons, thus linking the neurotrophic and GABA hypotheses of depression.

  9. Neuropeptide S and BDNF gene expression in the amygdala are influenced by social decision-making under stress

    Directory of Open Access Journals (Sweden)

    Justin P. Smith

    2014-04-01

    Full Text Available In a newly developed conceptual model of stressful social decision making, the Stress-Alternatives Model (SAM; used for the 1st time in mice elicits two types of response: escape or remain submissively. Daily (4d aggressive social interaction in a neutral arena between a C57BL6/N test mouse and a larger, novel aggressive CD1 mouse, begin after an audible tone (conditioned stimulus; CS. Although escape holes (only large enough for smaller test animals are available, and the aggressor is unremittingly antagonistic, only half of the mice tested utilize the possibility of escape. During training, for mice that choose to leave the arena and social interaction, latency to escape dramatically decreases over time; this is also true for control C57BL6/N mice which experienced no aggression. Therefore, the open field of the SAM apparatus is intrinsically anxiogenic. It also means that submission to the aggressor is chosen despite this anxiety and the high intensity of the aggressive attacks and defeat. While both groups that received aggression displayed stress responsiveness, corticosterone levels were significantly higher in animals that chose submissive coexistence. Although both escaping and non-escaping groups of animals experienced aggression and defeat, submissive animals also exhibited classic fear conditioning, freezing in response to the CS alone, while escaping animals did not. In the basolateral amygdala, gene expression of BDNF was diminished, but NPS expression was significantly elevated, but only in submissive animals. This increase in submission-evoked NPS mRNA expression was greatest in the central amygdala, which coincided with decreased BDNF expression. Reduced expression of BDNF is only in submissive animals that also exhibit elevated NPS expression, despite elevated corticosterone in all socially interacting animals. The results suggest an interwoven relationship, linked by social context, between amygdalar BDNF, NPS and plasma

  10. Opiate sensitization induces FosB/ΔFosB expression in prefrontal cortical, striatal and amygdala brain regions.

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    Gary B Kaplan

    Full Text Available Sensitization to the effects of drugs of abuse and associated stimuli contributes to drug craving, compulsive drug use, and relapse in addiction. Repeated opiate exposure produces behavioral sensitization that is hypothesized to result from neural plasticity in specific limbic, striatal and cortical systems. ΔFosB and FosB are members of the Fos family of transcription factors that are implicated in neural plasticity in addiction. This study examined the effects of intermittent morphine treatment, associated with motor sensitization, on FosB/ΔFosB levels using quantitative immunohistochemistry. Motor sensitization was tested in C57BL/6 mice that received six intermittent pre-treatments (on days 1, 3, 5, 8, 10, 12 with either subcutaneous morphine (10 mg/kg or saline followed by a challenge injection of morphine or saline on day 16. Mice receiving repeated morphine injections demonstrated significant increases in locomotor activity on days 8, 10, and 12 of treatment (vs. day 1, consistent with development of locomotor sensitization. A morphine challenge on day 16 significantly increased locomotor activity of saline pre-treated mice and produced even larger increases in motor activity in the morphine pre-treated mice, consistent with the expression of opiate sensitization. Intermittent morphine pre-treatment on these six pre-treatment days produced a significant induction of FosB/ΔFosB, measured on day 16, in multiple brain regions including prelimbic (PL and infralimbic (IL cortex, nucleus accumbens (NAc core, dorsomedial caudate-putamen (CPU, basolateral amygdala (BLA and central nucleus of the amygdala (CNA but not in a motor cortex control region. Opiate induced sensitization may develop via Fos/ΔFosB plasticity in motivational pathways (NAc, motor outputs (CPU, and associative learning (PL, IL, BLA and stress pathways (CNA.

  11. Expression and distribution of Kv4 potassium channel subunits and potassium channel interacting proteins in subpopulations of interneurons in the basolateral amygdala.

    Science.gov (United States)

    Dabrowska, J; Rainnie, D G

    2010-12-15

    The Kv4 potassium channel α subunits, Kv4.1, Kv4.2, and Kv4.3, determine some of the fundamental physiological properties of neurons in the CNS. Kv4 subunits are associated with auxiliary β-subunits, such as the potassium channel interacting proteins (KChIP1 - 4), which are thought to regulate the trafficking and gating of native Kv4 potassium channels. Intriguingly, KChIP1 is thought to show cell type-selective expression in GABA-ergic inhibitory interneurons, while other β-subunits (KChIP2-4) are associated with principal glutamatergic neurons. However, nothing is known about the expression of Kv4 family α- and β-subunits in specific interneurons populations in the BLA. Here, we have used immunofluorescence, co-immunoprecipitation, and Western Blotting to determine the relative expression of KChIP1 in the different interneuron subtypes within the BLA, and its co-localization with one or more of the Kv4 α subunits. We show that all three α-subunits of Kv4 potassium channel are found in rat BLA neurons, and that the immunoreactivity of KChIP1 closely resembles that of Kv4.3. Indeed, Kv4.3 showed almost complete co-localization with KChIP1 in the soma and dendrites of a distinct subpopulation of BLA neurons. Dual-immunofluorescence studies revealed this to be in BLA interneurons immunoreactive for parvalbumin, cholecystokin-8, and somatostatin. Finally, co-immunoprecipitation studies showed that KChIP1 was associated with all three Kv4 α subunits. Together our results suggest that KChIP1 is selectively expressed in BLA interneurons where it may function to regulate the activity of A-type potassium channels. Hence, KChIP1 might be considered as a cell type-specific regulator of GABAergic inhibitory circuits in the BLA.

  12. Electroconvulsive stimulations prevent chronic stress-induced increases in L-type calcium channel mRNAs in the hippocampus and basolateral amygdala

    DEFF Research Database (Denmark)

    Maigaard, Katrine; Pedersen, Ida Hageman; Jørgensen, Anders;

    2012-01-01

    Although affective disorders have high prevalence, morbidity and mortality, we do not fully understand disease etiopathology, nor have we determined the exact mechanisms by which treatment works. Recent research indicates that intracellular calcium ion dysfunction might be involved. Here we use...... the chronic restraint stress model of affective disorder (6 h restraint per day for 21 days) in combination with electroconvulsive stimulations to examine the effects of stress and an effective antidepressive treatment modality on L-type voltage gated calcium channel subunit mRNA expression patterns......, while stress only upregulated Ca(v)1.3 channel expression significantly in the dentate gyrus. ECS effects on Ca(v)1.2 channel expression were generally specific to stressed animals. Our findings are consistent with and extent previous studies on the involvement of intracellular calcium ion dysfunction...

  13. Angiotensin II's role in sodium lactate-induced panic-like responses in rats with repeated urocortin 1 injections into the basolateral amygdala

    DEFF Research Database (Denmark)

    Johnson, Philip L; Sajdyk, Tammy J; Fitz, Stephanie D;

    2013-01-01

    into the BLA daily for 3 days. Five to seven days following the intra-BLA injections, we microinjected either the nonspecific A-II type 1 (AT1r) and 2 (AT2r) receptor antagonist saralasin, or the AT2r-selective antagonist PD123319 into the BLA prior to the NaLac challenge. The UCN/BLA-primed rats pre...

  14. Tissue plasminogen activator promotes the effects of corticotropin-releasing factor on the amygdala and anxiety-like behavior.

    Science.gov (United States)

    Matys, Tomasz; Pawlak, Robert; Matys, Elzbieta; Pavlides, Constantine; McEwen, Bruce S; Strickland, Sidney

    2004-11-16

    Stress-induced plasticity in the brain requires a precisely orchestrated sequence of cellular events involving novel as well as well known mediators. We have previously demonstrated that tissue plasminogen activator (tPA) in the amygdala promotes stress-induced synaptic plasticity and anxiety-like behavior. Here, we show that tPA activity in the amygdala is up-regulated by a major stress neuromodulator, corticotropin-releasing factor (CRF), acting on CRF type-1 receptors. Compared with WT, tPA-deficient mice responded to CRF treatment with attenuated expression of c-fos (an indicator of neuronal activation) in the central and medial amygdala but had normal c-fos responses in paraventricular nuclei. They exhibited reduced anxiety-like behavior to CRF but had a sustained corticosterone response after CRF administration. This effect of tPA deficiency was not mediated by plasminogen, because plasminogen-deficient mice demonstrated normal behavioral and hormonal changes to CRF. These studies establish tPA as an important mediator of cellular, behavioral, and hormonal responses to CRF.

  15. Active and passive Na+ fluxes across the basolateral membrane of rabbit urinary bladder.

    Science.gov (United States)

    Eaton, D C; Frace, A M; Silverthorn, S U

    1982-01-01

    The apical membrane of rabbit urinary bladder can be functionally removed by application of nystatin at high concentration if the mucosal surface of the tissue is bathed in a saline which mimics intracellular ion concentrations. Under these conditions, the tissue is as far as the movement of univalent ions no more than a sheet of basolateral membrane with some tight junctional membrane in parallel. In this manner the Na+ concentration at the inner surface of the basolateral membrane can be varied by altering the concentration in the mucosal bulk solution. When this was done both mucosal-to-serosal 22Na flux and net change in basolateral current were measured. The flux and the current could be further divided into the components of each that were either blocked by ouabain or insensitive to ouabain. Ouabain-insensitive mucosal-to-serosal Na+ flux was a linear function of mucosal Na+ concentration. Ouabain-sensitive Na+ flux and ouabain-sensitive, Na+-induced current both display a saturating relationship which cannot be accounted for by the presence of unstirred layers. If the interaction of Na+ with the basolateral transport process is assumed to involve the interaction of some number of Na+ ions, n, with a maximal flux, MMAX, then the data can be fit by assuming 3.2 equivalent sites for interaction and a value for MMAX of 287.8 pM cm-2 sec-1 with an intracellular Na concentration of 2.0 mM Na+ at half-maximal saturation. By comparing these values with the ouabain-sensitive, Na+-induced current, we calculate a Na+ to K+ coupling ratio of 1.40 +/- 0.07 for the transport process.

  16. Vectorial transport of nucleoside analogs from the apical to the basolateral membrane in double-transfected cells expressing the human concentrative nucleoside transporter hCNT3 and the export pump ABCC4.

    Science.gov (United States)

    Rius, Maria; Keller, Daniela; Brom, Manuela; Hummel-Eisenbeiss, Johanna; Lyko, Frank; Keppler, Dietrich

    2010-07-01

    The identification of the transport proteins responsible for the uptake and the efflux of nucleosides and their metabolites enables the characterization of their vectorial transport and a better understanding of their absorption, distribution, and elimination. Human concentrative nucleoside transporters (hCNTs/SLC28A) are known to mediate the transport of natural nucleosides and some nucleoside analogs into cells in a sodium-dependent and unidirectional manner. On the other hand, several human multidrug resistance proteins [human ATP-binding cassette transporter, subfamily C (ABCC)] cause resistance against nucleoside analogs and mediate transport of phosphorylated nucleoside derivatives out of the cells in an ATP-dependent manner. For the integrated analysis of uptake and efflux of these compounds, we established a double-transfected Madin-Darby canine kidney (MDCK) II cell line stably expressing the human uptake transporter hCNT3 in the apical membrane and the human efflux pump ABCC4 in the basolateral membrane. The direction of transport was from the apical to the basolateral compartment, which is in line with the unidirectional transport and the localization of both recombinant proteins in the MDCKII cells. Recombinant hCNT3 mediated the transport of several known nucleoside substrates, and we identified 5-azacytidine as a new substrate for hCNT3. It is of interest that coexpression of both transporters was confirmed in pancreatic adenocarcinomas, which represent an important clinical indication for the therapeutic use of nucleoside analogs. Thus, our results establish a novel cell system for studies on the vectorial transport of nucleosides and their analogs from the apical to the basolateral compartment. The results contribute to a better understanding of the cellular transport characteristics of nucleoside drugs.

  17. Amygdala-prefrontal pathways and the dopamine system affect nociceptive responses in the prefrontal cortex

    Directory of Open Access Journals (Sweden)

    Onozawa Kitaro

    2011-11-01

    Full Text Available Abstract Background We previously demonstrated nociceptive discharges to be evoked by mechanical noxious stimulation in the prefrontal cortex (PFC. The nociceptive responses recorded in the PFC are conceivably involved in the affective rather than the sensory-discriminative dimension of pain. The PFC receives dense projection from the limbic system. Monosynaptic projections from the basolateral nucleus of the amygdala (BLA to the PFC are known to produce long-lasting synaptic plasticity. We examined effects of high frequency stimulation (HFS delivered to the BLA on nociceptive responses in the rat PFC. Results HFS induced long lasting suppression (LLS of the specific high threshold responses of nociceptive neurons in the PFC. Microinjection of N-methyl-D-aspartic acid (NMDA receptor antagonists (2-amino-5-phosphonovaleric acid (APV, dizocilpine (MK-801 and also metabotropic glutamate receptor (mGluR group antagonists (α-methyl-4-carboxyphenylglycine (MCPG, and 2-[(1S,2S-2-carboxycyclopropyl]-3-(9H-xanthen-9-yl-D-alanine (LY341495, prevented the induction of LLS of nociceptive responses. We also examined modulatory effects of dopamine (DA on the LLS of nociceptive responses. With depletion of DA in response to 6-hydroxydopamine (6-OHDA injection into the ipsilateral forebrain bundle, LLS of nociceptive responses was decreased, while nociceptive responses were normally evoked. Antagonists of DA receptor subtypes D2 (sulpiride and D4 (3-{[4-(4-chlorophenyl piperazin-1-yl] methyl}-1H-pyrrolo [2, 3-b] pyridine (L-745,870, microinjected into the PFC, inhibited LLS of nociceptive responses. Conclusions Our results indicate that BLA-PFC pathways inhibited PFC nociceptive cell activities and that the DA system modifies the BLA-PFC regulatory function.

  18. Activity-dependent structural plasticity after aversive experiences in amygdala and auditory cortex pyramidal neurons.

    Science.gov (United States)

    Gruene, Tina; Flick, Katelyn; Rendall, Sam; Cho, Jin Hyung; Gray, Jesse; Shansky, Rebecca

    2016-07-22

    The brain is highly plastic and undergoes changes in response to many experiences. Learning especially can induce structural remodeling of dendritic spines, which is thought to relate to memory formation. Classical Pavlovian fear conditioning (FC) traditionally pairs an auditory cue with an aversive footshock, and has been widely used to study neural processes underlying associative learning and memory. Past research has found dendritic spine changes after FC in several structures. But, due to heterogeneity of cells within brain structures and limitations of traditional neuroanatomical techniques, it is unclear if all cells included in analyses were actually active during learning processes, even if known circuits are isolated. In this study, we employed a novel approach to analyze structural plasticity explicitly in neurons activated by exposure to either cued or uncued footshocks. We used male and female Arc-dVenus transgenic mice, which express the Venus fluorophore driven by the activity-related Arc promoter, to identify neurons that were active during either scenario. We then targeted fluorescent microinjections to Arc+ and neighboring Arc- neurons in the basolateral area of the amygdala (BLA) and auditory association cortex (TeA). In both BLA and TeA, Arc+ neurons had reduced thin and mushroom spine densities compared to Arc- neurons. This effect was present in males and females alike and also in both cued and uncued shock groups. Overall, this study adds to our understanding of how neuronal activity affects structural plasticity, and represents a methodological advance in the ways we can directly relate structural changes to experience-related neural activity.

  19. Effects of amygdala lesions on overexpectation phenomena in food cup approach and autoshaping procedures.

    Science.gov (United States)

    Holland, Peter C

    2016-08-01

    Prediction error (PE) plays a critical role in most modern theories of associative learning, by determining the effectiveness of conditioned stimuli (CS) or unconditioned stimuli (US). Here, we examined the effects of lesions of central (CeA) or basolateral (BLA) amygdala on performance in overexpectation tasks. In 2 experiments, after 2 CSs were separately paired with the US, they were combined and followed by the same US. In a subsequent test, we observed losses in strength of both CSs, as expected if the negative PE generated on reinforced compound trials encouraged inhibitory learning. CeA lesions, known to interfere with PE-induced enhancements in CS effectiveness, reduced those losses, suggesting that normally the negative PE also enhances cue associability in this task. BLA lesions had no effect. When a novel cue accompanied the reinforced compound, it acquired net conditioned inhibition, despite its consistent pairings with the US, consonant with US effectiveness models. That acquisition was unaffected by either CeA or BLA lesions, suggesting different rules for assignment of credit of changes in cue strength and cue associability. Finally, we examined a puzzling autoshaping phenomenon previously attributed to overexpectation effects. When a previously food-paired auditory cue was combined with the insertion of a lever and paired with the same food US, the auditory cue not only failed to block conditioning to the lever, but also lost strength, as in an overexpectation experiment. This effect was abolished by BLA lesions but unaffected by CeA lesions, suggesting it was unrelated to other overexpectation effects. (PsycINFO Database Record

  20. Role of the amygdala in antidepressant effects on hippocampal cell proliferation and survival and on depression-like behavior in the rat.

    Directory of Open Access Journals (Sweden)

    Jorge E Castro

    Full Text Available The stimulation of adult hippocampal neurogenesis by antidepressants has been associated with multiple molecular pathways, but the potential influence exerted by other brain areas has received much less attention. The basolateral complex of the amygdala (BLA, a region involved in anxiety and a site of action of antidepressants, has been implicated in both basal and stress-induced changes in neural plasticity in the dentate gyrus. We investigated here whether the BLA modulates the effects of the SSRI antidepressant fluoxetine on hippocampal cell proliferation and survival in relation to a behavioral index of depression-like behavior (forced swim test. We used a lesion approach targeting the BLA along with a chronic treatment with fluoxetine, and monitored basal anxiety levels given the important role of this behavioral trait in the progress of depression. Chronic fluoxetine treatment had a positive effect on hippocampal cell survival only when the BLA was lesioned. Anxiety was related to hippocampal cell survival in opposite ways in sham- and BLA-lesioned animals (i.e., negatively in sham- and positively in BLA-lesioned animals. Both BLA lesions and low anxiety were critical factors to enable a negative relationship between cell proliferation and depression-like behavior. Therefore, our study highlights a role for the amygdala on fluoxetine-stimulated cell survival and on the establishment of a link between cell proliferation and depression-like behavior. It also reveals an important modulatory role for anxiety on cell proliferation involving both BLA-dependent and -independent mechanisms. Our findings underscore the amygdala as a potential target to modulate antidepressants' action in hippocampal neurogenesis and in their link to depression-like behaviors.

  1. Midazolam treatment before re-exposure to contextual fear reduces freezing behavior and amygdala activity differentially in high- and low-anxiety rats.

    Science.gov (United States)

    Skórzewska, Anna; Lehner, Małgorzata; Wisłowska-Stanek, Aleksandra; Turzyńska, Danuta; Sobolewska, Alicja; Krząścik, Paweł; Płaźnik, Adam

    2015-02-01

    The aim of this study was to examine the effects of benzodiazepine (midazolam) administration on rat conditioned fear responses and on local brain activity (c-Fos and CRF expressions) of low- (LR) and high- (HR)anxiety rats after the first and second contextual fear test sessions. The animals were divided into LR and HR groups based on the duration of their conditioned freezing response in the first contextual fear test. The fear-re-conditioned LR and HR animals (28 days later) had increased freezing durations compared with those durations during the first conditioned fear test. These behavioral effects were accompanied by increased c-Fos expression in the medial amygdala (MeA), the basolateral amygdala (BLA), and the paraventricular hypothalamic nuclei and elevated CRF expression in the MeA. All these behavioral and immunochemical effects of fear re-conditioning were stronger in the LR group compared with the effects in the HR group. Moreover, in the LR rats, the re-conditioning led to decreased CRF expression in the primary motor cortex (M1) and to increased CRF expression in the BLA. The pretreatment of rats with midazolam before the second exposure to the aversive context significantly attenuated the conditioned fear response, lowered the serum corticosterone concentration, decreased c-Fos and CRF expressions in the MeA and in the BLA, and increased CRF complex density in M1 area only in the LR group. These studies have demonstrated that LR rats are more sensitive to re-exposure to fear stimuli and that midazolam pretreatment was associated with modified brain activity in the amygdala and in the prefrontal cortex in this group of animals. The current data may facilitate a better understanding of the neurobiological mechanisms responsible for individual differences in the psychopathological processes accompanying some anxiety disorders characterized by stronger reactivity to re-exposure to stressful challenges, e.g., posttraumatic stress disorder.

  2. Comparison of the activation of somatostatin- and neuropeptide Y-containing neuronal populations of the rat amygdala following two different anxiogenic stressors

    Science.gov (United States)

    Butler, Ryan K.; White, L. Casey; Frederick-Duus, Dani; Kaigler, Kris F.; Fadel, Jim R.; Wilson, Marlene A.

