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Sample records for preoptic neurons project

  1. Synaptic contact between median preoptic neurons and subfornical organ neurons projecting to the paraventricular hypothalamic nucleus.

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    Kawano, Hitoshi

    2017-04-01

    It is known that the median preoptic nucleus (POMe) sends dense projections to the subfornical organ (SFO). However, the functional significance of these projections have not been well discussed. In this electron microscopic study, we investigated the presence of synapses between POMe-derived axon terminals and SFO neurons that project to the paraventricular hypothalamic nucleus (PVN). After injection of a retrograde tracer, wheat germ agglutinin-conjugated horseradish peroxidase-colloidal gold complex, into the PVN, many labeled neurons were found in the SFO. In contrast, after injection of an anterograde tracer, biotinylated dextran amine, in the POMe, abundant labeled axon varicosities were observed in the SFO. Using electron microscopy, synapses were identified between retrogradely labeled dendrites and cell bodies, and anterogradely labeled axon terminals, indicating that POMe neurons innervate SFO neurons projecting to the PVN. The possibility that POMe neurons play multiple roles in the neuronal circuit responsible for vasopressin release and/or cardiovascular regulation is also discussed.

  2. Identification of preoptic sleep neurons using retrograde labelling and gene profiling.

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    Chung, Shinjae; Weber, Franz; Zhong, Peng; Tan, Chan Lek; Nguyen, Thuc Nghi; Beier, Kevin T; Hörmann, Nikolai; Chang, Wei-Cheng; Zhang, Zhe; Do, Johnny Phong; Yao, Shenqin; Krashes, Michael J; Tasic, Bosiljka; Cetin, Ali; Zeng, Hongkui; Knight, Zachary A; Luo, Liqun; Dan, Yang

    2017-05-25

    In humans and other mammalian species, lesions in the preoptic area of the hypothalamus cause profound sleep impairment, indicating a crucial role of the preoptic area in sleep generation. However, the underlying circuit mechanism remains poorly understood. Electrophysiological recordings and c-Fos immunohistochemistry have shown the existence of sleep-active neurons in the preoptic area, especially in the ventrolateral preoptic area and median preoptic nucleus. Pharmacogenetic activation of c-Fos-labelled sleep-active neurons has been shown to induce sleep. However, the sleep-active neurons are spatially intermingled with wake-active neurons, making it difficult to target the sleep neurons specifically for circuit analysis. Here we identify a population of preoptic area sleep neurons on the basis of their projection target and discover their molecular markers. Using a lentivirus expressing channelrhodopsin-2 or a light-activated chloride channel for retrograde labelling, bidirectional optogenetic manipulation, and optrode recording, we show that the preoptic area GABAergic neurons projecting to the tuberomammillary nucleus are both sleep active and sleep promoting. Furthermore, translating ribosome affinity purification and single-cell RNA sequencing identify candidate markers for these neurons, and optogenetic and pharmacogenetic manipulations demonstrate that several peptide markers (cholecystokinin, corticotropin-releasing hormone, and tachykinin 1) label sleep-promoting neurons. Together, these findings provide easy genetic access to sleep-promoting preoptic area neurons and a valuable entry point for dissecting the sleep control circuit.

  3. Multiparametric characterization of neuronal subpopulations in the ventrolateral preoptic nucleus.

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    Dubourget, Romain; Sangare, Aude; Geoffroy, Hélène; Gallopin, Thierry; Rancillac, Armelle

    2017-04-01

    The characterization of neuronal properties is a necessary first step toward understanding how the ventrolateral preoptic nucleus (VLPO) neuronal network regulates slow-wave sleep (SWS). Indeed, the electrophysiological heterogeneity of VLPO neurons suggests the existence of subtypes that could differently contribute in SWS induction and maintenance. The aim of the present study was to define cell classes in the VLPO using an unsupervised clustering classification method. Electrophysiological features extracted from 289 neurons recorded in whole-cell patch-clamp allowed the identification of three main classes of VLPO neurons subdivided into five distinct subpopulations (cluster 1, 2a, 2b, 3a and 3b). The high occurrence of a low-threshold calcium spike (LTS) was one of the most distinctive features of cluster 1 and 3. Since sleep-promoting neurons are generally identified by their ability to generate an LTS and by their inhibitory response to noradrenaline (NA), 189 neurons from our dataset were also tested for this neurotransmitter. Neurons from cluster 3 were the most frequently inhibited by NA. Biocytin labeling and Neurolucida reconstructions of 112 neurons furthermore revealed a small dendritic arbor of cluster 3b neurons compared, in particular, to cluster 2b neurons. Altogether, we performed an exhaustive characterization of VLPO neuronal subtypes that is a crucial step toward a better understanding of the neuronal network within the VLPO and thereby sleep physiology.

  4. Muscarinic M1 receptors regulate propofol modulation of GABAergic transmission in rat ventrolateral preoptic neurons.

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    Zhang, Yu; Yu, Tian; Liu, Yang; Qian, Kun; Yu, Bu-Wei

    2015-04-01

    GABAergic neurons within the ventrolateral preoptic area (VLPO) play an important role in sleep-wakefulness regulation. Propofol, a widely used systemic anesthetic, has lately been reported to excite noradrenaline (NA)-inhibited type of VLPO neurons. Present study tested if acetylcholine system takes part in the propofol modulation of GABAergic spontaneous miniature inhibitory postsynaptic currents (mIPSCs) in mechanically dissociated rat VLPO neurons using a conventional whole-cell patch clamp technique. Propofol reversibly decreased mIPSC frequency without affecting the current amplitude, indicating that propofol acts presynaptically to decrease the probability of spontaneous GABA release. The propofol action on GABAergic mIPSC frequency was completely blocked by atropine, a nonselective muscarinic acetylcholine (mACh) receptor antagonist, and pirenzepine, a selective M1 receptor antagonist. These results suggest that propofol acts on M1 receptors on GABAergic nerve terminals projecting to VLPO neurons to inhibit spontaneous GABA release. The M1 receptor-mediated modulation of GABAergic transmission onto VLPO neurons may contribute to the regulation of loss of consciousness induced by propofol.

  5. Neuronal activity in the preoptic hypothalamus during sleep deprivation and recovery sleep.

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    Alam, Md Aftab; Kumar, Sunil; McGinty, Dennis; Alam, Md Noor; Szymusiak, Ronald

    2014-01-01

    The preoptic hypothalamus is implicated in sleep regulation. Neurons in the median preoptic nucleus (MnPO) and the ventrolateral preoptic area (VLPO) have been identified as potential sleep regulatory elements. However, the extent to which MnPO and VLPO neurons are activated in response to changing homeostatic sleep regulatory demands is unresolved. To address this question, we continuously recorded the extracellular activity of neurons in the rat MnPO, VLPO and dorsal lateral preoptic area (LPO) during baseline sleep and waking, during 2 h of sleep deprivation (SD) and during 2 h of recovery sleep (RS). Sleep-active neurons in the MnPO (n = 11) and VLPO (n = 13) were activated in response to SD, such that waking discharge rates increased by 95.8 ± 29.5% and 59.4 ± 17.3%, respectively, above waking baseline values. During RS, non-rapid eye movement (REM) sleep discharge rates of MnPO neurons initially increased to 65.6 ± 15.2% above baseline values, then declined to baseline levels in association with decreases in EEG delta power. Increase in non-REM sleep discharge rates in VLPO neurons during RS averaged 40.5 ± 7.6% above baseline. REM-active neurons (n = 16) in the LPO also exhibited increased waking discharge during SD and an increase in non-REM discharge during RS. Infusion of A2A adenosine receptor antagonist into the VLPO attenuated SD-induced increases in neuronal discharge. Populations of LPO wake/REM-active and state-indifferent neurons and dorsal LPO sleep-active neurons were unresponsive to SD. These findings support the hypothesis that sleep-active neurons in the MnPO and VLPO, and REM-active neurons in the LPO, are components of neuronal circuits that mediate homeostatic responses to sustained wakefulness.

  6. Leptin Responsive and GABAergic Projections to the Rostral Preoptic Area in Mice.

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    Zuure, W A; Quennell, J H; Anderson, G M

    2016-03-01

    The adipocyte-derived hormone leptin plays a critical role in the control of reproduction via signalling in hypothalamic neurones. The drivers of the hypothalamic-pituitary-gonadal axis, the gonadotrophin-releasing hormone (GnRH) neurones, do not have the receptors for leptin. Therefore, intermediate leptin responsive neurones must provide leptin-to-GnRH signalling. We investigated the populations of leptin responsive neurones that provide input to the rostral preoptic area (rPOA) where GnRH cell bodies reside. Fluorescent retrograde tracer beads (RetroBeads; Lumafluor Inc., Naples, FL, USA) were injected into the rPOA of transgenic leptin receptor enhanced green fluorescent protein (Lepr-eGFP) reporter mice. Uptake of the RetroBeads by Lepr-eGFP neurones was assessed throughout the hypothalamus. RetroBead uptake was most evident in the medial arcuate nucleus (ARC), the dorsomedial nucleus (DMN) and the ventral premammillary nucleus (PMV) of the hypothalamus. The uptake of RetroBeads specifically by Lepr-eGFP neurones was highest in the medial ARC (18% of tracer-labelled neurones Lepr-eGFP-positive). Because neurones that are both leptin responsive and GABAergic play a critical role in the regulation of fertility by leptin, we next focussed on the location of these populations. To address whether GABAergic neurones in leptin-responsive hypothalamic regions project to the rPOA, the experiment was repeated in GABA neurone reporter mice (Vgat-tdTomato). Between 10% and 45% of RetroBead-labelled neurones in the ARC were GABAergic, whereas uptake of tracer by GABAergic neurones in the DMN and PMV was very low (leptin responsive and GABAergic neurones from the ARC project to the region of the GnRH cell bodies. Our findings suggest that LEPR-expressing GABA neurones from the ARC may be mediators of leptin-to-GnRH signalling.

  7. Morphological changes of gonadotropin-releasing hormone neurons in the rat preoptic area across puberty

    Institute of Scientific and Technical Information of China (English)

    Haogang Xue; Xiaodong Gai; Weiqi Sun; Chun Li; Quan Liu

    2014-01-01

    Gonadotropin-releasing hormone (GnRH) neurons in the preoptic area may undergo mor-phological changes during the pubertal period when their activities are upregulated. To clarify the regulatory mechanism of puberty onset, this study aimed to investigate the morphological changes of GnRH neurons in the preoptic area of GnRH-enhanced green lfuorescent protein transgenic rats. Under confocal laser microscopy, pubertal GnRH neurons exhibited an inverted Y distribution pattern. Prepubertal GnRH neurons were generally unipolar and bipolar, and were distinguished as smooth type cells with few small processes or irregular type cells with many spine-like processes in the proximal dendrites. The number of GnRH neurons in the preoptic area and spine-like processes were increased during the course of reproductive matu-ration. There was no signiifcant difference between male and female rats. Immunolfuorescence staining revealed synaptophysin punctae close to the distal end of GnRH neurons, indicating that some presynaptic terminals may form a synaptic linkage with these neurons.

  8. Kv4.2 mediates histamine modulation of preoptic neuron activity and body temperature.

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    Jasmine Sethi

    Full Text Available Histamine regulates arousal, circadian rhythms, and thermoregulation. Activation of H3 histamine receptors expressed by preoptic GABAergic neurons results in a decrease of their firing rate and hyperthermia. Here we report that an increase in the A-type K⁺ current in preoptic GABAergic neurons in response to activation of H3 histamine receptors results in decreased firing rate and hyperthermia in mice. The Kv4.2 subunit is required for these actions in spite of the fact that Kv4.2⁻/⁻ preoptic GABAergic neurons display A-type currents and firing characteristics similar to those of wild-type neurons. This electrical remodeling is achieved by robust upregulation of the expression of the Kv4.1 subunit and of a delayed rectifier current. Dynamic clamp experiments indicate that enhancement of the A-type current by a similar amount to that induced by histamine is sufficient to mimic its robust effect on firing rates. These data indicate a central role played by the Kv4.2 subunit in histamine regulation of body temperature and its interaction with pERK1/2 downstream of the H3 receptor. We also reveal that this pathway provides a mechanism for selective modulation of body temperature at the beginning of the active phase of the circadian cycle.

  9. Disrupted Sleep in Narcolepsy: Exploring the Integrity of Galanin Neurons in the Ventrolateral Preoptic Area.

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    Gavrilov, Yury V; Ellison, Brian A; Yamamoto, Mihoko; Reddy, Hasini; Haybaeck, Johannes; Mignot, Emmanuel; Baumann, Christian R; Scammell, Thomas E; Valko, Philipp O

    2016-05-01

    To examine the integrity of sleep-promoting neurons of the ventrolateral preoptic nucleus (VLPO) in postmortem brains of narcolepsy type 1 patients. Postmortem examination of five narcolepsy and eight control brains. VLPO galanin neuron count did not differ between narcolepsy patients (11,151 ± 3,656) and controls (13,526 ± 9,544). A normal number of galanin-immunoreactive VLPO neurons in narcolepsy type 1 brains at autopsy suggests that VLPO cell loss is an unlikely explanation for the sleep fragmentation that often accompanies the disease. © 2016 Associated Professional Sleep Societies, LLC.

  10. Hyperglycemia decreased medial amygdala projections to medial preoptic area in experimental model of Diabetes Mellitus.

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    Yousef Mohamadi

    2015-01-01

    Full Text Available In Wistar rats, reproductive behavior is controlled in a neural circuit of ventral forebrain including the medial amygdala (Me, bed nucleus of the stria terminalis (BNST and medial preoptic area (MPOA via perception of social odors. Diabetes Mellitus (DM is a widespread metabolic disease that affects many organs in a variety of levels. DM can cause central neuropathies such as neuronal apoptosis, dendritic atrophy, neurochemical alterations and also causes reproductive dysfunctions. So we hypothesized damage to the nuclei of this circuit can cause reproductive dysfunctions. Therefore in this project we assessed diabetic effect on these nuclei. For this purpose neuron tracing technique and TUNEL assay were used. We injected HRP in the MPOA and counted labeled cells in the Me and BNST to evaluate the reduction of neurons in diabetic animals. Also, coronal sections were analyzed with the TMB histochemistry method. Animals in this study were adult male Wistar rats (230 ± 8g divided to control and 10-week streptozotocin-induced diabetic groups. After data analysis by SPSS 16 software, a significant reduction of HRP-labeled neurons was shown in both Me and BNST nuclei in the diabetic group. Moreover, apoptotic cells were significantly observed in diabetic animals in contrast to control the group. In conclusion, these alterations of the circuit as a result of diabetes might be one of the reasons for reproductive dysfunctions.

  11. Electrical remodeling of preoptic GABAergic neurons involves the Kv1.5 subunit.

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    Iustin V Tabarean

    Full Text Available The electrogenic machinery of an excitable cell can adapt in response to changes in input, genetic deficit or in pathological conditions, however the underlying molecular mechanisms are not understood. In cases of genetic deletion it is commonly observed that a channel subunit from the same family replaces the missing one. We have previously reported that Kv4.2-/- preoptic GABAergic neurons display identical firing characteristics to those of wild-type neurons despite having reduced A-type currents, and that, surprisingly, they present a robust upregulation of a delayed rectifier current, the nature of which is unknown. Here, using pharmacology, qPCR and Western blots we report that, although the wild-type neurons express several Kv subunits, the upregulated current is conducted by the Kv1.5 subunit exclusively. Thus, this study reveals the molecular nature of a novel mechanism of electrical remodeling in central neurons.

  12. Electrophysiological characterization of male goldfish (Carassius auratus ventral preoptic area neurons receiving olfactory inputs

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    Wudu E. Lado

    2014-06-01

    Full Text Available Chemical communication via sex pheromones is critical for successful reproduction but the underlying neural mechanisms are not well-understood. The goldfish is a tractable model because sex pheromones have been well-characterized in this species. We used male goldfish forebrain explants in vitro and performed whole-cell current clamp recordings from single neurons in the ventral preoptic area (vPOA to characterize their membrane properties and synaptic inputs from the olfactory bulbs (OB. Principle component and cluster analyses based on intrinsic membrane properties of vPOA neurons (N = 107 revealed five (I-V distinct cell groups. These cells displayed differences in their input resistance (Rinput: I II = IV > III = V. Evidence from electrical stimulation of the OB and application of receptor antagonists suggests that vPOA neurons receive monosynaptic glutamatergic inputs via the medial olfactory tract, with connectivity varying among neuronal groups [I (24%, II (40%, III (0%, IV (34% and V (2%].

  13. Activation of Strychnine-Sensitive Glycine Receptors by Shilajit on Preoptic Hypothalamic Neurons of Juvenile Mice.

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    Bhattarai, Janardhan Prasad; Cho, Dong Hyu; Han, Seong Kyu

    2016-02-29

    Shilajit, a mineral pitch, has been used in Ayurveda and Siddha system of medicine to treat many human ailments, and is reported to contain at least 85 minerals in ionic form. This study examined the possible mechanism of Shilajit action on preoptic hypothalamic neurons using juvenile mice. The hypothalamic neurons are the key regulator of many hormonal systems. In voltage clamp mode at a holding potential of -60 mV, and under a high chloride pipette solution, Shilajit induced dose-dependent inward current. Shilajit-induced inward currents were reproducible and persisted in the presence of 0.5 μM tetrodotoxin (TTX) suggesting a postsynaptic action of Shilajit on hypothalamic neurons. The currents induced by Shilajit were almost completely blocked by 2 μM strychnine (Stry), a glycine receptor antagonist. In addition, Shilajit-induced inward currents were partially blocked by bicuculline. Under a gramicidin-perforated patch clamp mode, Shilajit induced membrane depolarization on juvenile neurons. These results show that Shilajit affects hypothalamic neuronal activities by activating the Stry-sensitive glycine receptor with α₂/α₂β subunit. Taken together, these results suggest that Shilajit contains some ingredients with possible glycine mimetic activities and might influence hypothalamic neurophysiology through activation of Stry-sensitive glycine receptor-mediated responses on hypothalamic neurons postsynaptically.

  14. Hyperglycemia decreased medial amygdala projections to medial preoptic area in experimental model of Diabetes Mellitus.

    OpenAIRE

    Yousef Mohamadi; Seyed Behnam-edin Jameie; Mohammad Akbari; Masumeh Staji; Fatemeh Moradi; Tahmineh Mokhtari; Maryam Khanehzad; Gholamreza Hassanzadeh

    2015-01-01

    In Wistar rats, reproductive behavior is controlled in a neural circuit of ventral forebrain including the medial amygdala (Me), bed nucleus of the stria terminalis (BNST) and medial preoptic area (MPOA) via perception of social odors. Diabetes Mellitus (DM) is a widespread metabolic disease that affects many organs in a variety of levels. DM can cause central neuropathies such as neuronal apoptosis, dendritic atrophy, neurochemical alterations and also causes reproductive dysfunctions. So we...

  15. Sleep is related to neuron numbers in the ventrolateral preoptic/intermediate nucleus in older adults with and without Alzheimer's disease.

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    Lim, Andrew S P; Ellison, Brian A; Wang, Joshua L; Yu, Lei; Schneider, Julie A; Buchman, Aron S; Bennett, David A; Saper, Clifford B

    2014-10-01

    Fragmented sleep is a common and troubling symptom in ageing and Alzheimer's disease; however, its neurobiological basis in many patients is unknown. In rodents, lesions of the hypothalamic ventrolateral preoptic nucleus cause fragmented sleep. We previously proposed that the intermediate nucleus in the human hypothalamus, which has a similar location and neurotransmitter profile, is the homologue of the ventrolateral preoptic nucleus, but physiological data in humans were lacking. We hypothesized that if the intermediate nucleus is important for human sleep, then intermediate nucleus cell loss may contribute to fragmentation and loss of sleep in ageing and Alzheimer's disease. We studied 45 older adults (mean age at death 89.2 years; 71% female; 12 with Alzheimer's disease) from the Rush Memory and Aging Project, a community-based study of ageing and dementia, who had at least 1 week of wrist actigraphy proximate to death. Upon death a median of 15.5 months later, we used immunohistochemistry and stereology to quantify the number of galanin-immunoreactive intermediate nucleus neurons in each individual, and related this to ante-mortem sleep fragmentation. Individuals with Alzheimer's disease had fewer galaninergic intermediate nucleus neurons than those without (estimate -2872, standard error = 829, P = 0.001). Individuals with more galanin-immunoreactive intermediate nucleus neurons had less fragmented sleep, after adjusting for age and sex, and this association was strongest in those for whom the lag between actigraphy and death was Alzheimer's disease, and similar associations were not seen for two other cell populations near the intermediate nucleus. These data are consistent with the intermediate nucleus being the human homologue of the ventrolateral preoptic nucleus. Moreover, they demonstrate that a paucity of galanin-immunoreactive intermediate nucleus neurons is accompanied by sleep fragmentation in older adults with and without Alzheimer's disease.

  16. Preoptic neuronal nitric oxide synthase induction by testosterone is consistent with a role in gating male copulatory behavior

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    Sanderson, Nicholas S. R.; Le, Brandon; Zhou, Zifei; Crews, David

    2008-01-01

    Copulatory behaviors are generally dependent on testicular androgens in male vertebrates, being eliminated by castration and re-instated by testosterone administration. It is postulated that a critical factor in this hormonal gating is up-regulation of neuronal nitric oxide synthase (nNOS) in the preoptic area, and consequent enhanced nitric oxide synthesis in response to stimuli associated with a receptive female. Previous studies have suggested that nNOS protein is more abundant in behaviorally relevant preoptic regions of testosterone-exposed animals than in hormone-deprived controls. This study sought to elucidate the molecular events underlying this apparent up-regulation by examining preoptic nNOS mRNA abundance at several time points following testosterone administration in a castration and replacement paradigm. Castrated male whiptails (Cnemidophorus inornatus) were implanted with testosterone, and at four time points over the subsequent 18 days their sexual behavior was tested. A rostral periventricular area previously implicated in hormonal gating of male-typical copulatory behavior was then excised by laser microdissection, and nNOS transcript abundance was assessed by quantitative PCR. As neither this technique nor nNOS mRNA measurements have previously been performed in this area of the brain, expression was concommitantly assayed on adjacent sections by in situ hybridization or NADPH diaphorase histochemistry. Results are consistent with transcriptional up-regulation of nNOS by testosterone and a central role for the enzyme in mediating hormonal gating of copulatory behavior. PMID:18184320

  17. Histaminergic H1 and H2 Receptors Mediate the Effects of Propofol on the Noradrenalin-Inhibited Neurons in Rat Ventrolateral Preoptic Nucleus.

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    Liu, Yang; Zhang, Yu; Qian, Kun; Zhang, Lin; Yu, Tian

    2017-02-09

    The ventrolateral preoptic nucleus is a sleep-promoting nucleus located in the basal forebrain. A commonly used intravenous anesthetic, propofol, had been reported to induce sleep spindles and augment the firing rate of neurons in ventrolateral preoptic nucleus, but the underlining mechanism is yet to be known. By using patch clamp recording on neuron in acute brain slice, present study tested if histaminergic H1 and H2 receptors play a role in the effect of propofol on the noradrenalin-inhibited neurons in ventrolateral preoptic nucleus. We found that the firing rate of noradrenalin-inhibited neurons were significantly augmented by propofol; the frequency of inhibitory postsynaptic currents of noradrenalin-inhibited neuron were evidently attenuated by propofol; such inhibition effect was suppressed by histamine; and both triprolidine (antagonist for H1 histamine receptor) and ranitidine (antagonist for H2 histamine receptor) were able to increase the inhibition rate of propofol in presence of histamine. Present study demonstrated that propofol-induced inhibition of inhibitory postsynaptic currents on noradrenalin-inhibited neurons were mediated by histaminergic H1 and H2 receptors.

  18. Effects of Prolactin and Lactation on A15 Dopamine Neurones in the Rostral Preoptic Area of Female Mice.

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    Brown, R S E; Herbison, A E; Grattan, D R

    2015-09-01

    There are several distinct populations of dopamine neurones in the hypothalamus. Some of these, such as the A12 tuberoinfundibular dopamine neurones and the A14 periventricular dopamine neurones, are known to be regulated by the anterior pituitary hormone prolactin, whereas others, such as the A13 zona incerta dopaminergic neurones, are not. The present study aimed to investigate the role of prolactin in the regulation of a fourth population of hypothalamic dopamine neurones: the A15 dopamine population in the rostral hypothalamus. These neurones may play a role in the regulation of gonadotrophin-releasing hormone (GnRH) secretion, and we hypothesised that they might contribute to the suppression of GnRH release and infertility caused by hyperprolactinaemia. Under basal (low prolactin) conditions, only 8% of A15 dopamine neurones in the anteroventral periventricular nucleus (AVPV) of vehicle-treated dioestrous mice expressed phosphorylated signal transducer and activator of transcription 5 (pSTAT5), as labelled by immunohistochemistry. We have previously shown that this transcription factor can be used as an index of prolactin-receptor activation. Following acute prolactin administration, 35% of AVPV dopamine neurones co-expressed pSTAT5, whereas, during lactation, when endogenous prolactin levels are chronically elevated, 55% of AVPV dopamine neurones expressed pSTAT5. There was also a significant increase in dopamine turnover in the rostral hypothalamus, both in the diagonal band of Broca at the level of the organum vasculosum of the lamina terminalis and in the rostral preoptic area during lactation, with the 3,4-dihydroxyphenylacetic acid/dopamine ratio increasing from 0.28 ± 0.04 and 0.14 ± 0.01 in dioestrous mice to 0.82 ± 0.06 and 0.38 ± 0.03, respectively, in day 7 lactating mice. It is not yet known whether this change is driven by the hyperprolactinaemia of lactation, or another lactation-specific signal. These data demonstrate that the A15

  19. Release of norepinephrine in the preoptic area activates anteroventral periventricular nucleus neurons and stimulates the surge of luteinizing hormone.