    2012-01-01

    Rats exposed to the odor of a predator or to the elevated plus maze express fear behaviors without a prior exposure to either stimulus. The expression of innate fear provides for an ideal model of anxiety which can aid in the elucidation of brain circuits involved in anxiety-related behaviors. The current experiments compared activation of neuropeptide-containing neuronal populations in the amygdala of rats exposed to either the elevated plus maze (EPM; 5 minutes) versus home cage controls, or predator ferret odor versus butyric acid, or no odor (30 minutes). Sections of the brains were prepared for dual-labeled immunohistochemistry and counts of c-Fos co-localized with somatostatin (SOM) or neuropeptide Y (NPY) were made in the basolateral (BLA), central (CEA), medial (MEA) nucleus of the amygdala. Ferret odor and butyric acid exposure significantly decreased the percentage of SOM–positive neurons also immunoreactive for c-Fos in the anterior BLA compared to controls, whereas EPM exposure yielded a significant increase in the activation of SOM-positive neurons versus home cage controls. In the CEA, ferret odor and butyric exposure significantly decreased the percentage of SOM-positive neurons also immunoreactive for c-Fos compared to no-odor controls whereas EPM exposure yielded no change versus controls. In the MEA, both ferret odor exposure and EPM exposure resulted in increased SOM co-localized with c-Fos compared to control groups whereas NPY co-localized with c-Fos occurred following ferret odor exposure, but not EPM exposure. These results indicate that phenotypically distinct neuronal populations of the amygdala are differentially activated following exposure to different anxiogenic stimuli. These studies further elucidate the fundamental neurocircuitry of anxiety and could possibly explain the differential behavioral effects of predator versus novelty-induced stress. PMID:22917777

  3. Prefrontal cortical circuit for depression- and anxiety-related behaviors mediated by cholecystokinin: role of ΔFosB.

    Science.gov (United States)

    Vialou, Vincent; Bagot, Rosemary C; Cahill, Michael E; Ferguson, Deveroux; Robison, Alfred J; Dietz, David M; Fallon, Barbara; Mazei-Robison, Michelle; Ku, Stacy M; Harrigan, Eileen; Winstanley, Catherine A; Joshi, Tej; Feng, Jian; Berton, Olivier; Nestler, Eric J

    2014-03-12

    Decreased medial prefrontal cortex (mPFC) neuronal activity is associated with social defeat-induced depression- and anxiety-like behaviors in mice. However, the molecular mechanisms underlying the decreased mPFC activity and its prodepressant role remain unknown. We show here that induction of the transcription factor ΔFosB in mPFC, specifically in the prelimbic (PrL) area, mediates susceptibility to stress. ΔFosB induction in PrL occurred selectively in susceptible mice after chronic social defeat stress, and overexpression of ΔFosB in this region, but not in the nearby infralimbic (IL) area, enhanced stress susceptibility. ΔFosB produced these effects partly through induction of the cholecystokinin (CCK)-B receptor: CCKB blockade in mPFC induces a resilient phenotype, whereas CCK administration into mPFC mimics the anxiogenic- and depressant-like effects of social stress. We previously found that optogenetic stimulation of mPFC neurons in susceptible mice reverses several behavioral abnormalities seen after chronic social defeat stress. Therefore, we hypothesized that optogenetic stimulation of cortical projections would rescue the pathological effects of CCK in mPFC. After CCK infusion in mPFC, we optogenetically stimulated mPFC projections to basolateral amygdala or nucleus accumbens, two subcortical structures involved in mood regulation. Stimulation of corticoamygdala projections blocked the anxiogenic effect of CCK, although no effect was observed on other symptoms of social defeat. Conversely, stimulation of corticoaccumbens projections reversed CCK-induced social avoidance and sucrose preference deficits but not anxiogenic-like effects. Together, these results indicate that social stress-induced behavioral deficits are mediated partly by molecular adaptations in mPFC involving ΔFosB and CCK through cortical projections to distinct subcortical targets.

  4. The acceleration of amygdala kindling epileptogenesis by chronic low-dose corticosterone involves both mineralocorticoid and glucocorticoid receptors.

    Science.gov (United States)

    Kumar, Gaurav; Couper, Abbie; O'Brien, Terence J; Salzberg, Michael R; Jones, Nigel C; Rees, Sandra M; Morris, Margaret J

    2007-08-01

    We have previously demonstrated that low-dose corticosterone (CS) administration, used as a model of the effect of chronic stress, accelerates epileptogenesis in the electrical amygdala kindling rat model of temporal lobe epilepsy (TLE). This current study examined the relative contributions to this effect of mineralocorticoid (MR) and glucocorticoid (GR) subtypes of glucocorticoid receptors. Female non-epileptic wistar rats 10-13 weeks of age were implanted with a bipolar electrode into the left amygdala. Five treatment groups were subjected to rapid amygdala kindling: water-control (n=9), CS treated (6 mg/100 ml added to drinking water; n=9), CS+spironolactone (MR antagonist, 50 mg/kg sc; n=9), CS+mifepristone (GR antagonist, 25 mg/kg sc; n=9), and CS+both antagonists (n=7). Rats were injected with vehicle or the relevant antagonist twice daily for the entire kindling period. Experimental groups differed significantly in the number of stimulations required to reach the 'fully kindled state' (Racine, 1972) ANOVA, F(4,38)=2.73, p=0.04). Amygdala kindling was accelerated in the CS-treated group compared with water controls (mean stimulations for full kindling: 45.2 vs. 86.5, pkindling rates in these groups not significantly different from water-treated subjects (p=0.26 and 0.29, respectively). The kindling rates in the MR and GR antagonist treatment groups did not significantly differ from each other (p=0.93), nor from the combined treatment group (mean stimulations: 62.8, p=0.59 and 0.54, respectively). This study demonstrates that activation of both high-affinity (MR) and low-affinity (GR) glucocorticoid receptors are involved in mediating CS-induced acceleration of amygdala kindling epileptogenesis.

  5. Pre-Training Reversible Inactivation of the Basal Amygdala (BA Disrupts Contextual, but Not Auditory, Fear Conditioning, in Rats.

    Directory of Open Access Journals (Sweden)

    Elisa Mari Akagi Jordão

    Full Text Available The basolateral amygdala complex (BLA, including the lateral (LA, basal (BA and accessory basal (AB nuclei, is involved in acquisition of contextual and auditory fear conditioning. The BA is one of the main targets for hippocampal information, a brain structure critical for contextual learning, which integrates several discrete stimuli into a single configural representation. Congruent with the hodology, selective neurotoxic damage to the BA results in impairments in contextual, but not auditory, fear conditioning, similarly to the behavioral impairments found after hippocampal damage. This study evaluated the effects of muscimol-induced reversible inactivation of the BA during a simultaneous contextual and auditory fear conditioning training on later fear responses to both the context and the tone, tested separately, without muscimol administration. As compared to control rats micro-infused with vehicle, subjects micro-infused with muscimol before training exhibited, during testing without muscimol, significant reduction of freezing responses to the conditioned context, but not to the conditioned tone. Therefore, reversible inactivation of the BA during training impaired contextual, but not auditory fear conditioning, thus confirming and extending similar behavioral observations following selective neurotoxic damage to the BA and, in addition, revealing that this effect is not related to the lack of a functional BA during testing.

  6. Long-range orbitofrontal and amygdala axons show divergent patterns of maturation in the frontal cortex across adolescence.

    Science.gov (United States)

    Johnson, Carolyn M; Loucks, F Alexandra; Peckler, Hannah; Thomas, A Wren; Janak, Patricia H; Wilbrecht, Linda

    2016-04-01

    The adolescent transition from juvenile to adult is marked by anatomical and functional remodeling of brain networks. Currently, the cellular and synaptic level changes underlying the adolescent transition are only coarsely understood. Here, we use two-photon imaging to make time-lapse observations of long-range axons that innervate the frontal cortex in the living brain. We labeled cells in the orbitofrontal cortex (OFC) and basolateral amygdala (BLA) and imaged their axonal afferents to the dorsomedial prefrontal cortex (dmPFC). We also imaged the apical dendrites of dmPFC pyramidal neurons. Images were taken daily in separate cohorts of juvenile (P24-P28) and young adult mice (P64-P68), ages where we have previously discovered differences in dmPFC dependent decision-making. Dendritic spines were pruned across this peri-adolescent period, while BLA and OFC afferents followed alternate developmental trajectories. OFC boutons showed no decrease in density, but did show a decrease in daily bouton gain and loss with age. BLA axons showed an increase in both bouton density and daily bouton gain at the later age, suggesting a delayed window of enhanced plasticity. Our findings reveal projection specific maturation of synaptic structures within a single frontal region and suggest that stabilization is a more general characteristic of maturation than pruning.

  7. Cell-type-specific recruitment of amygdala interneurons to hippocampal theta rhythm and noxious stimuli in vivo.

    Science.gov (United States)

    Bienvenu, Thomas C M; Busti, Daniela; Magill, Peter J; Ferraguti, Francesco; Capogna, Marco

    2012-06-21

    Neuronal synchrony in the basolateral amygdala (BLA) is critical for emotional behavior. Coordinated theta-frequency oscillations between the BLA and the hippocampus and precisely timed integration of salient sensory stimuli in the BLA are involved in fear conditioning. We characterized GABAergic interneuron types of the BLA and determined their contribution to shaping these network activities. Using in vivo recordings in rats combined with the anatomical identification of neurons, we found that the firing of BLA interneurons associated with network activities was cell type specific. The firing of calbindin-positive interneurons targeting dendrites was precisely theta-modulated, but other cell types were heterogeneously modulated, including parvalbumin-positive basket cells. Salient sensory stimuli selectively triggered axo-axonic cells firing and inhibited firing of a disctinct projecting interneuron type. Thus, GABA is released onto BLA principal neurons in a time-, domain-, and sensory-specific manner. These specific synaptic actions likely cooperate to promote amygdalo-hippocampal synchrony involved in emotional memory formation.

  8. Prenatal stress alters amygdala functional connectivity in preterm neonates

    Directory of Open Access Journals (Sweden)

    Dustin Scheinost

    2016-01-01

    Functional connectivity from the amygdala to other subcortical regions is decreased in preterm neonates compared to term controls. In addition, these data, for the first time, suggest that prenatal stress exposure amplifies these decreases.

  9. Dynamic modulation of amygdala-hippocampal connectivity by emotional arousal.

    Science.gov (United States)

    Fastenrath, Matthias; Coynel, David; Spalek, Klara; Milnik, Annette; Gschwind, Leo; Roozendaal, Benno; Papassotiropoulos, Andreas; de Quervain, Dominique J F

    2014-10-15

    Positive and negative emotional events are better remembered than neutral events. Studies in animals suggest that this phenomenon depends on the influence of the amygdala upon the hippocampus. In humans, however, it is largely unknown how these two brain structures functionally interact and whether these interactions are similar between positive and negative information. Using dynamic causal modeling of fMRI data in 586 healthy subjects, we show that the strength of the connection from the amygdala to the hippocampus was rapidly and robustly increased during the encoding of both positive and negative pictures in relation to neutral pictures. We also observed an increase in connection strength from the hippocampus to the amygdala, albeit at a smaller scale. These findings indicate that, during encoding, emotionally arousing information leads to a robust increase in effective connectivity from the amygdala to the hippocampus, regardless of its valence.

  10. A unique role for the human amygdala in novelty detection

    OpenAIRE

    2010-01-01

    Previous research indicates that the amygdala and hippocampus are sensitive to novelty; however, two types of novelty can be distinguished – stimuli that are ordinary, but novel in the current context, and stimuli that are unusual. Using functional magnetic resonance imaging, we examined blood oxygen dependent level (BOLD) response of the human amygdala and hippocampus to novel, commonly seen objects versus novel unusual objects. When presented with the novel common stimuli, the BOLD signal i...

  11. Corticotropin releasing factor and catecholamines enhance glutamatergic neurotransmission in the lateral subdivision of the central amygdala.

    Science.gov (United States)

    Silberman, Yuval; Winder, Danny G

    2013-07-01

    Glutamatergic neurotransmission in the central nucleus of the amygdala (CeA) plays an important role in many behaviors including anxiety, memory consolidation and cardiovascular responses. While these behaviors can be modulated by corticotropin releasing factor (CRF) and catecholamine signaling, the mechanism(s) by which these signals modify CeA glutamatergic neurotransmission remains unclear. Utilizing whole-cell patch-clamp electrophysiology recordings from neurons in the lateral subdivision of the CeA (CeAL), we show that CRF, dopamine (DA) and the β-adrenergic receptor agonist isoproterenol (ISO) all enhance the frequency of spontaneous excitatory postsynaptic currents (sEPSC) without altering sEPSC kinetics, suggesting they increase presynaptic glutamate release. The effect of CRF on sEPSCs was mediated by a combination of CRFR1 and CRFR2 receptors. While previous work from our lab suggests that CRFRs mediate the effect of catecholamines on excitatory transmission in other subregions of the extended amygdala, blockade of CRFRs in the CeAL failed to significantly alter effects of DA and ISO on glutamatergic transmission. These findings suggest that catecholamine and CRF enhancement of glutamatergic transmission onto CeAL neurons occurs via distinct mechanisms. While CRF increased spontaneous glutamate release in the CeAL, CRF caused no significant changes to optogenetically evoked glutamate release in this region. The dissociable effects of CRF on different types of glutamatergic neurotransmission suggest that CRF may specifically regulate spontaneous excitatory transmission.

  12. Heritable influences on amygdala and orbitofrontal cortex contribute to genetic variation in core dimensions of personality.

    Science.gov (United States)

    Lewis, G J; Panizzon, M S; Eyler, L; Fennema-Notestine, C; Chen, C-H; Neale, M C; Jernigan, T L; Lyons, M J; Dale, A M; Kremen, W S; Franz, C E

    2014-12-01

    While many studies have reported that individual differences in personality traits are genetically influenced, the neurobiological bases mediating these influences have not yet been well characterized. To advance understanding concerning the pathway from genetic variation to personality, here we examined whether measures of heritable variation in neuroanatomical size in candidate regions (amygdala and medial orbitofrontal cortex) were associated with heritable effects on personality. A sample of 486 middle-aged (mean=55 years) male twins (complete MZ pairs=120; complete DZ pairs=84) underwent structural brain scans and also completed measures of two core domains of personality: positive and negative emotionality. After adjusting for estimated intracranial volume, significant phenotypic (r(p)) and genetic (r(g)) correlations were observed between left amygdala volume and positive emotionality (r(p)=.16, porbitofrontal cortex thickness and negative emotionality were also observed (r(g)=.34, p<.01; r(e)=-.19, p<.05, respectively). These findings support a model positing that heritable bases of personality are, at least in part, mediated through individual differences in the size of brain structures, although further work is still required to confirm this causal interpretation.

  13. Heritable influences on amygdala and orbitofrontal cortex contribute to genetic variation in core dimensions of personality

    Science.gov (United States)

    Lewis, G.J.; Panizzon, M.S.; Eyler, L.; Fennema-Notestine, C.; Chen, C.-H.; Neale, M.C.; Jernigan, T.L.; Lyons, M.J.; Dale, A.M.; Kremen, W.S.; Franz, C.E.

    2015-01-01

    While many studies have reported that individual differences in personality traits are genetically influenced, the neurobiological bases mediating these influences have not yet been well characterized. To advance understanding concerning the pathway from genetic variation to personality, here we examined whether measures of heritable variation in neuroanatomical size in candidate regions (amygdala and medial orbitofrontal cortex) were associated with heritable effects on personality. A sample of 486 middle-aged (mean = 55 years) male twins (complete MZ pairs = 120; complete DZ pairs = 84) underwent structural brain scans and also completed measures of two core domains of personality: positive and negative emotionality. After adjusting for estimated intracranial volume, significant phenotypic (rp) and genetic (rg) correlations were observed between left amygdala volume and positive emotionality (rp = .16, p < .01; rg = .23, p < .05, respectively). In addition, after adjusting for mean cortical thickness, genetic and nonshared-environmental correlations (re) between left medial orbitofrontal cortex thickness and negative emotionality were also observed (rg = .34, p < .01; re = −.19, p < .05, respectively). These findings support a model positing that heritable bases of personality are, at least in part, mediated through individual differences in the size of brain structures, although further work is still required to confirm this causal interpretation. PMID:25263286

  14. Association between neuroticism and amygdala responsivity emerges under stressful conditions.

    Science.gov (United States)

    Everaerd, Daphne; Klumpers, Floris; van Wingen, Guido; Tendolkar, Indira; Fernández, Guillén

    2015-05-15

    Increased amygdala reactivity in response to salient stimuli is seen in patients with affective disorders, in healthy subjects at risk for these disorders, and in stressed individuals, making it a prime target for mechanistic studies into the pathophysiology of affective disorders. However, whereas individual differences in neuroticism are thought to modulate the effect of stress on mental health, the mechanistic link between stress, neuroticism and amygdala responsivity is unknown. Thus, we studied the relationship between experimentally induced stress, individual differences in neuroticism, and amygdala responsivity. To this end, fearful and happy faces were presented to a large cohort of young, healthy males (n=120) in two separate functional MRI sessions (stress versus control) in a randomized, controlled cross-over design. We revealed that amygdala reactivity was modulated by an interaction between the factors of stress, neuroticism, and the emotional valence of the facial stimuli. Follow-up analysis showed that neuroticism selectively enhanced amygdala responses to fearful faces in the stress condition. Thus, we show that stress unmasks an association between neuroticism and amygdala responsivity to potentially threatening stimuli. This effect constitutes a possible mechanistic link within the complex pathophysiology of affective disorders, and our novel approach appears suitable for further studies targeting the underlying mechanisms.

  15. Amygdala signals subjective appetitiveness and aversiveness of mixed gambles

    DEFF Research Database (Denmark)

    Gelskov, Sofie V.; Henningsson, Susanne; Madsen, Kristoffer Hougaard

    2015-01-01

    People are more sensitive to losses than to equivalent gains when making financial decisions. We used functional magnetic resonance imaging (fMRI) to illuminate how the amygdala contributes to loss aversion. The blood oxygen level dependent (BOLD) response of the amygdala was mapped while healthy...... with individual differences in loss aversion. Together, the results show that the amygdala signals subjective appetitiveness or aversiveness of gain-loss ratios at the time of choice. (C) 2015 Elsevier Ltd. All rights reserved....... individuals were responding to 50/50 gambles with varying potential gain and loss amounts. Overall, subjects demanded twice as high potential gain as loss to accept a gamble. The individual level of loss aversion was expressed by the decision boundary, i.e., the gain-loss ratio at which subjects accepted...... and rejected gambles with equal probability. Amygdala activity increased the more the gain-loss ratio deviated from the individual decision boundary showing that the amygdala codes action value. This response pattern was more strongly expressed in loss aversive individuals, linking amygdala activity...

  16. Amygdala's involvement in facilitating associative learning-induced plasticity: a promiscuous role for the amygdala in memory acquisition.

    Science.gov (United States)

    Chau, Lily S; Galvez, Roberto

    2012-01-01

    It is widely accepted that the amygdala plays a critical role in acquisition and consolidation of fear-related memories. Some of the more widely employed behavioral paradigms that have assisted in solidifying the amygdala's role in fear-related memories are associative learning paradigms. With most associative learning tasks, a neutral conditioned stimulus (CS) is paired with a salient unconditioned stimulus (US) that elicits an unconditioned response (UR). After multiple CS-US pairings, the subject learns that the CS predicts the onset or delivery of the US, and thus elicits a learned conditioned response (CR). Most fear-related associative paradigms have suggested that an aspect of the fear association is stored in the amygdala; however, some fear-motivated associative paradigms suggest that the amygdala is not a site of storage, but rather facilitates consolidation in other brain regions. Based upon various learning theories, one of the most likely sites for storage of long-term memories is the neocortex. In support of these theories, findings from our laboratory, and others, have demonstrated that trace-conditioning, an associative paradigm where there is a separation in time between the CS and US, induces learning-specific neocortical plasticity. The following review will discuss the amygdala's involvement, either as a site of storage or facilitating storage in other brain regions such as the neocortex, in fear- and non-fear-motivated associative paradigms. In this review, we will discuss recent findings suggesting a broader role for the amygdala in increasing the saliency of behaviorally relevant information, thus facilitating acquisition for all forms of memory, both fear- and non-fear-related. This proposed promiscuous role of the amygdala in facilitating acquisition for all memories further suggests a potential role of the amygdala in general learning disabilities.

  17. Tension-related activity in the orbitofrontal cortex and amygdala: an fMRI study with music.

    Science.gov (United States)

    Lehne, Moritz; Rohrmeier, Martin; Koelsch, Stefan

    2014-10-01

    Tonal music is characterized by a continuous flow of tension and resolution. This flow of tension and resolution is closely related to processes of expectancy and prediction and is a key mediator of music-evoked emotions. However, the neural correlates of subjectively experienced tension and resolution have not yet been investigated. We acquired continuous ratings of musical tension for four piano pieces. In a subsequent functional magnetic resonance imaging experiment, we identified blood oxygen level-dependent signal increases related to musical tension in the left lateral orbitofrontal cortex (pars orbitalis of the inferior frontal gyrus). In addition, a region of interest analysis in bilateral amygdala showed activation in the right superficial amygdala during periods of increasing tension (compared with decreasing tension). This is the first neuroimaging study investigating the time-varying changes of the emotional experience of musical tension, revealing brain activity in key areas of affective processing.

  18. Bioactive dietary polyphenols decrease heme iron absorption by decreasing basolateral iron release in human intestinal Caco-2 cells.

    Science.gov (United States)

    Ma, Qianyi; Kim, Eun-Young; Han, Okhee

    2010-06-01

    Because dietary polyphenolic compounds have a wide range of effects in vivo and vitro, including chelation of metals such as iron, it is prudent to test whether the regular consumption of dietary bioactive polyphenols impair the utilization of dietary iron. Because our previous study showed the inhibitory effect of (-) -epigallocatechin-3-gallate (EGCG) and grape seed extract (GSE) on nonheme iron absorption, we investigated whether EGCG and GSE also affect iron absorption from heme. The fully differentiated intestinal Caco-2 cells grown on microporous membrane inserts were incubated with heme (55)Fe in uptake buffer containing EGCG or GSE in the apical compartment for 7 h. Both EGCG and GSE decreased (P heme-derived iron. However, apical heme iron uptake was increased (P heme (55)Fe, the transfer of iron across the intestinal basolateral membrane was extremely low, indicating that basolateral export was impaired by GSE. In contrast, EGCG moderately decreased the cellular assimilation of heme (55)Fe, but the basolateral iron transfer was extremely low, suggesting that the basolateral efflux of heme iron was also inhibited by EGCG. Expression of heme oxygenase, ferroportin, and hephaestin protein was not changed by EGCG and GSE. The apical uptake of heme iron was temperature dependent and saturable in fully differentiated Caco-2 cells. Our data show that bioactive dietary polyphenols inhibit heme iron absorption mainly by reducing basolateral iron exit rather than decreasing apical heme iron uptake in intestinal cells.

  19. Inhibition of adenylyl cyclase in amygdala blocks the effect of audiogenic seizure kindling in genetically epilepsy-prone rats.

    Science.gov (United States)

    Tupal, Srinivasan; Faingold, Carl

    2010-01-01

    Genetically epilepsy-prone rats of the severe seizure strain (GEPR-9s) exhibit audiogenic seizures (AGS) beginning with wild running and ending with tonic hind limb extension (TE). AGS kindling in GEPR-9s involves periodic repetition of >/=14 seizures over 7-21 days and results in prolonged seizures and an additional phase of generalized post-tonic clonus (PTC) that follows TE. AGS kindling behavior changes are long-lasting and involve expansion of the requisite seizure neuronal network from the brainstem to include the amygdala, mediated by neuroplasticity in lateral amygdala. Recent evidence indicates that focal activation of adenylyl cyclase (AC) in lateral amygdala leads to precipitous acquisition of AGS-kindled seizure behaviors, suggesting that activation of AC activity is important in development and maintenance of AGS kindling. The present study further examined the role of AC in AGS-kindled seizures in GEPR-9s by focally inhibiting AC in the amygdala. Bilateral microinjection of an AC inhibitor, SQ22,536 (0.25 and 0.50 nmol/side), in AGS-kindled GEPR-9s selectively blocked PTC during AGS at 1 h after microinjection, but the pre-kindled AGS behaviors remained intact. The incidence of PTC during AGS returned to pre-drug levels 12 h after the lower dose of SQ22,536 (0.25 nmol/side). However, after the higher dose of SQ22,536 (0.5 nmol/side), complete return to AGS with PTC was seen in all GEPR-9s at 120 h. These results indicate that maintenance of AGS kindling-mediated PTC in GEPR-9s may involve activation of AC. These data provide further evidence for the involvement of AC in the epileptogenic mechanisms subserving AGS kindling.

  20. Intracellular calcium modulates basolateral K(+)-permeability in frog skin epithelium

    DEFF Research Database (Denmark)

    Brodin, Birger; Rytved, K A; Nielsen, R

    1994-01-01

    Cytosolic calcium ([Ca2+]i) has been suggested as a key modulator in the regulation of active sodium transport across electrically "tight" (high resistance) epithelia. In this study we investigated the effects of calcium on cellular electrophysiological parameters in a classical model tissue......, the frog skin. [Ca2+]i was measured with fura-2 in an epifluorescence microscope setup. An inhibition of basolateral potassium permeability was observed when cytosolic calcium was increased. This inhibition was reversible upon removal of calcium from the serosal solution....

  1. Ensemble coding of context-dependent fear memory in the amygdala

    Directory of Open Access Journals (Sweden)

    Caitlin A Orsini

    2013-12-01

    Full Text Available After fear conditioning, presenting the conditioned stimulus (CS alone yields a context-specific extinction memory; fear is suppressed in the extinction context, but renews in any other context. The context-dependence of extinction is mediated by a brain circuit consisting of the hippocampus, prefrontal cortex and amygdala. In the present work, we sought to determine at what level of this circuit context-dependent representations of the CS emerge. To explore this question, we used cellular compartment analysis of temporal activity by fluorescent in situ hybridization (catFISH. This method exploits the intracellular expression profile of the immediate early gene, Arc, to visualize neuronal activation patterns to two different behavioral experiences. Rats were fear conditioned in one context and extinguished in another; twenty-four hours later, they were sequentially exposed to the CS in the extinction context and another context. Control rats were also tested in each context, but were never extinguished. We assessed Arc mRNA expression within the basal amygdala (BA, lateral amygdala (LA, ventral hippocampus (VH, prelimbic cortex (PL and infralimbic cortex (IL. We observed that the sequential retention tests induced context-dependent patterns of Arc expression in the BA, LA, and IL of extinguished rats; this was not observed in non-extinguished controls. In general, non-extinguished animals had proportionately greater numbers of non-selective (double-labeled neurons than extinguished animals. Collectively, these findings suggest that extinction learning results in pattern separation, particularly within the BA, in which unique neuronal ensembles represent fear memories after extinction.

  2. In vivo knockdown of GAD67 in the amygdala disrupts fear extinction and the anxiolytic-like effect of diazepam in mice.

    Science.gov (United States)

    Heldt, S A; Mou, L; Ressler, K J

    2012-11-13

    In mammals, γ-aminobutyric acid (GABA) transmission in the amygdala is particularly important for controlling levels of fear and anxiety. Most GABA synthesis in the brain is catalyzed in inhibitory neurons from L-glutamic acid by the enzyme glutamic acid decarboxylase 67 (GAD67). In the current study, we sought to examine the acquisition and extinction of conditioned fear in mice with knocked down expression of the GABA synthesizing enzyme GAD67 in the amygdala using a lentiviral-based (LV) RNA interference strategy to locally induce loss-of-function. In vitro experiments revealed that our LV-siRNA-GAD67 construct diminished the expression of GAD67 as determined with western blot and fluorescent immunocytochemical analyses. In vivo experiments, in which male C57BL/6J mice received bilateral amygdala microinjections, revealed that LV-siRNA-GAD67 injections produce significant inhibition of endogenous GAD67 when compared with control injections. In contrast, no significant changes in GAD65 expression were detected in the amygdala, validating the specificity of LV knockdown. Behavioral experiments showed that LV knockdown of GAD67 results in a deficit in the extinction, but not the acquisition or retention, of fear as measured by conditioned freezing. GAD67 knockdown did not affect baseline locomotion or basal measures of anxiety as measured in open field apparatus. However, diminished GAD67 in the amygdala blunted the anxiolytic-like effect of diazepam (1.5 mg kg(-1)) as measured in the elevated plus maze. Together, these studies suggest that of GABAergic transmission in amygdala mediates the inhibition of conditioned fear and the anxiolytic-like effect of diazepam in adult mice.

  3. Diverting attention suppresses human amygdala responses to faces

    Directory of Open Access Journals (Sweden)

    Carmen eMorawetz

    2010-12-01

    Full Text Available Recent neuroimaging studies disagree as to whether the processing of emotion-laden visual stimuli is dependent upon the availability of attentional resources or entirely capacity-free. Two main factors have been proposed to be responsible for the discrepancies: the differences in the perceptual attentional demands of the tasks used to divert attentional resources from emotional stimuli and the spatial location of the affective stimuli in the visual field. To date, no neuroimaging report addressed these two issues in the same set of subjects. Therefore, the aim of the study was to investigate the effects of high and low attentional load as well as different stimulus locations on face processing in the amygdala using fMRI to provide further evidence for one of the two opposing theories. We were able for the first time to directly test the interaction of attentional load and spatial location. The results revealed a strong attenuation of amygdala activity when the attentional load was high. The eccentricity of the emotional stimuli did not affect responses in the amygdala and no interaction effect between attentional load and spatial location was found. We conclude that the processing of emotional stimuli in the amygdala is strongly dependent on the availability of attentional resources without a preferred processing of stimuli presented in the periphery and provide firm evidence for the concept of the attentional load theory of emotional processing in the amygdala.

  4. Insulin-like growth factor II stimulates production of inositol trisphosphate in proximal tubular basolateral membranes from canine kidney.

    OpenAIRE

    Rogers, S A; Hammerman, M R

    1988-01-01

    To determine whether insulin-like growth factor II (IGF-II) activates phospholipase C in the basolateral membrane of the renal proximal tubular cell, we incubated basolateral membranes isolated from canine kidney with rat IGF-II (rIGF-II) and measured levels of inositol trisphosphate (Ins-P3) in suspensions and of diacylglycerol extractable from the membranes. Incubation with rIGF-II increased levels of Ins-P3 and diacylglycerol in a concentration-dependent manner. Significant enhancement of ...

  5. Amygdala-kindling induces a lasting reduction of GABA-immunoreactive neurons in a discrete area of the ipsilateral piriform cortex.

    Science.gov (United States)

    Lehmann, H; Ebert, U; Löscher, W

    1998-08-01

    Several lines of evidence indicate a critical role of the piriform cortex (PC) in the kindling model of temporal lobe epilepsy, suggesting that the PC is part of an epileptic network that is pivotal in the genesis of kindling, facilitating, and intensifying the spread of seizures from a focus in amygdala, hippocampus, or other limbic brain regions to cortical and subcortical regions. Kindling of the amygdala has been shown to induce long-lasting changes in synaptic efficacy in the ipsilateral PC comparable to abnormalities seen in epileptic foci, but the neurochemical alterations possibly underlying these functional changes are not known. The possibility that the enhanced excitability of the PC in response to kindling is related to a reduction of GABAergic neurotransmission prompted us to examine if a lasting reduction in GABA-immunoreactive PC neurons is detectable after kindling of the basolateral amygdala (BLA) in rats. Furthermore, GABA immunoreactivity was determined in the BLA in order to investigate whether GABAergic neurons decrease in focal tissue, as previously suggested by neurochemical and immunocytochemical studies in amygdala-kindled rats. Three groups of age-matched rats were used: (1) a group of rats that was kindled via electrical stimulation by a bipolar electrode implanted in the right BLA, (2) a group of BLA-implanted but nonstimulated rats, and (3) a group of non-implanted, naive control rats. The kindled rats were sacrificed 40 days after the last fully kindled seizure. The two other groups of rats were sacrificed together with the kindled rats on the same days, and tissues from kindled and control rats were treated concurrently throughout the immunohistochemical analysis. GABA neurons were stained by a monoclonal antibody to GABA. Kindling of the BLA led to a pronounced decrease in the number of GABA immunoreactive neurons in the ipsi- and contralateral BLA at all section levels examined. In the PC, no significant differences between groups

  6. Depressive Symptoms and Amygdala Volume in Elderly with Cerebral Small Vessel Disease: The RUN DMC Study

    Directory of Open Access Journals (Sweden)

    I. W. M. van Uden

    2011-01-01

    Conclusion. Lower left amygdala volume is associated with LODS, independent of SVD. This may suggest differential mechanisms, in which individuals with a small amygdala might be vulnerable to develop LODS.

  7. Neural substrates for expectation-modulated fear learning in the amygdala and periaqueductal gray.

    Science.gov (United States)

    Johansen, Joshua P; Tarpley, Jason W; LeDoux, Joseph E; Blair, Hugh T

    2010-08-01

    A form of aversively motivated learning called fear conditioning occurs when a neutral conditioned stimulus is paired with an aversive unconditioned stimulus (UCS). UCS-evoked depolarization of amygdala neurons may instruct Hebbian plasticity that stores memories of the conditioned stimulus-unconditioned stimulus association, but the origin of UCS inputs to the amygdala is unknown. Theory and evidence suggest that instructive UCS inputs to the amygdala will be inhibited when the UCS is expected, but this has not been found during fear conditioning. We investigated neural pathways that relay information about the UCS to the amygdala by recording neurons in the amygdala and periaqueductal gray (PAG) of rats during fear conditioning. UCS-evoked responses in both amygdala and PAG were inhibited by expectation. Pharmacological inactivation of the PAG attenuated UCS-evoked responses in the amygdala and impaired acquisition of fear conditioning, indicating that PAG may be an important part of the pathway that relays instructive signals to the amygdala.

  8. Neuropeptide Y (NPY) in the extended amygdala is recruited during the transition to alcohol dependence.

    Science.gov (United States)

    Gilpin, Nicholas W

    2012-12-01

    Neuropeptide Y (NPY) is abundant in the extended amygdala, a conceptual macrostructure in the basal forebrain important for regulation of negative affective states. NPY has been attributed a central role in anxiety-like behavior, fear, nociception, and reward in rodents. Deletion of the NPY gene in mice produces a high-anxiety high-alcohol-drinking phenotype. NPY infused into the brains of rats selectively bred to consume high quantities of alcohol suppresses alcohol drinking by those animals, an effect that is mediated by central amygdala (CeA). Likewise, alcohol-preferring rats exhibit basal NPY deficits in CeA. NPY infused into the brains of alcohol-dependent rats blocks excessive alcohol drinking by those animals, an effect that also has been localized to the CeA. NPY in CeA may rescue dependence-induced increases in anxiety and alcohol drinking via inhibition of downstream effector regions that receive GABAergic inputs from CeA. It is hypothesized here that NPY modulates anxiety-like behavior via Y2R regulation of NPY release, whereas NPY modulation of alcohol-drinking behavior in alcohol-dependent animals occurs via Y2R regulation of GABA release.

  9. Amphetamine sensitization and amygdala kindling: pharmacological evaluation of catecholaminergic and cholinergic mechanisms.

    Science.gov (United States)

    Kirkby, R D; Kokkinidis, L

    1991-03-01

    Chronic pharmacological experiments were conducted to evaluate the relationship between sensitization induced by repeated administration of amphetamine (AMPH) and electrical stimulation of the amygdala. While AMPH withdrawal did not influence the kindling process, AMPH administered during the kindling procedure increased the rate at which seizures evolved, and under these conditions withdrawal from chronic AMPH further facilitated the propensity to kindle. Haloperidol (HAL) treatment failed to block the stimulant-induced increase in kindling acquisition indicating that changes in dopamine (DA) are not necessary for the AMPH/kindling synergism to develop. Scopolamine dose-dependently retarded kindling evolution irrespective of prior AMPH pretreatment also ruling out a cholinergic mechanism in the kindling sensitization. Subsequent experiments assessed the interactive effects of AMPH and desipramine (DMI) on the kindling process. Animals chronically exposed to AMPH and switched to DMI treatment during the kindling procedure kindled faster than control subjects. In addition, withdrawal from DMI preexposure advanced the AMPH-induced increase in kindling rate. These results were discussed in terms of the role of norepinephrine-mediated inhibition of the kindling process, and were related to drug-elicited alterations in beta-adrenergic receptor functioning. Taken together, these findings implicate the amygdala as an important structure in the development of non-DA forms of AMPH sensitization.

  10. Oxytocin promotes facial emotion recognition and amygdala reactivity in adults with asperger syndrome.

    Science.gov (United States)

    Domes, Gregor; Kumbier, Ekkehardt; Heinrichs, Markus; Herpertz, Sabine C

    2014-02-01

    The neuropeptide oxytocin has recently been shown to enhance eye gaze and emotion recognition in healthy men. Here, we report a randomized double-blind, placebo-controlled trial that examined the neural and behavioral effects of a single dose of intranasal oxytocin on emotion recognition in individuals with Asperger syndrome (AS), a clinical condition characterized by impaired eye gaze and facial emotion recognition. Using functional magnetic resonance imaging, we examined whether oxytocin would enhance emotion recognition from facial sections of the eye vs the mouth region and modulate regional activity in brain areas associated with face perception in both adults with AS, and a neurotypical control group. Intranasal administration of the neuropeptide oxytocin improved performance in a facial emotion recognition task in individuals with AS. This was linked to increased left amygdala reactivity in response to facial stimuli and increased activity in the neural network involved in social cognition. Our data suggest that the amygdala, together with functionally associated cortical areas mediate the positive effect of oxytocin on social cognitive functioning in AS.

  11. CREB regulates spine density of lateral amygdala neurons: implications for memory allocation

    Directory of Open Access Journals (Sweden)

    Derya eSargin

    2013-12-01

    Full Text Available Neurons may compete against one another for integration into a memory trace. Specifically, neurons in the lateral nucleus of the amygdala with relatively higher levels of CREB seem to be preferentially allocated to a fear memory trace, while neurons with relatively decreased CREB function seem to be excluded from a fear memory trace. CREB is a ubiquitous transcription factor that modulates many diverse cellular processes, raising the question as to which of these CREB-mediated processes underlie memory allocation. CREB is implicated in modulating dendritic spine number and morphology. As dendritic spines are intimately involved in memory formation, we investigated whether manipulations of CREB function alter spine number or morphology of neurons at the time of fear conditioning. We used viral vectors to manipulate CREB function in the lateral amygdala principal neurons in mice maintained in their homecages. At the time that fear conditioning normally occurs, we observed that neurons with high levels of CREB had more dendritic spines, while neurons with low CREB function had relatively fewer spines compared to control neurons. These results suggest that the modulation of spine density provides a potential mechanism for preferential allocation of a subset of neurons to the memory trace.

  12. Persistent affective biases in human amygdala response following implicit priming with negative emotion concepts.

    Science.gov (United States)

    Pichon, Swann; Rieger, Sebastian W; Vuilleumier, Patrik

    2012-09-01

    To what extent do past experiences shape our behaviors, perceptions, and thoughts even without explicit knowledge of these influences? Behavioral research has demonstrated that various cognitive processes can be influenced by conceptual representations implicitly primed during a preceding and unrelated task. Here we investigated whether emotion processing might also be influenced by prior incidental exposure to negative semantic material and which neural substrates would mediate these effects. During a first (priming) task, participants performed a variant of the hangman game with either negative or neutral emotion-laden words. Subsequently, they performed a second, unrelated visual task with fearful and neutral faces presented at attended or unattended locations. Participants were generally not aware of any relationships between the two tasks. We found that priming with emotional words enhanced amygdala sensitivity to faces in the subsequent visual task, while decreasing discriminative responses to threat. Furthermore, the magnitude of the induced bias in behavior and amygdala activation was predicted by the effectiveness of semantic access observed in the priming task. This demonstrates that emotional processing can be modulated by implicit influence of environmental information processed at an earlier time, independently of volitional control.

  13. Inhibitory networks of the amygdala for emotional memory

    Directory of Open Access Journals (Sweden)

    Seungho eLee

    2013-08-01

    Full Text Available The amygdala is important for emotional memory, including learned fear. A number of studies for amygdala neural circuits that underlie fear conditioning have elucidated specific cellular and molecular mechanisms of emotional memory. Recent technical advances such as optogenetic approaches have not only confirmed the importance of excitatory circuits in fear conditioning, but have also shed new light for a direct role of inhibitory circuits in both the acquisition and extinction of fear memory in addition to their role in fine tuning of excitatory neural circuitry. As a result, the circuits in amygdala could be drawn more elaborately, and it led us to understand how fear or extinction memories are formed in the detailed circuit level, and various neuromodulators affect these circuit activities, inducing subtle behavioral changes.

  14. Intradentate colchicine retards the development of amygdala kindling.

    Science.gov (United States)

    Dasheiff, R M; McNamara, J O

    1982-04-01

    The mechanisms underlying the kindling model of epilepsy are unknown. Presumably, an altered network of neural circuits underlie amygdala kindling. Biochemical and radiohistochemical studies have pointed to the dentate granule cells (DGC) of the hippocampal formation as a member of this altered circuit. To test the role of these cells, colchicine, a neurotoxin of DGC, was directly injected into the dentate gyrus. Prior destruction of DGC retarded the development of amygdala kindling. Destruction of DGC after kindling was completed did not reverse the kindling effect. We conclude that DGC play a key role in the development, but not the permanence, of amygdala kindling. We propose a model whereby the greater the input to the hippocampal formation, the faster limbic kindling will proceed.

  15. Amygdala activation for eye contact despite complete cortical blindness.

    Science.gov (United States)

    Burra, Nicolas; Hervais-Adelman, Alexis; Kerzel, Dirk; Tamietto, Marco; de Gelder, Beatrice; Pegna, Alan J

    2013-06-19

    Cortical blindness refers to the loss of vision that occurs after destruction of the primary visual cortex. Although there is no sensory cortex and hence no conscious vision, some cortically blind patients show amygdala activation in response to facial or bodily expressions of emotion. Here we investigated whether direction of gaze could also be processed in the absence of any functional visual cortex. A well-known patient with bilateral destruction of his visual cortex and subsequent cortical blindness was investigated in an fMRI paradigm during which blocks of faces were presented either with their gaze directed toward or away from the viewer. Increased right amygdala activation was found in response to directed compared with averted gaze. Activity in this region was further found to be functionally connected to a larger network associated with face and gaze processing. The present study demonstrates that, in human subjects, the amygdala response to eye contact does not require an intact primary visual cortex.

  16. "The Cooties Effect": Amygdala Reactivity to Opposite- versus Same-sex Faces Declines from Childhood to Adolescence.