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    Szawka, Raphael E; Poletini, Maristela O; Leite, Cristiane M; Bernuci, Marcelo P; Kalil, Bruna; Mendonça, Leonardo B D; Carolino, Ruither O G; Helena, Cleyde V V; Bertram, Richard; Franci, Celso R; Anselmo-Franci, Janete A

    2013-01-01

    The role of norepinephrine (NE) in regulation of LH is still controversial. We investigated the role played by NE in the positive feedback of estradiol and progesterone. Ovarian-steroid control over NE release in the preoptic area (POA) was determined using microdialysis. Compared with ovariectomized (OVX) rats, estradiol-treated OVX (OVX+E) rats displayed lower release of NE in the morning but increased release coincident with the afternoon surge of LH. OVX rats treated with estradiol and progesterone (OVX+EP) exhibited markedly greater NE release than OVX+E rats, and amplification of the LH surge. The effect of NE on LH secretion was confirmed using reverse microdialysis. The LH surge and c-Fos expression in anteroventral periventricular nucleus neurons were significantly increased in OVX+E rats dialyzed with 100 nm NE in the POA. After Fluoro-Gold injection in the POA, c-Fos expression in Fluoro-Gold/tyrosine hydroxylase-immunoreactive neurons increased during the afternoon in the A2 of both OVX+E and OVX+EP rats, in the locus coeruleus (LC) of OVX+EP rats, but was unchanged in the A1. The selective lesion of LC terminals, by intracerebroventricular N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine, reduced the surge of LH in OVX+EP but not in OVX+E rats. Thus, estradiol and progesterone activate A2 and LC neurons, respectively, and this is associated with the increased release of NE in the POA and the magnitude of the LH surge. NE stimulates LH secretion, at least in part, through activation of anteroventral periventricular neurons. These findings contribute to elucidation of the role played by NE during the positive feedback of ovarian steroids.

  20. Both olfactory epithelial and vomeronasal inputs are essential for activation of the medial amygdala and preoptic neurons of male rats.

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    Dhungel, S; Masaoka, M; Rai, D; Kondo, Y; Sakuma, Y

    2011-12-29

    Chemosensory inputs signaling volatile and nonvolatile molecules play a pivotal role in sexual and social behavior in rodents. We have demonstrated that olfactory preference in male rats, that is, attraction to receptive female odors, is regulated by the medial amygdala (MeA), the cortical amygdala (CoA), and the preoptic area (POA). In this paper, we investigated the involvement of two chemosensory organs, the olfactory epithelium (OE) and the vomeronasal organ (VNO), in olfactory preference and copulatory behavior in male rats. We found that olfactory preferences were impaired by zinc sulfate lesion of the OE but not surgical removal of the VNO. Copulatory behaviors, especially intromission frequency and ejaculation, were also suppressed by zinc sulfate treatment. Neuronal activation in the accessory olfactory bulb (AOB), the MeA, the CoA, and the POA was analyzed after stimulation by airborne odors or soiled bedding of estrous females using cFos immunohistochemistry. Although the OE and VNO belong to different neural systems, the main and accessory olfactory systems, respectively, both OE lesion and VNO removal almost equally suppressed the number of cFos-immunoreactive cells in those areas that regulate olfactory preference. These results suggest that signals received by the OE and VNO interact and converge in the early stage of olfactory processing, in the AOB and its targets, although they have distinct roles in the regulation of social behaviors.

  1. Expression of glutamic acid decarboxylase messenger RNA in rat medial preoptic area neurones during the oestrous cycle and after ovariectomy.

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    Herbison, A E; Augood, S J; McGowan, E M

    1992-08-01

    Evidence suggests that medial preoptic area (MPOA) neurones containing gamma-aminobutyric acid (GABA) are modulated directly by oestrogen. We have used an alkaline phosphatase-labelled antisense oligonucleotide probe to examine glutamic acid decarboxylase67 (GAD) mRNA expression within individual cells of the MPOA, diagonal band of Broca (DBB) and parietal cortex in rats killed at noon on each day of the oestrous cycle and after ovariectomy (n = 4-5). As a fall in extracellular GABA concentrations occurs in the MPOA on the afternoon of proestrus, the GAD67 mRNA content of cells was also examined in proestrous rats at 15:00h immediately prior to the preovulatory luteinising hormone (LH) surge. The MPOA was found to have an intermediate number of GAD67 mRNA-containing cells compared with the DBB and cortex (P less than 0.01) but expressed the lowest mean hybridisation signal (P less than 0.01). The parietal cortex had significantly fewer (P less than 0.01) GAD mRNA-containing cells than either the MPOA or DBB but these contained higher mean density of signal (P less than 0.01). The hybridisation signal for GAD mRNA was abolished by either ribonuclease pre-treatment or the use of excess non-labelled probe. No significant (P greater than 0.05) differences in GAD67 mRNA were detected in animals killed at noon throughout the oestrous cycle or after ovariectomy. On the afternoon of proestrus (15:00h) there was a significant 40% reduction in mean GAD67 mRNA content within cells of only the MPOA compared with noon (P less than 0.05). The numbers of cells in the MPOA expressing GAD67 mRNA were not significantly different.(ABSTRACT TRUNCATED AT 250 WORDS)

  2. Descending projections from the basal forebrain to the orexin neurons in mice.

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    Agostinelli, Lindsay J; Ferrari, Loris L; Mahoney, Carrie E; Mochizuki, Takatoshi; Lowell, Bradford B; Arrigoni, Elda; Scammell, Thomas E

    2017-05-01

    The orexin (hypocretin) neurons play an essential role in promoting arousal, and loss of the orexin neurons results in narcolepsy, a condition characterized by chronic sleepiness and cataplexy. The orexin neurons excite wake-promoting neurons in the basal forebrain (BF), and a reciprocal projection from the BF back to the orexin neurons may help promote arousal and motivation. The BF contains at least three different cell types (cholinergic, glutamatergic, and γ-aminobutyric acid (GABA)ergic neurons) across its different regions (medial septum, diagonal band, magnocellular preoptic area, and substantia innominata). Given the neurochemical and anatomical heterogeneity of the BF, we mapped the pattern of BF projections to the orexin neurons across multiple BF regions and neuronal types. We performed conditional anterograde tracing using mice that express Cre recombinase only in neurons producing acetylcholine, glutamate, or GABA. We found that the orexin neurons are heavily apposed by axon terminals of glutamatergic and GABAergic neurons of the substantia innominata (SI) and magnocellular preoptic area, but there was no innervation by the cholinergic neurons. Channelrhodopsin-assisted circuit mapping (CRACM) demonstrated that glutamatergic SI neurons frequently form functional synapses with the orexin neurons, but, surprisingly, functional synapses from SI GABAergic neurons were rare. Considering their strong reciprocal connections, BF and orexin neurons likely work in concert to promote arousal, motivation, and other behaviors. J. Comp. Neurol. 525:1668-1684, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  3. Chemical Topography of Efferent Projections from the Median Preoptic Nucleus to Pontine Monoaminergic Cell Groups in the Rat

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    Zardetto-Smith, Andrea M.; Johnson, Alan Kim

    1995-01-01

    This study examined efferent output from the median preoptic nucleus (MNPO) to pontine noradrenergic and serotonergic cell groups using an anterograde tracing technique (Phaseolus vulgaris leucoagglutinin, PHA-L) combined with glucose oxidase immunocytochemistry to serotonin (5-HT) or to dopamine-beta-hydroxylase (DBH). Injections of PHA-L into the ventral MNPO resulted in moderate axonal labeling within the region of the B7 and B8 serotonergic groups in the dorsal raphe. PHA-L labeled fibers and punctate processes were observed in close apposition to many of the 5-HT immunoreactive neurons in these regions. In contrast, sparse terminal labeling was found within the B5 group in the raphe pontis nucleus, and only trace fiber labeling observed in the B3 and B6 groups. Efferents from the MNPO also provided moderate innervation to the A6 and A7 noradrenergic groups. PHA-L labeled punctate processes were found most frequently in close apposition to DBH-immunoreactive neurons at mid- to caudal levels of the locus coeruleus. Some labeled axons were also present within the A7 and A5 groups. Additionally, a close apposition between labeled MNPO efferents and 5-HT fibers within the lateral parabrachial nucleus was observed. The results indicate the MNPO provides a topographic innervation of monoaminergic groups in the upper brainstem.

  4. Regeneration of supraspinal projection neurons in the adult goldfish.

    Science.gov (United States)

    Sharma, S C; Jadhao, A G; Rao, P D

    1993-08-27

    Regeneration of descending supraspinal projections were identified in adult goldfish following administration of HRP to different levels of the spinal cord. While in the untreated normal fish 17 nuclei were shown to project into the spinal cord, only 11 of them seem to have participated in the process of regeneration. The nuclei whose axons regenerated include the nucleus ventromedialis (NVMD), nucleus of the median longitudinal fasciculus (NMLF), nucleus reticularis superior (NRS), nucleus reticularis medialis (NRM), nucleus reticularis inferior (NRI), anterior octaval nucleus (AON), magnocellular octaval nucleus (MON), descending octaval nucleus (DON) and certain neurons of the facial lobe. The neurons of the magnocellular preoptic nucleus (NPO), raphe nucleus (NR), Mauthner cell (MC), posterior octaval nucleus (PON) and somata located adjacent to the descending trigeminal tract were not labeled. The nuclei that apparently participated in the regeneration process were significantly larger in size than the corresponding cell bodies in the untreated normal fish.

  5. Effect of Testosterone on Neuronal Morphology and Neuritic Growth of Fetal Lamb Hypothalamus-Preoptic Area and Cerebral Cortex in Primary Culture.

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    Radhika C Reddy

    Full Text Available Testosterone plays an essential role in sexual differentiation of the male sheep brain. The ovine sexually dimorphic nucleus (oSDN, is 2 to 3 times larger in males than in females, and this sex difference is under the control of testosterone. The effect of testosterone on oSDN volume may result from enhanced expansion of soma areas and/or dendritic fields. To test this hypothesis, cells derived from the hypothalamus-preoptic area (HPOA and cerebral cortex (CTX of lamb fetuses were grown in primary culture to examine the direct morphological effects of testosterone on these cellular components. We found that within two days of plating, neurons derived from both the HPOA and CTX extend neuritic processes and express androgen receptors and aromatase immunoreactivity. Both treated and control neurites continue to grow and branch with increasing time in culture. Treatment with testosterone (10 nM for 3 days significantly (P < 0.05 increased both total neurite outgrowth (35% and soma size (8% in the HPOA and outgrowth (21% and number of branch points (33% in the CTX. These findings indicate that testosterone-induced somal enlargement and neurite outgrowth in fetal lamb neurons may contribute to the development of a fully masculine sheep brain.

  6. Topological and histological description of preoptic area and hypothalamus in cardinal tetra Paracheirodon axelrodi (Characiformes: Characidae)

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    Rincón,Laura; Martha J Obando; Tovar,Mario O.; Pandolfi, Matías; Hurtado,Hernan

    2017-01-01

    ABSTRACT Topological and histological descriptions of the preoptic area and hypothalamus of the cardinal tetra Paracheirodon axelrodi were performed. Standard histological paraffin sections were used and stained with Nissl technique, and plastic sections for high-resolution optic microscopy (HROM). The preoptic area showed some differences related to the location of the magnocellular preoptic nucleus (PM) and the size of the neurons in this region, as they were the biggest in all the preoptic...

  7. Cholinergic Neurons Excite Cortically Projecting Basal Forebrain GABAergic Neurons

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    Yang, Chun; McKenna, James T.; Zant, Janneke C.; Winston, Stuart; Basheer, Radhika

    2014-01-01

    The basal forebrain (BF) plays an important role in the control of cortical activation and attention. Understanding the modulation of BF neuronal activity is a prerequisite to treat disorders of cortical activation involving BF dysfunction, such as Alzheimer's disease. Here we reveal the interaction between cholinergic neurons and cortically projecting BF GABAergic neurons using immunohistochemistry and whole-cell recordings in vitro. In GAD67-GFP knock-in mice, BF cholinergic (choline acetyltransferase-positive) neurons were intermingled with GABAergic (GFP+) neurons. Immunohistochemistry for the vesicular acetylcholine transporter showed that cholinergic fibers apposed putative cortically projecting GABAergic neurons containing parvalbumin (PV). In coronal BF slices from GAD67-GFP knock-in or PV-tdTomato mice, pharmacological activation of cholinergic receptors with bath application of carbachol increased the firing rate of large (>20 μm diameter) BF GFP+ and PV (tdTomato+) neurons, which exhibited the intrinsic membrane properties of cortically projecting neurons. The excitatory effect of carbachol was blocked by antagonists of M1 and M3 muscarinic receptors in two subpopulations of BF GABAergic neurons [large hyperpolarization-activated cation current (Ih) and small Ih, respectively]. Ion substitution experiments and reversal potential measurements suggested that the carbachol-induced inward current was mediated mainly by sodium-permeable cation channels. Carbachol also increased the frequency of spontaneous excitatory and inhibitory synaptic currents. Furthermore, optogenetic stimulation of cholinergic neurons/fibers caused a mecamylamine- and atropine-sensitive inward current in putative GABAergic neurons. Thus, cortically projecting, BF GABAergic/PV neurons are excited by neighboring BF and/or brainstem cholinergic neurons. Loss of cholinergic neurons in Alzheimer's disease may impair cortical activation, in part, through disfacilitation of BF cortically

  8. The Increase in Signaling by Kisspeptin Neurons in the Preoptic Area and Associated Changes in Clock Gene Expression That Trigger the LH Surge in Female Rats Are Dependent on the Facilitatory Action of a Noradrenaline Input.

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    Kalil, Bruna; Ribeiro, Aline B; Leite, Cristiane M; Uchôa, Ernane T; Carolino, Ruither O; Cardoso, Thais S R; Elias, Lucila L K; Rodrigues, José A; Plant, Tony M; Poletini, Maristela O; Anselmo-Franci, Janete A

    2016-01-01

    In rodents, kisspeptin neurons in the rostral periventricular area of the third ventricle (RP3V) of the preoptic area are considered to provide a major stimulatory input to the GnRH neuronal network that is responsible for triggering the preovulatory LH surge. Noradrenaline (NA) is one of the main modulators of GnRH release, and NA fibers are found in close apposition to kisspeptin neurons in the RP3V. Our objective was to interrogate the role of NA signaling in the kisspeptin control of GnRH secretion during the estradiol induced LH surge in ovariectomized rats, using prazosin, an α1-adrenergic receptor antagonist. In control rats, the estradiol-induced LH surge at 17 hours was associated with a significant increase in GnRH and kisspeptin content in the median eminence with the increase in kisspeptin preceding that of GnRH and LH. Prazosin, administered 5 and 3 hours prior to the predicted time of the LH surge truncated the LH surge and abolished the rise in GnRH and kisspeptin in the median eminence. In the preoptic area, prazosin blocked the increases in Kiss1 gene expression and kisspeptin content in association with a disruption in the expression of the clock genes, Per1 and Bmal1. Together these findings demonstrate for the first time that NA modulates kisspeptin synthesis in the RP3V through the activation of α1-adrenergic receptors prior to the initiation of the LH surge and indicate a potential role of α1-adrenergic signaling in the circadian-controlled pathway timing of the preovulatory LH surge.

  9. A dual role of EphB1/ephrin-B3 reverse signaling on migrating striatal and cortical neurons originating in the preoptic area: should I stay or go away ?

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    Judith eRudolph

    2014-07-01

    Full Text Available During embryonic development the preoptic area (POA gives rise to two populations of neurons which are generated at the same time, cortical interneurons and striatal cells. POA-derived cortical interneurons take a superficial path and avoid the developing striatum when they migrate to their target region. We found that EphB1, which is expressed in the striatal anlage, prevents cortical interneurons from entering the striatum via ephrin-B3 reverse signaling. In contrast, for striatal neurons which also express ephrin-B3, EphB1 acts as a stop signal. This dual role of EphB1 is due to differences in ephrin-B3 reverse signaling cascades. For striatal neurons, binding of EphB1 to ephrin-B3 reduces endogenously high levels of pSrc and pFAK, which then causes the cells to stop migration. In contrast, in cortical interneurons EphB1-ephrin-B3 reverse signaling leads to phosphorylation of Src and FAK which then mediates repulsion. Consistent with these in vitro findings, in an ephrin-B3 knockout mouse line, we discovered misrouted cortical interneurons in the striatum and an over-migration of striatal neurons in their target region. Thus, EphB1/ephrin-B3 reverse signaling has a different impact on two sets of neurons which are generated at the same time and place: it can act as a repulsive cue for migrating neurons or it can terminate neuronal migration, a novel role of the Eph/ephrin system.

  10. Selective serotonergic excitation of callosal projection neurons

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    Daniel eAvesar

    2012-03-01

    Full Text Available Serotonin (5-HT acting as a neurotransmitter in the cerebral cortex is critical for cognitive function, yet how 5-HT regulates information processing in cortical circuits is not well understood. We tested the serotonergic responsiveness of layer 5 pyramidal neurons (L5PNs of the mouse medial prefrontal cortex (mPFC, and found 3 distinct response types: long-lasting 5-HT1A (1A receptor-dependent inhibitory responses (84% of L5PNs, 5-HT2A (2A receptor-dependent excitatory responses (9%, and biphasic responses in which 2A-dependent excitation followed brief inhibition (5%. Relative to 5-HT-inhibited neurons, those excited by 5-HT had physiological properties characteristic of callosal/commissural (COM neurons that project to the contralateral cortex. We tested whether serotonergic responses in cortical pyramidal neurons are correlated with their axonal projection pattern using retrograde fluorescent labeling of COM and corticopontine-projecting (CPn neurons. 5-HT generated excitatory or biphasic responses in all 5-HT-responsive layer 5 COM neurons. Conversely, CPn neurons were universally inhibited by 5-HT. Serotonergic excitation of COM neurons was blocked by the 2A antagonist MDL 11939, while serotonergic inhibition of CPn neurons was blocked by the 1A antagonist WAY 100635, confirming a role for these two receptor subtypes in regulating pyramidal neuron activity. Selective serotonergic excitation of COM neurons was not layer-specific, as COM neurons in layer 2/3 were also selectively excited by 5-HT relative to their non-labeled pyramidal neuron neighbors. Because neocortical 2A receptors are implicated in the etiology and pathophysiology of schizophrenia, we propose that COM neurons may represent a novel cellular target for intervention in psychiatric disease.

  11. Activation of noradrenergic neurons projecting to the diencephalon following central administration of histamine is mediated by H1 receptors.

    Science.gov (United States)

    Fleckenstein, A E; Lookingland, K J; Moore, K E

    1994-02-28

    The effect of histamine on the activity of noradrenergic neurons terminating in discrete regions of the diencephalon was examined in male rats. Noradrenergic neuronal activity was estimated by measuring the concentration of norepinephrine and its metabolite 3-methoxy-4-hydroxyphenylethyleneglycol [MHPG] in the medial zona incerta [MZI] and in the dorsomedial [DMN], periventricular [PeVN] and medial preoptic hypothalamic nuclei [MPN]. The intracerebroventricular administration of histamine effected a time-related increase in MHPG concentrations in the MZI, DMN, PeVN and MPN; these effects were blocked by the H1 antagonist mepyramine but not the H2 antagonist zolantidine. Neither mepyramine nor zolantidine affected basal MHPG concentrations in any of the brain regions examined. These results indicate that central administration of histamine increases the activity of noradrenergic neurons projecting to the diencephalon via an action at H1 but not H2 receptors.

  12. Npas1+ Pallidal Neurons Target Striatal Projection Neurons.

    Science.gov (United States)

    Glajch, Kelly E; Kelver, Daniel A; Hegeman, Daniel J; Cui, Qiaoling; Xenias, Harry S; Augustine, Elizabeth C; Hernández, Vivian M; Verma, Neha; Huang, Tina Y; Luo, Minmin; Justice, Nicholas J; Chan, C Savio

    2016-05-18

    Compelling evidence demonstrates that the external globus pallidus (GPe) plays a key role in processing sensorimotor information. An anatomical projection from the GPe to the dorsal striatum has been described for decades. However, the cellular target and functional impact of this projection remain unknown. Using cell-specific transgenic mice, modern monosynaptic tracing techniques, and optogenetics-based mapping, we discovered that GPe neurons provide inhibitory inputs to direct and indirect pathway striatal projection neurons (SPNs). Our results indicate that the GPe input to SPNs arises primarily from Npas1-expressing neurons and is strengthened in a chronic Parkinson's disease (PD) model. Alterations of the GPe-SPN input in a PD model argue for the critical position of this connection in regulating basal ganglia motor output and PD symptomatology. Finally, chemogenetic activation of Npas1-expressing GPe neurons suppresses motor output, arguing that strengthening of the GPe-SPN connection is maladaptive and may underlie the hypokinetic symptoms in PD. An anatomical projection from the pallidum to the striatum has been described for decades, but little is known about its connectivity pattern. The authors dissect the presynaptic and postsynaptic neurons involved in this projection, and show its cell-specific remodeling and strengthening in parkinsonian mice. Chemogenetic activation of Npas1(+) pallidal neurons that give rise to the principal pallidostriatal projection increases the time that the mice spend motionless. This argues that maladaptive strengthening of this connection underlies the paucity of volitional movements, which is a hallmark of Parkinson's disease. Copyright © 2016 the authors 0270-6474/16/365472-17$15.00/0.

  13. Hindbrain lactate regulates preoptic gonadotropin-releasing hormone (GnRH) neuron GnRH-I protein but not AMPK responses to hypoglycemia in the steroid-primed ovariectomized female rat.

    Science.gov (United States)

    Shrestha, P K; Briski, K P

    2015-07-09

    Steroid positive-feedback activation of the gonadotropin-releasing hormone (GnRH)-pituitary luteinizing hormone (LH) neuroendocrine axis propagates the pre ovulatory LH surge, a crucial component of female reproduction. Our work shows that this key event is restrained by inhibitory metabolic input from hindbrain A2 noradrenergic neurons. GnRH neurons express the ultra-sensitive energy sensor adenosine 5'-monophosphate-activated protein kinase (AMPK); here, we investigated the hypothesis that GnRH nerve cell AMPK and peptide neurotransmitter responses to insulin-induced hypoglycemia are controlled by hindbrain lack of the oxidizable glycolytic end-product L-lactate. Data show that hypoglycemic inhibition of LH release in steroid-primed ovariectomized female rats was reversed by coincident caudal hindbrain lactate infusion. Western blot analyses of laser-microdissected A2 neurons demonstrate hypoglycemic augmentation [Fos, estrogen receptor-beta (ER-β), phosphoAMPK (pAMPK)] and inhibition (dopamine-beta-hydroxylase, GLUT3, MCT2) of protein expression in these cells, responses that were normalized by insulin plus lactate treatment. Hypoglycemia diminished rostral preoptic GnRH nerve cell GnRH-I protein and pAMPK content; the former, but not the latter response was reversed by lactate. Results implicate caudal hindbrain lactoprivic signaling in hypoglycemia-induced suppression of the LH surge, demonstrating that lactate repletion of that site reverses decrements in A2 catecholamine biosynthetic enzyme and GnRH neuropeptide precursor protein expression. Lack of effect of lactate on hypoglycemic patterns of GnRH AMPK activity suggests that this sensor is uninvolved in metabolic-inhibition of positive-feedback-stimulated hypophysiotropic signaling to pituitary gonadotropes.

  14. Extra-neurohypophyseal axonal projections from individual vasopressin-containing magnocellular neurons in rat hypothalamus

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    Vito Salvador Hernandez

    2015-10-01

    Full Text Available Conventional neuroanatomical, immunohistochemical techniques and electrophysiological recording, as well as in vitro labeling methods may fail to detect long range extra-neurohypophyseal-projecting axons from vasopressin (AVP-containing magnocellular neurons (magnocells in the hypothalamic paraventricular nucleus (PVN. Here, we used in vivo extracellular recording, juxtacellular labeling, post hoc anatomo-immunohistochemical analysis and camera lucida reconstruction to address this question. We demonstrate that all well-labeled AVP immunopositive neurons inside the PVN possess main axons joining the tract of Greving and multi-axon-like processes, as well as axonal collaterals branching very near to the somata, which project to extra-neurohypophyseal regions. The detected regions in this study include the medial and lateral preoptical area, suprachiasmatic nucleus, lateral habenula, medial and central amygdala and the conducting systems, such as stria medullaris, the fornix and the internal capsule. Expression of vesicular glutamate transporter 2 was observed in axon-collaterals. These results, in congruency with several previous reports in the literature, provided unequivocal evidence that AVP magnocells have an uncommon feature of possessing multiple axon-like processes emanating from somata or proximal dendrites. Furthermore, the long-range non-neurohypophyseal projections are more common than an occasional phenomenon as previously thought.