    Science.gov (United States)

    Telzer, Eva H; Flannery, Jessica; Humphreys, Kathryn L; Goff, Bonnie; Gabard-Durman, Laurel; Gee, Dylan G; Tottenham, Nim

    2015-09-01

    One of the most important social identities that children learn to define themselves and others by is sex, becoming a salient social category by early childhood. Although older children begin to show greater flexibility in their gendered behaviors and attitudes, gender rigidity intensifies again around the time of puberty. In the current study, we assessed behavioral and neural biases to sex across a wide age group. Ninety-three youth (ages 7-17 years) provided behavioral rating of same- and opposite-sex attitudes, and 52 youth (ages 4-18 years) underwent an fMRI scan as they matched the emotion of same- and opposite-sex faces. We demonstrate significant age-related behavioral biases of sex that are mediated by differential amygdala response to opposite-sex relative to same-sex faces in children, an effect that completely attenuates by the teenage years. Moreover, we find a second peak in amygdala sensitivity to opposite-sex faces around the time of puberty. Thus, the amygdala codes for developmentally dependent and motivationally relevant social identification across development.

  17. Context-dependent encoding of fear and extinction memories in a large-scale network model of the basal amygdala.

    Directory of Open Access Journals (Sweden)

    Ioannis Vlachos

    2011-03-01

    Full Text Available The basal nucleus of the amygdala (BA is involved in the formation of context-dependent conditioned fear and extinction memories. To understand the underlying neural mechanisms we developed a large-scale neuron network model of the BA, composed of excitatory and inhibitory leaky-integrate-and-fire neurons. Excitatory BA neurons received conditioned stimulus (CS-related input from the adjacent lateral nucleus (LA and contextual input from the hippocampus or medial prefrontal cortex (mPFC. We implemented a plasticity mechanism according to which CS and contextual synapses were potentiated if CS and contextual inputs temporally coincided on the afferents of the excitatory neurons. Our simulations revealed a differential recruitment of two distinct subpopulations of BA neurons during conditioning and extinction, mimicking the activation of experimentally observed cell populations. We propose that these two subgroups encode contextual specificity of fear and extinction memories, respectively. Mutual competition between them, mediated by feedback inhibition and driven by contextual inputs, regulates the activity in the central amygdala (CEA thereby controlling amygdala output and fear behavior. The model makes multiple testable predictions that may advance our understanding of fear and extinction memories.

  18. Neuropeptide Y Administration into the Amygdala Suppresses Ethanol Drinking in Alcohol-Preferring (P) Rats Following Multiple Deprivations

    Science.gov (United States)

    Gilpin, Nicholas W.; Stewart, Robert B.; Badia-Elder, Nancy E.

    2008-01-01

    The present experiment examines the effects of NPY administered into the amygdala on ethanol drinking by alcohol-preferring P rats following long-term continuous ethanol access, with and without multiple periods of imposed ethanol abstinence. P rats had access to 15% (v/v) ethanol and water for 11 weeks followed by 2 weeks of ethanol abstinence, re-exposure to ethanol for 2 weeks, 2 more weeks of ethanol abstinence, and a final ethanol re-exposure. Immediately prior to the second ethanol re-exposure, 4 groups of rats received bilateral infusions NPY (0.25, 0.5, 1.0 μg) or artificial cerebrospinal fluid (aCSF) into the amygdala. Two additional groups were given uninterrupted ethanol access and were infused with a single NPY dose (1.0 μg) or aCSF. The highest NPY dose (1.0 μg) suppressed ethanol intake for 24 hrs in rats with a history of ethanol abstinence (i.e. deprivation) periods, but had no effect in rats with a history of continuous ethanol access. Water and food intakes were not altered. These results suggest that the amygdala mediates the suppressive effects of centrally administered NPY on ethanol drinking, and that NPY may block relapse-like drinking by opposing the anxiogenic effects of ethanol abstinence. PMID:18499241

  19. Meta-Analysis of Amygdala Volumes in Children and Adolescents with Bipolar Disorder

    Science.gov (United States)

    Pfeifer, Jonathan C.; Welge, Jeffrey; Strakowski. Stephen M.; Adler, Caleb M.; Delbello, Melissa P.

    2008-01-01

    The size of amygdala of bipolar youths and adults is investigated using neuroimaging studies. Findings showed that smaller volumes of amygdala were observed in youths with bipolar youths compared with children and adolescents without bipolar disorder. The structural amygdala abnormalities in bipolar youths are examined further.

  20. Shared Genetic Factors Influence Amygdala Volumes and Risk for Alcoholism

    Science.gov (United States)

    Dager, Alecia D; McKay, D Reese; Kent, Jack W; Curran, Joanne E; Knowles, Emma; Sprooten, Emma; Göring, Harald HH; Dyer, Thomas D; Pearlson, Godfrey D; Olvera, Rene L; Fox, Peter T; Lovallo, William R; Duggirala, Ravi; Almasy, Laura; Blangero, John; Glahn, David C

    2015-01-01

    Alcohol abuse and dependence (alcohol use disorders, AUDs) are associated with brain shrinkage. Subcortical structures including the amygdala, hippocampus, ventral striatum, dorsal striatum, and thalamus subserve reward functioning and may be particularly vulnerable to alcohol-related damage. These structures may also show pre-existing deficits impacting the development and maintenance of AUD. It remains unclear whether there are common genetic features underlying both subcortical volumes and AUD. In this study, structural brain images were acquired from 872 Mexican-American individuals from extended pedigrees. Subcortical volumes were obtained using FreeSurfer, and quantitative genetic analyses were performed in SOLAR. We hypothesized the following: (1) reduced subcortical volumes in individuals with lifetime AUD relative to unrelated controls; (2) reduced subcortical volumes in individuals with current relative to past AUD; (3) in non-AUD individuals, reduced subcortical volumes in those with a family history of AUD compared to those without; and (4) evidence for common genetic underpinnings (pleiotropy) between AUD risk and subcortical volumes. Results showed that individuals with lifetime AUD showed larger ventricular and smaller amygdala volumes compared to non-AUD individuals. For the amygdala, there were no differences in volume between current vs past AUD, and non-AUD individuals with a family history of AUD demonstrated reductions compared to those with no such family history. Finally, amygdala volume was genetically correlated with the risk for AUD. Together, these results suggest that reduced amygdala volume reflects a pre-existing difference rather than alcohol-induced neurotoxic damage. Our genetic correlation analysis provides evidence for a common genetic factor underlying both reduced amygdala volumes and AUD risk. PMID:25079289

  1. Shared genetic factors influence amygdala volumes and risk for alcoholism.

    Science.gov (United States)

    Dager, Alecia D; McKay, D Reese; Kent, Jack W; Curran, Joanne E; Knowles, Emma; Sprooten, Emma; Göring, Harald H H; Dyer, Thomas D; Pearlson, Godfrey D; Olvera, Rene L; Fox, Peter T; Lovallo, William R; Duggirala, Ravi; Almasy, Laura; Blangero, John; Glahn, David C

    2015-01-01

    Alcohol abuse and dependence (alcohol use disorders, AUDs) are associated with brain shrinkage. Subcortical structures including the amygdala, hippocampus, ventral striatum, dorsal striatum, and thalamus subserve reward functioning and may be particularly vulnerable to alcohol-related damage. These structures may also show pre-existing deficits impacting the development and maintenance of AUD. It remains unclear whether there are common genetic features underlying both subcortical volumes and AUD. In this study, structural brain images were acquired from 872 Mexican-American individuals from extended pedigrees. Subcortical volumes were obtained using FreeSurfer, and quantitative genetic analyses were performed in SOLAR. We hypothesized the following: (1) reduced subcortical volumes in individuals with lifetime AUD relative to unrelated controls; (2) reduced subcortical volumes in individuals with current relative to past AUD; (3) in non-AUD individuals, reduced subcortical volumes in those with a family history of AUD compared to those without; and (4) evidence for common genetic underpinnings (pleiotropy) between AUD risk and subcortical volumes. Results showed that individuals with lifetime AUD showed larger ventricular and smaller amygdala volumes compared to non-AUD individuals. For the amygdala, there were no differences in volume between current vs past AUD, and non-AUD individuals with a family history of AUD demonstrated reductions compared to those with no such family history. Finally, amygdala volume was genetically correlated with the risk for AUD. Together, these results suggest that reduced amygdala volume reflects a pre-existing difference rather than alcohol-induced neurotoxic damage. Our genetic correlation analysis provides evidence for a common genetic factor underlying both reduced amygdala volumes and AUD risk.

  2. Bilateral lesions of the central but not anterior or posterior parts of the piriform cortex retard amygdala kindling in rats.

    Science.gov (United States)

    Schwabe, K; Ebert, U; Löscher, W

    2000-01-01

    The piriform cortex is thought to be involved in temporal lobe seizure propagation, such as that occurring during kindling of the amygdala or hippocampus. A number of observations suggested that the circuits of the piriform cortex might act as a critical pathway for limbic seizure discharges to assess motor systems, but direct evidence for this suggestion is scarce. Furthermore, the piriform cortex is not a homogeneous structure, which complicates studies on its role in limbic epileptogenesis. We have previously reported data indicating that the central part of the piriform cortex might be particularly involved during amygdala kindling. In order to further evaluate the role of different parts of the piriform cortex during kindling development, we bilaterally destroyed either the central, anterior or posterior piriform cortex by microinjections of ibotenate two weeks before onset of amygdala kindling. Lesions of the anterior piriform cortex hardly affected kindling acquisition, except that fewer animals exhibited stage 3 (unilateral forelimb) seizures compared to sham controls. Lesions of the central piriform cortex significantly retarded kindling, which was due to a decreased progression from stage 3 to stage 4/5 seizures, i.e. the lesioned rats needed significantly longer for the acquisition of generalized clonic seizures in the late stages of kindling development. Lesions of the posterior piriform cortex did not significantly affect kindling development. The data demonstrate that different parts of the piriform cortex mediate qualitatively different effects on amygdala kindling. The central piriform cortex seems to be a neural substrate involved in the continuous development of kindling from stage 3 to stages 4/5, indicating that this part of the piriform cortex may have preferred access, either directly or indirectly, to structures capable of supporting generalized kindled seizure expression.

  3. OCD-like behavior is caused by dysfunction of thalamo-amygdala circuits and upregulated TrkB/ERK-MAPK signaling as a result of SPRED2 deficiency.

    Science.gov (United States)

    Ullrich, M; Weber, M; Post, A M; Popp, S; Grein, J; Zechner, M; Guerrero González, H; Kreis, A; Schmitt, A G; Üçeyler, N; Lesch, K-P; Schuh, K

    2017-01-10

    Obsessive-compulsive disorder (OCD) is a common neuropsychiatric disease affecting about 2% of the general population. It is characterized by persistent intrusive thoughts and repetitive ritualized behaviors. While gene variations, malfunction of cortico-striato-thalamo-cortical (CSTC) circuits, and dysregulated synaptic transmission have been implicated in the pathogenesis of OCD, the underlying mechanisms remain largely unknown. Here we show that OCD-like behavior in mice is caused by deficiency of SPRED2, a protein expressed in various brain regions and a potent inhibitor of Ras/ERK-MAPK signaling. Excessive self-grooming, reflecting OCD-like behavior in rodents, resulted in facial skin lesions in SPRED2 knockout (KO) mice. This was alleviated by treatment with the selective serotonin reuptake inhibitor fluoxetine. In addition to the previously suggested involvement of cortico-striatal circuits, electrophysiological measurements revealed altered transmission at thalamo-amygdala synapses and morphological differences in lateral amygdala neurons of SPRED2 KO mice. Changes in synaptic function were accompanied by dysregulated expression of various pre- and postsynaptic proteins in the amygdala. This was a result of altered gene transcription and triggered upstream by upregulated tropomyosin receptor kinase B (TrkB)/ERK-MAPK signaling in the amygdala of SPRED2 KO mice. Pathway overactivation was mediated by increased activity of TrkB, Ras, and ERK as a specific result of SPRED2 deficiency and not elicited by elevated brain-derived neurotrophic factor levels. Using the MEK inhibitor selumetinib, we suppressed TrkB/ERK-MAPK pathway activity in vivo and reduced OCD-like grooming in SPRED2 KO mice. Altogether, this study identifies SPRED2 as a promising new regulator, TrkB/ERK-MAPK signaling as a novel mediating mechanism, and thalamo-amygdala synapses as critical circuitry involved in the pathogenesis of OCD.Molecular Psychiatry advance online publication, 10 January

  4. Basolateral localisation of KCNQ1 potassium channels in MDCK cells: molecular identification of an N-terminal targeting motif

    DEFF Research Database (Denmark)

    Jespersen, Thomas; Rasmussen, Hanne B; Grunnet, Morten;

    2004-01-01

    KCNQ1 potassium channels are expressed in many epithelial tissues as well as in the heart. In epithelia KCNQ1 channels play an important role in salt and water transport and the channel has been reported to be located apically in some cell types and basolaterally in others. Here we show that KCNQ...

  5. Anti-inflammatory activity of the basolateral fraction of Caco-2 cells exposed to a rosemary supercritical extract

    NARCIS (Netherlands)

    Arranz, E.; Mes, J.J.; Wichers, H.J.; Jaime, L.; Reglero, G.; Santoyo, S.

    2015-01-01

    The anti-inflammatory activity of the basolateral fraction of Caco-2 cells exposed to a rosemary supercritical extract was examined. Uptake of rosemary extract fractions was tested on Caco-2 cell monolayers (2–12 h incubation times) and the quantification of carnosic acid and carnosol was performed

  6. Conditioned reinforcement can be mediated by either outcome-specific or general affective representations

    Directory of Open Access Journals (Sweden)

    Kathryn A Burke

    2007-11-01

    Full Text Available Conditioned reinforcers are Pavlovian cues that support the acquisition and maintenance of new instrumental responses. Responding on the basis of conditioned rather than primary reinforcers is a pervasive part of modern life, yet we have a remarkably limited understanding of what underlying associative information is triggered by these cues to guide responding. Specifically, it is not certain whether conditioned reinforcers are effective because they evoke representations of specific outcomes or because they trigger general affective states that are independent of any specific outcome. This question has important implications for how different brain circuits might be involved in conditioned reinforcement. Here, we use specialized Pavlovian training procedures, reinforcer devaluation and transreinforcer blocking, to create cues that were biased to preferentially evoke either devaluation-insensitive, general affect representations or, devaluationsensitive, outcome-specific representations. Subsequently, these cues, along with normally conditioned control cues, were presented contingent on lever pressing.We found that intact rats learned to lever press for either the outcome or the affect cues to the same extent as for a normally conditioned cue. These results demonstrate that conditioned reinforcers can guide responding through either type of associative information. Interestingly, conditioned reinforcement was abolished in rats with basolateral amygdala lesions. Consistent with the extant literature, this result suggests a general role for basolateral amygdala in conditioned reinforcement. The implications of these data, combined with recent reports from our laboratory of a more specialized role of orbitofrontal cortex in conditioned reinforcement, will be discussed.

  7. Features of compulsive checking behavior mediated by nucleus accumbens and orbital frontal cortex.

    Science.gov (United States)

    Dvorkin, Anna; Silva, Charmaine; McMurran, Thomas; Bisnaire, Liane; Foster, Jane; Szechtman, Henry

    2010-11-01

    The quinpirole sensitization model of obsessive-compulsive disorder was used to investigate the functional role that brain regions implicated in a neuroanatomical circuit of obsessive-compulsive disorder may play in compulsive checking behavior. Following repeated injections of saline or quinpirole (0.5mg/kg, twice per week, ×8 injections) to induce compulsive checking, rats received N-methyl-d-aspartate lesions of the nucleus accumbens core (NAc), orbital frontal cortex (OFC) and basolateral amygdala, or sham lesions. When retested at 17days post-surgery, the results showed effects of NAc and OFC but not basolateral amygdala lesion. NAc lesions affected measures indicative of the amount of checking behavior, whereas OFC lesions affected indices of staying away from checking. The pattern of results suggested that the functional roles of the NAc and OFC in checking behavior are to control the vigor of motor performance and focus on goal-directed activity, respectively. Furthermore, similarities in behavior between quinpirole sham rats and saline NAc lesion rats suggested that quinpirole may drive the vigor of checking by inhibition of NAc neurons, and that the NAc may be a site for the negative feedback control of checking.

  8. Rescue of Impaired Fear Extinction and Normalization of Cortico-Amygdala Circuit Dysfunction in a Genetic Mouse Model by Dietary Zinc Restriction

    OpenAIRE

    Whittle, Nigel; Hauschild, Markus; Lubec, Gert; Holmes, Andrew; Singewald, Nicolas

    2010-01-01

    Fear extinction is impaired in neuropsychiatric disorders, including posttraumatic stress disorder. Identifying drugs that facilitate fear extinction in animal models provides leads for novel pharmacological treatments for these disorders. Zinc (Zn) is expressed in neurons in a cortico-amygdala circuit mediating fear extinction, and modulates neurotransmitter systems regulating extinction. We previously found that the 129S1/SvImJ mouse strain (S1) exhibited a profound impairment in fear extin...

  9. Toward a systems-oriented approach to the role of the extended amygdala in adaptive responding.

    Science.gov (United States)

    Waraczynski, Meg

    2016-09-01

    Research into the structure and function of the basal forebrain macrostructure called the extended amygdala (EA) has recently seen considerable growth. This paper reviews that work, with the objectives of identifying underlying themes and developing a common goal towards which investigators of EA function might work. The paper begins with a brief review of the structure and the ontological and phylogenetic origins of the EA. It continues with a review of research into the role of the EA in both aversive and appetitive states, noting that these two seemingly disparate avenues of research converge on the concept of reinforcement - either negative or positive - of adaptive responding. These reviews lead to a proposal as to where the EA may fit in the organization of the basal forebrain, and an invitation to investigators to place their findings in a unifying conceptual framework of the EA as a collection of neural ensembles that mediate adaptive responding.

  10. Changes of glucocorticoid receptor mRNA expression in basolateral amygdale-kindled rats

    Institute of Scientific and Technical Information of China (English)

    BAO Guan-shui; CHENG Xu-qin; HUA Yin; WANG Zhe-dong; LIU Zhen-guo

    2011-01-01

    Background Glucocorticoid receptor (GR) is believed to be a major factor in brain maturation and in modulation of a series of brain activity.Hippocampal neurons are abundant in glucocorticoid receptor,and there is significant change in GR expression under certain pathological state.Epilepsy is a special pathological state of the central nervous system.This study aimed to explore the role of GR in epilepsy by observing the change and functions of GR in hippocampus with a basolateral amygdale-electrical kindled rat epilepsy model.Methods Firstly,we established the basolateral amygdale-electrical kindled rat epilepsy model.Then GR mRNA expression in the hippocampus was assayed by semi-quantitative reverse transcription-PCR in this experiment.In addition,the processes of epileptic seizures were observed and electroencephalograms were recorded.One-way analysis of variance (ANOVA) was employed for comparing means of multiple groups,followed Fisher's least significant difference (LSD) for paired comparison.Results The rats were successfully kindled after an average of (13.50±3.99) times electrical stimulation,in which it was showed that GR mRNA expression reduced obviously as compared with the control group and the sham groups (P<0.001).The down-regulation of GR mRNA expression was abated or reversed by some anti-epilepsy drugs (P <0.001 compared with the epilepsy group),accompanied by attenuation of seizures and improvement of electroencephalograms.Conclusions Down-regulation of hippocampal GR mRNA expression may be related to the kindling.Anti-epilepsy drugs exposure can retard this change.

  11. Macula densa basolateral ATP release is regulated by luminal [NaCl] and dietary salt intake.

    Science.gov (United States)

    Komlosi, Peter; Peti-Peterdi, Janos; Fuson, Amanda L; Fintha, Attila; Rosivall, Laszlo; Bell, Phillip Darwin

    2004-06-01

    One component of the macula densa (MD) tubuloglomerular feedback (TGF) signaling pathway may involve basolateral release of ATP through a maxi-anion channel. Release of ATP has previously been studied during a maximal luminal NaCl concentration ([NaCl](L)) stimulus (20-150 mmol/l). Whether MD ATP release occurs during changes in [NaCl](L) within the physiological range (20-60 mmol/l) has not been examined. Also, because TGF is known to be enhanced by low dietary salt intake, we examined the pattern of MD ATP release from salt-restricted rabbits. Fluorescence microscopy, with fura 2-loaded cultured mouse mesangial cells as biosensors, was used to assess ATP release from the isolated, perfused thick ascending limb containing the MD segment. The mesangial biosensor cells, which contain purinergic receptors and elevate intracellular Ca(2+) concentration ([Ca(2+)](i)) on ATP binding, were placed adjacent to the MD basolateral membrane. Elevations in [NaCl](L) between 0 and 80 mmol/l, in 20-mmol/l increments, caused stepwise increases in [Ca(2+)](i), with the highest increase at [NaCl](L) of approximately 60 mmol/l. Luminal furosemide at 10(-4) mol/l blocked ATP release, which suggests that the efflux of ATP required MD Na-2Cl-K cotransport. A low-salt diet for 1 wk increased the magnitude of [NaCl](L)-dependent elevations in biosensor [Ca(2+)](i) by twofold, whereas high-salt intake had no effect. In summary, ATP release occurs over the same range of [NaCl](L) (20-60 mmol/l) previously reported for TGF responses, and, similar to TGF, ATP release was enhanced by dietary salt restriction. Thus these two findings are consistent with the role of MD ATP release as a signaling component of the TGF pathway.