  15. Optogenetic identification of hypothalamic orexin neuron projections to paraventricular spinally projecting neurons.

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    Dergacheva, Olga; Yamanaka, Akihiro; Schwartz, Alan R; Polotsky, Vsevolod Y; Mendelowitz, David

    2017-04-01

    Orexin neurons, and activation of orexin receptors, are generally thought to be sympathoexcitatory; however, the functional connectivity between orexin neurons and a likely sympathetic target, the hypothalamic spinally projecting neurons (SPNs) in the paraventricular nucleus of the hypothalamus (PVN) has not been established. To test the hypothesis that orexin neurons project directly to SPNs in the PVN, channelrhodopsin-2 (ChR2) was selectively expressed in orexin neurons to enable photoactivation of ChR2-expressing fibers while examining evoked postsynaptic currents in SPNs in rat hypothalamic slices. Selective photoactivation of orexin fibers elicited short-latency postsynaptic currents in all SPNs tested (n = 34). These light-triggered responses were heterogeneous, with a majority being excitatory glutamatergic responses (59%) and a minority of inhibitory GABAergic (35%) and mixed glutamatergic and GABAergic currents (6%). Both glutamatergic and GABAergic responses were present in the presence of tetrodotoxin and 4-aminopyridine, suggesting a monosynaptic connection between orexin neurons and SPNs. In addition to generating postsynaptic responses, photostimulation facilitated action potential firing in SPNs (current clamp configuration). Glutamatergic, but not GABAergic, postsynaptic currents were diminished by application of the orexin receptor antagonist almorexant, indicating orexin release facilitates glutamatergic neurotransmission in this pathway. This work identifies a neuronal circuit by which orexin neurons likely exert sympathoexcitatory control of cardiovascular function.NEW & NOTEWORTHY This is the first study to establish, using innovative optogenetic approaches in a transgenic rat model, that there are robust heterogeneous projections from orexin neurons to paraventricular spinally projecting neurons, including excitatory glutamatergic and inhibitory GABAergic neurotransmission. Endogenous orexin release modulates glutamatergic, but not GABAergic

  16. Corticofugal GABAergic projection neurons in the mouse frontal cortex

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    Ryohei eTomioka

    2015-10-01

    Full Text Available Cortical projection neurons are classified by hodology in corticocortical, commissural and corticofugal subtypes. Although cortical projection neurons had been regarded as only glutamatergic neurons, recently corticocortical GABAergic projection neurons has been also reported in several species. Here we demonstrate corticofugal GABAergic projection neurons in the mouse frontal cortex. We employed viral-vector-mediated anterograde tracing, classical retrograde tracing, and immunohistochemistry to characterize neocortical GABAergic projection neurons. Injections of the Cre-dependent adeno-associated virus into glutamate decarboxylase 67-Cre knock-in mice revealed neocortical GABAergic projections widely to the forebrain, including the cerebral cortices, caudate putamen, ventral pallidum, lateral globus pallidus, nucleus accumbens, and olfactory tubercle. Minor GABAergic projections were also found in the mediodorsal thalamic nucleus, diagonal band of Broca, medial globus pallidus, substantial nigra, and dorsal raphe nucleus. Retrograde tracing studies also demonstrated corticofugal GABAergic projection neurons in the mouse frontal cortex. Further immunohistochemical screening with neurochemical markers revealed the majority of corticostriatal GABAergic projection neurons were positive for somatostatin-immunoreactivity. In contrast, corticothalamic GABAergic projection neurons were not identified by representative neurochemical markers for GABAergic neurons. These findings suggest that corticofugal GABAergic projection neurons are heterogeneous in terms of their neurochemical properties and target nuclei, and provide axonal innervations mainly to the nuclei in the basal ganglia.

  17. Estradiol Valerate and Remifemin ameliorate ovariectomy-induced decrease in a serotonin dorsal raphe-preoptic hypothalamus pathway in rats.

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    Wang, Wenjuan; Cui, Guangxia; Jin, Biao; Wang, Ke; Chen, Xing; Sun, Yu; Qin, Lihua; Bai, Wenpei

    2016-11-01

    Perimenopausal syndromes begin as ovarian function ceases and the most common symptoms are hot flushes. Data indicate that the projections of serotonin to hypothalamus may be involved in the mechanism of hot flushes. Therefore, the aim of this study is to investigate the potential role of the serotonin dorsal raphe-preoptic hypothalamus pathway for hot flushes in an animal model of menopause. We determined the changes in serotonin expression in the dorsal raphe (DR) and preoptic anterior hypothalamus (POAH) in ovariectomized rats. We also explored the therapeutical effects of estradiol valerate and Remifemin in this model. Eighty female Sprague-Dawley rats were randomly assigned to sham-operated (SHAM) group, ovariectomy (OVX) group with vehicle, ovariectomy with estradiol valerate treatment (OVX+E) group and ovariectomy with Remifemin (OVX+ICR) group. Serotonin expression was evaluated in the DR and POAH using immunofluorescence and quantified in the DR using an enzyme-linked immunosorbent assay (ELISA). Apoptosis was analyzed in the DR by TUNEL assay. The number of serotonin immunoreactive neurons and the level of serotonin expression in the DR decreased significantly following OVX compared to the SHAM group. No TUNEL-positive cells were detected in the DR in any group. In addition, following OVX, the number of serotonin-positive fibers decreased significantly in the ventromedial preoptic nucleus (VMPO), especially in the ventrolateral preoptic nucleus (VLPO). Treatment with either estradiol or Remifemin for 4 weeks countered the OVX-induced decreases in serotonin levels in both the DR and the hypothalamus, with levels in the treated rats similar to those in the SHAM group. A fluorescently labeled retrograde tracer was injected into the VLPO at the 4-week time point. A significantly lower percentage of serotonin with CTB double-labeled neurons in CTB-labeled neurons was demonstrated after ovariectomy, and both estradiol and Remifemin countered this OVX

  18. The preoptic-suprachiasmatic nuclei though morphologically heterogeneous are equally affected by streptozotocin diabetes.

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    Bestetti, G; Hofer, R; Rossi, G L

    1987-01-01

    Pituitary and gonadal disorders consistent with abnormal LHRH and LH secretion occur in streptozotocin-diabetic rats. A key role in the synthesis and regulation of LHRH and in the phasic LH release is played by the preoptic-suprachiasmatic region which is mainly formed by the medial preoptic area, the sexually dimorphic nucleus of the medial preoptic area, and the suprachiasmatic nucleus. Therefore we have studied this region by morphology and morphometry in normal and streptozotocin-diabetic rats. In normal animals, the neurons of the above mentioned nuclei were morphologically and morphometrically dissimilar. Independent of their localization, reduced cytoplasmic and nuclear areas were observed in the neurons of diabetic animals. These lesions are consistent with hypotrophied neurons. Consequently, diabetes may impair both synthesis and regulation of LHRH and may therefore account for pituitary disorders, testicular atrophy, and lacking preovulatory LH peaks. The structural differences of the neurons of the three nuclei in normal animals underline their different physiological role. Yet, the similarity of the changes found in all three nuclei suggests a generalized hypofunction of the whole preoptic-suprachiasmatic region under diabetic condition.

  19. Distribution, structure and projections of the frog intracardiac neurons.

    Science.gov (United States)

    Batulevicius, Darius; Skripkiene, Gertruda; Batuleviciene, Vaida; Skripka, Valdas; Dabuzinskiene, Anita; Pauza, Dainius H

    2012-05-21

    Histochemistry for acetylcholinesterase was used to determine the distribution of intracardiac neurons in the frog Rana temporaria. Seventy-nine intracardiac neurons from 13 frogs were labelled iontophoretically by the intracellular markers Alexa Fluor 568 and Lucifer Yellow CH to determine their structure and projections. Total neuronal number per frog heart was (Mean ± SE) 1374 ± 56. Largest collections of neurons were found in the interatrial septum (46%), atrioventricular junction (25%) and venal sinus (12%). Among the intracellularly labelled neurons, we found the cells of unipolar (71%), multipolar (20%) and bipolar (9%) types. Multiple processes originated from the neuron soma, hillock and proximal axon. These processes projected onto adjacent neuron somata and cardiac muscle fibers within the interatrial septum. Average total length of the processes from proximal axon was 348 ± 50 μm. Average total length of processes from soma and hillock was less, 118 ± 27 μm and 109 ± 24 μm, respectively. The somata of 59% of neurons had bubble- or flake-shaped extensions. Most neurons from the major nerves in the interatrial septum sent their axons towards the ventricle. In contrast, most neurons from the ventral part of the interatrial septum sent their axons towards the atria. Our findings contradict to a view that the frog intracardiac ganglia contain only non-dendritic neurons of the unipolar type. We conclude that the frog intracardiac neurons are structurally complex and diverse. This diversity may account for the complicated integrative functions of the frog intrinsic cardiac ganglia.

  20. Projections of nucleus accumbens adenosine A2A receptor neurons in the mouse brain and their implications in mediating sleep-wake regulation

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    Jianping eZhang

    2013-12-01

    Full Text Available Adenosine A2A receptors (A2ARs in the nucleus accumbens (Acb have been demonstrated to play an important role in the arousal effect of adenosine receptor antagonist caffeine, and may be involved in physiological sleep. To better understand the functions of these receptors in sleep, projections of A2AR neurons were mapped utilizing adeno-associated virus (AAV encoding humanized Renilla green fluorescent protein (hrGFP as a tracer for long axonal pathways. The Cre-dependent AAV was injected into the core (AcbC and shell (AcbSh of the Acb in A2AR-Cre mice. Immunohistochemistry was then used to visualize hrGFP, highlighting the perikarya of the A2AR neurons in the injection sites, and their axons in projection regions. The data revealed that A2AR neurons exhibit medium-sized and either round or elliptic perikarya with their processes within the Acb. Moreover, the projections from the Acb distributed to nuclei in the forebrain, diencephalon, and brainstem. In the forebrain, A2AR neurons from all Acb sub-regions jointly projected to the ventral pallidum, the nucleus of the diagonal band, and the substantia innominata. Heavy projections from the AcbC and the ventral AcbSh, and weaker projections from the medial AcbSh, were observed in the lateral hypothalamus and lateral preoptic area. In the brainstem, the Acb projections were found in the ventral tegmental area, while AcbC and ventral AcbSh also projected to the median raphe nucleus, the dorsal raphe nucleus, and the ventrolateral periaqueductal gray. The results supply a solid base for understanding the roles of the A2AR and A2AR neurons in the Acb, especially in the regulation of sleep.

  1. Subtypes of GABAergic neurons project axons in the neocortex

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    Shigeyoshi Higo

    2009-11-01

    Full Text Available γ-aminobutyric acid (GABAergic neurons in the neocortex have been regarded as interneurons and speculated to modulate the activity of neurons locally. Recently, however, several experiments revealed that neuronal nitric oxide synthase (nNOS-positive GABAergic neurons project cortico-cortically with long axons. In this study, we illustrate Golgi-like images of the nNOS-positive GABAergic neurons using a nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d reaction and follow the emanating axon branches in cat brain sections. These axon branches projected cortico-cortically with other non-labeled arcuate fibers, contra-laterally via the corpus callosum and anterior commissure. The labeled fibers were not limited to the neocortex but found also in the fimbria of the hippocampus. In order to have additional information on these GABAergic neuron projections, we investigated green fluorescent protein (GFP-labeled GABAergic neurons in GAD67-Cre knock-in / GFP Cre-reporter mice. GFP-labeled axons emanate densely, especially in the fimbria, a small number in the anterior commissure, and very sparsely in the corpus callosum. These two different approaches confirm that not only nNOS-positive GABAergic neurons but also other subtypes of GABAergic neurons project long axons in the cerebral cortex and are in a position to be involved in information processing.

  2. Dopaminergic Neurons Controlling Anterior Pituitary Functions: Anatomy and Ontogenesis in Zebrafish.

    Science.gov (United States)

    Fontaine, Romain; Affaticati, Pierre; Bureau, Charlotte; Colin, Ingrid; Demarque, Michaël; Dufour, Sylvie; Vernier, Philippe; Yamamoto, Kei; Pasqualini, Catherine

    2015-08-01

    Dopaminergic (DA) neurons located in the preoptico-hypothalamic region of the brain exert a major neuroendocrine control on reproduction, growth, and homeostasis by regulating the secretion of anterior pituitary (or adenohypophysis) hormones. Here, using a retrograde tract tracing experiment, we identified the neurons playing this role in the zebrafish. The DA cells projecting directly to the anterior pituitary are localized in the most anteroventral part of the preoptic area, and we named them preoptico-hypophyseal DA (POHDA) neurons. During development, these neurons do not appear before 72 hours postfertilization (hpf) and are the last dopaminergic cell group to differentiate. We found that the number of neurons in this cell population continues to increase throughout life proportionally to the growth of the fish. 5-Bromo-2'-deoxyuridine incorporation analysis suggested that this increase is due to continuous neurogenesis and not due to a phenotypic change in already-existing neurons. Finally, expression profiles of several genes (foxg1a, dlx2a, and nr4a2a/b) were different in the POHDA compared with the adjacent suprachiasmatic DA neurons, suggesting that POHDA neurons develop as a distinct DA cell population in the preoptic area. This study offers some insights into the regional identity of the preoptic area and provides the first bases for future functional genetic studies on the development of DA neurons controlling anterior pituitary functions.

  3. Preoptic hypnogenic area and reticular activating system.

    Science.gov (United States)

    Bremer, F

    1973-06-01

    The stimulation, in the encéphale isolé cat, of the basal preoptic hypnogenic area be brief electrical pulses evokes bilaterally an extracellular positive (P) field potential of 20 to 60 msec duration in the brain stem and thalamic activating ascending reticular system. The properties of this P wave have led to consider it as the extracellular and abbreviated counterpart of an hyperpolarizing postsynaptic inhibitory process which, by the functional depression it exerts on the arousal system, would be instrumental in the induction and maintenance of synchronized sleep. The positive field potential response of the reticular system shows the same recruiting build-up and amplitude modulation, and the same sensibility to amphetamine and to barbiturates, as the cortical potential of diffuse distribution which is evoked simultaneously. It is strychnine--and picrotoxin--resistant. Preoptic stimulation exerts, within a 100 msec interval, a strong suppressive effect on the excitatory response evoked in the n. centromedian by a mesencephalic reticular testing shock. On the other hand, the application of the latter as a conditioning stimulus results in a marked increase of the amplitude of the P wave response of the CM to a testing preoptic shock. A negative feedback interpretation of this interaction is suggested. No clear evidence of a tonic functioning of the preoptic hypnogenic structure could be found in experiments involving the production of small bilateral lesions in the basal preoptic area in the encéphale isolé cat. Reasons limiting the interpretation of this negative result are given. The functional significance, on the basis of experimental data, of the diffuse cortical synchronization produced by the low frequency stimulation of the basal preoptic area and of other hypnogenic structures is discussed.

  4. Anatomic and Molecular Development of Corticostriatal Projection Neurons in Mice

    Science.gov (United States)

    Sohur, U. Shivraj; Padmanabhan, Hari K.; Kotchetkov, Ivan S.; Menezes, Joao R.L.; Macklis, Jeffrey D.

    2014-01-01

    Corticostriatal projection neurons (CStrPN) project from the neocortex to ipsilateral and contralateral striata to control and coordinate motor programs and movement. They are clinically important as the predominant cortical population that degenerates in Huntington's disease and corticobasal ganglionic degeneration, and their injury contributes to multiple forms of cerebral palsy. Together with their well-studied functions in motor control, these clinical connections make them a functionally, behaviorally, and clinically important population of neocortical neurons. Little is known about their development. “Intratelencephalic” CStrPN (CStrPNi), projecting to the contralateral striatum, with their axons fully within the telencephalon (intratelencephalic), are a major population of CStrPN. CStrPNi are of particular interest developmentally because they share hodological and axon guidance characteristics of both callosal projection neurons (CPN) and corticofugal projection neurons (CFuPN); CStrPNi send axons contralaterally before descending into the contralateral striatum. The relationship of CStrPNi development to that of broader CPN and CFuPN populations remains unclear; evidence suggests that CStrPNi might be evolutionary “hybrids” between CFuPN and deep layer CPN—in a sense “chimeric” with both callosal and corticofugal features. Here, we investigated the development of CStrPNi in mice—their birth, maturation, projections, and expression of molecular developmental controls over projection neuron subtype identity. PMID:23118198

  5. A map of taste neuron projections in the Drosophila CNS

    Indian Academy of Sciences (India)

    Jae Young Kwon; Anupama Dahanukar; Linnea A Weiss; John R Carlson

    2014-09-01

    We provide a map of the projections of taste neurons in the CNS of Drosophila. Using a collection of 67 GAL4 drivers representing the entire repertoire of Gr taste receptors, we systematically map the projections of neurons expressing these drivers in the thoracico-abdominal ganglion and the suboesophageal ganglion (SOG). We define 9 categories of projections in the thoracico-abdominal ganglia and 10 categories in the SOG. The projection patterns are modular, and can be interpreted as combinations of discrete pattern elements. The elements can be interpreted in terms of the taste organ from which the projections originate, the structures from which they originate, and the quality of taste information that they represent. The extensive diversity in projection patterns provides an anatomical basis for functional diversity in responses elicited by different taste stimuli.

  6. Projections of color coding retinal neurons in urodele amphibians.

    Science.gov (United States)

    Himstedt, W; Helas, A; Sommer, T J

    1981-01-01

    Optic fiber projection in the brain of Salamandra salamandra was investigated by degeneration techniques. Terminal fields are described in the thalamus and in the optic tectum. Microelectrode recordings were performed from ganglion cells in the retina and from their terminals in the thalamus and tectum in Salamandra and Triturus alpestris. 'On' cells showed maximal sensitivity either in the blue or in the yellow spectral region; they project to the thalamus. Color coding 'on-off' cells project to the tectum opticum. In Triturus a seasonal change in these neurons occurs. Probably due to transition of vitamin A2 into vitamin A1 the spectral sensitivity is different. In springtime blue-red opponent-color neurons were recorded, in fall however, blue-yellow neurons were found.

  7. Correlative microscopy of densely labeled projection neurons using neural tracers.

    Science.gov (United States)

    Oberti, Daniele; Kirschmann, Moritz A; Hahnloser, Richard H R

    2010-01-01

    Three-dimensional morphological information about neural microcircuits is of high interest in neuroscience, but acquiring this information remains challenging. A promising new correlative technique for brain imaging is array tomography (Micheva and Smith, 2007), in which series of ultrathin brain sections are treated with fluorescent antibodies against neurotransmitters and synaptic proteins. Treated sections are repeatedly imaged in the fluorescence light microscope (FLM) and then in the electron microscope (EM). We explore a similar correlative imaging technique in which we differentially label distinct populations of projection neurons, the key routers of electrical signals in the brain. In songbirds, projection neurons can easily be labeled using neural tracers, because the vocal control areas are segregated into separate nuclei. We inject tracers into areas afferent and efferent to the main premotor area for vocal production, HVC, to retrogradely and anterogradely label different classes of projection neurons. We optimize tissue preparation protocols to achieve high fluorescence contrast in the FLM and good ultrastructure in the EM (using osmium tetroxide). Although tracer fluorescence is lost during EM preparation, we localize the tracer molecules after fixation and embedding by using fluorescent antibodies against them. We detect signals mainly in somata and dendrites, allowing us to classify synapses within a single ultrathin section as belonging to a particular type of projection neuron. The use of our method will be to provide statistical information about connectivity among different neuron classes, and to elucidate how signals in the brain are processed and routed among different areas.

  8. Correlative microscopy of densely labeled projection neurons using neural tracers

    Directory of Open Access Journals (Sweden)

    Daniele Oberti

    2010-06-01

    Full Text Available Three-dimensional morphological information about neural microcircuits is of high interest in neuroscience, but acquiring this information remains challenging. A promising new correlative technique for brain imaging is array tomography (Micheva and Smith, 2007, in which series of ultrathin brain sections are treated with fluorescent antibodies against neurotransmitters and synaptic proteins. Treated sections are repeatedly imaged in the fluorescence light microscope (FLM and then in the electron microscope (EM. We explore a similar correlative imaging technique in which we differentially label distinct populations of projection neurons, the key routers of electrical signals in the brain. In songbirds, projection neurons can easily be labeled using neural tracers, because the vocal control areas are segregated into separate nuclei. We inject tracers into areas afferent and efferent to the main premotor area for vocal production, HVC, to retrogradely and anterogradely label different classes of projection neurons. We optimize tissue preparation protocols to achieve high fluorescence contrast in the FLM and good ultrastructure in the EM (using osmium tetroxide. Although tracer fluorescence is lost during EM preparation, we localize the tracer molecules after fixation and embedding by using fluorescent antibodies against them. We detect signals mainly in somata and dendrites, allowing us to classify synapses within a single ultrathin section as belonging to a particular type of projection neuron. The use of our method will be to provide statistical information about connectivity among different neuron classes, and to elucidate how signals in the brain are processed and routed among different areas.

  9. Multiple redundant medulla projection neurons mediate color vision in Drosophila.

    Science.gov (United States)

    Melnattur, Krishna V; Pursley, Randall; Lin, Tzu-Yang; Ting, Chun-Yuan; Smith, Paul D; Pohida, Thomas; Lee, Chi-Hon

    2014-01-01

    The receptor mechanism for color vision has been extensively studied. In contrast, the circuit(s) that transform(s) photoreceptor signals into color percepts to guide behavior remain(s) poorly characterized. Using intersectional genetics to inactivate identified subsets of neurons, we have uncovered the first-order interneurons that are functionally required for hue discrimination in Drosophila. We developed a novel aversive operant conditioning assay for intensity-independent color discrimination (true color vision) in Drosophila. Single flying flies are magnetically tethered in an arena surrounded by blue and green LEDs (light-emitting diodes). The flies' optomotor response is used to determine the blue-green isoluminant intensity. Flies are then conditioned to discriminate between equiluminant blue or green stimuli. Wild-type flies are successfully trained in this paradigm when conditioned to avoid either blue or green. Functional color entrainment requires the function of the narrow-spectrum photoreceptors R8 and/or R7, and is within a limited range, intensity independent, suggesting that it is mediated by a color vision system. The medulla projection neurons, Tm5a/b/c and Tm20, receive direct inputs from R7 or R8 photoreceptors and indirect input from the broad-spectrum photoreceptors R1-R6 via the lamina neuron L3. Genetically inactivating these four classes of medulla projection neurons abolished color learning. However, inactivation of subsets of these neurons is insufficient to block color learning, suggesting that true color vision is mediated by multiple redundant pathways. We hypothesize that flies represent color along multiple axes at the first synapse in the fly visual system. The apparent redundancy in learned color discrimination sharply contrasts with innate ultraviolet (UV) spectral preference, which is dominated by a single pathway from the amacrine neuron Dm8 to the Tm5c projection neurons.

  10. Anatomic and Molecular Development of Corticostriatal Projection Neurons in Mice

    OpenAIRE

    Macklis, Jeffrey Daniel; Sohur, Usharbudh Shivraj; Padmanabhan, Hari; Kotchetkov, Ivan S.; Menezes, Joao R.L.

    2012-01-01

    Corticostriatal projection neurons (CStrPN) project from the neocortex to ipsilateral and contralateral striata to control and coordinate motor programs and movement. They are clinically important as the predominant cortical population that degenerates in Huntington's disease and corticobasal ganglionic degeneration, and their injury contributes to multiple forms of cerebral palsy. Together with their well-studied functions in motor control, these clinical connections make them a functionally...

  11. Novel hypophysiotropic AgRP2 neurons and pineal cells revealed by BAC transgenesis in zebrafish

    Science.gov (United States)

    Shainer, Inbal; Buchshtab, Adi; Hawkins, Thomas A.; Wilson, Stephen W.; Cone, Roger D.; Gothilf, Yoav

    2017-01-01

    The neuropeptide agouti-related protein (AgRP) is expressed in the arcuate nucleus of the mammalian hypothalamus and plays a key role in regulating food consumption and energy homeostasis. Fish express two agrp genes in the brain: agrp1, considered functionally homologous with the mammalian AgRP, and agrp2. The role of agrp2 and its relationship to agrp1 are not fully understood. Utilizing BAC transgenesis, we generated transgenic zebrafish in which agrp1- and agrp2-expressing cells can be visualized and manipulated. By characterizing these transgenic lines, we showed that agrp1-expressing neurons are located in the ventral periventricular hypothalamus (the equivalent of the mammalian arcuate nucleus), projecting throughout the hypothalamus and towards the preoptic area. The agrp2 gene was expressed in the pineal gland in a previously uncharacterized subgroup of cells. Additionally, agrp2 was expressed in a small group of neurons in the preoptic area that project directly towards the pituitary and form an interface with the pituitary vasculature, suggesting that preoptic AgRP2 neurons are hypophysiotropic. We showed that direct synaptic connection can exist between AgRP1 and AgRP2 neurons in the hypothalamus, suggesting communication and coordination between AgRP1 and AgRP2 neurons and, therefore, probably also between the processes they regulate. PMID:28317906

  12. Armodafinil-induced wakefulness in animals with ventrolateral preoptic lesions

    Directory of Open Access Journals (Sweden)

    Vetrivelan R

    2014-05-01

    Full Text Available Ramalingam Vetrivelan, Clifford B Saper, Patrick M Fuller Department of Neurology, Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, MA, USA Abstract: Armodafinil is the pharmacologically active R-enantiomer of modafinil, a widely prescribed wake-promoting agent used to treat several sleep-related disorders including excessive daytime sleepiness associated with narcolepsy, shift work sleep disorder, and obstructive sleep apnea/hypopnea syndrome. Remarkably, however, the neuronal circuitry through which modafinil exerts its wake-promoting effects remains unresolved. In the present study, we sought to determine if the wake-promoting effects of armodafinil are mediated, at least in part, by inhibiting the sleep-promoting neurons of the ventrolateral preoptic (VLPO nucleus. To do so, we measured changes in waking following intraperitoneal administration of armodafinil (200 mg/kg or the psychostimulant methamphetamine (1 mg/kg in rats with cell-body specific lesion of the VLPO. Rats with histologically confirmed lesions of the VLPO demonstrated a sustained increase in wakefulness at baseline, but the increase in wakefulness following administration of both armodafinil and methamphetamine was similar to that of intact animals. These data suggest that armodafinil increases wakefulness by mechanisms that extend beyond inhibition of VLPO neurons. Keywords: EEG, sleep, orexin-saporin, methamphetamine

  13. Armodafinil-induced wakefulness in animals with ventrolateral preoptic lesions.

    Science.gov (United States)

    Vetrivelan, Ramalingam; Saper, Clifford B; Fuller, Patrick M

    2014-01-01

    Armodafinil is the pharmacologically active R-enantiomer of modafinil, a widely prescribed wake-promoting agent used to treat several sleep-related disorders including excessive daytime sleepiness associated with narcolepsy, shift work sleep disorder, and obstructive sleep apnea/hypopnea syndrome. Remarkably, however, the neuronal circuitry through which modafinil exerts its wake-promoting effects remains unresolved. In the present study, we sought to determine if the wake-promoting effects of armodafinil are mediated, at least in part, by inhibiting the sleep-promoting neurons of the ventrolateral preoptic (VLPO) nucleus. To do so, we measured changes in waking following intraperitoneal administration of armodafinil (200 mg/kg) or the psychostimulant methamphetamine (1 mg/kg) in rats with cell-body specific lesion of the VLPO. Rats with histologically confirmed lesions of the VLPO demonstrated a sustained increase in wakefulness at baseline, but the increase in wakefulness following administration of both armodafinil and methamphetamine was similar to that of intact animals. These data suggest that armodafinil increases wakefulness by mechanisms that extend beyond inhibition of VLPO neurons.

  14. Projection neurons of the vestibulo-sympathetic reflex pathway.

    Science.gov (United States)

    Holstein, Gay R; Friedrich, Victor L; Martinelli, Giorgio P

    2014-06-15

    Changes in head position and posture are detected by the vestibular system and are normally followed by rapid modifications in blood pressure. These compensatory adjustments, which allow humans to stand up without fainting, are mediated by integration of vestibular system pathways with blood pressure control centers in the ventrolateral medulla. Orthostatic hypotension can reflect altered activity of this neural circuitry. Vestibular sensory input to the vestibulo-sympathetic pathway terminates on cells in the vestibular nuclear complex, which in turn project to brainstem sites involved in the regulation of cardiovascular activity, including the rostral and caudal ventrolateral medullary regions (RVLM and CVLM, respectively). In the present study, sinusoidal galvanic vestibular stimulation was used to activate this pathway, and activated neurons were identified through detection of c-Fos protein. The retrograde tracer Fluoro-Gold was injected into the RVLM or CVLM of these animals, and immunofluorescence studies of vestibular neurons were conducted to visualize c-Fos protein and Fluoro-Gold concomitantly. We observed activated projection neurons of the vestibulo-sympathetic reflex pathway in the caudal half of the spinal, medial, and parvocellular medial vestibular nuclei. Approximately two-thirds of the cells were ipsilateral to Fluoro-Gold injection sites in both the RVLM and CVLM, and the remainder were contralateral. As a group, cells projecting to the RVLM were located slightly rostral to those with terminals in the CVLM. Individual activated projection neurons were multipolar, globular, or fusiform in shape. This study provides the first direct demonstration of the central vestibular neurons that mediate the vestibulo-sympathetic reflex.

  15. The control of preoptic aromatase activity by afferent inputs in Japanese quail.

    Science.gov (United States)

    Absil, P; Baillien, M; Ball, G F; Panzica, G C; Balthazart, J

    2001-11-01

    This review summarizes current knowledge on the mechanisms that control aromatase activity in the quail preoptic area, a brain region that plays a key role in the control of reproduction. Aromatase and aromatase mRNA synthesis in the preoptic area are enhanced by testosterone and its metabolite estradiol, but estradiol receptors of the alpha subtype are not regularly colocalized with aromatase. Estradiol receptors of the beta subtype are present in the preoptic area but it is not yet known whether these receptors are colocalized with aromatase. The regulation by estrogen of aromatase activity may be, in part, trans-synaptically mediated, in a manner that is reminiscent of the ways in which steroids control the activity of gonadotropic hormone releasing hormone neurons. Aromatase-immunoreactive neurons are surrounded by dense networks of vasotocin-immunoreactive and tyrosine hydroxylase-immunoreactive fibers and punctate structures. These inputs are in part steroid-sensitive and could therefore mediate the effects of steroids on aromatase activity. In vivo pharmacological experiments indicate that catecholaminergic depletions significantly affect aromatase activity presumably by modulating aromatase transcription. In addition, in vitro studies on brain homogenates or on preoptic-hypothalamic explants show that aromatase activity can be rapidly modulated by a variety of dopaminergic compounds. These effects do not appear to be mediated by the membrane dopamine receptors and could involve changes in the phosphorylation state of the enzyme. Together, these results provide converging evidence for a direct control of aromatase activity by catecholamines consistent with the anatomical data indicating the presence of a catecholaminergic innervation of aromatase cells. These dopamine-induced changes in aromatase activity are observed after several hours or days and presumably result from changes in aromatase transcription but rapid non-genomic controls have also been

  16. Projection neuron circuits resolved using correlative array tomography

    Directory of Open Access Journals (Sweden)

    Daniele eOberti

    2011-04-01

    Full Text Available Assessment of three-dimensional morphological structure and synaptic connectivity is essential for a comprehensive understanding of neural processes controlling behavior. Different microscopy approaches have been proposed based on light microcopy (LM, electron microscopy (EM, or a combination of both. Correlative array tomography (CAT is a technique in which arrays of ultrathin serial sections are repeatedly stained with fluorescent antibodies against synaptic molecules and neurotransmitters and imaged with LM and EM (Micheva and Smith, 2007. The utility of this correlative approach is limited by the ability to preserve fluorescence and antigenicity on the one hand, and EM tissue ultrastructure on the other. We demonstrate tissue staining and fixation protocols and a workflow that yield an excellent compromise between these multimodal imaging constraints. We adapt CAT for the study of projection neurons between different vocal brain regions in the songbird. We inject fluorescent tracers of different colors into afferent and efferent areas of HVC in zebra finches. Fluorescence of some tracers is lost during tissue preparation but recovered using anti-dye antibodies. Synapses are identified in EM imagery based on their morphology and ultrastructure and classified into projection neuron type based on fluorescence signal. Our adaptation of array tomography, involving the use of fluorescent tracers and heavy-metal rich staining and embedding protocols for high membrane contrast in EM will be useful for research aimed at statistically describing connectivity between different projection neuron types and for elucidating how sensory signals are routed in the brain and transformed into a meaningful motor output.

  17. Central projections of auditory receptor neurons of crickets.

    Science.gov (United States)

    Imaizumi, Kazuo; Pollack, Gerald S

    2005-12-19

    We describe the central projections of physiologically characterized auditory receptor neurons of crickets as revealed by confocal microscopy. Receptors tuned to ultrasonic frequencies (similar to those produced by echolocating, insectivorous bats), to a mid-range of frequencies, and a subset of those tuned to low, cricket-like frequencies have similar projections, terminating medially within the auditory neuropile. Quantitative analysis shows that despite the general similarity of these projections they are tonotopic, with receptors tuned to lower frequencies terminating more medially. Another subset of cricket-song-tuned receptors projects more laterally and posteriorly than the other types. Double-fills of receptors and identified interneurons show that the three medially projecting receptor types are anatomically well positioned to provide monosynaptic input to interneurons that relay auditory information to the brain and to interneurons that modify this ascending information. The more laterally and posteriorly branching receptor type may not interact directly with this ascending pathway, but is well positioned to provide direct input to an interneuron that carries auditory information to more posterior ganglia. These results suggest that information about cricket song is segregated into functionally different pathways as early as the level of receptor neurons. Ultrasound-tuned and mid-frequency tuned receptors have approximately twice as many varicosities, which are sites of transmitter release, per receptor as either anatomical type of cricket-song-tuned receptor. This may compensate in part for the numerical under-representation of these receptor types.

  18. Molecular and functional differences in voltage-activated sodium currents between GABA projection neurons and dopamine neurons in the substantia nigra

    OpenAIRE

    Ding, Shengyuan; Wei, Wei; Zhou, Fu-Ming

    2011-01-01

    GABA projection neurons (GABA neurons) in the substantia nigra pars reticulata (SNr) and dopamine projection neurons (DA neurons) in substantia nigra pars compacta (SNc) have strikingly different firing properties. SNc DA neurons fire low-frequency, long-duration spikes, whereas SNr GABA neurons fire high-frequency, short-duration spikes. Since voltage-activated sodium (NaV) channels are critical to spike generation, the different firing properties raise the possibility that, compared with DA...

  19. Fezf2 expression in layer 5 projection neurons of mature mouse motor cortex.

    Science.gov (United States)

    Tantirigama, Malinda L S; Oswald, Manfred J; Clare, Alison J; Wicky, Hollie E; Day, Robert C; Hughes, Stephanie M; Empson, Ruth M

    2016-03-01

    The mature cerebral cortex contains a wide diversity of neuron phenotypes. This diversity is specified during development by neuron-specific expression of key transcription factors, some of which are retained for the life of the animal. One of these key developmental transcription factors that is also retained in the adult is Fezf2, but the neuron types expressing it in the mature cortex are unknown. With a validated Fezf2-Gfp reporter mouse, whole-cell electrophysiology with morphology reconstruction, cluster analysis, in vivo retrograde labeling, and immunohistochemistry, we identify a heterogeneous population of Fezf2(+) neurons in both layer 5A and layer 5B of the mature motor cortex. Functional electrophysiology identified two distinct subtypes of Fezf2(+) neurons that resembled pyramidal tract projection neurons (PT-PNs) and intratelencephalic projection neurons (IT-PNs). Retrograde labeling confirmed the former type to include corticospinal projection neurons (CSpPNs) and corticothalamic projection neurons (CThPNs), whereas the latter type included crossed corticostriatal projection neurons (cCStrPNs) and crossed-corticocortical projection neurons (cCCPNs). The two Fezf2(+) subtypes expressed either CTIP2 or SATB2 to distinguish their physiological identity and confirmed that specific expression combinations of key transcription factors persist in the mature motor cortex. Our findings indicate a wider role for Fezf2 within gene expression networks that underpin the diversity of layer 5 cortical projection neurons.

  20. Human pluripotent stem cell differentiation into authentic striatal projection neurons.

    Science.gov (United States)

    Delli Carri, Alessia; Onorati, Marco; Castiglioni, Valentina; Faedo, Andrea; Camnasio, Stefano; Toselli, Mauro; Biella, Gerardo; Cattaneo, Elena

    2013-08-01

    Here we present the principles and steps of a protocol that we have recently developed for the differentiation of hES/iPS cells into the authentic human striatal projection medium spiny neurons (MSNs) that die in Huntington's Disease (HD). Authenticity is judged by the convergence of multiple features within individual cells. Our procedure lasts 80 days and couples neural induction via BMP/TGF-β inhibition with exposure to the developmental factors sonic hedgehog (SHH) and dickkopf1 (DKK-1) to drive ventral telencephalic specification, followed by terminal differentiation [1]. Authenticity of the resulting neuronal population is monitored by the appearance of FOXG1(+)/GSX2(+) progenitor cells of the lateral ganglionic eminence (LGE) at day 15-25 of differentiation, followed by appearance of CTIP2-, FOXP1- and FOXP2-positive cells at day 45. These precursor cells then mature into MAP2(+)/GABA(+) neurons with 20 % of them ultimately co-expressing the DARPP-32 and CTIP2 diagnostic markers and carrying electrophysiological properties expected for fully functional MSNs.The protocol is characterized by its replicability in at least three human pluripotent cell lines. Altogether this protocol defines a useful platform for in vitro developmental neurobiology studies, drug screening, and regenerative medicine approaches.

  1. Prenatal cocaine exposure decreases parvalbumin-immunoreactive neurons and GABA-to-projection neuron ratio in the medial prefrontal cortex.

    Science.gov (United States)

    McCarthy, Deirdre M; Bhide, Pradeep G

    2012-01-01

    Cocaine abuse during pregnancy produces harmful effects not only on the mother but also on the unborn child. The neurotransmitters dopamine and serotonin are known as the principal targets of the action of cocaine in the fetal and postnatal brain. However, recent evidence suggests that cocaine can impair cerebral cortical GABA neuron development and function. We sought to analyze the effects of prenatal cocaine exposure on the number and distribution of GABA and projection neurons (inhibitory interneurons and excitatory output neurons, respectively) in the mouse cerebral cortex. We found that the prenatal cocaine exposure decreased GABA neuron numbers and GABA-to-projection neuron ratio in the medial prefrontal cortex of 60-day-old mice. The neighboring prefrontal cortex did not show significant changes in either of these measures. However, there was a significant increase in projection neuron numbers in the prefrontal cortex but not in the medial prefrontal cortex. Thus, the effects of cocaine on GABA and projection neurons appear to be cortical region specific. The population of parvalbumin-immunoreactive GABA neurons was decreased in the medial prefrontal cortex following the prenatal cocaine exposure. The cocaine exposure also delayed the developmental decline in the volume of the medial prefrontal cortex. Thus, prenatal cocaine exposure produced persisting and region-specific effects on cortical cytoarchitecture and impaired the physiological balance between excitatory and inhibitory neurotransmission. These structural changes may underlie the electrophysiological and behavioral effects of prenatal cocaine exposure observed in animal models and human subjects.

  2. Planar multipolar cells in the cochlear nucleus project to medial olivocochlear neurons in mouse.

    Science.gov (United States)

    Darrow, Keith N; Benson, Thane E; Brown, M Christian

    2012-05-01

    Medial olivocochlear (MOC) neurons originate in the superior olivary complex and project to the cochlea, where they act to reduce the effects of noise masking and protect the cochlea from damage. MOC neurons respond to sound via a reflex pathway; however, in this pathway the cochlear nucleus cell type that provides input to MOC neurons is not known. We investigated whether multipolar cells of the ventral cochlear nucleus have projections to MOC neurons by labeling them with injections into the dorsal cochlear nucleus. The projections of one type of labeled multipolar cell, planar neurons, were traced into the ventral nucleus of the trapezoid body, where they were observed terminating on MOC neurons (labeled in some cases by a second cochlear injection of FluoroGold). These terminations formed what appear to be excitatory synapses, i.e., containing small, round vesicles and prominent postsynaptic densities. These data suggest that cochlear nucleus planar multipolar neurons drive the MOC neuron's response to sound.

  3. Genetic evidence for p75NTR-dependent tetraploidy in cortical projection neurons from adult mice.

    Science.gov (United States)

    López-Sánchez, Noelia; Frade, José M

    2013-04-24

    A subpopulation of chick retinal projection neurons becomes tetraploid during development, an event prevented by blocking antibodies against p75 neurotrophin receptor (p75(NTR)). We have used an optimized flow cytometric assay, based on the analysis of unfixed brain cell nuclei, to study whether p75(NTR)-dependent neuronal tetraploidization takes place in the cerebral cortex, giving rise to projection neurons as well. We show that 3% of neurons in both murine neocortex and chick telencephalic derivatives are tetraploid, and that in the mouse ~85% of these neurons express the immediate early genes Erg-1 and c-Fos, indicating that they are functionally active. Tetraploid cortical neurons (65-80%) express CTIP2, a transcription factor specific for subcortical projection neurons in the mouse neocortex. During the period in which these neurons are born, p75(NTR) is detected in differentiating neurons undergoing DNA replication. Accordingly, p75(NTR)-deficient mice contain a reduced proportion of both NeuN and CTIP2-positive neocortical tetraploid neurons, thus providing genetic evidence for the participation of p75(NTR) in the induction of neuronal tetraploidy in the mouse neocortex. In the striatum tetraploidy is mainly associated with long-range projection neurons as well since ~80% of tetraploid neurons in this structure express calbindin, a marker of neostriatal-matrix spiny neurons, known to establish long-range projections to the substantia nigra and globus pallidus. In contrast, only 20% of tetraploid cortical neurons express calbindin, which is mainly expressed in layers II-III, where CTIP2 is absent. We conclude that tetraploidy mainly affects long-range projection neurons, being facilitated by p75(NTR) in the neocortex.

  4. Ascending projections of nociceptive neurons from trigeminal subnucleus caudalis: A population approach.

    Science.gov (United States)

    Saito, Hiroto; Katagiri, Ayano; Okada, Shinji; Mikuzuki, Lou; Kubo, Asako; Suzuki, Tatsuro; Ohara, Kinuyo; Lee, Jun; Gionhaku, Nobuhito; Iinuma, Toshimitsu; Bereiter, David A; Iwata, Koichi

    2017-07-01

    Second-order neurons in trigeminal subnucleus caudalis (Vc) and upper cervical spinal cord (C1) are critical for craniofacial pain processing and project rostrally to terminate in: ventral posteromedial thalamic nucleus (VPM), medial thalamic nuclei (MTN) and parabrachial nuclei (PBN). The contribution of each region to trigeminal nociception was assessed by the number of phosphorylated extracellular signal-regulated kinase-immunoreactive (pERK-IR) neurons co-labeled with fluorogold (FG). The phenotype of pERK-IR neurons was further defined by the expression of neurokinin 1 receptor (NK1). The retrograde tracer FG was injected into VPM, MTN or PBN of the right hemisphere and after seven days, capsaicin was injected into the left upper lip in male rats. Nearly all pERK-IR neurons were found in superficial laminae of Vc-C1 ipsilateral to the capsaicin injection. Nearly all VPM and MTN FG-labeled neurons in Vc-C1 were found contralateral to the injection site, whereas FG-labeled neurons were found bilaterally after PBN injection. The percentage of FG-pERK-NK1-IR neurons was significantly greater (>10%) for PBN projection neurons than for VPM and MTN projection neurons (NK1-IR VPM projection neurons were found mainly in the middle-Vc, while pERK-NK1-immunoreactive MTN or PBN projection neurons were found in the middle-Vc and caudal Vc-C1. These results suggest that a significant percentage of capsaicin-responsive neurons in superficial laminae of Vc-C1 project directly to PBN, while neurons that project to VPM and MTN are subject to greater modulation by pERK-IR local interneurons. Furthermore, the rostrocaudal distribution differences of FG-pERK-NK1-IR neurons in Vc-C1 may reflect functional differences between these projection areas regarding craniofacial pain. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Diversity of Layer 5 Projection Neurons in the Mouse Motor Cortex

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    Manfred J Oswald

    2013-10-01

    Full Text Available In the primary motor cortex (M1, layer 5 projection neurons signal directly to distant motor structures to drive movement. Despite their pivotal position and acknowledged diversity these neurons are traditionally separated into broad commissural and corticofugal types, and until now no attempt has been made at resolving the basis for their diversity. We therefore probed the electrophysiological and morphological properties of retrogradely labelled M1 corticospinal (CSp, corticothalamic (CTh, and commissural projecting corticostriatal (CStr and corticocortical (CC neurons. An unsupervised cluster analysis established at least four phenotypes with additional differences between lumbar and cervical projecting CSp neurons. Distinguishing parameters included the action potential (AP waveform, firing behaviour, the hyperpolarisation-activated sag potential, sublayer position, and soma and dendrite size. CTh neurons differed from CSp neurons in showing spike frequency acceleration and a greater sag potential. CStr neurons had the lowest AP amplitude and maximum rise rate of all neurons. Temperature influenced spike train behaviour in corticofugal neurons. At 26 ºC CTh neurons fired bursts of APs more often than CSp neurons, but at 36 ºC both groups fired regular APs. Our findings provide reliable phenotypic fingerprints to identify distinct M1 projection neuron classes as a tool to understand their unique contributions to motor function.

  6. Kölliker-Fuse GABAergic and glutamatergic neurons project to distinct targets.

    Science.gov (United States)

    Geerling, Joel C; Yokota, Shigefumi; Rukhadze, Irma; Roe, Dan; Chamberlin, Nancy L

    2017-06-01

    The Kölliker-Fuse nucleus (KF) is known primarily for its respiratory function as the "pneumotaxic center" or "pontine respiratory group." Considered part of the parabrachial (PB) complex, KF contains glutamatergic neurons that project to respiratory-related targets in the medulla and spinal cord (Yokota, Oka, Tsumori, Nakamura, & Yasui, 2007). Here we describe an unexpected population of neurons in the caudal KF and adjacent lateral crescent subnucleus (PBlc), which are γ-aminobutyric acid (GABA)ergic and have an entirely different pattern of projections than glutamatergic KF neurons. First, immunofluorescence, in situ hybridization, and Cre-reporter labeling revealed that many of these GABAergic neurons express FoxP2 in both rats and mice. Next, using Cre-dependent axonal tracing in Vgat-IRES-Cre and Vglut2-IRES-Cre mice, we identified different projection patterns from GABAergic and glutamatergic neurons in this region. GABAergic neurons in KF and PBlc project heavily and almost exclusively to trigeminal sensory nuclei, with minimal projections to cardiorespiratory nuclei in the brainstem, and none to the spinal cord. In contrast, glutamatergic KF neurons project heavily to the autonomic, respiratory, and motor regions of the medulla and spinal cord previously identified as efferent targets mediating KF cardiorespiratory effects. These findings identify a novel, GABAergic subpopulation of KF/PB neurons with a distinct efferent projection pattern targeting the brainstem trigeminal sensory system. Rather than regulating breathing, we propose that these neurons influence vibrissal sensorimotor function. © 2017 Wiley Periodicals, Inc.

  7. High-Throughput Mapping of Single-Neuron Projections by Sequencing of Barcoded RNA.

    Science.gov (United States)

    Kebschull, Justus M; Garcia da Silva, Pedro; Reid, Ashlan P; Peikon, Ian D; Albeanu, Dinu F; Zador, Anthony M

    2016-09-01

    Neurons transmit information to distant brain regions via long-range axonal projections. In the mouse, area-to-area connections have only been systematically mapped using bulk labeling techniques, which obscure the diverse projections of intermingled single neurons. Here we describe MAPseq (Multiplexed Analysis of Projections by Sequencing), a technique that can map the projections of thousands or even millions of single neurons by labeling large sets of neurons with random RNA sequences ("barcodes"). Axons are filled with barcode mRNA, each putative projection area is dissected, and the barcode mRNA is extracted and sequenced. Applying MAPseq to the locus coeruleus (LC), we find that individual LC neurons have preferred cortical targets. By recasting neuroanatomy, which is traditionally viewed as a problem of microscopy, as a problem of sequencing, MAPseq harnesses advances in sequencing technology to permit high-throughput interrogation of brain circuits.

  8. Neuropeptides in the hypothalamo-hypophyseal system: lateral retrochiasmatic area as a common gate for neuronal fibers towards the median eminence.

    Science.gov (United States)

    Palkovits, M

    1984-01-01

    The source and topography of neuropeptide-containing axons in the median eminence are summarized. Several of these neuropeptide-containing neurons (thyrotropin-releasing hormone, corticotropin-releasing hormone, vasopressin, oxytocin, cholecystokinin) are localized in the paraventricular nucleus. The periventricular and medial preoptic nuclei constitute the main sources of somatostatin and luteinizing hormone releasing hormone axons in the median eminence, respectively. Dynorphins and alpha-neo-endorphin-synthetizing neurons in the supraoptic nucleus also project to the median eminence. Wherever they originate, the projections may follow a common organization pattern and use a common gate--the lateral retrochiasmatic area--to enter the median eminence.

  9. Draxin from neocortical neurons controls the guidance of thalamocortical projections into the neocortex.

    Science.gov (United States)

    Shinmyo, Yohei; Asrafuzzaman Riyadh, M; Ahmed, Giasuddin; Bin Naser, Iftekhar; Hossain, Mahmud; Takebayashi, Hirohide; Kawasaki, Hiroshi; Ohta, Kunimasa; Tanaka, Hideaki

    2015-12-14

    The thalamocortical tract carries sensory information to the neocortex. It has long been recognized that the neocortical pioneer axons of subplate neurons are essential for thalamocortical development. Herein we report that an axon guidance cue, draxin, is expressed in early-born neocortical neurons, including subplate neurons, and is necessary for thalamocortical development. In draxin(-/-) mice, thalamocortical axons do not enter the neocortex. This phenotype is sufficiently rescued by the transgenic expression of draxin in neocortical neurons. Genetic interaction data suggest that draxin acts through Deleted in colorectal cancer (DCC) and Neogenin (Neo1), to regulate thalamocortical projections in vivo. Draxin promotes the outgrowth of thalamic axons in vitro and this effect is abolished in thalamic neurons from Dcc and Neo1 double mutants. These results suggest that draxin from neocortical neurons controls thalamocortical projections into the neocortex, and that this effect is mediated through the DCC and Neo1 receptors.

  10. Feed-forward and feedback projections of midbrain reticular formation neurons in the cat

    Directory of Open Access Journals (Sweden)

    Eddie ePerkins

    2014-01-01

    Full Text Available Gaze changes involving the eyes and head are orchestrated by brainstem gaze centers found within the superior colliculus (SC, paramedian pontine reticular formation (PPRF, and medullary reticular formation (MdRF. The mesencephalic reticular formation (MRF also plays a role in gaze. It receives a major input from the ipsilateral SC and contains cells that fire in relation to gaze changes. Moreover, it provides a feedback projection to the SC and feed-forward projections to the PPRF and MdRF. We sought to determine whether these MRF feedback and feed-forward projections originate from the same or different neuronal populations by utilizing paired fluorescent retrograde tracers in cats. Specifically, we tested: 1. whether MRF neurons that control eye movements form a single population by injecting the SC and PPRF with different tracers, and 2. whether MRF neurons that control head movements form a single population by injecting the SC and MdRF with different tracers. In neither case were double labeled neurons observed, indicating that feedback and feed-forward projections originate from separate MRF populations. In both cases, the labeled reticulotectal and reticuloreticular neurons were distributed bilaterally in the MRF. However, neurons projecting to the MdRF were generally constrained to the medial half of the MRF, while those projecting to the PPRF, like MRF reticulotectal neurons, were spread throughout the mediolateral axis. Thus, the medial MRF may be specialized for control of head movements, with control of eye movements being more widespread in this structure.