  12. A Transient Upregulation of Glutamine Synthetase in the Dentate Gyrus Is Involved in Epileptogenesis Induced by Amygdala Kindling in the Rat.

    Directory of Open Access Journals (Sweden)

    Hong-Liu Sun

    Full Text Available Reduction of glutamine synthetase (GS function is closely related to established epilepsy, but little is known regarding its role in epileptogenesis. The present study aimed to elucidate the functional changes of GS in the brain and its involvement in epileptogenesis using the amygdala kindling model of epilepsy induced by daily electrical stimulation of basolateral amygdala in rats. Both expression and activity of GS in the ipsilateral dentate gyrus (DG were upregulated when kindled seizures progressed to stage 4. A single dose of L-methionine sulfoximine (MSO, in 2 µl, a selective GS inhibitor, was administered into the ipsilateral DG on the third day following the first stage 3 seizure (just before GS was upregulated. It was found that low doses of MSO (5 or 10 µg significantly and dose-dependently reduced the severity of and susceptibility to evoked seizures, whereas MSO at a high dose (20 µg aggravated kindled seizures. In animals that seizure acquisition had been successfully suppressed with 10 µg MSO, GS upregulation reoccurred when seizures re-progressed to stage 4 and re-administration of 10 µg MSO consistently reduced the seizures. GLN at a dose of 1.5 µg abolished the alleviative effect of 10 µg MSO and deleterious effect of 20 µg MSO on kindled seizures. Moreover, appropriate artificial microRNA interference (1 and 1.5×10(6 TU/2 µl of GS expression in the ipsilateral DG also inhibited seizure progression. In addition, a transient increase of GS expression and activity in the cortex was also observed during epileptogenesis evoked by pentylenetetrazole kindling. These results strongly suggest that a transient and region-specific upregulation of GS function occurs when epilepsy develops into a certain stage and eventually promotes the process of epileptogenesis. Inhibition of GS to an adequate degree and at an appropriate timing may be a potential therapeutic approach to interrupting epileptogenesis.

  13. Preferential reduction of binding of sup 125 I-iodopindolol to beta-1 adrenoceptors in the amygdala of rat after antidepressant treatments

    Energy Technology Data Exchange (ETDEWEB)

    Ordway, G.A.; Gambarana, C.; Tejani-Butt, S.M.; Areso, P.; Hauptmann, M.; Frazer, A. (Veterans Affairs Medical Center, Philadelphia, PA (USA))

    1991-05-01

    This study utilized quantitative receptor autoradiography to examine the effects of repeated administration of antidepressants to rats on the binding of the beta adrenoceptor antagonist, {sup 125}I-iodopindolol ({sup 125}I-IPIN) to either beta-1 or beta-2 adrenoceptors in various regions of brain. Antidepressants were selected to represent various chemical and pharmacological classes including tricyclic compounds (desipramine and protriptyline), monoamine oxidase inhibitors (clorgyline, phenelzine and tranylcypromine), atypical antidepressants (mianserin and trazodone) and selective inhibitors of the uptake of serotonin (citalopram and sertraline). Additionally, rats were treated with various psychotropic drugs that lack antidepressant efficacy (cocaine, deprenyl, diazepam and haloperidol). Repeated treatment of rats with desipramine, protriptyline, clorgyline, phenelzine, tranylcypromine or mianserin reduced the binding of {sup 125}I-IPIN to beta-1 adrenoceptors in many brain areas. Only in the basolateral and lateral nuclei of the amygdala did all six of these antidepressants significantly reduce {sup 125}I-IPIN binding to beta-1 adrenoceptors. In these amygdaloid nuclei, the magnitude of the reduction in the binding of {sup 125}I-IPIN caused by each of these drugs was comparable to or greater than the reduction in binding produced in any other region of brain. Reductions of binding of {sup 125}I-IPIN after antidepressant treatments were not consistently observed in the cortex, the area of brain examined most often in homogenate binding studies. Only the monoamine oxidase inhibitors caused reductions in the binding of {sup 125}I-IPIN to beta-2 adrenoceptors, and this effect was generally localized to the amygdala and hypothalamus.

  14. Spike-timing precision and neuronal synchrony are enhanced by an interaction between synaptic inhibition and membrane oscillations in the amygdala.

    Directory of Open Access Journals (Sweden)

    Steven J Ryan

    Full Text Available The basolateral complex of the amygdala (BLA is a critical component of the neural circuit regulating fear learning. During fear learning and recall, the amygdala and other brain regions, including the hippocampus and prefrontal cortex, exhibit phase-locked oscillations in the high delta/low theta frequency band (∼2-6 Hz that have been shown to contribute to the learning process. Network oscillations are commonly generated by inhibitory synaptic input that coordinates action potentials in groups of neurons. In the rat BLA, principal neurons spontaneously receive synchronized, inhibitory input in the form of compound, rhythmic, inhibitory postsynaptic potentials (IPSPs, likely originating from burst-firing parvalbumin interneurons. Here we investigated the role of compound IPSPs in the rat and rhesus macaque BLA in regulating action potential synchrony and spike-timing precision. Furthermore, because principal neurons exhibit intrinsic oscillatory properties and resonance between 4 and 5 Hz, in the same frequency band observed during fear, we investigated whether compound IPSPs and intrinsic oscillations interact to promote rhythmic activity in the BLA at this frequency. Using whole-cell patch clamp in brain slices, we demonstrate that compound IPSPs, which occur spontaneously and are synchronized across principal neurons in both the rat and primate BLA, significantly improve spike-timing precision in BLA principal neurons for a window of ∼300 ms following each IPSP. We also show that compound IPSPs coordinate the firing of pairs of BLA principal neurons, and significantly improve spike synchrony for a window of ∼130 ms. Compound IPSPs enhance a 5 Hz calcium-dependent membrane potential oscillation (MPO in these neurons, likely contributing to the improvement in spike-timing precision and synchronization of spiking. Activation of the cAMP-PKA signaling cascade enhanced the MPO, and inhibition of this cascade blocked the MPO. We discuss

  15. Vagus nerve stimulation enhances extinction of conditioned fear and modulates plasticity in the pathway from the infralimbic prefrontal cortex to the amygdala.

    Directory of Open Access Journals (Sweden)

    David Frausto Peña

    2014-09-01

    Full Text Available Fearful experiences can produce long-lasting and debilitating memories. Extinction of the fear response requires consolidation of new memories that compete with fearful associations. Subjects with posttraumatic stress disorder (PTSD show impaired extinction of conditioned fear, which is associated with decreased ventromedial prefrontal cortex (vmPFC control over amygdala activity. Vagus nerve stimulation (VNS enhances memory consolidation in both rats and humans, and pairing VNS with exposure to conditioned cues enhances the consolidation of extinction learning in rats. Here we investigated whether pairing VNS with extinction learning facilitates plasticity between the infralimbic (IL medial prefrontal cortex and the basolateral complex of the amygdala (BLA. Rats were trained on an auditory fear conditioning task, which was followed by a retention test and one day of extinction training. Vagus nerve stimulation or sham-stimulation was administered concurrently with exposure to the fear-conditioned stimulus and retention of fear conditioning was tested again 24 hours later. VNS-treated rats demonstrated a significant reduction in freezing after a single extinction training session similar to animals that received 5x the number of extinction pairings. To study plasticity in the IL-BLA pathway, we recorded evoked field potentials in the BLA in anesthetized animals 24 h after retention testing. Brief burst stimulation in the IL produced LTD in the BLA field response in fear-conditioned and sham-treated animals. In contrast, the same stimulation resulted in potentiation of the IL-BLA pathway in the VNS-treated group. The present findings suggest that VNS promotes plasticity in the IL-BLA pathway to facilitate extinction of conditioned fear responses.

  16. Paternal deprivation affects the development of corticotrophin-releasing factor-expressing neurones in prefrontal cortex, amygdala and hippocampus of the biparental Octodon degus.

    Science.gov (United States)

    Seidel, K; Poeggel, G; Holetschka, R; Helmeke, C; Braun, K

    2011-11-01

    Although the critical role of maternal care on the development of brain and behaviour of the offspring has been extensively studied, knowledge about the importance of paternal care is comparatively scarce. In biparental species, paternal care significantly contributes to a stimulating socio-emotional family environment, which most likely also includes protection from stressful events. In the biparental caviomorph rodent Octodon degus, we analysed the impact of paternal care on the development of neurones in prefrontal-limbic brain regions, which express corticotrophin-releasing factor (CRF). CRF is a polypeptidergic hormone that is expressed and released by a neuronal subpopulation in the brain, and which not only is essential for regulating stress and emotionality, but also is critically involved in cognitive functions. At weaning age [postnatal day (P)21], paternal deprivation resulted in an elevated density of CRF-containing neurones in the orbitofrontal cortex and in the basolateral amygdala of male degus, whereas a reduced density of CRF-expressing neurones was measured in the dentate gyrus and stratum pyramidale of the hippocampal CA1 region at this age. With the exception of the CA1 region, the deprivation-induced changes were no longer evident in adulthood (P90), which suggests a transient change that, in later life, might be normalised by other socio-emotional experience. The central amygdala, characterised by dense clusters of CRF-immunopositive neuropil, and the precentral medial, anterior cingulate, infralimbic and prelimbic cortices, were not affected by paternal deprivation. Taken together, this is the first evidence that paternal care interferes with the developmental expression pattern of CRF-expressing interneurones in an age- and region-specific manner.

  17. A Transient Upregulation of Glutamine Synthetase in the Dentate Gyrus Is Involved in Epileptogenesis Induced by Amygdala Kindling in the Rat

    Science.gov (United States)

    Zhong, Kai; Xu, Zheng-Hao; Feng, Bo; Yu, Jie; Fang, Qi; Wang, Shuang; Wu, Deng-Chang; Zhang, Jian-Min; Chen, Zhong

    2013-01-01

    Reduction of glutamine synthetase (GS) function is closely related to established epilepsy, but little is known regarding its role in epileptogenesis. The present study aimed to elucidate the functional changes of GS in the brain and its involvement in epileptogenesis using the amygdala kindling model of epilepsy induced by daily electrical stimulation of basolateral amygdala in rats. Both expression and activity of GS in the ipsilateral dentate gyrus (DG) were upregulated when kindled seizures progressed to stage 4. A single dose of L-methionine sulfoximine (MSO, in 2 µl), a selective GS inhibitor, was administered into the ipsilateral DG on the third day following the first stage 3 seizure (just before GS was upregulated). It was found that low doses of MSO (5 or 10 µg) significantly and dose-dependently reduced the severity of and susceptibility to evoked seizures, whereas MSO at a high dose (20 µg) aggravated kindled seizures. In animals that seizure acquisition had been successfully suppressed with 10 µg MSO, GS upregulation reoccurred when seizures re-progressed to stage 4 and re-administration of 10 µg MSO consistently reduced the seizures. GLN at a dose of 1.5 µg abolished the alleviative effect of 10 µg MSO and deleterious effect of 20 µg MSO on kindled seizures. Moreover, appropriate artificial microRNA interference (1 and 1.5×106 TU/2 µl) of GS expression in the ipsilateral DG also inhibited seizure progression. In addition, a transient increase of GS expression and activity in the cortex was also observed during epileptogenesis evoked by pentylenetetrazole kindling. These results strongly suggest that a transient and region-specific upregulation of GS function occurs when epilepsy develops into a certain stage and eventually promotes the process of epileptogenesis. Inhibition of GS to an adequate degree and at an appropriate timing may be a potential therapeutic approach to interrupting epileptogenesis. PMID:23825580

  18. Chronic stress disrupts fear extinction and enhances amygdala and hippocampal Fos expression in an animal model of post-traumatic stress disorder.

    Science.gov (United States)

    Hoffman, Ann N; Lorson, Nickolaus G; Sanabria, Federico; Foster Olive, M; Conrad, Cheryl D

    2014-07-01

    Chronic stress may impose a vulnerability to develop maladaptive fear-related behaviors after a traumatic event. Whereas previous work found that chronic stress impairs the acquisition and recall of extinguished fear, it is unknown how chronic stress impacts nonassociative fear, such as in the absence of the conditioned stimulus (CS) or in a novel context. Male rats were subjected to chronic stress (STR; wire mesh restraint 6 h/d/21d) or undisturbed (CON), then tested on fear acquisition (3 tone-footshock pairings), and two extinction sessions (15 tones/session) within the same context. Then each group was tested (6 tones) in the same context (SAME) or a novel context (NOVEL), and brains were processed for functional activation using Fos immunohistochemistry. Compared to CON, STR showed facilitated fear acquisition, resistance to CS extinction on the first extinction day, and robust recovery of fear responses on the second extinction day. STR also showed robust freezing to the context alone during the first extinction day compared to CON. When tested in the same or a novel context, STR exhibited higher freezing to context than did CON, suggesting that STR-induced fear was independent of context. In support of this, STR showed increased Fos-like expression in the basolateral amygdala and CA1 region of the hippocampus in both the SAME and NOVEL contexts. Increased Fos-like expression was also observed in the central amygdala in STR-NOVEL vs. CON-NOVEL. These data demonstrate that chronic stress enhances fear learning and impairs extinction, and affects nonassociative processes as demonstrated by enhanced fear in a novel context.

  19. Prenatal stress alters amygdala functional connectivity in preterm neonates.

    Science.gov (United States)

    Scheinost, Dustin; Kwon, Soo Hyun; Lacadie, Cheryl; Sze, Gordon; Sinha, Rajita; Constable, R Todd; Ment, Laura R

    2016-01-01

    Exposure to prenatal and early-life stress results in alterations in neural connectivity and an increased risk for neuropsychiatric disorders. In particular, alterations in amygdala connectivity have emerged as a common effect across several recent studies. However, the impact of prenatal stress exposure on the functional organization of the amygdala has yet to be explored in the prematurely-born, a population at high risk for neuropsychiatric disorders. We test the hypothesis that preterm birth and prenatal exposure to maternal stress alter functional connectivity of the amygdala using two independent cohorts. The first cohort is used to establish the effects of preterm birth and consists of 12 very preterm neonates and 25 term controls, all without prenatal stress exposure. The second is analyzed to establish the effects of prenatal stress exposure and consists of 16 extremely preterm neonates with prenatal stress exposure and 10 extremely preterm neonates with no known prenatal stress exposure. Standard resting-state functional magnetic resonance imaging and seed connectivity methods are used. When compared to term controls, very preterm neonates show significantly reduced connectivity between the amygdala and the thalamus, the hypothalamus, the brainstem, and the insula (p cortex (p subcortical regions is decreased in preterm neonates compared to term controls. In addition, these data, for the first time, suggest that prenatal stress exposure amplifies these decreases.

  20. Dynamic modulation of amygdala-hippocampal connectivity by emotional arousal

    NARCIS (Netherlands)

    Fastenrath, M.; Coynel, D.; Spalek, K.; Milnik, A.; Gschwind, L.; Roozendaal, B.; Papassotiropoulos, A.; Quervain, D.J. de

    2014-01-01

    Positive and negative emotional events are better remembered than neutral events. Studies in animals suggest that this phenomenon depends on the influence of the amygdala upon the hippocampus. In humans, however, it is largely unknown how these two brain structures functionally interact and whether

  1. Amygdala response to emotional stimuli without awareness : Facts and Interpretations

    NARCIS (Netherlands)

    Diano, M.; Celeghin, A.; Bagnis, Arianna; Tamietto, M.

    2017-01-01

    Over the past two decades, evidence has accumulated that the human amygdala exerts some of its functions also when the observer is not aware of the content, or even presence, of the triggering emotional stimulus. Nevertheless, there is as of yet no consensus on the limits and conditions that affect

  2. A Model of Differential Amygdala Activation in Psychopathy

    Science.gov (United States)

    Moul, Caroline; Killcross, Simon; Dadds, Mark R.

    2012-01-01

    This article introduces a novel hypothesis regarding amygdala function in psychopathy. The first part of this article introduces the concept of psychopathy and describes the main cognitive and affective impairments demonstrated by this population; that is, a deficit in fear-recognition, lower conditioned fear responses and poor performance in…

  3. Progesterone selectively increases amygdala reactivity in women.

    NARCIS (Netherlands)

    Wingen, G.A. van; Broekhoven, F. van; Verkes, R.J.; Petersson, K.M.; Backstrom, T.; Buitelaar, J.K.; Fernandez, G.S.E.

    2008-01-01

    The acute neural effects of progesterone are mediated by its neuroactive metabolites allopregnanolone and pregnanolone. These neurosteroids potentiate the inhibitory actions of gamma-aminobutyric acid (GABA). Progesterone is known to produce anxiolytic effects in animals, but recent animal studies s

  4. Dexamethasone Treatment Leads to Enhanced Fear Extinction and Dynamic Fkbp5 Regulation in Amygdala.

    Science.gov (United States)

    Sawamura, Takehito; Klengel, Torsten; Armario, Antonio; Jovanovic, Tanja; Norrholm, Seth D; Ressler, Kerry J; Andero, Raül

    2016-02-01

    Posttraumatic stress disorder (PTSD) is both a prevalent and debilitating trauma-related disorder associated with dysregulated fear learning at the core of many of its signs and symptoms. Improvements in the currently available psychological and pharmacological treatments are needed in order to improve PTSD treatment outcomes and to prevent symptom relapse. In the present study, we used a putative animal model of PTSD that included presentation of immobilization stress (IMO) followed by fear conditioning (FC) a week later. We then investigated the acute effects of GR receptor activation on the extinction (EXT) of conditioned freezing, using dexamethasone administered systemically which is known to result in suppression of the HPA axis. In our previous work, IMO followed by tone-shock-mediated FC was associated with impaired fear EXT. In this study, we administered dexamethasone 4 h before EXT training and then examined EXT retention (RET) 24 h later to determine whether dexamethasone suppression rescued EXT deficits. Dexamethasone treatment produced dose-dependent enhancement of both EXT and RET. Dexamethasone was also associated with reduced amygdala Fkbp5 mRNA expression following EXT and after RET. Moreover, DNA methylation of the Fkbp5 gene occurred in a dose-dependent and time course-dependent manner within the amygdala. Additionally, we found dynamic changes in epigenetic regulation, including Dnmt and Tet gene pathways, as a function of both fear EXT and dexamethasone suppression of the HPA axis. Together, these data suggest that dexamethasone may serve to enhance EXT by altering Fkbp5-mediated glucocorticoid sensitivity via epigenetic regulation of Fkbp5 expression.

  5. A amígdala e a tênue fronteira entre memória e emoção Amygdala and the slight boundary between memory and emotion

    Directory of Open Access Journals (Sweden)

    Fabíola da Silva Albuquerque

    2009-01-01

    Full Text Available Embora os mecanismos neurobiológicos envolvidos na memória para situações aversivas não estejam completamente esclarecidos, o complexo basolateral da amígdala parece exercer um papel fundamental nesse tipo de memória. O presente trabalho tem como objetivo revisar os principais estudos acerca da participação da amígdala na memória e discutir os aspectos teóricos dos modelos utilizados. Foi realizada uma revisão dos estudos em humanos e em modelos animais que visam investigar e discutir a participação da amígdala na memória. Duas hipóteses norteiam as investigações aqui revisadas: 1 a amígdala seria o local dos processos plásticos envolvidos na aquisição e consolidação de informações de conteúdo aversivo e 2 essa estrutura modularia os processos de aquisição e consolidação que ocorreriam em outras estruturas. Os resultados que embasam a primeira hipótese foram obtidos em um modelo de resposta de medo condicionada em ratos, enquanto que a segunda hipótese provém de estudos que utilizam um modelo experimental que envolve aspectos mais declarativos da informação aversiva. Apesar de os trabalhos aqui revisados fornecerem fortes evidências de que a amígdala modula as estruturas relacionadas com a consolidação da memória, novos estudos poderão esclarecer melhor essa relação, principalmente com novos paradigmas de investigação.Although the neurobiological events involved with the memory of aversive events are not completely understood, the basolateral amygdala seems to play an important role in this process. The objectives of the present study were to review the main human and animal studies on the role played by the amygdala in memory and to discuss the theoretical aspects of the models used. We reviewed the available studies using human and animal models that investigated and discussed the involvement of amygdala with memory. Current investigation on this issue is mainly based on two hypotheses: 1 the

  6. Cannabinoid receptors activation and glucocorticoid receptors deactivation in the amygdala prevent the stress-induced enhancement of a negative learning experience.

    Science.gov (United States)

    Ramot, Assaf; Akirav, Irit

    2012-05-01

    The enhancement of emotional memory is clearly important as emotional stimuli are generally more significant than neutral stimuli for surviving and reproduction purposes. Yet, the enhancement of a negative emotional memory following exposure to stress may result in dysfunctional or intrusive memory that underlies several psychiatric disorders. Here we examined the effects of stress exposure on a negative emotional learning experience as measured by a decrease in the magnitude of the expected quantity of reinforcements in an alley maze. In contrast to other fear-related negative experiences, reward reduction is more associated with frustration and is assessed by measuring the latency to run the length of the alley to consume the reduced quantity of reward. We also examined whether the cannabinoid receptors agonist WIN55,212-2 (5 μg/side) and the glucocorticoid receptors (GRs) antagonist RU-486 (10 ng/side) administered into the rat basolateral amygdala (BLA) could prevent the stress-induced enhancement. We found that intra-BLA RU-486 or WIN55,212 before stress exposure prevented the stress-induced enhancement of memory consolidation for reduction in reward magnitude. These findings suggest that cannabinoid receptors and GRs in the BLA are important modulators of stress-induced enhancement of emotional memory.