  11. Instructing Perisomatic Inhibition by Direct Lineage Reprogramming of Neocortical Projection Neurons.

    Science.gov (United States)

    Ye, Zhanlei; Mostajo-Radji, Mohammed A; Brown, Juliana R; Rouaux, Caroline; Tomassy, Giulio Srubek; Hensch, Takao K; Arlotta, Paola

    2015-11-01

    During development of the cerebral cortex, local GABAergic interneurons recognize and pair with excitatory projection neurons to ensure the fine excitatory-inhibitory balance essential for proper circuit function. Whether the class-specific identity of projection neurons has a role in the establishment of afferent inhibitory synapses is debated. Here, we report that direct in vivo lineage reprogramming of layer 2/3 (L2/3) callosal projection neurons (CPNs) into induced corticofugal projection neurons (iCFuPNs) increases inhibitory input onto the converted neurons to levels similar to that of endogenous CFuPNs normally found in layer 5 (L5). iCFuPNs recruit increased numbers of inhibitory perisomatic synapses from parvalbumin (PV)-positive interneurons, with single-cell precision and despite their ectopic location in L2/3. The data show that individual reprogrammed excitatory projection neurons extrinsically modulate afferent input by local PV(+) interneurons, suggesting that projection neuron class-specific identity can actively control the wiring of the cortical microcircuit.

  12. Beyond laminar fate: toward a molecular classification of cortical projection/pyramidal neurons.

    NARCIS (Netherlands)

    Hevner, R.F.; Daza, R.A.; Rubenstein, J.L.; Stunnenberg, H.G.; Olavarria, J.F.; Englund, C.

    2003-01-01

    Cortical projection neurons exhibit diverse morphological, physiological, and molecular phenotypes, but it is unknown how many distinct types exist. Many projection cell phenotypes are associated with laminar fate (radial position), but each layer may also contain multiple types of projection cells.

  13. Functional heterogeneity among neurons in the nucleus retroambiguus with lumbosacral projections in female cats

    NARCIS (Netherlands)

    Boers, J; Ford, TW; Holstege, G; Kirkwood, PA

    2005-01-01

    Nucleus retroambiguus (NRA), in the caudal medulla, projects to all spinal levels. One physiological role is abdominal pressure control, evidenced by projections to intercostal and abdominal motoneurons from expiratory bulbospinal neurons (EBSNs) within NRA. The roles of NRA projections to the lumbo

  14. Functional heterogeneity among neurons in the nucleus retroambiguus with lumbosacral projections in female cats

    NARCIS (Netherlands)

    Boers, J; Ford, TW; Holstege, G; Kirkwood, PA

    2005-01-01

    Nucleus retroambiguus (NRA), in the caudal medulla, projects to all spinal levels. One physiological role is abdominal pressure control, evidenced by projections to intercostal and abdominal motoneurons from expiratory bulbospinal neurons (EBSNs) within NRA. The roles of NRA projections to the

  15. Lola regulates Drosophila olfactory projection neuron identity and targeting specificity

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    Giniger Edward

    2007-07-01

    Full Text Available Abstract Background Precise connections of neural circuits can be specified by genetic programming. In the Drosophila olfactory system, projection neurons (PNs send dendrites to single glomeruli in the antenna lobe (AL based upon lineage and birth order and send axons with stereotyped terminations to higher olfactory centers. These decisions are likely specified by a PN-intrinsic transcriptional code that regulates the expression of cell-surface molecules to instruct wiring specificity. Results We find that the loss of longitudinals lacking (lola, which encodes a BTB-Zn-finger transcription factor with 20 predicted splice isoforms, results in wiring defects in both axons and dendrites of all lineages of PNs. RNA in situ hybridization and quantitative RT-PCR suggest that most if not all lola isoforms are expressed in all PNs, but different isoforms are expressed at widely varying levels. Overexpression of individual lola isoforms fails to rescue the lola null phenotypes and causes additional phenotypes. Loss of lola also results in ectopic expression of Gal4 drivers in multiple cell types and in the loss of transcription factor gene lim1 expression in ventral PNs. Conclusion Our results indicate that lola is required for wiring of axons and dendrites of most PN classes, and suggest a need for its molecular diversity. Expression pattern changes of Gal4 drivers in lola-/- clones imply that lola normally represses the expression of these regulatory elements in a subset of the cells surrounding the AL. We propose that Lola functions as a general transcription factor that regulates the expression of multiple genes ultimately controlling PN identity and wiring specificity.

  16. Differential effects of histamine on the activity of hypothalamic dopaminergic neurons in the rat.

    Science.gov (United States)

    Fleckenstein, A E; Lookingland, K J; Moore, K E

    1994-01-01

    The effect of intracerebroventricular administration of histamine on hypothalamic dopaminergic neuronal activity was estimated in male rats by measuring concentrations of dopamine and its metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) in brain regions containing terminals or perikarya of these neurons. Three distinct, regionally specific neurochemical responses were apparent. In the median eminence and intermediate lobe of the pituitary, histamine affected neither DOPAC nor dopamine concentrations, suggesting no effect on tuberoinfundibular or periventricular-hypophysial dopaminergic neuronal activity. In the medial zona incerta and in the dorsomedial, rostral periventricular and medial preoptic hypothalamic nuclei, histamine effected a dose- and time-related increase in both DOPAC and dopamine concentrations; these effects were blocked by destruction of noradrenergic neurons projecting to these regions, suggesting that these changes are attributable to noradrenergic neuronal activation, and that histamine does not affect the activity of incertohypothalamic or periventricular-preoptic dopaminergic neurons located in these brain regions. In the suprachiasmatic, caudal periventricular and paraventricular hypothalamic nuclei, histamine effected a dose- and time-related increase in DOPAC, but not dopamine, concentrations; these effects were blocked by the H1 antagonist mepyramine, but not the H2 antagonist zolantidine. Destruction of noradrenergic neurons projecting to these regions did not prevent the histamine-induced increases in DOPAC concentrations. These data indicate that histamine increases the activity of dopaminergic neurons projecting to the suprachiasmatic, caudal periventricular and paraventricular nuclei via an action at H1 receptors. Overall, these results reveal that i.c.v. administration of histamine differentially affects the activity of the various dopaminergic neuronal systems of the rat hypothalamus.

  17. Exercise promotes axon regeneration of newborn striatonigral and corticonigral projection neurons in rats after ischemic stroke

    National Research Council Canada - National Science Library

    Zhang, Qiu-Wan; Deng, Xu-Xu; Sun, Xiao; Xu, Jin-Xiu; Sun, Feng-Yan

    2013-01-01

    Newborn striatal neurons induced by middle cerebral artery occlusion (MCAO) can form functional projections targeting into the substantia nigra, which should be very important for the recovery of motor function...

  18. Extensive projections of myenteric serotonergic neurons suggest they comprise the central processing unit in the colon.

    Science.gov (United States)

    Okamoto, T; Barton, M J; Hennig, G W; Birch, G C; Grainger, N; Corrigan, R D; Koh, S D; Sanders, K M; Smith, T K

    2014-04-01

    5-Hydroxytryptamine (5-HT, serotonin) is an important regulator of colonic motility and secretion; yet the role of serotonergic neurons in the colon is controversial. We used immunohistochemical techniques to examine their projections throughout the enteric nervous system and interstitial cells of Cajal (ICC) networks in the murine proximal to mid colon. Serotonergic neurons, which were mainly calbindin positive, occurred only in myenteric ganglia (1 per 3 ganglia). They were larger than nNOS neurons but similar in size to Dogiel Type II (AH) neurons. 5-HT neurons, appeared to make numerous varicose contacts with each other, most nNOS neurons, Dogiel Type II/AH neurons and glial cells. 5-HT, calbindin and nNOS nerve fibers also formed a thin perimuscular nerve plexus that was associated with ganglia, which contained both nNOS positive and negative neurons, which lay directly upon the submucosal pacemaker ICC network. Neurons in perimuscular ganglia were surrounded by 5-HT varicosities. Submucous ganglia contained nNOS positive and negative neurons, and calbindin positive neurons, which also appeared richly supplied by serotonergic nerve varicosities. Serotonergic nerve fibers ran along submucosal arterioles, but not veins. Varicosities of serotonergic nerve fibers were closely associated with pacemaker ICC networks and with intramuscular ICC (ICC-IM). 5-HT2B receptors were found on a subpopulation of non-5-HT containing myenteric neurons and their varicosities, pacemaker ICC-MY and ICC-IM. Myenteric serotonergic neurons, whose axons exhibit considerable divergence, regulate the entire enteric nervous system and are important in coordinating motility with secretion. They are not just interneurons, as regularly assumed, but possibly also motor neurons to ICC and blood vessels, and some may even be sensory neurons. © 2014 John Wiley & Sons Ltd.

  19. Cell-Type-Specific Sensorimotor Processing in Striatal Projection Neurons during Goal-Directed Behavior.

    Science.gov (United States)

    Sippy, Tanya; Lapray, Damien; Crochet, Sylvain; Petersen, Carl C H

    2015-10-21

    Goal-directed sensorimotor transformation drives important aspects of mammalian behavior. The striatum is thought to play a key role in reward-based learning and action selection, receiving glutamatergic sensorimotor signals and dopaminergic reward signals. Here, we obtain whole-cell membrane potential recordings from the dorsolateral striatum of mice trained to lick a reward spout after a whisker deflection. Striatal projection neurons showed strong task-related modulation, with more depolarization and action potential firing on hit trials compared to misses. Direct pathway striatonigral neurons, but not indirect pathway striatopallidal neurons, exhibited a prominent early sensory response. Optogenetic stimulation of direct pathway striatonigral neurons, but not indirect pathway striatopallidal neurons, readily substituted for whisker stimulation evoking a licking response. Our data are consistent with direct pathway striatonigral neurons contributing a "go" signal for goal-directed sensorimotor transformation leading to action initiation. VIDEO ABSTRACT.

  20. Projection-Target-Defined Effects of Orexin and Dynorphin on VTA Dopamine Neurons

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    Corey Baimel

    2017-02-01

    Full Text Available Circuit-specific signaling of ventral tegmental area (VTA dopamine neurons drives different aspects of motivated behavior, but the neuromodulatory control of these circuits is unclear. We tested the actions of co-expressed lateral hypothalamic peptides, orexin A (oxA and dynorphin (dyn, on projection-target-defined dopamine neurons in mice. We determined that VTA dopamine neurons that project to the nucleus accumbens lateral shell (lAcbSh, medial shell (mAcbSh, and basolateral amygdala (BLA are largely non-overlapping cell populations with different electrophysiological properties. Moreover, the neuromodulatory effects of oxA and dyn on these three projections differed. OxA selectively increased firing in lAcbSh- and mAcbSh-projecting dopamine neurons. Dyn decreased firing in the majority of mAcbSh- and BLA-projecting dopamine neurons but reduced firing only in a small fraction of those that project to the lAcbSh. In conclusion, the oxA-dyn input to the VTA may drive reward-seeking behavior by tuning dopaminergic output in a projection-target-dependent manner.

  1. Transformation of odor selectivity from projection neurons to single mushroom body neurons mapped with dual-color calcium imaging.

    Science.gov (United States)

    Li, Hao; Li, Yiming; Lei, Zhengchang; Wang, Kaiyu; Guo, Aike

    2013-07-16

    Although the response properties of most neurons are, to a large extent, determined by the presynaptic inputs that they receive, comprehensive functional characterization of the presynaptic inputs of a single neuron remains elusive. Toward this goal, we introduce a dual-color calcium imaging approach that simultaneously monitors the responses of a single postsynaptic neuron together with its presynaptic axon terminal inputs in vivo. As a model system, we applied the strategy to the feed-forward connections from the projection neurons (PNs) to the Kenyon cells (KCs) in the mushroom body of Drosophila and functionally mapped essentially all PN inputs for some of the KCs. We found that the output of single KCs could be well predicted by a linear summation of the PN input signals, indicating that excitatory PN inputs play the major role in generating odor-selective responses in KCs. When odors failed to activate KC output, local calcium transients restricted to individual postsynaptic sites could be observed in the KC dendrites. The response amplitudes of the local transients often correlated linearly with the presynaptic response amplitudes, allowing direct assay of the strength of single synaptic sites. Furthermore, we found a scaling relationship between the total number of PN terminals that a single KC received and the average synaptic strength of these PN-KC synapses. Our strategy provides a unique perspective on the process of information transmission and integration in a model neural circuit and may be broadly applicable for the study of the origin of neuronal response properties.

  2. The circuitry of olfactory projection neurons in the brain of the honeybee, Apis mellifera

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    Hanna Zwaka

    2016-09-01

    Full Text Available In the honeybee brain, two prominent tracts - the medial and the lateral antennal lobe tract - project from the primary olfactory center, the antennal lobes, to the central brain, the mushroom bodies, and the protocerebral lobe. Intracellularly stained uniglomerular projection neurons (uPN were reconstructed, registered to the 3D honeybee standard brain atlas, and then used to derive the spatial properties and quantitative morphology of the neurons of both tracts. We evaluated putative synaptic contacts of projection neurons using confocal microscopy. Analysis of the patterns of axon terminals revealed a domain-like innervation within the mushroom body lip neuropil. Projection neurons of the lateral tract arborized more sparsely within the lips and exhibited fewer synaptic boutons, while medial tract neurons occupied broader regions in the mushroom body calyces and the protocerebral lobe. Our data show that uPNs from the medial and lateral tract innervate both the core and the cortex of the ipsilateral mushroom body lip but differ in their innervation patterns in these regions. In the mushroombody neuropil collar we found evidence for ALT boutons suggesting the collar as a multi modal input site including olfactory input similar to lip and basal ring. In addition, our data support the conclusion drawn in previous studies that reciprocal synapses exist between projection neurons, octopaminergic-, and GABAergic cells in the mushroom body calyces. For the first time, we found evidence for connections between both tracts within the antennal lobe.

  3. Fos induction in lamina I projection neurons in response to noxious thermal stimuli.

    Science.gov (United States)

    Todd, A J; Spike, R C; Young, S; Puskár, Z

    2005-01-01

    Lamina I of the spinal cord contains many projection neurons: the majority of these are activated by noxious stimulation, although some respond to other stimuli, such as innocuous cooling. In the rat, approximately 80% of lamina I projection neurons express the neurokinin 1 (NK1) receptor, on which substance P acts. Lamina I neurons can be classified into three main morphological classes: pyramidal, fusiform and multipolar cells. It has been reported that in the cat, pyramidal cells respond to innocuous cooling, and whilst both fusiform and multipolar cells are activated by noxious mechanical and heat stimuli, only cells in the latter group respond to noxious cold [Nat Neurosci 1 (1998) 218]. However, we have previously shown that NK1 receptor-immunoreactive projection neurons belonging to each morphological class are equally likely to up-regulate the transcription factor Fos after noxious chemical stimulation, and that the density of innervation by substance P-containing (nociceptive) afferents is similar for cells of each type [J Neurosci 22 (2002) 4103]. This suggests that the morphological-physiological correlation that has been reported in the cat may not apply in the rat. We have tested this further by examining Fos expression in lamina I spinoparabrachial neurons in the rat after application of noxious heat or noxious cold stimuli under general anesthesia. Following noxious heat, 57-69% of NK1 receptor-immunoreactive spinoparabrachial neurons expressed Fos, and the proportion did not differ significantly between morphological groups. However, after noxious cold stimulation Fos was present in 63% of multipolar neurons, but only 19-26% of fusiform or pyramidal cells. These results suggest that although most NK1 receptor-expressing spinoparabrachial neurons are activated by noxious stimuli, responsiveness to noxious cold is significantly more common in those of the multipolar type. There therefore appears to be a correlation between morphology and function for

  4. Projections from a single NUCB2/nesfatin-1 neuron in the paraventricular nucleus to different brain regions involved in feeding.

    Science.gov (United States)

    Maejima, Yuko; Kumamoto, Kensuke; Takenoshita, Seiichi; Shimomura, Kenju

    2016-12-01

    The anorexigenic neuropeptide NEFA/nucleobindin 2 (NUCB2)/nesfatin-1-containing neurons are distributed in the brain regions involved in feeding regulation, including the hypothalamic paraventricular nucleus (PVN). Functionally, NUCB2/nesfatin-1 neurons in the PVN regulate feeding through the hypothalamus and brain stem. However, the neural network of PVN NUCB2/nesfatin-1 neurons has yet to be elucidated. Axon collateral branches allow individual neurons to target multiple neurons. In some cases, each target neuron can be located in different nuclei. Here we show that a single neuron in the PVN projects axonal collaterals to both the dorsal vagal complex (DVC) and the arcuate nucleus (ARC), which are important brain regions for feeding regulation. In this study, after injection of different retrograde tracers into the DVC and ARC, both tracer-labeled neurons were detected in the identical PVN neuron, indicating the axon collateral projections from the single PVN neuron to the DVC and ARC. Furthermore, immunohistochemical analysis revealed that approximately 50 % of the neurons with axon collateral projections from the PVN to the DVC and ARC were found to be NUCB2/nesfatin-1 neurons. Our data suggest that a single NUCB2/nesfatin-1 neuron in the PVN projects to both the ARC and the DVC with axon collateral projection. Although the physiological significance remains to be elucidated, our data offer new perspectives on NUCB2/nesfatin-1 function at the neural network level and food intake regulation.

  5. Subpallial origin of a population of projecting pioneer neurons during corticogenesis.

    Science.gov (United States)

    Morante-Oria, Javier; Carleton, Alan; Ortino, Barbara; Kremer, Eric J; Fairén, Alfonso; Lledo, Pierre-Marie

    2003-10-14

    Pyramidal neurons of the mammalian cerebral cortex are generated in the ventricular zone of the pallium whereas the subpallium provides the cortex with inhibitory interneurons. The marginal zone contains a subpial stream of migratory interneurons and two different classes of transient neurons, the pioneer neurons provided with corticofugal axons, and the reelin-expressing Cajal-Retzius cells. We found in cultured slices that the medial ganglionic eminence provides the reelin-negative pioneer neurons of the marginal zone. Pioneer neurons sent long projection axons that went through the cortical plate and reached the subplate and the lateral border of the lateral ganglionic eminence. In the cultured slices, pioneer neurons were functionally mature: they displayed a voltage-gated sodium current, expressed functional alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, and showed gamma-aminobutyric acid type A (GABAA) postsynaptic events that were modulated by presynaptic AMPA receptors. Pioneer neurons expressed the adhesion molecules L1 and TAG-1; the latter has been reported to control tangential migrations to the neocortex [Denaxa, M., Chan, C.-H., Schachner, M., Parnavelas, J. & Karagogeos, D. (2001) Development (Cambridge, U.K.) 128, 4635-4644], and we show here that the pioneer neurons of the marginal zone are the cellular substrate of such a function. Finally, we show that, in early corticogenesis, reelin controls both the tangential migration of cortical interneurons toward the cortical plate and the tangential migration of pioneer neurons toward the marginal zone.

  6. Exercise promotes axon regeneration of newborn striatonigral and corticonigral projection neurons in rats after ischemic stroke.

    Directory of Open Access Journals (Sweden)

    Qiu-Wan Zhang

    Full Text Available Newborn striatal neurons induced by middle cerebral artery occlusion (MCAO can form functional projections targeting into the substantia nigra, which should be very important for the recovery of motor function. Exercise training post-stroke improves motor recovery in clinic patients and increases striatal neurogenesis in experimental animals. This study aimed to investigate the effects of exercise on axon regeneration of newborn projection neurons in adult rat brains following ischemic stroke. Rats were subjected to a transient MCAO to induce focal cerebral ischemic injury, followed by 30 minutes of exercise training daily from 5 to 28 days after MCAO. Motor function was tested using the rotarod test. We used fluorogold (FG nigral injection to trace striatonigral and corticonigral projection neurons, and green fluorescent protein (GFP-targeting retroviral vectors combined with FG double labeling (GFP(+ -FG(+ to detect newborn projection neurons. The results showed that exercise improved the recovery of motor function of rats after MCAO. Meanwhile, exercise also increased the levels of BDNF and VEGF, and reduced Nogo-A in ischemic brain. On this condition, we further found that exercise significantly increased the number of GFP(+ -FG(+ neurons in the striatum and frontal and parietal cortex ipsilateral to MCAO, suggesting an increase of newborn striatonigral and corticonigral projection neurons by exercise post-stroke. In addition, we found that exercise also increased NeuN(+ and FG(+ cells in the striatum and frontal and parietal cortex, the ischemic territory, and tyrosine hydroxylase (TH immunopositive staining cells in the substantia nigra, a region remote from the ischemic territory. Our results provide the first evidence that exercise can effectively enhance the capacity for regeneration of newborn projection neurons in ischemic injured mammalian brains while improving motor function. Our results provide a very important cellular mechanism

  7. Visualization of Sensory Neurons and Their Projections in an Upper Motor Neuron Reporter Line.

    Science.gov (United States)

    Genç, Barış; Lagrimas, Amiko Krisa Bunag; Kuru, Pınar; Hess, Robert; Tu, Michael William; Menichella, Daniela Maria; Miller, Richard J; Paller, Amy S; Özdinler, P Hande

    2015-01-01

    Visualization of peripheral nervous system axons and cell bodies is important to understand their development, target recognition, and integration into complex circuitries. Numerous studies have used protein gene product (PGP) 9.5 [a.k.a. ubiquitin carboxy-terminal hydrolase L1 (UCHL1)] expression as a marker to label sensory neurons and their axons. Enhanced green fluorescent protein (eGFP) expression, under the control of UCHL1 promoter, is stable and long lasting in the UCHL1-eGFP reporter line. In addition to the genetic labeling of corticospinal motor neurons in the motor cortex and degeneration-resistant spinal motor neurons in the spinal cord, here we report that neurons of the peripheral nervous system are also fluorescently labeled in the UCHL1-eGFP reporter line. eGFP expression is turned on at embryonic ages and lasts through adulthood, allowing detailed studies of cell bodies, axons and target innervation patterns of all sensory neurons in vivo. In addition, visualization of both the sensory and the motor neurons in the same animal offers many advantages. In this report, we used UCHL1-eGFP reporter line in two different disease paradigms: diabetes and motor neuron disease. eGFP expression in sensory axons helped determine changes in epidermal nerve fiber density in a high-fat diet induced diabetes model. Our findings corroborate previous studies, and suggest that more than five months is required for significant skin denervation. Crossing UCHL1-eGFP with hSOD1G93A mice generated hSOD1G93A-UeGFP reporter line of amyotrophic lateral sclerosis, and revealed sensory nervous system defects, especially towards disease end-stage. Our studies not only emphasize the complexity of the disease in ALS, but also reveal that UCHL1-eGFP reporter line would be a valuable tool to visualize and study various aspects of sensory nervous system development and degeneration in the context of numerous diseases.

  8. Exclusive and common targets of neostriatofugal projections of rat striosome neurons: a single neuron-tracing study using a viral vector.

    Science.gov (United States)

    Fujiyama, Fumino; Sohn, Jaerin; Nakano, Takashi; Furuta, Takahiro; Nakamura, Kouichi C; Matsuda, Wakoto; Kaneko, Takeshi

    2011-02-01

    The rat neostriatum has a mosaic organization composed of striosome/patch compartments embedded in a more extensive matrix compartment, which are distinguished from each other by the input-output organization as well as by the expression of many molecular markers. The matrix compartment gives rise to the dual γ-aminobutyric acid (GABA)ergic striatofugal systems, i.e. direct and indirect pathway neurons, whereas the striosome compartment is considered to involve direct pathway neurons alone. Although the whole axonal arborization of matrix striatofugal neurons has been examined in vivo by intracellular staining, that of striosome neurons has never been studied at the single neuron level. In the present study, the axonal arborizations of single striosome projection neurons in rat neostriatum were visualized in their entirety using a viral vector expressing membrane-targeted green fluorescent protein, and compared with that of matrix projection neurons. We found that not only matrix but also striosome compartments contained direct and indirect pathway neurons. Furthermore, only striatonigral neurons in the striosome compartment projected directly to the substantia nigra pars compacta (SNc), although they sent a substantial number of axon collaterals to the globus pallidus, entopeduncular nucleus and/or substantia nigra pars reticulata. These results suggest that striosome neurons play a more important role in the formation of reward-related signals of SNc dopaminergic neurons than do matrix neurons. Together with data from previous studies in the reinforcement learning theory, our results suggest that these direct and indirect striosome-SNc pathways together with nigrostriatal dopaminergic neurons may help striosome neurons to acquire the state-value function.

  9. VTA Projection Neurons Releasing GABA and Glutamate in the Dentate Gyrus

    Science.gov (United States)

    2016-01-01

    Abstract Both dopamine and nondopamine neurons from the ventral tegmental area (VTA) project to a variety of brain regions. Here we examine nondopaminergic neurons in the mouse VTA that send long-range projections to the hippocampus. Using a combination of retrograde tracers, optogenetic tools, and electrophysiological recordings, we show that VTA GABAergic axons make synaptic contacts in the granule cell layer of the dentate gyrus, where we can elicit small postsynaptic currents. Surprisingly, the currents displayed a partial sensitivity to both bicuculline and NBQX, suggesting that these mesohippocampal neurons corelease both GABA and glutamate. Finally, we show that this projection is functional in vivo and its stimulation reduces granule cell-firing rates under anesthesia. Altogether, the present results describe a novel connection between GABA and glutamate coreleasing of cells of the VTA and the dentate gyrus. This connection could be relevant for a variety of functions, including reward-related memory and neurogenesis. PMID:27648470

  10. Area-specific development of distinct projection neuron subclasses is regulated by postnatal epigenetic modifications.