  7. Early versus late-phase consolidation of opiate reward memories requires distinct molecular and temporal mechanisms in the amygdala-prefrontal cortical pathway.

    Directory of Open Access Journals (Sweden)

    Shervin Gholizadeh

    Full Text Available The consolidation of newly acquired memories involves the temporal transition from a recent, less stable trace to a more permanent consolidated form. Opiates possess potent rewarding effects and produce powerful associative memories. The activation of these memories is associated with opiate abuse relapse phenomena and the persistence of compulsive opiate dependence. However, the neuronal, molecular and temporal mechanisms by which associative opiate reward memories are consolidated are not currently understood. We report that the consolidation of associative opiate reward memories involves a temporal and molecular switch between the basolateral nucleus of the amygdala (BLA (early consolidation phase to the medial prefrontal cortex (mPFC (late consolidation phase. We demonstrate at the molecular, behavioral and neuronal levels that the consolidation of a recently acquired opiate reward memory involves an extracellular signal-related kinase (ERK-dependent phosphorylation process within the BLA. In contrast, later-stage consolidation of a newly acquired memory is dependent upon a calcium-calmodulin-dependent (CaMKII, ERK-independent, mechanism in the mPFC, over a 12 hr temporal gradient. In addition, using in vivo multi-unit neuronal recordings in the mPFC, we report that protein synthesis within the BLA modulates the consolidation of opiate-reward memory in neuronal mPFC sub-populations, via the same temporal dynamic.

  8. Early versus late-phase consolidation of opiate reward memories requires distinct molecular and temporal mechanisms in the amygdala-prefrontal cortical pathway.

    Science.gov (United States)

    Gholizadeh, Shervin; Sun, Ninglei; De Jaeger, Xavier; Bechard, Melanie; Coolen, Lique; Laviolette, Steven R

    2013-01-01

    The consolidation of newly acquired memories involves the temporal transition from a recent, less stable trace to a more permanent consolidated form. Opiates possess potent rewarding effects and produce powerful associative memories. The activation of these memories is associated with opiate abuse relapse phenomena and the persistence of compulsive opiate dependence. However, the neuronal, molecular and temporal mechanisms by which associative opiate reward memories are consolidated are not currently understood. We report that the consolidation of associative opiate reward memories involves a temporal and molecular switch between the basolateral nucleus of the amygdala (BLA) (early consolidation phase) to the medial prefrontal cortex (mPFC) (late consolidation phase). We demonstrate at the molecular, behavioral and neuronal levels that the consolidation of a recently acquired opiate reward memory involves an extracellular signal-related kinase (ERK)-dependent phosphorylation process within the BLA. In contrast, later-stage consolidation of a newly acquired memory is dependent upon a calcium-calmodulin-dependent (CaMKII), ERK-independent, mechanism in the mPFC, over a 12 hr temporal gradient. In addition, using in vivo multi-unit neuronal recordings in the mPFC, we report that protein synthesis within the BLA modulates the consolidation of opiate-reward memory in neuronal mPFC sub-populations, via the same temporal dynamic.

  9. Increased basolateral sorting of carcinoembryonic antigen in a polarized colon carcinoma cell line after cholesterol depletion-Implications for treatment of inflammatory bowel disease

    Institute of Scientific and Technical Information of China (English)

    Robert Ehehalt; Markus Krautter; Martin Zorn; Richard Sparla; Joachim Fūllekrug; Hasan Kulaksiz; Wolfgang Stremmel

    2008-01-01

    AIM:To investigate a possible increase of basolateral expression of carcinoembryonic antigen(CEA)by interfering with the apical transport machinery,we studied the effect of cholesterol depletion on CEA sorting and secretion.METHODS:Cholesterol depletion was performed in polarized Caco-2 cells using Iovastatin and methyl-βcyclodextrin.RESULTS:We show that CEA is predominantly expressed and secreted at the apical surface.Reduction of the cholesterol level of the cell by 40%-50% with Iovastatin and methyl-β-cyclodextrin led to a significant change of the apical-to-basolateral transport ratio towards the basolateral membrane.CONCLUSION:As basolateral expression of CEA has been suggested to have anti-inflamatory properties,Cholesterol depletion of enterocytes might be a potential approach to influence the course of inflammatory bowel disease.

  10. The Role of the Medial Prefrontal Cortex-Amygdala Circuit in Stress Effects on the Extinction of Fear

    Directory of Open Access Journals (Sweden)

    Irit Akirav

    2007-01-01

    Full Text Available Stress exposure, depending on its intensity and duration, affects cognition and learning in an adaptive or maladaptive manner. Studies addressing the effects of stress on cognitive processes have mainly focused on conditioned fear, since it is suggested that fear-motivated learning lies at the root of affective and anxiety disorders. Inhibition of fear-motivated response can be accomplished by experimental extinction of the fearful response to the fear-inducing stimulus. Converging evidence indicates that extinction of fear memory requires plasticity in both the medial prefrontal cortex and the amygdala. These brain areas are also deeply involved in mediating the effects of exposure to stress on memory. Moreover, extensive evidence indicates that gamma-aminobutyric acid (GABA transmission plays a primary role in the modulation of behavioral sequelae resulting from a stressful experience, and may also partially mediate inhibitory learning during extinction. In this review, we present evidence that exposure to a stressful experience may impair fear extinction and the possible involvement of the GABA system. Impairment of fear extinction learning is particularly important as it may predispose some individuals to the development of posttraumatic stress disorder. We further discuss a possible dysfunction in the medial prefrontal cortex-amygdala circuit following a stressful experience that may explain the impaired extinction caused by exposure to a stressor.

  11. The Possible Contribution of the Amygdala to Memory

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    R. Babinsky

    1993-01-01

    Full Text Available The processing of episodic memories is believed to depend on the proper functioning of so-called bottleneck structures through which information apparently must pass in order to be stored long term. These regions are seen in the basal forebrain, the medial diencephalon, and the medial temporal lobe. We here report a case with circumscribed bilateral temporal lobe damage, principally involving the amygdaloid area. Neuropsychological investigation demonstrated preserved intelligence, intact general memory and several other undisturbed cognitive functions, but a specific, affect-related, memory disorder. We conclude from these findings that the role of the amygdala is to process mnemonic events in a way that a specific emotional significance can be found and reactivated. Therefore it is suggested that the amygdala is likely to be a bottleneck structure for affect-related long-term memory functions.

  12. PAH clearance after renal ischemia and reperfusion is a function of impaired expression of basolateral Oat1 and Oat3

    OpenAIRE

    Bischoff, Ariane; Bucher, Michael; Gekle, Michael; Sauvant, Christoph

    2014-01-01

    Abstract Determination of renal plasma flow (RPF) by para‐aminohippurate (PAH) clearance leads to gross underestimation of this respective parameter due to impaired renal extraction of PAH after renal ischemia and reperfusion injury. However, no mechanistic explanation for this phenomenon is available. Based on our own previous studies we hypothesized that this may be due to impairment of expression of the basolateral rate limiting organic anion transporters Oat1 and Oat3. Thus, we investigat...

  13. Amygdala lesions selectively impair familiarity in recognition memory.

    Science.gov (United States)

    Farovik, Anja; Place, Ryan James; Miller, Danielle Renée; Eichenbaum, Howard

    2011-09-25

    A major controversy in the study of memory concerns whether there are distinct medial temporal lobe (MTL) substrates of recollection and familiarity. Studies using receiver operating characteristics analyses of recognition memory indicate that the hippocampus is essential for recollection, but not for familiarity. We found the converse pattern in the amygdala, wherein damage impaired familiarity while sparing recollection. Combined with previous findings, these results dissociate recollection and familiarity by selective MTL damage.

  14. Mothers’ Unresolved Trauma Blunts Amygdala Response to Infant Distress

    OpenAIRE

    Kim, S.; Fonagy, P; Allen, J.; Strathearn, L.

    2014-01-01

    While the neurobiology of post-traumatic stress disorder has been extensively researched, much less attention has been paid to the neural mechanisms underlying more covert but pervasive types of trauma (e.g., those involving disrupted relationships and insecure attachment). Here, we report on a neurobiological study documenting that mothers' attachment-related trauma, when unresolved, undermines her optimal brain response to her infant's distress. We examined the amygdala blood oxygenation le...

  15. Structural lipid changes and Na(+)/K(+)-ATPase activity of gill cells' basolateral membranes during saltwater acclimation in sea lamprey (Petromyzon marinus, L.) juveniles.

    Science.gov (United States)

    Lança, Maria João; Machado, Maria; Ferreira, Ana Filipa; Quintella, Bernardo Ruivo; de Almeida, Pedro Raposo

    2015-11-01

    Seawater acclimation is a critical period for anadromous species and a process yet to be understood in lampreys. Considering that changes in lipid composition of the gill cells' basolateral membranes may disrupt the major transporter Na(+)K(+)-ATPase, the goal of this study was to detect changes at this level during juvenile sea lamprey seawater acclimation. The results showed that saltwater acclimation has a direct effect on the fatty acid composition of gill cells basolateral membrane's phospholipids. When held in full-strength seawater, the fatty acid profile of basolateral membrane's phospholipids suffered a restructure by increasing either saturation or the ratio between oleic acid and eicosapentaenoic acid. Simultaneously, the activity of Na(+)K(+)-ATPase revealed a significant and positive correlation with basolateral membrane's cholesterol content in the presence of highest salinity. Our results pointed out for lipid adjustments involving the functional transporter present on the gill cell basolateral membranes to ensure the role played by branchial Na(+)K(+)-ATPase in ion transport during saltwater acclimation process. The responses observed contributed to the strategy adopted by gill cell's basolateral membranes to compensate for osmotic and ionic stressors, to ensure the success of the process of seawater acclimation associated with the downstream trophic migration of juvenile sea lamprey.

  16. Absence of gender effect on amygdala volume in temporal lobe epilepsy.

    Science.gov (United States)

    Silva, Ivaldo; Lin, Katia; Jackowski, Andrea P; Centeno, Ricardo da Silva; Pinto, Magali L; Carrete, Henrique; Yacubian, Elza M; Amado, Débora

    2010-11-01

    Sexual dimorphism has already been described in temporal lobe epilepsy with mesial temporal sclerosis (TLE-MTS). This study evaluated the effect of gender on amygdala volume in patients with TLE-MTS. One hundred twenty-four patients with refractory unilateral or bilateral TLE-MTS who were being considered for epilepsy surgery underwent a comprehensive presurgical evaluation and MRI. Amygdalas of 67 women (27 with right; 32 with left, and 8 with bilateral TLE) and 57 men (22 with right, 30 with left, and 5 with bilateral TLE) were manually segmented. Significant ipsilateral amygdala volume reduction was observed for patients with right and left TLE. No gender effect on amygdala volume was observed. Contralateral amygdalar asymmetry was observed for patients with right and left TLE. Although no gender effect was observed on amygdala volume, ipsilateral amygdala volume reductions in patients with TLE might be related to differential rates of cerebral maturation between hemispheres.

  17. Threat-related amygdala functional connectivity is associated with 5-HTTLPR genotype and neuroticism

    DEFF Research Database (Denmark)

    Madsen, Martin Korsbak; Mc Mahon, Brenda; Andersen, Sofie Bech

    2016-01-01

    is not fully understood. Using functional magnetic resonance imaging, we evaluated independent and interactive effects of the 5-HTTLPR genotype and neuroticism on amygdala functional connectivity during an emotional faces paradigm in 76 healthy individuals. Functional connectivity between left amygdala...... and medial prefrontal cortex (mPFC) and between both amygdalae and a cluster including posterior cingulate cortex, precuneus and visual cortex was significantly increased in 5-HTTLPR S' allele carriers relative to L(A)L(A) individuals. Neuroticism was negatively correlated with functional connectivity...... between right amygdala and mPFC and visual cortex, and between both amygdalae and left lateral orbitofrontal (lOFC) and ventrolateral prefrontal cortex (vlPFC). Notably, 5-HTTLPR moderated the association between neuroticism and functional connectivity between both amygdalae and left l...

  18. PAH clearance after renal ischemia and reperfusion is a function of impaired expression of basolateral Oat1 and Oat3.

    Science.gov (United States)

    Bischoff, Ariane; Bucher, Michael; Gekle, Michael; Sauvant, Christoph

    2014-02-01

    Determination of renal plasma flow (RPF) by para-aminohippurate (PAH) clearance leads to gross underestimation of this respective parameter due to impaired renal extraction of PAH after renal ischemia and reperfusion injury. However, no mechanistic explanation for this phenomenon is available. Based on our own previous studies we hypothesized that this may be due to impairment of expression of the basolateral rate limiting organic anion transporters Oat1 and Oat3. Thus, we investigated this phenomenon in a rat model of renal ischemia and reperfusion by determining PAH clearance, PAH extraction, PAH net secretion, and the expression of rOat1 and rOat3. PAH extraction was seriously impaired after ischemia and reperfusion which led to a threefold underestimation of RPF when PAH extraction ratio was not considered. PAH extraction directly correlated with the expression of basolateral Oat1 and Oat3. Tubular PAH secretion directly correlated with PAH extraction. Consequently, our data offer an explanation for impaired renal PAH extraction by reduced expression of the rate limiting basolateral organic anion transporters Oat1 and Oat3. Moreover, we show that determination of PAH net secretion is suitable to correct PAH clearance for impaired extraction after ischemia and reperfusion in order to get valid results for RPF.

  19. Psychopaths Show Enhanced Amygdala Activation during Fear Conditioning.

    Science.gov (United States)

    Schultz, Douglas H; Balderston, Nicholas L; Baskin-Sommers, Arielle R; Larson, Christine L; Helmstetter, Fred J

    2016-01-01

    Psychopathy is a personality disorder characterized by emotional deficits and a failure to inhibit impulsive behavior and is often subdivided into "primary" and "secondary" psychopathic subtypes. The maladaptive behavior related to primary psychopathy is thought to reflect constitutional "fearlessness," while the problematic behavior related to secondary psychopathy is motivated by other factors. The fearlessness observed in psychopathy has often been interpreted as reflecting a fundamental deficit in amygdala function, and previous studies have provided support for a low-fear model of psychopathy. However, many of these studies fail to use appropriate screening procedures, use liberal inclusion criteria, or have used unconventional approaches to assay amygdala function. We measured brain activity with BOLD imaging in primary and secondary psychopaths and non-psychopathic control subjects during Pavlovian fear conditioning. In contrast to the low-fear model, we observed normal fear expression in primary psychopaths. Psychopaths also displayed greater differential BOLD activity in the amygdala relative to matched controls. Inverse patterns of activity were observed in the anterior cingulate cortex (ACC) for primary versus secondary psychopaths. Primary psychopaths exhibited a pattern of activity in the dorsal and ventral ACC consistent with enhanced fear expression, while secondary psychopaths exhibited a pattern of activity in these regions consistent with fear inhibition. These results contradict the low-fear model of psychopathy and suggest that the low fear observed for psychopaths in previous studies may be specific to secondary psychopaths.

  20. Rapid amygdala responses during trace fear conditioning without awareness.

    Directory of Open Access Journals (Sweden)

    Nicholas L Balderston

    Full Text Available The role of consciousness in learning has been debated for nearly 50 years. Recent studies suggest that conscious awareness is needed to bridge the gap when learning about two events that are separated in time, as is true for trace fear conditioning. This has been repeatedly shown and seems to apply to other forms of classical conditioning as well. In contrast to these findings, we show that individuals can learn to associate a face with the later occurrence of a shock, even if they are unable to perceive the face. We used a novel application of magnetoencephalography (MEG to non-invasively record neural activity from the amygdala, which is known to be important for fear learning. We demonstrate rapid (∼ 170-200 ms amygdala responses during the stimulus free period between the face and the shock. These results suggest that unperceived faces can serve as signals for impending threat, and that rapid, automatic activation of the amygdala contributes to this process. In addition, we describe a methodology that can be applied in the future to study neural activity with MEG in other subcortical structures.

  1. Rapid amygdala responses during trace fear conditioning without awareness.

    Science.gov (United States)

    Balderston, Nicholas L; Schultz, Douglas H; Baillet, Sylvain; Helmstetter, Fred J

    2014-01-01

    The role of consciousness in learning has been debated for nearly 50 years. Recent studies suggest that conscious awareness is needed to bridge the gap when learning about two events that are separated in time, as is true for trace fear conditioning. This has been repeatedly shown and seems to apply to other forms of classical conditioning as well. In contrast to these findings, we show that individuals can learn to associate a face with the later occurrence of a shock, even if they are unable to perceive the face. We used a novel application of magnetoencephalography (MEG) to non-invasively record neural activity from the amygdala, which is known to be important for fear learning. We demonstrate rapid (∼ 170-200 ms) amygdala responses during the stimulus free period between the face and the shock. These results suggest that unperceived faces can serve as signals for impending threat, and that rapid, automatic activation of the amygdala contributes to this process. In addition, we describe a methodology that can be applied in the future to study neural activity with MEG in other subcortical structures.

  2. Electrical amygdala kindling in alcohol-withdrawal kindled rats.

    Science.gov (United States)

    Ulrichsen, J; Woldbye, D P; Madsen, T M; Clemmesen, L; Haugbøl, S; Olsen, C H; Laursen, H; Bolwig, T G; Hemmingsen, R

    1998-01-01

    Repeated alcohol withdrawal has been shown to kindle seizure activity. The purpose of the present investigation was to study electrical amygdala kindling in rats previously exposed to alcohol-withdrawal kindling. In three independent experiments, male Wistar rats were subjected to multiple episodes each consisting of 2 days of severe alcohol intoxication and 5 days of alcohol withdrawal. In the first experiment, the alcohol-withdrawal kindled animals were divided into two groups depending on whether spontaneous alcohol-withdrawal seizures were observed in episodes 10-13. In the second and third experiments, the alcohol-withdrawal kindled animals were compared to a group in which alcohol-withdrawal kindling was prevented by diazepam treatment during the withdrawal reactions in order to discriminate between the effect of withdrawal and intoxication. Electrical kindling was initiated 28-35 days after the last alcohol dose by exposing the animals to daily electrical stimulations of the right amygdala. The results showed that amygdala kindling was facilitated in alcohol-withdrawal kindled animals which showed spontaneous withdrawal seizure activity, compared with animals exposed to multiple episodes of alcohol withdrawal which did not develop withdrawal seizures or with animals exposed to a single episode of alcohol intoxication. When compared to the control group, the alcohol-withdrawal kindled group with seizures also kindled at a faster rate, but the difference did not reach statistical significance and therefore the results must be regarded as preliminary at present.

  3. Psychopaths show enhanced amygdala activation during fear conditioning

    Directory of Open Access Journals (Sweden)

    Douglas eSchultz

    2016-03-01

    Full Text Available Psychopathy is a personality disorder characterized by emotional deficits and a failure to inhibit impulsive behavior and is often subdivided into primary and secondary psychopathic subtypes. The maladaptive behavior related to primary psychopathy is thought to reflect constitutional fearlessness, while the problematic behavior related to secondary psychopathy is motivated by other factors. The fearlessness observed in psychopathy has often been interpreted as reflecting a fundamental deficit in amygdala function, and previous studies have provided support for a low-fear model of psychopathy. However, many of these studies fail to use appropriate screening procedures, use liberal inclusion criteria, or have used unconventional approaches to assay amygdala function. We measured brain activity with BOLD imaging in primary and secondary psychopaths and non-psychopathic control subjects during Pavlovian fear conditioning. In contrast to the low-fear model, we observed normal fear expression in primary psychopaths. Psychopaths also displayed greater differential BOLD activity in the amygdala relative to matched controls. Inverse patterns of activity were observed in the anterior cingulate cortex (ACC for primary versus secondary psychopaths. Primary psychopaths exhibited a pattern of activity in the dorsal and ventral ACC consistent with enhanced fear expression, while secondary psychopaths exhibited a pattern of activity in these regions consistent with fear inhibition. These results contradict the low-fear model of psychopathy and suggest that the low fear observed for psychopaths in previous studies may be specific to secondary psychopaths.

  4. Prefrontal-amygdala fear networks come into focus

    Directory of Open Access Journals (Sweden)

    Maithe eArruda-Carvalho

    2015-10-01

    Full Text Available The ability to form associations between aversive threats and their predictors is fundamental to survival. However, fear and anxiety in excess are detrimental and are a hallmark of psychiatric diseases such as post-traumatic stress disorder (PTSD. PTSD symptomatology includes persistent and intrusive thoughts of an experienced trauma, suggesting an inability to downregulate fear when a corresponding threat has subsided. Convergent evidence from human and rodent studies supports a role for the medial prefrontal cortex (mPFC-amygdala network in both PTSD and the regulation of fear memory expression. In particular, current models stipulate that the prelimbic and infralimbic subdivisions of the rodent mPFC bidirectionally regulate fear expression via differential recruitment of amygdala neuronal subpopulations. However, an array of recent studies that employ new technical approaches has fundamentally challenged this interpretation. Here we explore how a new emphasis on the contribution of inhibitory neuronal populations, subcortical structures and the passage of time is reshaping our understanding of mPFC-amygdala circuits and their control over fear.

  5. Protein kinase A dependent phosphorylation activates Mg2+ efflux in the basolateral region of the liver.

    Science.gov (United States)

    Cefaratti, C; Ruse, Cristian

    2007-03-01

    Isolated hepatocytes in physiological [Na(+)]( 0 ) tightly maintain [Mg(2+)]( i ). Upon beta-adrenergic stimulation or in the presence of permeable cAMP, hepatocytes release 5-10% (1-3 mM Mg(2+)) of their total Mg(2+) content. However, isolated basolateral liver plasma membranes (bLPM), release Mg(2+) in the presence of [Na(+)]( o ) even in the absence of catecholamine stimulation. The data indicate that a physiological brake for Mg(2+) efflux is present in the hepatocyte and is removed upon cellular signaling. In contrast, this regulation "brake" is absent in purified bLPM thus rendering them fully active. The present study was carried out to reconstruct the missing regulatory component. Activation of Mg(2+) extrusion in intact cells is consistent with cAMP dependent phosphorylation of the transporter or a regulatory protein. Treatment of bLPM with a non-specific phosphatase such as alkaline phosphatase (AP), decreased Mg(2+) efflux by 70% compared to untreated bLPM. When AP-treated bLPM were loaded with protein kinase A (PKA), and stimulated with permeable cAMP, Mg(2+) transport fully recovered. These data suggest that phosphorylation of the Na(+)/Mg(2+) exchanger or a nearby protein activates the Mg(2+) transport mechanism in hepatocytes.

  6. Bi-Directional Tuning of Amygdala Sensitivity in Combat Veterans Investigated with fMRI.

    Directory of Open Access Journals (Sweden)

    Tom Brashers-Krug

    Full Text Available Combat stress can be followed by persistent emotional consequences. It is thought that these emotional consequences are caused in part by increased amygdala reactivity. It is also thought that amygdala hyper-reactivity results from decreased inhibition from portions of the anterior cingulate cortex (ACC in which activity is negatively correlated with activity in the amygdala. However, experimental support for these proposals has been inconsistent.We showed movies of combat and civilian scenes during a functional magnetic resonance imaging (fMRI session to 50 veterans of recent combat. We collected skin conductance responses (SCRs as measures of emotional arousal. We examined the relation of blood oxygenation-level dependent (BOLD signal in the amygdala and ACC to symptom measures and to SCRs.Emotional arousal, as measured with SCR, was greater during the combat movie than during the civilian movie and did not depend on symptom severity. As expected, amygdala signal during the less-arousing movie increased with increasing symptom severity. Surprisingly, during the more-arousing movie amygdala signal decreased with increasing symptom severity. These differences led to the unexpected result that amygdala signal in highly symptomatic subjects was lower during the more-arousing movie than during the less-arousing movie. Also unexpectedly, we found no significant inverse correlation between any portions of the amygdala and ACC. Rather, signal throughout more than 80% of the ACC showed a strong positive correlation with signal throughout more than 90% of the amygdala.Amygdala reactivity can be tuned bi-directionally, either up or down, in the same person depending on the stimulus and the degree of post-traumatic symptoms. The exclusively positive correlations in BOLD activity between the amygdala and ACC contrast with findings that have been cited as evidence for inhibitory control of the amygdala by the ACC. The conceptualization of post

  7. The Neurosteroids Allopregnanolone and DHEA Modulate Resting-State Amygdala Connectivity

    Science.gov (United States)

    Sripada, Rebecca K.; Welsh, Robert C.; Marx, Christine E.; Liberzon, Israel

    2016-01-01

    The neurosteroids allopregnanolone and dehydroepiandrosterone (DHEA) are integral components of the stress response and exert positive modulatory effects on emotion in both human and animal studies. Though these antidepressant and anxiolytic effects have been well established, little research to date has examined their neural correlates, and no research has been conducted into the effects of neurosteroids on large-scale networks at rest. To investigate the neurosteroid impact on intrinsic connectivity networks, participants were administered 400 mg of pregnenolone (N = 16), 400 mg of DHEA (N = 14), or placebo (N = 15) and underwent 3T fMRI. Resting-state brain connectivity was measured using amygdala as a seed region. Compared to placebo, pregnenolone administration reduced connectivity between amygdala and dmPFC, between amygdala and precuneus, and between amygdala and hippocampus. DHEA reduced connectivity between amygdala and peri-amygdala and between amygdala and insula. Reductions in amygdala to precuneus connectivity were associated with less self-reported negative affect. These results demonstrate that neurosteroids modulate amygdala functional connectivity during resting-state, and may be a target for pharmacological intervention. Additionally, allopregnanolone and DHEA may shift the balance between salience network and default network, a finding that could provide insight into the neurocircuitry of anxiety psychopathology. PMID:24302681

  8. Amygdala responses to salient social cues vary with oxytocin receptor genotype in youth

    Science.gov (United States)

    Marusak, Hilary A.; Furman, Daniella J.; Kuruvadi, Nisha; Shattuck, David W.; Joshi, Shantanu H.; Joshi, Anand A.; Etkin, Amit; Thomason, Moriah E.

    2015-01-01

    Depression, anxiety, and posttraumatic stress disorder are linked to altered limbic morphology, dysregulated neuroendocrine function, and heightened amygdala responses to salient social cues. Oxytocin appears to be a potent modulator of amygdala reactivity and neuroendocrine responses to psychosocial stress. Given these stress regulatory effects, there is increasing interest in understanding the role of oxytocin in vulnerability to stress-related clinical disorders. The present study examines the impact of a common functional variant within the oxytocin receptor (OXTR) gene (rs2254298) on structure and function of the amygdala in a high-risk sample of urban, low-income, minority youth with a high incidence of early life stress (ELS). Compared to G/G homozygotes, youth carrying the OXTR A-allele showed increased amygdala volume, reduced behavioral performance, and heightened amygdala response during two functional magnetic resonance imaging (fMRI) tasks that involved viewing socially-relevant face stimuli. Higher amygdala response was related to ELS in A-alleles carriers but not G/G homozygotes. These findings underscore a series of relationships among a common oxytocin system gene variant, ELS exposure, and structure and function of the amygdala in early life. Heightened amygdala response to salient social cues in OXTR A-allele carriers may elevate risk for emotional psychopathology by increasing amygdala involvement in disambiguating environmental cues, particularly for individuals with ELS. PMID:26477647

  9. Effects of gaze direction, head orientation and valence of facial expression on amygdala activity.

    Science.gov (United States)

    Sauer, Andreas; Mothes-Lasch, Martin; Miltner, Wolfgang H R; Straube, Thomas

    2014-08-01

    There is increasing evidence for a role of the amygdala in processing gaze direction and emotional relevance of faces. In this event-related functional magnetic resonance study we investigated amygdala responses while we orthogonally manipulated head direction, gaze direction and facial expression (angry, happy and neutral). This allowed us to investigate effects of stimulus ambiguity, low-level factors and non-emotional factors on amygdala activation. Averted vs direct gaze induced increased activation in the right dorsal amygdala regardless of facial expression and head orientation. Furthermore, valence effects were found in the ventral amygdala and strongly dependent on head orientation. We observed enhanced activation to angry and neutral vs happy faces for observer-directed faces in the left ventral amygdala while the averted head condition reversed this pattern resulting in increased activation to happy as compared to angry and neutral faces. These results suggest that gaze direction drives specifically dorsal amygdala activation regardless of facial expression, low-level perceptual factors or stimulus ambiguity. The role of the amygdala is thus not restricted to the detection of potential threat, but has a more general role in attention processes. Furthermore, valence effects are associated with activation of the ventral amygdala and strongly influenced by non-emotional factors.

  10. Carrier-mediated ¿-aminobutyric acid transport across the basolateral membrane of human intestinal Caco-2 cell monolayers

    DEFF Research Database (Denmark)

    Nielsen, Carsten Uhd; Carstensen, Mette; Brodin, Birger

    2012-01-01

    -affinity transporter is Na(+) and Cl(-) dependent. The substrate specificity of the high-affinity transporter was further studied and Gly-Sar, Leucine, gaboxadol, sarcosine, lysine, betaine, 5-hydroxythryptophan, proline and glycine reduced the GABA uptake to approximately 44-70% of the GABA uptake in the absence...

  11. Association between amygdala volume and anxiety level: magnetic resonance imaging (MRI) study in autistic children.

    Science.gov (United States)

    Juranek, Jenifer; Filipek, Pauline A; Berenji, Gholam R; Modahl, Charlotte; Osann, Kathryn; Spence, M Anne

    2006-12-01

    Our objective was to evaluate brain-behavior relationships between amygdala volume and anxious/depressed scores on the Child Behavior Checklist in a well-characterized population of autistic children. Volumes for the amygdala, hippocampus, and whole brain were obtained from three-dimensional magnetic resonance images (MRIs) captured from 42 children who met the criteria for autistic disorder. Anxious/depressed symptoms were assessed in these children by the Anxious/Depressed subscale of the Child Behavior Checklist. To investigate the association between anxious/depressed scores on the Child Behavior Checklist and amygdala volume, data were analyzed using linear regression methods with Pearson correlation coefficients. A multivariate model was used to adjust for potential covariates associated with amygdala volume, including age at MRI and total brain size. We found that anxious/depressed symptoms were significantly correlated with increased total amygdala volume (r = .386, P = .012) and right amygdala volume (r = .469, P = .002). The correlation between anxious/depressed symptoms and left amygdala volume did not reach statistical significance (r = .249, P = .112). Child Behavior Checklist anxious/depressed scores were found to be a significant predictor of amygdala total (P = .014) and right amygdala (P = .002) volumes. In conclusion, we have identified a significant brain-behavior relationship between amygdala volume and anxious/depressed scores on the Child Behavior Checklist in our autistic cohort. This specific relationship has not been reported in autism. However, the existing literature on human psychiatry and behavior supports our reported evidence for a neurobiologic relationship between symptoms of anxiety and depression with amygdala structure and function. Our results highlight the importance of characterizing comorbid psychiatric symptomatology in autism. The abundance of inconsistent findings in the published literature on autism might reflect

  12. Src family protein tyrosine kinase regulates the basolateral K channel in the distal convoluted tubule (DCT) by phosphorylation of KCNJ10 protein.

    Science.gov (United States)

    Zhang, Chengbiao; Wang, Lijun; Thomas, Sherin; Wang, Kemeng; Lin, Dao-Hong; Rinehart, Jesse; Wang, Wen-Hui

    2013-09-01

    The loss of function of the basolateral K channels in the distal nephron causes electrolyte imbalance. The aim of this study is to examine the role of Src family protein tyrosine kinase (SFK) in regulating K channels in the basolateral membrane of the mouse initial distal convoluted tubule (DCT1). Single-channel recordings confirmed that the 40-picosiemen (pS) K channel was the only type of K channel in the basolateral membrane of DCT1. The suppression of SFK reversibly inhibited the basolateral 40-pS K channel activity in cell-attached patches and decreased the Ba(2+)-sensitive whole-cell K currents in DCT1. Inhibition of SFK also shifted the K reversal potential from -65 to -43 mV, suggesting a role of SFK in determining the membrane potential in DCT1. Western blot analysis showed that KCNJ10 (Kir4.1), a key component of the basolateral 40-pS K channel in DCT1, was a tyrosine-phosphorylated protein. LC/MS analysis further confirmed that SFK phosphorylated KCNJ10 at Tyr(8) and Tyr(9). The single-channel recording detected the activity of a 19-pS K channel in KCNJ10-transfected HEK293T cells and a 40-pS K channel in the cells transfected with KCNJ10+KCNJ16 (Kir.5.1) that form a heterotetramer in the basolateral membrane of the DCT. Mutation of Tyr(9) did not alter the channel conductance of the homotetramer and heterotetramer. However, it decreased the whole-cell K currents, the probability of finding K channels, and surface expression of KCNJ10 in comparison to WT KCNJ10. We conclude that SFK stimulates the basolateral K channel activity in DCT1, at least partially, by phosphorylating Tyr(9) on KCNJ10. We speculate that the modulation of tyrosine phosphorylation of KCNJ10 should play a role in regulating membrane transport function in DCT1.

  13. Sulfate transport by chick renal tubule brush-border and basolateral membranes

    Energy Technology Data Exchange (ETDEWEB)

    Renfro, J.L.; Clark, N.B.; Metts, R.E.; Lynch, M.A.

    1987-01-01

    Brush-border and basolateral membrane vesicles (BBMV and BLMV, respectively) were prepared from chick kidney by a calcium precipitation method and by centrifugation on an 8% Percoll self-generating gradient, respectively. In BBMV a 100-mM Na gluconate gradient, out>in, caused concentrative (/sup 35/S) sulfate uptake approximately fivefold greater at 1 min than at 60 min (equilibrium) whether or not the membranes were short-circuited with 100 mM K gluconate, in=out, plus 20 ..mu..g valinomycin/mg protein. A 48-mM HCO/sub 3//sup -/ gradient, in>out, stimulated a 2.5-fold higher uptake at 1 min than at 60 min, and short circuiting as above had no effect on the magnitude of this response. Imposition of a H/sup +/ gradient caused concentrative uptake fourfold higher at 1 min than at equilibrium. Short circuiting as above or addition of 0.1 mM carbonyl cyanide m-chlorophenylhydrazone (CCCP) significantly inhibited the pH gradient effect. Creation of an inside positive electrical potential with 100 mM K gluconate, out>in, plus valinomycin, also caused concentrative sulfate uptake. Based on inhibitor/competitor effects, these are distinct sulfate transport processes. In chick BLMV, imposition of an HCO/sub 3//sup -/ gradient, in>out, produced concentrative sulfate uptake. 4-Acetamido-4'-isothiocyanostilbene 2,2'-disulfonic acid disodium at 0.1 mM was an effective inhibitor of BLMV bicarbonate-sulfate exchange.

  14. Luminal NaCl delivery regulates basolateral PGE2 release from macula densa cells.

    Science.gov (United States)

    Peti-Peterdi, Janos; Komlosi, Peter; Fuson, Amanda L; Guan, Youfei; Schneider, Andre; Qi, Zhonghua; Redha, Reyadh; Rosivall, Laszlo; Breyer, Matthew D; Bell, P Darwin

    2003-07-01

    Macula densa (MD) cells express COX-2 and COX-2-derived PGs appear to signal the release of renin from the renal juxtaglomerular apparatus, especially during volume depletion. However, the synthetic machinery and identity of the specific prostanoid released from intact MD cells remains uncertain. In the present studies, a novel biosensor tool was engineered to directly determine whether MD cells release PGE2 in response to low luminal NaCl concentration ([NaCl]L). HEK293 cells were transfected with the Ca2+-coupled E-prostanoid receptor EP1 (HEK/EP1) and loaded with fura-2. HEK/EP1 cells produced a significant elevation in intracellular [Ca2+] ([Ca2+]i) by 29.6 +/- 12.8 nM (n = 6) when positioned at the basolateral surface of isolated perfused MD cells and [NaCl]L was reduced from 150 mM to zero. HEK/EP1 [Ca2+]i responses were observed mainly in preparations from rabbits on a low-salt diet and were completely inhibited by either a selective COX-2 inhibitor or an EP1 antagonist, and also by 100 microM luminal furosemide. Also, 20-mM graduated reductions in [NaCl]L between 80 and 0 mM caused step-by-step increases in HEK/EP1 [Ca2+]i. Low-salt diet greatly increased the expression of both COX-2 and microsome-associated PGE synthase (mPGES) in the MD. These studies provide the first direct evidence that intact MD cells synthesize and release PGE2 during reduced luminal salt content and suggest that this response is important in the control of renin release and renal vascular resistance during salt deprivation.

  15. Basolateral membrane Na+/H+ exchange enhances HCO3- absorption in rat medullary thick ascending limb: evidence for functional coupling between basolateral and apical membrane Na+/H+ exchangers.

    Science.gov (United States)

    Good, D W; George, T; Watts, B A

    1995-01-01

    The role of basolateral membrane Na+/H+ exchange in transepithelial HCO3- absorption (JHCO3) was examined in the isolated, perfused medullary thick ascending limb (MTAL) of the rat. In Na(+)-free solutions, addition of Na+ to the bath resulted in a rapid, amiloride-sensitive increase in intracellular pH. In MTALs perfused and bathed with solutions containing 146 mM Na+ and 25 mM HCO3-, bath addition of amiloride (1 mM) or 5-(N-ethyl-N-isopropyl) amiloride (EIPA, 50 microM) reversibly inhibited JHCO3 by 50%. Evidence that the inhibition of JHCO3 by bath amiloride was the result of inhibition of Na+/H+ exchange included the following: (i) the IC50 for amiloride was 5-10 microM, (ii) EIPA was a 50-fold more potent inhibitor than amiloride, (iii) the inhibition by bath amiloride was Na+ dependent, and (iv) significant inhibition was observed with EIPA as low as 0.1 microM. Fifty micromolar amiloride or 1 microM EIPA inhibited JHCO3 by 35% when added to the bath but had no effect when added to the tubule lumen, indicating that addition of amiloride to the bath did not directly inhibit apical membrane Na+/H+ exchange. In experiments in which apical Na+/H+ exchange was assessed from the initial rate of cell acidification following luminal EIPA addition, bath EIPA secondarily inhibited apical Na+/H+ exchange activity by 46%. These results demonstrate basolateral membrane Na+/H+ exchange enhances transepithelial HCO3- absorption in the MTAL. This effect appears to be the result of cross-talk in which an increase in basolateral membrane Na+/H+ exchange activity secondarily increases apical membrane Na+/H+ exchange activity. PMID:8618934

  16. Ca2+-activated K+ (BK) channel inactivation contributes to spike broadening during repetitive firing in the rat lateral amygdala.

    Science.gov (United States)

    Faber, E S Louise; Sah, Pankaj

    2003-10-15

    In many neurons, trains of action potentials show frequency-dependent broadening. This broadening results from the voltage-dependent inactivation of K+ currents that contribute to action potential repolarisation. In different neuronal cell types these K+ currents have been shown to be either slowly inactivating delayed rectifier type currents or rapidly inactivating A-type voltage-gated K+ currents. Recent findings show that inactivation of a Ca2+-dependent K+ current, mediated by large conductance BK-type channels, also contributes to spike broadening. Here, using whole-cell recordings in acute slices, we examine spike broadening in lateral amygdala projection neurons. Spike broadening is frequency dependent and is reversed by brief hyperpolarisations. This broadening is reduced by blockade of voltage-gated Ca2+ channels and BK channels. In contrast, broadening is not blocked by high concentrations of 4-aminopyridine (4-AP) or alpha-dendrotoxin. We conclude that while inactivation of BK-type Ca2+-activated K+ channels contributes to spike broadening in lateral amygdala neurons, inactivation of another as yet unidentified outward current also plays a role.

  17. Dopaminergic drug effects during reversal learning depend on anatomical connections between the orbitofrontal cortex and the amygdala.

    Directory of Open Access Journals (Sweden)

    Marieke E. van der Schaaf

    2013-08-01

    Full Text Available Dopamine in the striatum is known to be important for reversal learning. However, the striatum does not act in isolation and reversal learning is also well accepted to depend on the orbitofrontal cortex (OFC and the amygdala. Here we assessed whether dopaminergic drug effects on human striatal BOLD signalling during reversal learning is associated with anatomical connectivity in an orbitofrontal-limbic-striatal network, as measured with diffusion tensor imaging. By using a fibre-based approach, we demonstrate that dopaminergic drug effects on striatal BOLD signal varied as a function of fractional anisotropy (FA in a pathway connecting the OFC with the amygdala. Moreover, our experimental design allowed us to establish that these white-matter dependent drug effects were mediated via D2 receptors. Thus, white matter dependent effects of the D2 receptor agonist bromocriptine on striatal BOLD signal were abolished by co-administration with the D2 receptor antagonist sulpiride. These data provide fundamental insight into the mechanism of action of dopaminergic drug effects during reversal learning. In addition, they may have important clinical implications by suggesting that white matter integrity can help predict dopaminergic drug effects on brain function, ultimately contributing to individual tailoring of dopaminergic drug treatment strategies in psychiatry.

  18. Increased amygdala response to shame in remitted major depressive disorder.

    Directory of Open Access Journals (Sweden)

    Erdem Pulcu

    Full Text Available Proneness to self-blaming moral emotions such as shame and guilt is increased in major depressive disorder (MDD, and may play an important role in vulnerability even after symptoms have subsided. Social psychologists have argued that shame-proneness is relevant for depression vulnerability and is distinct from guilt. Shame depends on the imagined critical perception of others, whereas guilt results from one's own judgement. The neuroanatomy of shame in MDD is unknown. Using fMRI, we compared 21 participants with MDD remitted from symptoms with no current co-morbid axis-I disorders, and 18 control participants with no personal or family history of MDD. The MDD group exhibited higher activation of the right amygdala and posterior insula for shame relative to guilt (SPM8. This neural difference was observed despite equal levels of rated negative emotional valence and frequencies of induced shame and guilt experience across groups. These same results were found in the medication-free MDD subgroup (N = 15. Increased amygdala and posterior insula activations, known to be related to sensory perception of emotional stimuli, distinguish shame from guilt responses in remitted MDD. People with MDD thus exhibit changes in the neural response to shame after symptoms have subsided. This supports the hypothesis that shame and guilt play at least partly distinct roles in vulnerability to MDD. Shame-induction may be a more sensitive probe of residual amygdala hypersensitivity in MDD compared with facial emotion-evoked responses previously found to normalize on remission.