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    Harb, Kawssar; Magrinelli, Elia; Nicolas, Céline S; Lukianets, Nikita; Frangeul, Laura; Pietri, Mariel; Sun, Tao; Sandoz, Guillaume; Grammont, Franck; Jabaudon, Denis; Studer, Michele; Alfano, Christian

    2016-01-27

    During cortical development, the identity of major classes of long-distance projection neurons is established by the expression of molecular determinants, which become gradually restricted and mutually exclusive. However, the mechanisms by which projection neurons acquire their final properties during postnatal stages are still poorly understood. In this study, we show that the number of neurons co-expressing Ctip2 and Satb2, respectively involved in the early specification of subcerebral and callosal projection neurons, progressively increases after birth in the somatosensory cortex. Ctip2/Satb2 postnatal co-localization defines two distinct neuronal subclasses projecting either to the contralateral cortex or to the brainstem suggesting that Ctip2/Satb2 co-expression may refine their properties rather than determine their identity. Gain- and loss-of-function approaches reveal that the transcriptional adaptor Lmo4 drives this maturation program through modulation of epigenetic mechanisms in a time- and area-specific manner, thereby indicating that a previously unknown genetic program postnatally promotes the acquisition of final subtype-specific features.

  11. Immunohistochemical Properties of the Peripheral Neurons Projecting to the Pig Bulbospongiosus Muscle.

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    Botti, Maddalena; Ragionieri, Luisa; Cacchioli, Antonio; Panu, Rino; Gazza, Ferdinando

    2016-09-01

    Retrograde neuronal tracing and single labelling immunofluorescence methods were used to define the neurochemical content of the peripheral autonomic and sensitive neurons projecting to the male pig striated bulbospongiosus muscle (BSM). The retrograde fluorescent neuronal tracer Fast Blue (FB) was injected into the left bulbospongiosus muscle of four intact impuberal pigs. After a 10-day survival time, the ipsilateral sacral sympathetic trunk ganglia (STGs), the caudal mesenteric ganglion (CMG), and the sacral spinal ganglia (SGs) were collected from each animal. In FB+ neurons of these ganglia, the presence of cathecolamine- (tyrosine hydroxylase-TH), acetylcholine- (vesicular acetylcholine transporter-VChAT), or nitric oxide-synthesizing (neuronal Nitric Oxide Synthase-nNOS) enzymes and of some biologically active peptides (calcitonine gene-related peptide-CGRP, Leu-Enkephaline-LENK, Neuropeptide Y-NPY, Substance P-SP and Vasoactive Intestinal Peptide-VIP) were studied. The ipsilateral STGs FB+ neurons showed immunoreactivity principally for TH and NPY and in decreasing order for VIP, VChAT, SP, CGRP, nNOS, and LENK. The left CMG FB+ neurons were immunoreactive to TH and NPY, and in smaller proportions for VIP, LENK, VChAT, CGRP, nNOS, and SP. The ipsilateral SGs FB+ neurons resulted immunoractive for CGRP, LENK, NPY, nNOS, SP, and VChAT. The heterogeneous neurochemical content of the peripheral neurons projecting to the pig BSM allows us to hypothesize the involvement of autonomic ganglia in the activity of both blood vessels and striated fibers of the muscle and the involvement of sensory ganglia in the afferent transmission from the muscle to spinal cord and in antidromic mechanisms that causes the relaxation of the BSM blood vessels. Anat Rec, 299:1192-1202, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  12. Conditional Viral Tract Tracing Delineates the Projections of the Distinct Kisspeptin Neuron Populations to Gonadotropin-Releasing Hormone (GnRH) Neurons in the Mouse.

    Science.gov (United States)

    Yip, Siew Hoong; Boehm, Ulrich; Herbison, Allan E; Campbell, Rebecca E

    2015-07-01

    Kisspeptin neurons play an essential role in the regulation of fertility through direct regulation of the GnRH neurons. However, the relative contributions of the two functionally distinct kisspeptin neuron subpopulations to this critical regulation are not fully understood. Here we analyzed the specific projection patterns of kisspeptin neurons originating from either the rostral periventricular nucleus of the third ventricle (RP3V) or the arcuate nucleus (ARN) using a cell-specific, viral-mediated tract-tracing approach. We stereotaxically injected a Cre-dependent recombinant adenovirus encoding farnesylated enhanced green fluorescent protein into the ARN or RP3V of adult male and female mice expressing Cre recombinase in kisspeptin neurons. Fibers from ARN kisspeptin neurons projected widely; however, we did not find any evidence for direct contact with GnRH neuron somata or proximal dendrites in either sex. In contrast, we identified RP3V kisspeptin fibers in close contact with GnRH neuron somata and dendrites in both sexes. Fibers originating from both the RP3V and ARN were observed in close contact with distal GnRH neuron processes in the ARN and in the lateral and internal aspects of the median eminence. Furthermore, GnRH nerve terminals were found in close contact with the proximal dendrites of ARN kisspeptin neurons in the ARN, and ARN kisspeptin fibers were found contacting RP3V kisspeptin neurons in both sexes. Together these data delineate selective zones of kisspeptin neuron inputs to GnRH neurons and demonstrate complex interconnections between the distinct kisspeptin populations and GnRH neurons.

  13. Pathway-specific reorganization of projection neurons in somatosensory cortex during learning.

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    Chen, Jerry L; Margolis, David J; Stankov, Atanas; Sumanovski, Lazar T; Schneider, Bernard L; Helmchen, Fritjof

    2015-08-01

    In the mammalian brain, sensory cortices exhibit plasticity during task learning, but how this alters information transferred between connected cortical areas remains unknown. We found that divergent subpopulations of cortico-cortical neurons in mouse whisker primary somatosensory cortex (S1) undergo functional changes reflecting learned behavior. We chronically imaged activity of S1 neurons projecting to secondary somatosensory (S2) or primary motor (M1) cortex in mice learning a texture discrimination task. Mice adopted an active whisking strategy that enhanced texture-related whisker kinematics, correlating with task performance. M1-projecting neurons reliably encoded basic kinematics features, and an additional subset of touch-related neurons was recruited that persisted past training. The number of S2-projecting touch neurons remained constant, but improved their discrimination of trial types through reorganization while developing activity patterns capable of discriminating the animal's decision. We propose that learning-related changes in S1 enhance sensory representations in a pathway-specific manner, providing downstream areas with task-relevant information for behavior.

  14. Synaptic connections of PDF-immunoreactive lateral neurons projecting to the dorsal protocerebrum of Drosophila melanogaster.

    Science.gov (United States)

    Yasuyama, Kouji; Meinertzhagen, Ian A

    2010-02-01

    Recent studies in Drosophila melanogaster indicate that the neuropeptide pigment-dispersing factor (PDF) is an important output signal from a set of major clock neurons, s-LN(v)s (small ventral lateral neurons), which transmit the circadian phase to subsets of other clock neurons, DNs (dorsal neurons). Both s-LN(v)s and DNs have fiber projections to the dorsal protocerebrum of the brain, so that this area is a conspicuous locus for coupling between different subsets of clock neurons. To unravel the neural circuits underlying the fly's circadian rhythms, we examined the detailed subcellular morphology of the PDF-positive fibers of the s-LN(v)s in the dorsal protocerebrum, focusing on their synaptic connections, using preembedding immunoelectron microscopy. To examine the distribution of synapses, we also reconstructed the three-dimensional morphology of PDF-positive varicosities from fiber profiles in the dorsal protocerebrum. The varicosities contained large dense-core vesicles (DCVs), and also numerous small clear vesicles, forming divergent output synapses onto unlabeled neurites. The DCVs apparently dock at nonsynaptic sites, suggesting their nonsynaptic release. In addition, a 3D reconstruction revealed the presence of input synapses onto the PDF-positive fibers. These were detected less frequently than output sites. These observations suggest that the PDF-positive clock neurons receive neural inputs directly through synaptic connections in the dorsal protocerebrum, in addition to supplying dual outputs, either synaptic or via paracrine release of the DCV contents, to unidentified target neurons.

  15. Sensory, motor somatic, and autonomic neurons projecting to the porcine cremaster muscle.

    Science.gov (United States)

    Botti, Maddalena; Minelli, Luisa Bo; Gazza, Ferdinando; Ragionieri, Luisa; Acone, Franca; Panu, Rino; Palmieri, Giovanni

    2006-10-01

    The location of sensory, somatic, and autonomic neurons projecting to the pig cremaster muscle (CM) was studied by means of the retrograde neuronal tracer Fast Blue (FB) technique. FB was randomly injected in the left CM of four impuberal pigs and serial sections of sensory and autonomic ganglia and spinal cord were examined under a fluorescence microscope. Additionally, some indications about the number and size of labeled neurons were given. Sensory pseudounipolar somata were located ipsilaterally in the L2-L6 and S1-S2 dorsal root ganglia, their total number ranging between 125 and 194, their mean diameter between 24 and 89 microm. Somatic multipolar motoneurons were located ipsilaterally in the L2-L4 neuromeres of the spinal cord, their total number ranging between 53 and 169, their mean diameter between 29 and 53 microm. Autonomic multipolar paravertebral ganglia neurons were located ipsilaterally from L1 to S4 and contralaterally from L2 to S2. Their total number ranged from 2,015 to 3,067 and their mean diameter between 25 and 55 microm. The multipolar caudal mesenteric ganglia neurons were located bilaterally, their total number ranging between 14 and 1,408 and their diameter from 22 to 39 microm. In two subjects only, multipolar neurons were also found ipsilaterally in the microganglia of pelvic plexus (2 and 13 neurons). Their mean diameter ranged between 28 and 54 microm. Our study documented that the CM-projecting neurons were located at different neural levels, with a predominance in the autonomic ganglia.

  16. Individual mediodorsal thalamic neurons project to multiple areas of the rat prefrontal cortex: A single neuron-tracing study using virus vectors.

    Science.gov (United States)

    Kuramoto, Eriko; Pan, Shixiu; Furuta, Takahiro; Tanaka, Yasuhiro R; Iwai, Haruki; Yamanaka, Atsushi; Ohno, Sachi; Kaneko, Takeshi; Goto, Tetsuya; Hioki, Hiroyuki

    2017-01-01

    The prefrontal cortex has an important role in a variety of cognitive and executive processes, and is generally defined by its reciprocal connections with the mediodorsal thalamic nucleus (MD). The rat MD is mainly subdivided into three segments, the medial (MDm), central (MDc), and lateral (MDl) divisions, on the basis of the cytoarchitecture and chemoarchitecture. The MD segments are known to topographically project to multiple prefrontal areas at the population level: the MDm mainly to the prelimbic, infralimbic, and agranular insular areas; the MDc to the orbital and agranular insular areas; and the MDl to the prelimbic and anterior cingulate areas. However, it is unknown whether individual MD neurons project to single or multiple prefrontal cortical areas. In the present study, we visualized individual MD neurons with Sindbis virus vectors, and reconstructed whole structures of MD neurons. While the main cortical projection targets of MDm, MDc, and MDl neurons were generally consistent with those of previous results, it was found that individual MD neurons sent their axon fibers to multiple prefrontal areas, and displayed various projection patterns in the target areas. Furthermore, the axons of single MD neurons were not homogeneously spread, but were rather distributed to form patchy axon arbors approximately 1 mm in diameter. The multiple-area projections and patchy axon arbors of single MD neurons might be able to coactivate cortical neuron groups in distant prefrontal areas simultaneously. Furthermore, considerable heterogeneity of the projection patterns is likely, to recruit the different sets of cortical neurons, and thus contributes to a variety of prefrontal functions. J. Comp. Neurol. 525:166-185, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  17. Activation of lateral hypothalamus-projecting parabrachial neurons by intraorally delivered gustatory stimuli

    Directory of Open Access Journals (Sweden)

    Kenichi eTokita

    2014-07-01

    Full Text Available The present study investigated a subpopulation of neurons in the mouse parabrachial nucleus (PbN, a gustatory and visceral relay area in the brainstem, that project to the lateral hypothalamus (LH. We made injections of the retrograde tracer Fluorogold (FG into LH, resulting in fluorescent labeling of neurons located in different regions of the PbN. Mice were stimulated through an intraoral cannula with one of seven different taste stimuli, and PbN sections were processed for immunohistochemical detection of the immediate early gene c-Fos, which labels activated neurons. LH projection neurons were found in all PbN subnuclei, but in greater concentration in lateral subnuclei, including the dorsal lateral subnucleus (dl. Fos-like immunoreactivity (FLI was observed in the PbN in a stimulus-dependent pattern, with the greatest differentiation between intraoral stimulation with sweet (0.5 M sucrose and bitter (0.003 M quinine compounds. In particular, sweet and umami-tasting stimuli evoked robust FLI in cells in the dl, whereas quinine evoked almost no FLI in cells in this subnucleus. Double-labeled cells were also found in the greatest quantity in the dl. Overall, these results support the hypothesis that the dl contains direct a projection to the LH that is activated preferentially by appetitive compounds; this projection may be mediated by taste and/or postingestive mechanisms.

  18. The Transcription Factor Orthodenticle Homeobox 2 Influences Axonal Projections and Vulnerability of Midbrain Dopaminergic Neurons

    Science.gov (United States)

    Chung, Chee Yeun; Licznerski, Pawel; Alavian, Kambiz N.; Simeone, Antonio; Lin, Zhicheng; Martin, Eden; Vance, Jeffery; Isacson, Ole

    2010-01-01

    Two adjacent groups of midbrain dopaminergic neurons, A9 (substantia nigra pars compacta) and A10 (ventral tegmental area), have distinct projections and exhibit differential vulnerability in Parkinson's disease. Little is known about transcription factors that influence midbrain dopaminergic subgroup phenotypes or their potential role in disease.…

  19. The Transcription Factor Orthodenticle Homeobox 2 Influences Axonal Projections and Vulnerability of Midbrain Dopaminergic Neurons

    Science.gov (United States)

    Chung, Chee Yeun; Licznerski, Pawel; Alavian, Kambiz N.; Simeone, Antonio; Lin, Zhicheng; Martin, Eden; Vance, Jeffery; Isacson, Ole

    2010-01-01

    Two adjacent groups of midbrain dopaminergic neurons, A9 (substantia nigra pars compacta) and A10 (ventral tegmental area), have distinct projections and exhibit differential vulnerability in Parkinson's disease. Little is known about transcription factors that influence midbrain dopaminergic subgroup phenotypes or their potential role in disease.…

  20. Spinal afferent neurons projecting to the rat lung and pleura express acid sensitive channels

    Directory of Open Access Journals (Sweden)

    Kummer Wolfgang

    2006-07-01

    Full Text Available Abstract Background The acid sensitive ion channels TRPV1 (transient receptor potential vanilloid receptor-1 and ASIC3 (acid sensing ion channel-3 respond to tissue acidification in the range that occurs during painful conditions such as inflammation and ischemia. Here, we investigated to which extent they are expressed by rat dorsal root ganglion neurons projecting to lung and pleura, respectively. Methods The tracer DiI was either injected into the left lung or applied to the costal pleura. Retrogradely labelled dorsal root ganglion neurons were subjected to triple-labelling immunohistochemistry using antisera against TRPV1, ASIC3 and neurofilament 68 (marker for myelinated neurons, and their soma diameter was measured. Results Whereas 22% of pulmonary spinal afferents contained neither channel-immunoreactivity, at least one is expressed by 97% of pleural afferents. TRPV1+/ASIC3- neurons with probably slow conduction velocity (small soma, neurofilament 68-negative were significantly more frequent among pleural (35% than pulmonary afferents (20%. TRPV1+/ASIC3+ neurons amounted to 14 and 10% respectively. TRPV1-/ASIC3+ neurons made up between 44% (lung and 48% (pleura of neurons, and half of them presumably conducted in the A-fibre range (larger soma, neurofilament 68-positive. Conclusion Rat pleural and pulmonary spinal afferents express at least two different acid-sensitive channels that make them suitable to monitor tissue acidification. Patterns of co-expression and structural markers define neuronal subgroups that can be inferred to subserve different functions and may initiate specific reflex responses. The higher prevalence of TRPV1+/ASIC3- neurons among pleural afferents probably reflects the high sensitivity of the parietal pleura to painful stimuli.

  1. Highly differentiated cellular and circuit properties of infralimbic pyramidal neurons projecting to the periaqueductal gray and amygdala.

    Directory of Open Access Journals (Sweden)

    Ashley N Ferreira

    2015-04-01

    Full Text Available The infralimbic (IL cortex is a key node in an inter-connected network involved in fear and emotion processing. The cellular and circuit-level mechanisms whereby IL neurons receive, filter, and modulate incoming signals they project onward to diverse downstream nodes in this complex network remain poorly understood. Using the mouse as our model, we applied anatomical labeling strategies, brain slice electrophysiology, and focal activation of caged glutamate via laser scanning photostimulation (glu-LSPS for quantitative neurophysiological analysis of projectionally defined neurons in IL. Injection of retrograde tracers into the periaqueductal grey (PAG and basolateral amygdala (BLA was used to identify cortico-PAG (CP and cortico-BLA (CA neurons in IL. CP neurons were found exclusively in layer 5 of IL whereas CA neurons were detected throughout layer 2, 3 and 5 of IL. We also identified a small percentage of IL neurons that project to both the PAG and the BLA. We found that layer 5 CP neurons have a more extensive dendritic structure compared to layer 5 CA neurons. Neurophysiological recordings performed on retrogradely labeled neurons in acute brain slice showed that CP and CA neurons in IL could be broadly classified in two groups: neuronal resonators and non-resonators. Layer 2 CA neurons were the only class that was exclusively non-resonating. CP, CA, and CP/CA neurons in layers 3 and 5 of IL consisted of heterogeneous populations of resonators and non-resonators showing that projection target is not an exclusive predictor of intrinsic physiology. Circuit mapping using glu-LSPS revealed that the strength and organization of local excitatory and inhibitory inputs were stronger to CP compared to CA neurons in IL. Together, our results establish an organizational scheme linking cellular neurophysiology with microcircuit parameters of defined neuronal subclasses in IL that send descending commands to subcortical structures involved in fear

  2. Regeneration of descending projections to the spinal motor neurons after spinal hemisection in the goldfish.

    Science.gov (United States)

    Takeda, Akihito; Goris, Richard C; Funakoshi, Kengo

    2007-06-25

    Following spinal transection, descending spinal projections from goldfish brainstem neurons spontaneously regenerate beyond the lesion site. The nucleus of the medial longitudinal fasciculus (nFLM), which has a critical role in swimming, also sends regenerated axons over a long distance to the ipsilateral spinal cord. To examine whether regenerated axons re-innervate the appropriate targets, we injected rhodamine dextran amine (RDA) into the nFLM of spinally transected goldfish and examined anterogradely labeled axons in the spinal cord. In intact controls, there were many RDA-labeled boutons or varicosities in the spinal cord in close apposition to both neurons positive for calcitonin gene-related peptide (CGRP), and those negative for CGRP. This suggests that the nFLM neurons project axons directly to the motoneurons and interneurons in the spinal cord. Four days after hemisection 1 mm caudal to the rostral end of the spinal cord, the number of RDA-labeled boutons in close apposition to the spinal neurons was significantly decreased on the side ipsilateral to the injection. Six to twelve weeks after spinal hemisection, regenerated axons ran through the repaired lesion site, and the number of RDA-labeled boutons or varicosities in close apposition to the ipsilateral spinal neurons had returned to the control level. These findings suggest that the midbrain-spinal pathway, critical for locomotion in fish, spontaneously regenerates beyond the lesion site to re-innervate the appropriately innervated targets after spinal lesion.

  3. The projection and synaptic organisation of NTS afferent connections with presympathetic neurons, GABA and nNOS neurons in the paraventricular nucleus of the hypothalamus.

    Science.gov (United States)

    Affleck, V S; Coote, J H; Pyner, S

    2012-09-01

    Elevated sympathetic nerve activity, strongly associated with cardiovascular disease, is partly generated from the presympathetic neurons of the paraventricular nucleus of the hypothalamus (PVN). The PVN-presympathetic neurons regulating cardiac and vasomotor sympathetic activity receive information about cardiovascular status from receptors in the heart and circulation. These receptors signal changes via afferent neurons terminating in the nucleus tractus solitarius (NTS), some of which may result in excitation or inhibition of PVN-presympathetic neurons. Understanding the anatomy and neurochemistry of NTS afferent connections within the PVN could provide important clues to the impairment in homeostasis cardiovascular control associated with disease. Transynaptic labelling has shown the presence of neuronal nitric oxide synthase (nNOS)-containing neurons and GABA interneurons that terminate on presympathetic PVN neurons any of which may be the target for NTS afferents. So far NTS connections to these diverse neuronal pools have not been demonstrated and were investigated in this study. Anterograde (biotin dextran amine - BDA) labelling of the ascending projection from the NTS and retrograde (fluorogold - FG or cholera toxin B subunit - CTB) labelling of PVN presympathetic neurons combined with immunohistochemistry for GABA and nNOS was used to identify the terminal neuronal targets of the ascending projection from the NTS. It was shown that NTS afferent terminals are apposed to either PVN-GABA interneurons or to nitric oxide producing neurons or even directly to presympathetic neurons. Furthermore, there was evidence that some NTS axons were positive for vesicular glutamate transporter 2 (vGLUT2). The data provide an anatomical basis for the different functions of cardiovascular receptors that mediate their actions via the NTS-PVN pathways.

  4. Neuronal diversity in GABAergic long-range projections from the hippocampus.

    Science.gov (United States)

    Jinno, Shozo; Klausberger, Thomas; Marton, Laszlo F; Dalezios, Yannis; Roberts, J David B; Fuentealba, Pablo; Bushong, Eric A; Henze, Darrell; Buzsáki, György; Somogyi, Peter

    2007-08-15

    The formation and recall of sensory, motor, and cognitive representations require coordinated fast communication among multiple cortical areas. Interareal projections are mainly mediated by glutamatergic pyramidal cell projections; only few long-range GABAergic connections have been reported. Using in vivo recording and labeling of single cells and retrograde axonal tracing, we demonstrate novel long-range GABAergic projection neurons in the rat hippocampus: (1) somatostatin- and predominantly mGluR1alpha-positive neurons in stratum oriens project to the subiculum, other cortical areas, and the medial septum; (2) neurons in stratum oriens, including somatostatin-negative ones; and (3) trilaminar cells project to the subiculum and/or other cortical areas but not the septum. These three populations strongly increase their firing during sharp wave-associated ripple oscillations, communicating this network state to the septotemporal system. Finally, a large population of somatostatin-negative GABAergic cells in stratum radiatum project to the molecular layers of the subiculum, presubiculum, retrosplenial cortex, and indusium griseum and fire rhythmically at high rates during theta oscillations but do not increase their firing during ripples. The GABAergic projection axons have a larger diameter and thicker myelin sheet than those of CA1 pyramidal cells. Therefore, rhythmic IPSCs are likely to precede the arrival of excitation in cortical areas (e.g., subiculum) that receive both glutamatergic and GABAergic projections from the CA1 area. Other areas, including the retrosplenial cortex, receive only rhythmic GABAergic CA1 input. We conclude that direct GABAergic projections from the hippocampus to other cortical areas and the septum contribute to coordinating oscillatory timing across structures.

  5. Parametric Anatomical Modeling: a method for modeling the anatomical layout of neurons and their projections.

    Science.gov (United States)

    Pyka, Martin; Klatt, Sebastian; Cheng, Sen

    2014-01-01

    Computational models of neural networks can be based on a variety of different parameters. These parameters include, for example, the 3d shape of neuron layers, the neurons' spatial projection patterns, spiking dynamics and neurotransmitter systems. While many well-developed approaches are available to model, for example, the spiking dynamics, there is a lack of approaches for modeling the anatomical layout of neurons and their projections. We present a new method, called Parametric Anatomical Modeling (PAM), to fill this gap. PAM can be used to derive network connectivities and conduction delays from anatomical data, such as the position and shape of the neuronal layers and the dendritic and axonal projection patterns. Within the PAM framework, several mapping techniques between layers can account for a large variety of connection properties between pre- and post-synaptic neuron layers. PAM is implemented as a Python tool and integrated in the 3d modeling software Blender. We demonstrate on a 3d model of the hippocampal formation how PAM can help reveal complex properties of the synaptic connectivity and conduction delays, properties that might be relevant to uncover the function of the hippocampus. Based on these analyses, two experimentally testable predictions arose: (i) the number of neurons and the spread of connections is heterogeneously distributed across the main anatomical axes, (ii) the distribution of connection lengths in CA3-CA1 differ qualitatively from those between DG-CA3 and CA3-CA3. Models created by PAM can also serve as an educational tool to visualize the 3d connectivity of brain regions. The low-dimensional, but yet biologically plausible, parameter space renders PAM suitable to analyse allometric and evolutionary factors in networks and to model the complexity of real networks with comparatively little effort.

  6. A divergent pattern of sensory axonal projections is rendered convergent by second-order neurons in the accessory olfactory bulb.

    Science.gov (United States)

    Del Punta, Karina; Puche, Adam; Adams, Niels C; Rodriguez, Ivan; Mombaerts, Peter

    2002-09-12

    The mammalian vomeronasal system is specialized in pheromone detection. The neural circuitry of the accessory olfactory bulb (AOB) provides an anatomical substrate for the coding of pheromone information. Here, we describe the axonal projection pattern of vomeronasal sensory neurons to the AOB and the dendritic connectivity pattern of second-order neurons. Genetically traced sensory neurons expressing a given gene of the V2R class of vomeronasal receptors project their axons to six to ten glomeruli distributed in globally conserved areas of the AOB, a theme similar to V1R-expressing neurons. Surprisingly, second-order neurons tend to project their dendrites to glomeruli innervated by axons of sensory neurons expressing the same V1R or the same V2R gene. Convergence of receptor type information in the olfactory bulb may represent a common design in olfactory systems.

  7. Projections of the nucleus of the basal optic root in pigeons (Columba livia): a comparison of the morphology and distribution of neurons with different efferent projections.

    Science.gov (United States)

    Wylie, Douglas R W; Pakan, Janelle M P; Elliott, Cameron A; Graham, David J; Iwaniuk, Andrew N

    2007-01-01

    The avian nucleus of the basal optic root (nBOR) is a visual structure involved in the optokinetic response. nBOR consists of several morphologically distinct cell types, and in the present study, we sought to determine if these different cell types had differential projections. Using retrograde tracers, we examined the morphology and distribution of nBOR neurons projecting to the vestibulocerebellum (VbC), inferior olive (IO), dorsal thalamus, the pretectal nucleus lentiformis mesencephali (LM), the contralateral nBOR, the oculomotor complex (OMC) and a group of structures along the midline of the mesencephalon. The retrogradely labeled neurons fell into two broad categories: large neurons, most of which were multipolar rather than fusiform and small neurons, which were either fusiform or multipolar. From injections into the IO, LM, contralateral nBOR, and structures along the midline-mesencephalon small nBOR neurons were labeled. Although there were no differences with respect to the size of the labeled neurons from these injections, there were some differences with the respect to the distribution of labeled neurons and the proportion of multipolar vs. fusiform neurons. From injections into the VbC, the large multipolar cells were labeled throughout nBOR. The only other cases in which these large neurons were labeled were contralateral OMC injections. To investigate if single neurons project to multiple targets we used paired injections of red and green fluorescent retrograde tracers into different targets. Double-labeled neurons were never observed indicating that nBOR neurons do not project to multiple targets. We conclude that individual nBOR neurons have unique projections, which may have differential roles in processing optic flow and controlling the optokinetic response.

  8. Cortical regulation of striatal projection neurons and interneurons in a Parkinson's disease rat model

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    Jia-jia Wu

    2016-01-01

    Full Text Available Striatal neurons can be either projection neurons or interneurons, with each type exhibiting distinct susceptibility to various types of brain damage. In this study, 6-hydroxydopamine was injected into the right medial forebrain bundle to induce dopamine depletion, and/or ibotenic acid was injected into the M1 cortex to induce motor cortex lesions. Immunohistochemistry and western blot assay showed that dopaminergic depletion results in significant loss of striatal projection neurons marked by dopamine- and cyclic adenosine monophosphate-regulated phosphoprotein, molecular weight 32 kDa, calbindin, and μ-opioid receptor, while cortical lesions reversed these pathological changes. After dopaminergic deletion, the number of neuropeptide Y-positive striatal interneurons markedly increased, which was also inhibited by cortical lesioning. No noticeable change in the number of parvalbumin-positive interneurons was found in 6-hydroxydopamine-treated rats. Striatal projection neurons and interneurons show different susceptibility to dopaminergic depletion. Further, cortical lesions inhibit striatal dysfunction and damage induced by 6-hydroxydopamine, which provides a new possibility for clinical treatment of Parkinson's disease.

  9. Variability in the distribution of callosal projection neurons in the adult rat parietal cortex.

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    Ivy, G O; Gould, H J; Killackey, H P

    1984-07-23

    Previous reports have shown that the barrel field area of the parietal cortex of the adult rat contains relatively few callosal projection neurons, even though callosal projection neurons are abundant in this cortical region in the neonatal rat. Furthermore, it has been shown that many of the callosal neurons which seem to disappear as the animal matures do not die, but project to ipsilateral cortical areas. These findings rely on the ability of retrograde transport techniques which utilize injections of horseradish peroxidase (HRP) or of fluorescent dyes into one hemisphere. We now show that several technical modifications of the HRP technique yield a wider distribution of HRP-containing neurons in the contralateral barrel field area of the adult rat than previously reported. These include implants of HRP pellets into transected axons of the corpus callosum, the addition of DMSO and nonidet P40 to Sigma VI HRP, wheat germ agglutinin HRP and the use of tetramethyl benzidine as the chromogen in the reaction procedure. Our findings have implications for transport studies in general and for the development of the cortical barrel field in particular.

  10. The Circuitry of Olfactory Projection Neurons in the Brain of the Honeybee, Apis mellifera

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    Zwaka, Hanna; Münch, Daniel; Manz, Gisela; Menzel, Randolf; Rybak, Jürgen

    2016-01-01

    In the honeybee brain, two prominent tracts – the medial and the lateral antennal lobe tract – project from the primary olfactory center, the antennal lobes (ALs), to the central brain, the mushroom bodies (MBs), and the protocerebral lobe (PL). Intracellularly stained uniglomerular projection neurons were reconstructed, registered to the 3D honeybee standard brain atlas, and then used to derive the spatial properties and quantitative morphology of the neurons of both tracts. We evaluated putative synaptic contacts of projection neurons (PNs) using confocal microscopy. Analysis of the patterns of axon terminals revealed a domain-like innervation within the MB lip neuropil. PNs of the lateral tract arborized more sparsely within the lips and exhibited fewer synaptic boutons, while medial tract neurons occupied broader regions in the MB calyces and the PL. Our data show that uPNs from the medial and lateral tract innervate both the core and the cortex of the ipsilateral MB lip but differ in their innervation patterns in these regions. In the mushroombody neuropil collar we found evidence for ALT boutons suggesting the collar as a multi modal input site including olfactory input similar to lip and basal ring. In addition, our data support the conclusion drawn in previous studies that reciprocal synapses exist between PNs, octopaminergic-, and GABAergic cells in the MB calyces. For the first time, we found evidence for connections between both tracts within the AL. PMID:27746723

  11. Expression of the M3 Muscarinic Receptor on Orexin Neurons that Project to the Rostral Ventrolateral Medulla.

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    Dai, Yu-Wen E; Lee, Yen-Hsien; Chen, Jennifer Y S; Lin, Yen-Kuang; Hwang, Ling-Ling

    2016-05-01

    Activation of central cholinergic receptors causes a pressor response in rats, and the hypothalamus is important for this response. Projections from hypothalamic orexin neurons to the rostral ventrolateral medulla (RVLM) are involved in sympatho-excitation of the cardiovascular system. A small population of orexin neurons is regulated by cholinergic inputs through M3 muscarinic acetylcholine receptor (M3 R). To elucidate whether the M3 R on orexin neurons is involved in cardiosympathetic regulation through the RVLM, we examined the presence of the M3 R on retrograde-labeled RVLM-projecting orexin neurons. The retrograde tracer was unilaterally injected into the RVLM. Within the hypothalamus, retrograde-labeled neurons were located predominantly ipsilateral to the injection side. In the anterior hypothalamus (-1.5 to -2.3 mm to the bregma), retrograde-labeled neurons were densely distributed in the paraventricular nuclei and scattered in the retrochiasmatic area. At -2.3 to -3.5 mm from the bregma, labeled neurons were located in the regions where orexin neurons were situated, that is, the tuberal lateral hypothalamic area, perifornical area, and dorsomedial nuclei. Very few retrograde-labeled neurons were observed in the hypothalamus at -3.5 to -4.5 mm from the bregma. About 19.5% ± 1.6% of RVLM-projecting neurons in the tuberal hypothalamus were orexinergic. The M3 R was present on 18.7% ± 3.0% of RVLM-projecting orexin neurons. Injection of a muscarinic agonist, oxotremorine, in the perifornical area resulted in a pressor response, which was attenuated by a pretreatment of atropine. We conclude that cholinergic inputs to orexin neurons may be involved in cardiosympathetic regulation through the M3 R on the orexin neurons that directly project to the RVLM.

  12. Morphology, classification, and distribution of the projection neurons in the dorsal lateral geniculate nucleus of the rat.

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    Changying Ling

    Full Text Available The morphology of confirmed projection neurons in the dorsal lateral geniculate nucleus (dLGN of the rat was examined by filling these cells retrogradely with biotinylated dextran amine (BDA injected into the visual cortex. BDA-labeled projection neurons varied widely in the shape and size of their cell somas, with mean cross-sectional areas ranging from 60-340 µm(2. Labeled projection neurons supported 7-55 dendrites that spanned up to 300 µm in length and formed dendritic arbors with cross-sectional areas of up to 7.0 × 10(4 µm(2. Primary dendrites emerged from cell somas in three broad patterns. In some dLGN projection neurons, primary dendrites arise from the cell soma at two poles spaced approximately 180° apart. In other projection neurons, dendrites emerge principally from one side of the cell soma, while in a third group of projection neurons primary dendrites emerge from the entire perimeter of the cell soma. Based on these three distinct patterns in the distribution of primary dendrites from cell somas, we have grouped dLGN projection neurons into three classes: bipolar cells, basket cells and radial cells, respectively. The appendages seen on dendrites also can be grouped into three classes according to differences in their structure. Short "tufted" appendages arise mainly from the distal branches of dendrites; "spine-like" appendages, fine stalks with ovoid heads, typically are seen along the middle segments of dendrites; and "grape-like" appendages, short stalks that terminate in a cluster of ovoid bulbs, appear most often along the proximal segments of secondary dendrites of neurons with medium or large cell somas. While morphologically diverse dLGN projection neurons are intermingled uniformly throughout the nucleus, the caudal pole of the dLGN contains more small projection neurons of all classes than the rostral pole.

  13. Mutual regulation between Satb2 and Fezf2 promotes subcerebral projection neuron identity in the developing cerebral cortex.

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    McKenna, William L; Ortiz-Londono, Christian F; Mathew, Thomas K; Hoang, Kendy; Katzman, Sol; Chen, Bin

    2015-09-15

    Generation of distinct cortical projection neuron subtypes during development relies in part on repression of alternative neuron identities. It was reported that the special AT-rich sequence-binding protein 2 (Satb2) is required for proper development of callosal neuron identity and represses expression of genes that are essential for subcerebral axon development. Surprisingly, Satb2 has recently been shown to be necessary for subcerebral axon development. Here, we unravel a previously unidentified mechanism underlying this paradox. We show that SATB2 directly activates transcription of forebrain embryonic zinc finger 2 (Fezf2) and SRY-box 5 (Sox5), genes essential for subcerebral neuron development. We find that the mutual regulation between Satb2 and Fezf2 enables Satb2 to promote subcerebral neuron identity in layer 5 neurons, and to repress subcerebral characters in callosal neurons. Thus, Satb2 promotes the development of callosal and subcerebral neurons in a cell context-dependent manner.

  14. Deletion of Nampt in Projection Neurons of Adult Mice Leads to Motor Dysfunction, Neurodegeneration, and Death

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    Xiaowan Wang

    2017-08-01

    Full Text Available Intracellular nicotinamide phosphoribosyltransferase (iNAMPT is the rate-limiting enzyme of the mammalian NAD+ biosynthesis salvage pathway. Using inducible and conditional knockout (cKO mice, we show that Nampt gene deletion in adult projection neurons leads to a progressive loss of body weight, hypothermia, motor neuron (MN degeneration, motor function deficits, paralysis, and death. Nampt deletion causes mitochondrial dysfunction, muscle fiber type conversion, and atrophy, as well as defective synaptic function at neuromuscular junctions (NMJs. When treated with nicotinamide mononucleotide (NMN, Nampt cKO mice exhibit reduced motor function deficits and prolonged lifespan. iNAMPT protein levels are significantly reduced in the spinal cord of amyotrophic lateral sclerosis (ALS patients, indicating the involvement of NAMPT in ALS pathology. Our findings reveal that neuronal NAMPT plays an essential role in mitochondrial bioenergetics, motor function, and survival. Our study suggests that the NAMPT-mediated NAD+ biosynthesis pathway is a potential therapeutic target for degenerative MN diseases.

  15. Computer-Aided Mapping of Vasopressin Neurons in the Hypothalamus of the Male Golden Hamster: Evidence of Magnocellular Neurons that do not Project to the Neurohypophysis.

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    Mahoney, P D; Koh, E T; Irvin, R W; Ferris, C F

    1990-04-01

    Abstract Vasopressin-sensitive neurons in the region of the anterior hypothalamus are necessary for the mediation of flank marking behavior in the Golden hamster. The precise nature of the vasopressinergic innervation to the anterior hypothalamus is unknown. In this study we seek to examine the potential sources of this innervation by mapping and counting the vasopressin-immunoreactive neurons that contribute to the hypothalamo-neurohypophysial system, and those that do not. Vasopressin-immunoreactive neurons in the hypothalamus were visualized by immunocytochemistry. Sections were mapped with a computer-aided microscope system, and labeled neurons counted. Two-dimensional maps were stacked into a three-dimensional wireframe model which could be manipulated for further examination. The average number of vasopressin neurons was 3,135, with over 60% of all perikarya localized to the lateral supraoptic nucleus. In a double-labeling study, neurons contributing to the hypothalamo-neurohypophysial system were retrogradely labeled by the injection of horseradish peroxidase into the neurohypophysis. The enzyme reaction product was visualized by treatment with tetramethylbenzidine followed by nickel-conjugated diaminobenzidine. Sections were subsequently stained for vasopressin by immunocytochemistry. Single- and double-stained neurons from serial sections were mapped and counted. Wireframe and contoured three-dimensional representations were generated. The average number of neurons projecting to the neurohypophysis was 5,619. However, an average of 981 neurons was immunoreactive to vasopressin but devoid of horseradish peroxidase. The greatest number of these non-projecting perikarya were found in and around the anterior hypothalamus, localized primarily in the lateral and medial aspect of the supraoptic nuclei, the ventral area of the paraventricular nucleus, and the nucleus circularis. By comparing the number of non-projecting neurons found by double-staining to the

  16. Hypothalamic Vasopressinergic Projections Innervate Central Amygdala GABAergic Neurons: Implications for Anxiety and Stress Coping

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    Hernández, Vito S.; Hernández, Oscar R.; Perez de la Mora, Miguel; Gómora, María J.; Fuxe, Kjell; Eiden, Lee E.; Zhang, Limei

    2016-01-01

    The arginine-vasopressin (AVP)-containing hypothalamic magnocellular neurosecretory neurons (VPMNNs) are known for their role in hydro-electrolytic balance control via their projections to the neurohypophysis. Recently, projections from these same neurons to hippocampus, habenula and other brain regions in which vasopressin infusion modulates contingent social and emotionally-affected behaviors, have been reported. Here, we present evidence that VPMNN collaterals also project to the amygdaloid complex, and establish synaptic connections with neurons in central amygdala (CeA). The density of AVP innervation in amygdala was substantially increased in adult rats that had experienced neonatal maternal separation (MS), consistent with our previous observations that MS enhances VPMNN number in the paraventricular (PVN) and supraoptic (SON) nuclei of the hypothalamus. In the CeA, V1a AVP receptor mRNA was only observed in GABAergic neurons, demonstrated by complete co-localization of V1a transcripts in neurons expressing Gad1 and Gad2 transcripts in CeA using the RNAscope method. V1b and V2 receptor mRNAs were not detected, using the same method. Water-deprivation (WD) for 24 h, which increased the metabolic activity of VPMNNs, also increased anxiety-like behavior measured using the elevated plus maze (EPM) test, and this effect was mimicked by bilateral microinfusion of AVP into the CeA. Anxious behavior induced by either WD or AVP infusion was reversed by CeA infusion of V1a antagonist. VPMNNs are thus a newly discovered source of CeA inhibitory circuit modulation, through which both early-life and adult stress coping signals are conveyed from the hypothalamus to the amygdala. PMID:27932956

  17. Hypothalamic vasopressinergic projections innervate central amygdala GABAergic neurons: implications for anxiety and stress coping

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    Vito Salvador Hernandez

    2016-11-01

    Full Text Available The arginine-vasopressin (AVP-containing hypothalamic magnocellular neurosecretory neurons (VPMNNs are known for their role in hydro-electrolytic balance control via their projections to neurohypophysis. Recently, projections from these same neurons to hippocampus, habenula, and other brain regions, in which vasopressin infusion modulates contingent social and emotionally-affected behaviors, have been reported. Here, we present evidence that VPMNN collaterals also project to the amygdaloid complex, and establish synaptic connections with neurons in central amygdala (CeA. The density of AVP innervation in amygdala was substantially increased in adult rats that had experienced neonatal maternal separation (MS, consistent with our previous observations that MS enhances VPMNN number in the paraventricular (PVN and supraoptic (SON nuclei of the hypothalamus. In the CeA, V1a AVP receptor mRNA was only observed in GABAergic neurons, demonstrated by complete co-localization of V1a transcripts in neurons expressing Gad1 and Gad2 transcripts in CeA using the RNAscope method. V1b and V2 receptors mRNA were not detected, using the same method. Water-deprivation for 24 hrs, which increased the metabolic activity of VPMNNs, also increased anxiety-like behavior measured using the elevated plus maze test, and this effect was mimicked by bilateral microinfusion of VP into the CeA. Anxious behavior induced by either water deprivation or VP infusion was reversed by CeA infusion of V1a antagonist. VPMNNs are thus a newly discovered source of central amygdala inhibitory circuit modulation, through which both early-life and adult stress coping signals are conveyed from the hypothalamus to the amygdala.

  18. Visualization of cortical projection neurons with retrograde TET-off lentiviral vector.

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    Akiya Watakabe

    Full Text Available We are interested in identifying and characterizing various projection neurons that constitute the neocortical circuit. For this purpose, we developed a novel lentiviral vector that carries the tetracycline transactivator (tTA and the transgene under the TET Responsive Element promoter (TRE on a single backbone. By pseudotyping such a vector with modified rabies G-protein, we were able to express palmitoylated-GFP (palGFP or turboFP635 (RFP in corticothalamic, corticocortical, and corticopontine neurons of mice. The high-level expression of the transgene achieved by the TET-Off system enabled us to observe characteristic elaboration of neuronal processes for each cell type. At higher magnification, we were able to observe fine structures such as boutons and spines as well. We also injected our retrograde TET-Off vector to the marmoset cortex and proved that it can be used to label the long-distance cortical connectivity of millimeter scale. In conclusion, our novel retrograde tracer provides an attractive option to investigate the morphologies of identified cortical projection neurons of various species.

  19. Molecular adaptations of striatal spiny projection neurons during levodopa-induced dyskinesia

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    Heiman, Myriam; Heilbut, Adrian; Francardo, Veronica; Kulicke, Ruth; Fenster, Robert J.; Kolaczyk, Eric D.; Mesirov, Jill P.; Surmeier, Dalton J.; Cenci, M. Angela; Greengard, Paul

    2014-01-01

    Levodopa treatment is the major pharmacotherapy for Parkinson's disease. However, almost all patients receiving levodopa eventually develop debilitating involuntary movements (dyskinesia). Although it is known that striatal spiny projection neurons (SPNs) are involved in the genesis of this movement disorder, the molecular basis of dyskinesia is not understood. In this study, we identify distinct cell-type–specific gene-expression changes that occur in subclasses of SPNs upon induction of a parkinsonian lesion followed by chronic levodopa treatment. We identify several hundred genes, the expression of which is correlated with levodopa dose, many of which are under the control of activator protein-1 and ERK signaling. Despite homeostatic adaptations involving several signaling modulators, activator protein-1–dependent gene expression remains highly dysregulated in direct pathway SPNs upon chronic levodopa treatment. We also discuss which molecular pathways are most likely to dampen abnormal dopaminoceptive signaling in spiny projection neurons, hence providing potential targets for antidyskinetic treatments in Parkinson's disease. PMID:24599591

  20. Genetic identity of thermosensory relay neurons in the lateral parabrachial nucleus.

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    Geerling, Joel C; Kim, Minjee; Mahoney, Carrie E; Abbott, Stephen B G; Agostinelli, Lindsay J; Garfield, Alastair S; Krashes, Michael J; Lowell, Bradford B; Scammell, Thomas E

    2016-01-01

    The parabrachial nucleus is important for thermoregulation because it relays skin temperature information from the spinal cord to the hypothalamus. Prior work in rats localized thermosensory relay neurons to its lateral subdivision (LPB), but the genetic and neurochemical identity of these neurons remains unknown. To determine the identity of LPB thermosensory neurons, we exposed mice to a warm (36°C) or cool (4°C) ambient temperature. Each condition activated neurons in distinct LPB subregions that receive input from the spinal cord. Most c-Fos+ neurons in these LPB subregions expressed the transcription factor marker FoxP2. Consistent with prior evidence that LPB thermosensory relay neurons are glutamatergic, all FoxP2+ neurons in these subregions colocalized with green fluorescent protein (GFP) in reporter mice for Vglut2, but not for Vgat. Prodynorphin (Pdyn)-expressing neurons were identified using a GFP reporter mouse and formed a caudal subset of LPB FoxP2+ neurons, primarily in the dorsal lateral subnucleus (PBdL). Warm exposure activated many FoxP2+ neurons within PBdL. Half of the c-Fos+ neurons in PBdL were Pdyn+, and most of these project into the preoptic area. Cool exposure activated a separate FoxP2+ cluster of neurons in the far-rostral LPB, which we named the rostral-to-external lateral subnucleus (PBreL). These findings improve our understanding of LPB organization and reveal that Pdyn-IRES-Cre mice provide genetic access to warm-activated, FoxP2+ glutamatergic neurons in PBdL, many of which project to the hypothalamus.

  1. Neurochemical, morphologic, and laminar characterization of cortical projection neurons in the cingulate motor areas of the macaque monkey

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    Nimchinsky, E. A.; Hof, P. R.; Young, W. G.; Morrison, J. H.; Bloom, F. E. (Principal Investigator)

    1996-01-01

    The primate cingulate gyrus contains multiple cortical areas that can be distinguished by several neurochemical features, including the distribution of neurofilament protein-enriched pyramidal neurons. In addition, connectivity and functional properties indicate that there are multiple motor areas in the cortex lining the cingulate sulcus. These motor areas were targeted for analysis of potential interactions among regional specialization, connectivity, and cellular characteristics such as neurochemical profile and morphology. Specifically, intracortical injections of retrogradely transported dyes and intracellular injection were combined with immunocytochemistry to investigate neurons projecting from the cingulate motor areas to the putative forelimb region of the primary motor cortex, area M1. Two separate groups of neurons projecting to area M1 emanated from the cingulate sulcus, one anterior and one posterior, both of which furnished commissural and ipsilateral connections with area M1. The primary difference between the two populations was laminar origin, with the anterior projection originating largely in deep layers, and the posterior projection taking origin equally in superficial and deep layers. With regard to cellular morphology, the anterior projection exhibited more morphologic diversity than the posterior projection. Commissural projections from both anterior and posterior fields originated largely in layer VI. Neurofilament protein distribution was a reliable tool for localizing the two projections and for discriminating between them. Comparable proportions of the two sets of projection neurons contained neurofilament protein, although the density and distribution of the total population of neurofilament protein-enriched neurons was very different in the two subareas of origin. Within a projection, the participating neurons exhibited a high degree of morphologic heterogeneity, and no correlation was observed between somatodendritic morphology and

  2. Divergent projections of catecholaminergic neurons in the nucleus of the solitary tract to limbic forebrain and medullary autonomic brain regions.

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    Reyes, Beverly A S; Van Bockstaele, Elisabeth J

    2006-10-30

    The nucleus of the solitary tract (NTS) is a critical structure involved in coordinating autonomic and visceral activities. Previous independent studies have demonstrated efferent projections from the NTS to the nucleus paragigantocellularis (PGi) and the central nucleus of the amygdala (CNA) in rat brain. To further characterize the neural circuitry originating from the NTS with postsynaptic targets in the amygdala and medullary autonomic targets, distinct green or red fluorescent latex microspheres were injected into the PGi and the CNA, respectively, of the same rat. Thirty-micron thick tissue sections through the lower brainstem and forebrain were collected. Every fourth section through the NTS region was processed for immunocytochemical detection of tyrosine hydroxylase (TH), a marker of catecholaminergic neurons. Retrogradely labeled neurons from the PGi or CNA were distributed throughout the rostro-caudal segments of the NTS. However, the majority of neurons containing both retrograde tracers were distributed within the caudal third of the NTS. Cell counts revealed that approximately 27% of neurons projecting to the CNA in the NTS sent collateralized projections to the PGi while approximately 16% of neurons projecting to the PGi sent collateralized projections to the CNA. Interestingly, more than half of the PGi and CNA-projecting neurons in the NTS expressed TH immunoreactivity. These data indicate that catecholaminergic neurons in the NTS are poised to simultaneously coordinate activities in limbic and medullary autonomic brain regions.

  3. Glycine immunoreactivity of multipolar neurons in the ventral cochlear nucleus which project to the dorsal cochlear nucleus.

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    Doucet, J R; Ross, A T; Gillespie, M B; Ryugo, D K

    1999-06-14

    Certain distinct populations of neurons in the dorsal cochlear nucleus are inhibited by a neural source that is responsive to a wide range of acoustic frequencies. In this study, we examined the glycine immunoreactivity of two types of ventral cochlear nucleus neurons (planar and radiate) in the rat which project to the dorsal cochlear nucleus (DCN) and thus, might be responsible for this inhibition. Previously, we proposed that planar neurons provided a tonotopic and narrowly tuned input to the DCN, whereas radiate neurons provided a broadly tuned input and thus, were strong candidates as the source of broadband inhibition (Doucet and Ryugo [1997] J. Comp. Neurol. 385:245-264). We tested this idea by combining retrograde labeling and glycine immunohistochemical protocols. Planar and radiate neurons were first retrogradely labeled by injecting biotinylated dextran amine into a restricted region of the dorsal cochlear nucleus. The labeled cells were visualized using streptavidin conjugated to indocarbocyanine (Cy3), a fluorescent marker. Sections that contained planar or radiate neurons were then processed for glycine immunocytochemistry using diaminobenzidine as the chromogen. Immunostaining of planar neurons was light, comparable to that of excitatory neurons (pyramidal neurons in the DCN), whereas immunostaining of radiate neurons was dark, comparable to that of glycinergic neurons (cartwheel cells in the dorsal cochlear nucleus and principal cells in the medial nucleus of the trapezoid body). These results are consistent with the hypothesis that radiate neurons in the ventral cochlear nucleus subserve the wideband inhibition observed in the dorsal cochlear nucleus.