  19. The left amygdala: A shared substrate of alexithymia and empathy.

    Science.gov (United States)

    Goerlich-Dobre, Katharina Sophia; Lamm, Claus; Pripfl, Juergen; Habel, Ute; Votinov, Mikhail

    2015-11-15

    Alexithymia, a deficit in emotional self-awareness, and deficits in empathy, which encompasses the awareness of other's emotions, are related constructs that are both associated with a range of psychopathological disorders. Neuroimaging studies suggest that there is overlap between the neural bases of alexithymia and empathy, but no systematic comparison has been conducted so far. The aim of this structural magnetic resonance imaging study was to disentangle the overlap and differences between the morphological profiles of the cognitive and affective dimensions of alexithymia and empathy, and to find out to what extent these differ between women and men. High-resolution T1 anatomical images were obtained from 125 healthy right-handers (18-42 years), 70 women and 55 men. By means of voxel-based morphometry, region of interest (ROI) analyses were performed on gray matter volumes of several anatomically defined a-priori regions previously linked to alexithymia and empathy. Partial correlations were conducted within the female and male group using ROI parameter estimates as dependent variables and the cognitive and affective dimensions of alexithymia and empathy, respectively, as predictors, controlling for age. Results were considered significant if they survived Holm-Bonferroni correction for multiple comparisons. The left amygdala was identified as a key substrate of both alexithymia and empathy. This association was characterized by an opposite pattern: The cognitive alexithymia dimension was linked to smaller, the two empathy dimensions to larger left amygdala volume. While sex-specific effects were not observed for empathy, they were evident for the affective alexithymia dimension: Men-but not women-with difficulty fantasizing had smaller gray matter volume in the middle cingulate cortex. Moreover, structural covariance patterns between the left amygdala and other emotion-related brain regions differed markedly between alexithymia and empathy. These differences

  20. Repeatedly stressed rats have enhanced vulnerability to amygdala kindling epileptogenesis.

    Science.gov (United States)

    Jones, Nigel C; Lee, Han Ee; Yang, Meng; Rees, Sandra M; Morris, Margaret J; O'Brien, Terence J; Salzberg, Michael R

    2013-02-01

    Psychiatric disorders associated with elevated stress levels, such as depression, are present in many epilepsy patients, including those with mesial Temporal Lobe Epilepsy (mTLE). Evidence suggests that these psychiatric disorders can predate the onset of epilepsy, suggesting a causal/contributory role. Prolonged exposure to elevated corticosterone, used as a model of chronic stress/depression, accelerates limbic epileptogenesis in the amygdala kindling model. The current study examined whether exposure to repeated stress could similarly accelerate experimental epileptogenesis. Female adult non-epileptic Wistar rats were implanted with a bipolar electrode into the left amygdala, and were randomly assigned into stressed (n=18) or non-stressed (n=19) groups. Rats underwent conventional amygdala kindling (two electrical stimulations per day) until 5 Class V seizures had been experienced ('the fully kindled state'). Stressed rats were exposed to 30min restraint immediately prior to each kindling stimulation, whereas non-stressed rats received control handling. Restraint stress increased circulating corticosterone levels (pre-stress: 122±17ng/ml; post-stress: 632±33ng/ml), with no habituation observed over the experiment. Stressed rats reached the 'fully kindled state' in significantly fewer stimulations than non-stressed rats (21±1 vs 33±3 stimulations; p=0.022; ANOVA), indicative of a vulnerability to epileptogenesis. Further, seizure durations were significantly longer in stressed rats (p<0.001; ANOVA). These data demonstrate that exposure to repeated experimental stress accelerates the development of limbic epileptogenesis, an effect which may be related to elevated corticosterone levels. This may have implications for understanding the effects of chronic stress and depression in disease onset and progression of mTLE in humans.

  1. Subchronic duloxetine administration alters the extended amygdala circuitry in healthy individuals

    NARCIS (Netherlands)

    Marle, H.J.F. van; Tendolkar, I.; Urner, M.; Verkes, R.J.; Fernandez, G.S.E.; Wingen, G.A. van

    2011-01-01

    Neuroimaging studies have consistently linked depression to hyperactivation of a (para)limbic affective processing network centered around the amygdala. Recent studies have started to investigate how antidepressant drugs affect amygdala reactivity in healthy individuals, but the influence of their s

  2. Learning Enhances Intrinsic Excitability in a Subset of Lateral Amygdala Neurons

    Science.gov (United States)

    Sehgal, Megha; Ehlers, Vanessa L.; Moyer, James R., Jr.

    2014-01-01

    Learning-induced modulation of neuronal intrinsic excitability is a metaplasticity mechanism that can impact the acquisition of new memories. Although the amygdala is important for emotional learning and other behaviors, including fear and anxiety, whether learning alters intrinsic excitability within the amygdala has received very little…

  3. Mechanisms Contributing to the Induction and Storage of Pavlovian Fear Memories in the Lateral Amygdala

    Science.gov (United States)

    Kim, Dongbeom; Pare, Denis; Nair, Satish S.

    2013-01-01

    The relative contributions of plasticity in the amygdala vs. its afferent pathways to conditioned fear remain controversial. Some believe that thalamic and cortical neurons transmitting information about the conditioned stimulus (CS) to the lateral amygdala (LA) serve a relay function. Others maintain that thalamic and/or cortical plasticity is…

  4. The neurosteroids allopregnanolone and dehydroepiandrosterone modulate resting-state amygdala connectivity.

    Science.gov (United States)

    Sripada, Rebecca K; Welsh, Robert C; Marx, Christine E; Liberzon, Israel

    2014-07-01

    The neurosteroids allopregnanolone and dehydroepiandrosterone (DHEA) are integral components of the stress response and exert positive modulatory effects on emotion in both human and animal studies. Although these antidepressant and anxiolytic effects have been well established, to date, little research has examined their neural correlates, and no research has been conducted into the effects of neurosteroids on large-scale networks at rest. To investigate the neurosteroid impact on intrinsic connectivity networks, participants were administered 400 mg of pregnenolone (N = 16), 400 mg of DHEA (N = 14), or placebo (N = 15) and underwent 3T fMRI. Resting-state brain connectivity was measured using amygdala as a seed region. When compared with placebo, pregnenolone administration reduced connectivity between amygdala and dorsal medial prefrontal cortex, between amygdala and precuneus, and between amygdala and hippocampus. DHEA reduced connectivity between amygdala and periamygdala and between amygdala and insula. Reductions in amygdala to precuneus connectivity were associated with less self-reported negative affect. These results demonstrate that neurosteroids modulate amygdala functional connectivity during resting state and may be a target for pharmacological intervention. Additionally, allopregnanolone and DHEA may shift the balance between salience network and default network, a finding that could provide insight into the neurocircuitry of anxiety psychopathology.

  5. Williams Syndrome Hypersociability: A Neuropsychological Study of the Amygdala and Prefrontal Cortex Hypotheses

    Science.gov (United States)

    Capitao, Liliana; Sampaio, Adriana; Fernandez, Montse; Sousa, Nuno; Pinheiro, Ana; Goncalves, Oscar F.

    2011-01-01

    Individuals with Williams syndrome display indiscriminate approach towards strangers. Neuroimaging studies conducted so far have linked this social profile to structural and/or functional abnormalities in WS amygdala and prefrontal cortex. In this study, the neuropsychological hypotheses of amygdala and prefrontal cortex involvement in WS…

  6. Reduced amygdala volume in newly admitted psychiatric in-patients with unipolar major depression.

    Science.gov (United States)

    Kronenberg, Golo; Tebartz van Elst, Ludger; Regen, Francesca; Deuschle, Michael; Heuser, Isabella; Colla, Michael

    2009-09-01

    Structural neuroimaging studies investigating amygdala volumes in patients suffering from major depression have yielded variable results. Discrepant findings across studies may be attributable in part to heterogeneity with respect to antidepressant medication and to lack of adequate control for the effects of total brain volume and age. Here, 24 unipolar depressed in-patients newly admitted to a psychiatric unit and 14 healthy control participants matched for age, gender, and years of education underwent quantitative magnetic resonance imaging (MRI) toward the end of a one-week washout period. Saliva cortisol was measured at 08.00 and at 16.00h in patients during washout. Absolute amygdala volumes were significantly reduced in the patient group (by 13% in left amygdala and 12% in right amygdala). The effect of reduced amygdala volumes in patients remained significant after correction for brain volume (BV) and age. Furthermore, amygdala volume measurements in the patient sample showed a significant inverse relationship to the number of preceding depressive episodes. In patients, severity of disease (baseline HAMD scores) and baseline cortisol levels were not related to amygdala volume. This study of a sample of unmedicated depressed in-patients adds to the small, yet growing, body of evidence linking untreated major depression to reduced amygdala volume.

  7. Functional and structural amygdala - anterior cingulate connectivity correlates with attentional bias to masked fearful faces.

    Science.gov (United States)

    Carlson, Joshua M; Cha, Jiook; Mujica-Parodi, Lilianne R

    2013-10-01

    An attentional bias to threat has been causally related to anxiety. Recent research has linked nonconscious attentional bias to threat with variability in the integrity of the amygdala - anterior cingulate pathway, which sheds light on the neuroanatomical basis for a behavioral precursor to anxiety. However, the extent to which structural variability in amygdala - anterior cingulate integrity relates to the functional connectivity within this pathway and how such functional connectivity may relate to attention bias behavior, remain critical missing pieces of the puzzle. In 15 individuals we measured the structural integrity of the amygdala - prefrontal pathway with diffusion tensor-weighted MRI (magnetic resonance imaging), amygdala-seeded intrinsic functional connectivity to the anterior cingulate, and attentional bias toward backward masked fearful faces with a dot-probe task. We found that greater biases in attention to threat predicted greater levels of uncinate fasciculus integrity, greater positive amygdala - anterior cingulate functional connectivity, and greater amygdala coupling with a broader social perception network including the superior temporal sulcus, tempoparietal junction (TPJ), and somatosensory cortex. Additionally, greater levels of uncinate fasciculus integrity correlated with greater levels of amygdala - anterior cingulate intrinsic functional connectivity. Thus, high bias individuals displayed a heightened degree of amygdala - anterior cingulate connectivity during basal conditions, which we believe predisposes these individuals to focus their attention on signals of threat within their environment.

  8. Modulation of instrumental responding by a conditioned threat stimulus requires lateral and central amygdala

    Directory of Open Access Journals (Sweden)

    Vincent eCampese

    2015-10-01

    Full Text Available Two studies explored the role of the amygdala in response modulation by an aversive conditioned stimulus (CS in rats. Experiment 1 investigated the role of amygdala circuitry in conditioned suppression using a paradigm in which licking for sucrose was inhibited by a tone CS that had been previously paired with footshock. Electrolytic lesions of the lateral amygdala impaired suppression relative to sham-operated animals, and produced the same pattern of results when applied to central amygdala. In addition, disconnection of the lateral and central amygdala, by unilateral lesion of each on opposite sides of the brain, also impaired suppression relative to control subjects that received lesions of both areas on the same side. In each case, lesions were placed following Pavlovian conditioning and instrumental training, but before testing. This procedure produced within-subjects measures of the effects of lesion on freezing and between-group comparisons for the effects on suppression. Experiment 2 extended this analysis to a task where an aversive CS suppressed shuttling responses that had been previously food reinforced and also found effects of bilateral lesions of the central amygdala in a pre-post design. Together, these studies demonstrate that connections between the lateral and central amygdala constitute a serial circuit involved in processing aversive Pavlovian stimuli, and add to a growing body of findings implicating central amygdala in the modulation of instrumental behavior.

  9. Comparison between substantia innominata and amygdala kindling in rats.

    Science.gov (United States)

    Mori, N; Hoshino, S; Kumashiro, H

    1990-11-26

    Kindling was induced in rats by electrical stimulation of the lateral portion of the substantia innominata (SI). The pattern of seizure development was similar to that of amygdala (AM) kindling. However, lateral SI kindling was associated with ipsilateral head turning as an initial manifestation. In addition, lateral SI kindling had a higher afterdischarge threshold than AM kindling, and the generalized seizure triggering threshold was more unstable in SI kindling than in AM kindling. These findings suggest that lateral SI participates in, but is not essential for, AM seizure development in rats.

  10. Differential effects of unilateral lesions in the medial amygdala on spontaneous and induced ovulation.

    Science.gov (United States)

    Sanchez, M A; Dominguez, R

    1995-01-01

    The possible existence of asymmetry in the control of ovulation by the medial amygdala was explored. Unilateral lesions of the medial amygdala were performed on each day of the estrous cycle. The estral index diminished in almost all animals with a lesion in the right side of medial amygdala. Lesions of the right medial amygdala, when performed on diestrus-1, resulted in a significant decrease in the number of rats ovulating compared to controls (4/8 vs. 8/8, p rats with lesions of the right medial amygdala. However, sequential injections of PMSG-hCG did result in ovulation by all members of a group of lesioned animals. In this last condition a significant decrease in the number of ova shed by the right ovary was found compared to animals in the lesion-only condition (1.5 +/- 0.5 vs. 6.0 +/- 1.5, p cycle.

  11. Chronic estradiol treatment decreases brain derived neurotrophic factor (BDNF) expression and monoamine levels in the amygdala--implications for behavioral disorders.

    Science.gov (United States)

    Balasubramanian, Priya; Subramanian, Madhan; Nunez, Joseph L; Mohankumar, Sheba M J; Mohankumar, P S

    2014-03-15

    Changes in serum estradiol levels are associated with mood disorders in women. However, the underlying mechanisms are not clear. Because alterations in Brain-Derived Neurotrophic Factor (BDNF) and monoamine levels in the hippocampus and amygdala have been associated with anxiety disorders, we hypothesized that chronic treatment with a low dose of estradiol would cause anxiety-like disorder by altering BDNF and monoamine levels in these regions. To test this hypothesis, female rats were sham-implanted (Controls) or implanted with pellets that release estradiol-17β (E2) for 90-days at the rate of 20 ng/day. Animals underwent behavioral tests such as the open field test and elevated plus maze test at the end of treatment. Brains from these animals were frozen, sectioned and the hippocampus, central amygdala and caudate putamen were microdissected and analyzed for monoamine levels using HPLC. BDNF protein levels in these areas were measured using ELISA and BDNF mRNA levels were analyzed using RT-PCR. In the open field test, animals chronically treated with E2 displayed anxiety-like behavior that was marked by a decrease in the number of inner zone crossings and increase in the rate of defecation compared to controls. However, no behavioral changes were observed in the elevated plus maze test. Chronic E2 treatment also decreased BDNF protein and mRNA levels in the central amygdala that was accompanied by a reduction in dopamine levels. No changes were observed in the hippocampus and caudate putamen. These results suggest that BDNF and dopamine in the central amygdala might possibly mediate chronic E2-induced behavioral alterations.

  12. The role of TNF-alpha in amygdala kindled rats.

    Science.gov (United States)

    Shandra, A A; Godlevsky, L S; Vastyanov, R S; Oleinik, A A; Konovalenko, V L; Rapoport, E N; Korobka, N N

    2002-02-01

    In the present study, the interaction between epileptogenesis and the immune system were studied in a kindling model. First, the effects of a single administration of TNF-alpha (5.0 microg/kg, i.p.) on seizure and EEG activity were investigated in amygdala-kindled rats. TNF-alpha treated rats showed more prolonged epileptiformic discharges than control rats. TNF-alpha also induced a decrease in the power of delta band and an increase in theta and alpha activity. In addition, a marked increase in the power of beta and gamma band was observed. The EEG changes were most numerous in the frontal cortex and amygdala. All effects were registered 24 h after TNF-alpha administration. Finally, electrical stimulation enhanced the level of TNF-alpha in blood serum from 1.9 +/- 1.5 to 12.7 +/- 3.8 pg/ml and in brain tissue 56.8 +/- 6.0 to 109.2 +/- 6.0 pg/mg, as was determined via the ELISA method. It can be concluded that there is a mutual facilitative interaction of both epileptogenic and cytokine-derived mechanisms on this type of seizure. The changes in the power spectrum of the EEG after TNF-alpha might contribute to intensify thalamic-derived facilitation of epileptic discharge in cortical structures.

  13. Consolidation of altered associability information by amygdala central nucleus.

    Science.gov (United States)

    Schiffino, Felipe L; Holland, Peter C

    2016-09-01

    The surprising omission of a reinforcer can enhance the associability of the stimuli that were present when the reward prediction error was induced, so that they more readily enter into new associations in the future. Previous research from this laboratory identified brain circuit elements critical to the enhancement of stimulus associability by the omission of an expected event and to the subsequent expression of that altered associability in more rapid learning. These elements include the amygdala, the midbrain substantia nigra, the basal forebrain substantia innominata, the dorsolateral striatum, the secondary visual cortex, and the posterior parietal cortex. Here, we found that consolidation of a surprise-enhanced associability memory in a serial prediction task depends on processing in the amygdala central nucleus (CeA) after completion of sessions that included the surprising omission of an expected event. Post-surprise infusions of anisomycin, lidocaine, or muscimol prevented subsequent display of surprise-enhanced associability. Because previous studies indicated that CeA function is unnecessary for the expression of associability enhancements that were induced previously when CeA function was intact (Holland & Gallagher, 2006), we interpreted these results as indicating that post-surprise activity of CeA ("surprise replay") is necessary for the consolidation of altered associability memories elsewhere in the brain, such as the posterior parietal cortex (Schiffino et al., 2014a).

  14. Purinergic receptor signaling at the basolateral membrane of macula densa cells.

    Science.gov (United States)

    Liu, Ruisheng; Bell, P Darwin; Peti-Peterdi, Janos; Kovacs, Gergly; Johansson, Alf; Persson, A Erik G

    2002-05-01

    Purinergic receptors are important in the regulation of renal hemodynamics; therefore, this study sought to determine if such receptors influence macula densa cell function. Isolated glomeruli containing macula densa cells, with and without the cortical thick ascending limb, were loaded with the Ca(2+) sensitive indicators, Fura Red (confocal microscopy) or fura 2 (conventional video image analysis). Studies were performed on an inverted microscope in a chamber with a flow-through perfusion system. Changes in cytosolic calcium concentration ([Ca(2+)](i)) from exposed macula densa plaques were assessed upon addition of adenosine, ATP, UTP, ADP, or 2-methylthio-ATP (2- MeS-ATP) for 2 min added to the bathing solution. There was no change in [Ca(2+)](i) with addition of adenosine (10(-7) to 10(-3) M). UTP and ATP (10(-4) M) caused [Ca(2+)](i) to increase by 268 +/- 40 nM (n = 21) and 295 +/- 53 nM (n = 21), respectively, whereas in response to 2MesATP and ADP, [Ca(2+)](i) increased by only 67 +/- 13 nM (n = 8) and 93 +/- 36 nM (n = 14), respectively. Dose response curve for ATP (10(-7) to 10(-3) M) added in bath showed an EC(50) of 15 microM. No effect on macula densa [Ca(2+)](i) was seen when ATP was added from the lumen. ATP caused similar increases in macula densa [Ca(2+)](i) in the presence or absence of bath Ca(2+) and addition of 5 mM ethyleneglycotetraacetic acid (EGTA). Suramin (an antagonist of P2X and P2Y receptors) completely inhibited ATP-induced [Ca(2+)](i) dynamics. Also, ATP-Ca(2+) responsiveness was prevented by the phospholipase C inhibitor, U-73122, but not by its inactive analog, U-73343. These results suggest that macula densa cells possess P2Y(2) purinergic receptors on basolateral but not apical membranes and that activation of these receptors results in the mobilization of Ca(2+).

  15. Fatty acids affect micellar properties and modulate vitamin D uptake and basolateral efflux in Caco-2 cells.

    Science.gov (United States)

    Goncalves, Aurélie; Gleize, Béatrice; Roi, Stéphanie; Nowicki, Marion; Dhaussy, Amélie; Huertas, Alain; Amiot, Marie-Josèphe; Reboul, Emmanuelle

    2013-10-01

    We have recently shown that vitamin D3 (cholecalciferol) absorption is not a simple passive diffusion but involves cholesterol transporters. As free fatty acids (FAs) modulate cholesterol intestinal absorption and metabolism, we hypothesized that FAs may also interact with vitamin D absorption. Effects of FAs were evaluated at different levels of cholecalciferol intestinal absorption. First, the physicochemical properties of micelles formed with different FAs were analyzed. The micelles were then administered to human Caco-2 cells in culture to evaluate FA effects on (i) cholecalciferol uptake and basolateral efflux and (ii) the regulation of genes coding proteins involved in lipid absorption process. Micellar electric charge was correlated with both FA chain length and degree of unsaturation. Long-chain FAs at 500 μM in mixed micelles decreased cholecalciferol uptake in Caco-2 cells. This decrease was annihilated as soon as the long-chain FAs were mixed with other FAs. Oleic acid significantly improved cholecalciferol basolateral efflux compared to other FAs. These results were partly explained by a modulation of genes coding for lipid transport proteins such as Niemann-pick C1-like 1 and scavenger receptor class B type I. The data reported here show for the first time that FAs can interact with cholecalciferol intestinal absorption at different key steps of the absorption process. Cholecalciferol intestinal absorption may thus be optimized according to oil FA composition.

  16. Role of capsaicin-sensitive C-fiber afferents in neuropathic pain-induced synaptic potentiation