  4. Excitatory projections from the amygdala to neurons in the nucleus pontis oralis in the rat: an intracellular study.

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    Xi, M; Fung, S J; Sampogna, S; Chase, M H

    2011-12-01

    There is a consensus that active (REM) sleep (AS) is controlled by cholinergic projections from the laterodorsal and pedunculopontine tegmental nuclei (LDT/PPT) to neurons in the nucleus pontis oralis (NPO) that generate AS (i.e. AS-Generator neurons). The present study was designed to provide evidence that other projections to the NPO, such as those from the amygdala, are also capable of inducing AS. Accordingly, the responses of neurons, recorded intracellularly in the NPO, were examined following stimulation of the ipsilateral central nucleus of the amygdala (CNA) in urethane-anesthetized rats. Single pulse stimulation in the CNA produced an early, fast depolarizing potential (EPSP) in neurons within the NPO. The mean latency to the onset of these excitatory postsynaptic potentials (EPSPs) was 3.6±0.2 ms. A late, small-amplitude inhibitory synaptic potential (IPSP) was present following EPSPs in a portion of the NPO neurons. Following stimulation of the CNA with a train of 8-10 pulses, NPO neurons exhibited a sustained depolarization (5-10 mV) of their resting membrane potential. When single subthreshold intracellular depolarizing current pulses were delivered to NPO neurons, CNA-induced EPSPs were sufficient to promote the discharge of these cells. Stimulation of the CNA with a short train of stimuli induced potent temporal facilitation of EPSPs in NPO neurons. Two forms of synaptic plasticity were revealed by the patterns of response of NPO neurons following stimulation of the CNA: paired-pulse facilitation (PPF) and post-tetanic potentiation (PTP). Six of recorded NPO neurons were identified morphologically with neurobiotin. They were medium to large, multipolar cells with diameters >20 μM, which resemble AS-on cells in the NPO. The present results demonstrate that amygdalar projections are capable of exerting a powerful excitatory postsynaptic drive that activates NPO neurons. Therefore, we suggest that the amygdala is capable of inducing AS via direct

  5. Expression of PGE2 EP3 receptor subtypes in the mouse preoptic region.

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    Vasilache, Ana Maria; Andersson, Josefin; Nilsberth, Camilla

    2007-08-23

    Inflammatory-induced fever is dependent on prostaglandin E(2) (PGE(2)) binding to its EP(3) receptor in the thermoregulatory region of the hypothalamus, but it is not known which EP(3) receptor isoform(s) that is/are involved. We identified the EP(3) receptor expression in the mouse preoptic region by in situ hybridization and isolated the corresponding area by laser capture microdissection. Real-time RT-PCR analysis of microdissected tissue revealed a predominant expression of the EP(3alpha) isoform, but there was also considerable expression of EP(3gamma), corresponding to approximately 15% of total EP(3) receptor expression, whereas EP(3beta) was sparsely expressed. This distribution was not changed by immune challenge induced by peripheral administration of LPS, indicating that EP(3) receptor splicing and distribution is not activity dependent. Considering that EP(3alpha) and EP(3gamma) are associated with inhibitory and stimulatory G-proteins, respectively, the present data demonstrate that the PGE(2) response of the target neurons is intricately regulated.

  6. Characteristics of rostral solitary tract nucleus neurons with identified afferent connections that project to the parabrachial nucleus in rats.

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    Suwabe, Takeshi; Bradley, Robert M

    2009-07-01

    Afferent information derived from oral chemoreceptors is transmitted to second-order neurons in the rostral solitary tract nucleus (rNST) and then relayed to other CNS locations responsible for complex sensory and motor behaviors. Here we investigate the characteristics of rNST neurons sending information rostrally to the parabrachial nucleus (PBN). Afferent connections to these rNST-PBN projection neurons were identified by anterograde labeling of the chorda tympani (CT), glossopharyngeal (IX), and lingual (LV) nerves. We used voltage- and current-clamp recordings in brain slices to characterize the expression of both the transient A-type potassium current, IKA and the hyperpolarization-activated inward current, Ih, important determinants of neuronal repetitive discharge characteristics. The majority of rNST-PBN neurons express IKA, and these IKA-expressing neurons predominate in CT and IX terminal fields but were expressed in approximately half of the neurons in the LV field. rNST-PBN neurons expressing Ih were evenly distributed among CT, IX and LV terminal fields. However, expression patterns of IKA and Ih differed among CT, IX, and LV fields. IKA-expressing neurons frequently coexpress Ih in CT and IX terminal fields, whereas neurons in LV terminal field often express only Ih. After GABAA receptor block all rNST-PBN neurons responded to afferent stimulation with all-or-none excitatory synaptic responses. rNST-PBN neurons had either multipolar or elongate morphologies and were distributed throughout the rNST, but multipolar neurons were more often encountered in CT and IX terminal fields. No correlation was found between the biophysical and morphological characteristics of the rNST-PBN projection neurons in each terminal field.

  7. Whole-brain mapping of inputs to projection neurons and cholinergic interneurons in the dorsal striatum.

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    Guo, Qingchun; Wang, Daqing; He, Xiaobin; Feng, Qiru; Lin, Rui; Xu, Fuqiang; Fu, Ling; Luo, Minmin

    2015-01-01

    The dorsal striatum integrates inputs from multiple brain areas to coordinate voluntary movements, associative plasticity, and reinforcement learning. Its projection neurons consist of the GABAergic medium spiny neurons (MSNs) that express dopamine receptor type 1 (D1) or dopamine receptor type 2 (D2). Cholinergic interneurons account for a small portion of striatal neuron populations, but they play important roles in striatal functions by synapsing onto the MSNs and other local interneurons. By combining the modified rabies virus with specific Cre- mouse lines, a recent study mapped the monosynaptic input patterns to MSNs. Because only a small number of extrastriatal neurons were labeled in the prior study, it is important to reexamine the input patterns of MSNs with higher labeling efficiency. Additionally, the whole-brain innervation pattern of cholinergic interneurons remains unknown. Using the rabies virus-based transsynaptic tracing method in this study, we comprehensively charted the brain areas that provide direct inputs to D1-MSNs, D2-MSNs, and cholinergic interneurons in the dorsal striatum. We found that both types of projection neurons and the cholinergic interneurons receive extensive inputs from discrete brain areas in the cortex, thalamus, amygdala, and other subcortical areas, several of which were not reported in the previous study. The MSNs and cholinergic interneurons share largely common inputs from areas outside the striatum. However, innervations within the dorsal striatum represent a significantly larger proportion of total inputs for cholinergic interneurons than for the MSNs. The comprehensive maps of direct inputs to striatal MSNs and cholinergic interneurons shall assist future functional dissection of the striatal circuits.

  8. Neurochemical properties of BDNF-containing neurons projecting to rostral ventromedial medulla in the ventrolateral periaqueductal gray

    Directory of Open Access Journals (Sweden)

    Jun-Bin eYin

    2014-11-01

    Full Text Available The periaqueductal gray (PAG modulates nociception via a descending pathway that relays in the rostral ventromedial medulla (RVM and terminates in the spinal cord. Previous behavioral pharmacology and electrophysiological evidence suggests that brain-derived neurotrophic factor (BDNF plays an important role in descending pain modulation, likely through the PAG-RVM pathway. However, there still lacks detailed information on the distribution of BDNF, activation of BDNF-containing neurons projecting to RVM in the condition of pain, and neurochemical properties of these neurons within the PAG. Through fluorescent in situ hybridization (FISH and immunofluorescent staining, the homogenous distributions of BDNF mRNA and protein were observed in the four subregions of PAG. Both neurons and astrocytes expressed BDNF, but not microglias. By combining retrograde tracing methods and formalin pain model, there were more BDNF-containing neurons projecting to RVM being activated in the ventrolateral PAG (vlPAG than other subregions of PAG. The neurochemical properties of BDNF-containing projection neurons in the vlPAG were investigated. BDNF-containing projection neurons expressed auto receptor Tropomyosin-related kinase B (TrkB in addition to serotonin (5-HT, neurotensin (NT, substance P (SP, calcitonin gene related peptide (CGRP, nitric oxide synthase (NOS, and parvalbumin (PV but not tyrosine decarboxylase (TH. It is speculated that BDNF released from projection neurons in the vlPAG might participate in the descending pain modulation through enhancing the presynaptic release of other neuroactive substances (NSs in the RVM.

  9. Neurofilament protein is differentially distributed in subpopulations of corticocortical projection neurons in the macaque monkey visual pathways

    Science.gov (United States)

    Hof, P. R.; Ungerleider, L. G.; Webster, M. J.; Gattass, R.; Adams, M. M.; Sailstad, C. A.; Morrison, J. H.; Bloom, F. E. (Principal Investigator)

    1996-01-01

    Previous studies of the primate cerebral cortex have shown that neurofilament protein is present in pyramidal neuron subpopulations displaying specific regional and laminar distribution patterns. In order to characterize further the neurochemical phenotype of the neurons furnishing feedforward and feedback pathways in the visual cortex of the macaque monkey, we performed an analysis of the distribution of neurofilament protein in corticocortical projection neurons in areas V1, V2, V3, V3A, V4, and MT. Injections of the retrogradely transported dyes Fast Blue and Diamidino Yellow were placed within areas V4 and MT, or in areas V1 and V2, in 14 adult rhesus monkeys, and the brains of these animals were processed for immunohistochemistry with an antibody to nonphosphorylated epitopes of the medium and heavy molecular weight subunits of the neurofilament protein. Overall, there was a higher proportion of neurons projecting from areas V1, V2, V3, and V3A to area MT that were neurofilament protein-immunoreactive (57-100%), than to area V4 (25-36%). In contrast, feedback projections from areas MT, V4, and V3 exhibited a more consistent proportion of neurofilament protein-containing neurons (70-80%), regardless of their target areas (V1 or V2). In addition, the vast majority of feedback neurons projecting to areas V1 and V2 were located in layers V and VI in areas V4 and MT, while they were observed in both supragranular and infragranular layers in area V3. The laminar distribution of feedforward projecting neurons was heterogeneous. In area V1, Meynert and layer IVB cells were found to project to area MT, while neurons projecting to area V4 were particularly dense in layer III within the foveal representation. In area V2, almost all neurons projecting to areas MT or V4 were located in layer III, whereas they were found in both layers II-III and V-VI in areas V3 and V3A. These results suggest that neurofilament protein identifies particular subpopulations of

  10. Morphological characterization of spinal cord dorsal horn lamina I neurons projecting to the parabrachial nucleus in the rat.

    Science.gov (United States)

    Almarestani, L; Waters, S M; Krause, J E; Bennett, G J; Ribeiro-da-Silva, A

    2007-09-20

    Many Rexed's lamina I neurons are nociceptive and project to the brain. Lamina I projection neurons can be classified as multipolar, fusiform, or pyramidal, based on cell body shape and characteristics of their proximal dendrites in the horizontal plane. There is also evidence that both multipolar and fusiform cells are nociceptive and pyramidal neurons nonnociceptive. In this investigation we identified which types of lamina I neurons belong to the spinoparabrachial tract in the rat and characterized them regarding the presence or absence of neurokinin-1 receptor (NK-1r) immunoreactivity. For this, cholera toxin subunit B (CTb), conjugated to a fluorescent marker was injected unilaterally into the parabrachial nucleus. Sections were additionally stained for the detection of NK-1r immunoreactivity and were examined using fluorescence and confocal microscopy. Serial confocal optical sections and 3D reconstructions were obtained for a considerable number of neurons per animal. Using immunofluorescence, we assessed the proportion of lamina I neurons belonging to the spinoparabrachial (SPB) tract and/or expressing NK-1r. The relative distribution of neurons belonging to the SPB tract was: 38.7% multipolar, 36.8% fusiform, 22.7% pyramidal, and 1.9% unclassified. Most of the SPB neurons expressing NK-1r were either multipolar or fusiform. Pyramidal SPB neurons were seldom immunoreactive for NK-1r, an observation that provides further support to the concept that most lamina I projection neurons of the pyramidal type are nonnociceptive. In addition, our study provides further evidence that these distinct morphological types of neurons differ in their phenotypic properties, but not in their projection patterns.

  11. Projections of specific morphological types of neurons within the myenteric plexus of the small intestine of the guinea-pig.

    Science.gov (United States)

    Song, Z M; Brookes, S J; Costa, M

    1996-07-01

    The projections of myenteric neurons within the myenteric plexus of the guinea-pig small intestine were established using retrograde tracing in organotypic culture. Three days after applying the fluorescent dye DiI to a single internodal strand in the myenteric plexus, 500-1000 nerve cell bodies were labelled. Of these, 77% were located oral to the application site, 15% were located anally and 7% were located within 1 mm of this site. Three major morphological types of neurons could be distinguished. Dogiel type I neurons had lamellar dendrites and single axons, Dogiel type II neurons had large smooth cell bodies and several long processes, and filamentous neurons had smooth ovoid cell bodies, single axons and several filamentous dendrites. Dogiel type I, II and filamentous neurons accounted for 54.6%, 38% and 7.4% of all filled cells, respectively. Labelled nerve cell bodies were present up to 13 mm aboral to the DiI application site; all neurons more than 2 mm aboral had Dogiel type I features. On the oral side, Dogiel type I neurons were found up to 110 mm, Dogiel type II neurons up to 100 mm and filamentous neurons up to 80 mm. Neurons with 2 mm oral or aboral to the DiI application site were located up to 7 mm circumferentially and were mainly Dogiel type II cells. This work revealed remarkable polarity within the myenteric plexus, with a significant prevalence of myenteric neurons projecting anally for longer distances than those projecting orally. These long pathways are probably involved in the coordination of intestinal motility.

  12. TReMAP: Automatic 3D Neuron Reconstruction Based on Tracing, Reverse Mapping and Assembling of 2D Projections.

    Science.gov (United States)

    Zhou, Zhi; Liu, Xiaoxiao; Long, Brian; Peng, Hanchuan

    2016-01-01

    Efficient and accurate digital reconstruction of neurons from large-scale 3D microscopic images remains a challenge in neuroscience. We propose a new automatic 3D neuron reconstruction algorithm, TReMAP, which utilizes 3D Virtual Finger (a reverse-mapping technique) to detect 3D neuron structures based on tracing results on 2D projection planes. Our fully automatic tracing strategy achieves close performance with the state-of-the-art neuron tracing algorithms, with the crucial advantage of efficient computation (much less memory consumption and parallel computation) for large-scale images.

  13. GABAergic inputs from direct and indirect striatal projection neurons onto cholinergic interneurons in the primate putamen.

    Science.gov (United States)

    Gonzales, Kalynda Kari; Pare, Jean-Francois; Wichmann, Thomas; Smith, Yoland

    2013-08-01

    Striatal cholinergic interneurons (ChIs) are involved in reward-dependent learning and the regulation of attention. The activity of these neurons is modulated by intrinsic and extrinsic γ-aminobutyric acid (GABA)ergic and glutamatergic afferents, but the source and relative prevalence of these diverse regulatory inputs remain to be characterized. To address this issue, we performed a quantitative ultrastructural analysis of the GABAergic and glutamatergic innervation of ChIs in the postcommissural putamen of rhesus monkeys. Postembedding immunogold localization of GABA combined with peroxidase immunostaining for choline acetyltransferase showed that 60% of all synaptic inputs to ChIs originate from GABAergic terminals, whereas 21% are from putatively glutamatergic terminals that establish asymmetric synapses, and 19% from other (non-GABAergic) sources of symmetric synapses. Double pre-embedding immunoelectron microscopy using substance P and Met-/Leu-enkephalin antibodies to label GABAergic terminals from collaterals of "direct" and "indirect" striatal projection neurons, respectively, revealed that 47% of the indirect pathway terminals and 36% of the direct pathway terminals target ChIs. Together, substance P- and enkephalin-positive terminals represent 24% of all synapses onto ChIs in the monkey putamen. These findings show that ChIs receive prominent GABAergic inputs from multiple origins, including a significant contingent from axon collaterals of direct and indirect pathway projection neurons. Copyright © 2013 Wiley Periodicals, Inc.

  14. Neonatal handling reduces the number of cells in the medial preoptic area of female rats.

    Science.gov (United States)

    Camozzato, Tatiane S C; Winkelmann-Duarte, Elisa C; Padilha, Camila B; Miguel, Sandro P R; Bonzanini, Laisa; Anselmo-Franci, Janete A; Fernandes, Marilda C; Lucion, Aldo B

    2009-01-09

    Early-life events may induce alterations in neuronal function in adulthood. A crucial aspect in studying long-lasting effects induced by environmental interventions imposed to the animal several weeks before is finding a stable change that could be causally related to the phenotype observed in adulthood. In order to explain an adult trait, it seems necessary to look back to early life and establish a temporal line between events. The neonatal handling procedure is an experimental tool to analyze the long-lasting impact of early-life events. Aside from the neuroendocrine response to stress, neonatal handling also alters the functionality of the hypothalamus-pituitary-gonad (HPG) axis. Reductions in ovulation and surge of the luteinizing hormone (LH) on the proestrous day were shown in female rats. Considering the importance of the medial preoptic area (MPA) for the control of ovulation, the present study aimed to verify the effects of neonatal handling on the numerical density and cell size in the MPA in 11-day-old and 90-day-old female rats. Cellular proliferation was also assessed using BrdU (5-bromo-2'-deoxyuridine) in 11-day-old pups. Results showed that neonatal handling induces a stable reduction in the number of cells and in the size of the cell soma, which were lower in handled females than in nonhandled ones at both ages. Cellular proliferation in the MPA was also reduced 24 h after the last manipulation. The repeated mother-infant disruption imposed by the handling procedure "lesioned" the MPA. The dysfunction in the ovulation mechanisms induced by the handling procedure could be related to that neuronal loss. The study also illustrates the impact of an environmental intervention on the development of the brain.

  15. Projections of the nucleus lentiformis mesencephali in pigeons (Columba livia): a comparison of the morphology and distribution of neurons with different efferent projections.

    Science.gov (United States)

    Pakan, Janelle M P; Krueger, Kimberly; Kelcher, Erin; Cooper, Sarah; Todd, Kathryn G; Wylie, Douglas R W

    2006-03-01

    The avian nucleus lentiformis mesencephali (LM) is a visual structure involved in the optokinetic response. The LM consists of several morphologically distinct cell types. In the present study we sought to determine if different cell types had differential projections. Using retrograde tracers, we examined the morphology and distribution of LM neurons projecting to the vestibulocerebellum (VbC), inferior olive (IO), dorsal thalamus, nucleus of the basal optic root (nBOR), and midline mesencephalon. From injections into the latter two structures, small LM cells were labeled. More were localized to the lateral LM as opposed to medial LM. From injections into the dorsal thalamus, small neurons were found throughout LM. From injections into the VbC, large multipolar cells were found throughout LM. From injections into IO, a strip of medium-sized fusiform neurons along the border of the medial and lateral subnuclei was labeled. To investigate if neurons project to multiple targets we used fluorescent retrograde tracers. After injections into IO and VbC, double-labeled neurons were not observed in LM. Likewise, after injections into nBOR and IO, double-labeled neurons were not observed. Finally, we processed sections through LM for glutamic acid decarboxylase (GAD). Small neurons, mostly in the lateral LM, were labeled, suggesting that projections from LM to nBOR and midline mesencephalon are GABAergic. We conclude that two efferents of LM, VbC and IO, receive input from morphologically distinct neurons: large multipolar and medium-sized fusiform neurons, respectively. The dorsal thalamus, nBOR, and midline mesencephalon receive input from small neurons, some of which are likely GABAergic.

  16. Projection neurons in Drosophila antennal lobes signal the acceleration of odor concentrations.

    Science.gov (United States)

    Kim, Anmo J; Lazar, Aurel A; Slutskiy, Yevgeniy B

    2015-05-14

    Temporal experience of odor gradients is important in spatial orientation of animals. The fruit fly Drosophila melanogaster exhibits robust odor-guided behaviors in an odor gradient field. In order to investigate how early olfactory circuits process temporal variation of olfactory stimuli, we subjected flies to precisely defined odor concentration waveforms and examined spike patterns of olfactory sensory neurons (OSNs) and projection neurons (PNs). We found a significant temporal transformation between OSN and PN spike patterns, manifested by the PN output strongly signaling the OSN spike rate and its rate of change. A simple two-dimensional model admitting the OSN spike rate and its rate of change as inputs closely predicted the PN output. When cascaded with the rate-of-change encoding by OSNs, PNs primarily signal the acceleration and the rate of change of dynamic odor stimuli to higher brain centers, thereby enabling animals to reliably respond to the onsets of odor concentrations.

  17. Regulation of progesterone receptor messenger ribonucleic acid in the rat medial preoptic nucleus by estrogenic and antiestrogenic compounds: an in situ hybridization study.

    Science.gov (United States)

    Shughrue, P J; Lane, M V; Merchenthaler, I

    1997-12-01

    Progesterone receptor (PR) messenger RNA (mRNA) is concentrated in neurons of the preoptic area and other regions of the rat hypothalamus where it is colocalized with the estrogen receptor and regulated by changes in the steroid hormonal milieu. To date, little is known about the regulation of PR mRNA by estrogens and whether antiestrogenic compounds are capable of modulating its expression. The present studies used in situ hybridization to ascertain the time course of PR mRNA regulation in the medial preoptic nucleus by 17beta-estradiol, determine the effective dose required to elicit a response, and compare the efficacy of 17beta-estradiol with a variety of estrogenic or antiestrogenic compounds. The first series of studies revealed that the treatment of ovariectomized rats with 17beta-estradiol resulted in an increase in PR expression within 2 h, after which it remained elevated until 10 h postinjection and then returned to baseline levels. When ovariectomized rats were injected with 25-1000 ng/kg of 17beta-estradiol and euthanized 6 h later, a dose-dependent increase in the level of PR mRNA was observed, with a maximal response at 1000 ng/kg and an EC50 of 93.5 ng/kg. Subsequent studies evaluated the efficacy of a variety of estrogenic and antiestrogenic compounds in the rat preoptic nucleus. 17Beta-estradiol, diethylstilbestrol, and 17alpha-estradiol all significantly increased the level of PR mRNA, although the degree of induction varied with each compound. The injection of tamoxifen, raloxifene, toremifene, droloxifene, clomiphene, GW 5638, or ICI 182,780 had no significant estrogenic effect on PR gene expression at the dose evaluated. In contrast, when tamoxifen or raloxifene, but not ICI 182,780, was administered in the antagonist mode, a significant dose-related decrease in the estradiol-induced level of PR mRNA was seen in the preoptic area. The results of these studies clearly demonstrate that PR mRNA expression in the rat preoptic area is rapidly

  18. Zbtb20 Defines a Hippocampal Neuronal Identity Through Direct Repression of Genes That Control Projection Neuron Development in the Isocortex

    DEFF Research Database (Denmark)

    Nielsen, Jakob V; Thomassen, Mads; Møllgård, Kjeld

    2014-01-01

    Hippocampal pyramidal neurons are important for encoding and retrieval of spatial maps and episodic memories. While previous work has shown that Zbtb20 is a cell fate determinant for CA1 pyramidal neurons, the regulatory mechanisms governing this process are not known. In this study, we demonstrate...... that Zbtb20 binds to genes that control neuronal subtype specification in the developing isocortex, including Cux1, Cux2, Fezf2, Foxp2, Mef2c, Rorb, Satb2, Sox5, Tbr1, Tle4, and Zfpm2. We show that Zbtb20 represses these genes during ectopic CA1 pyramidal neuron development in transgenic mice. These data...

  19. GnRH neuron firing and response to GABA in vitro depend on acute brain slice thickness and orientation.

    Science.gov (United States)

    Constantin, Stephanie; Piet, Richard; Iremonger, Karl; Hwa Yeo, Shel; Clarkson, Jenny; Porteous, Robert; Herbison, Allan E

    2012-08-01

    The GnRH neurons exhibit long dendrites and project to the median eminence. The aim of the present study was to generate an acute brain slice preparation that enabled recordings to be undertaken from GnRH neurons maintaining the full extent of their dendrites or axons. A thick, horizontal brain slice was developed, in which it was possible to record from the horizontally oriented GnRH neurons located in the anterior hypothalamic area (AHA). In vivo studies showed that the majority of AHA GnRH neurons projected outside the blood-brain barrier and expressed c-Fos at the time of the GnRH surge. On-cell recordings compared AHA GnRH neurons in the horizontal slice (AHAh) with AHA and preoptic area (POA) GnRH neurons in coronal slices [POA coronal (POAc) and AHA coronal (AHAc), respectively]. AHAh GnRH neurons exhibited tighter burst firing compared with other slice orientations. Although α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) excited GnRH neurons in all preparations, γ-aminobutyric acid (GABA) was excitatory in AHAc and POAc but inhibitory in AHAh slices. GABA(A) receptor postsynaptic currents were the same in AHAh and AHAc slices. Intriguingly, direct activation of GABA(A) or GABA(B) receptors respectively stimulated and inhibited GnRH neurons regardless of slice orientation. Subsequent experiments indicated that net GABA effects were determined by differences in the ratio of GABA(A) and GABA(B) receptor-mediated effects in "long" and "short" dendrites of GnRH neurons in the different slice orientations. These studies document a new brain slice preparation for recording from GnRH neurons with their extensive dendrites/axons and highlight the importance of GnRH neuron orientation relative to the angle of brain slicing in studying these neurons in vitro.

  20. Descending control of electroreception. II. Properties of nucleus praeeminentialis neurons projecting directly to the electrosensory lateral line lobe.

    Science.gov (United States)

    Bratton, B; Bastian, J

    1990-04-01

    The nucleus praeeminentialis projects to the electrosensory lateral line lobe via 2 distinct pathways. Neurons that project to the posterior eminentia granularis and therefore influence the electrosensory lateral line lobe indirectly are described in the preceding report. This report describes the physiological properties and anatomical characteristics, revealed with Lucifer yellow staining, of n. praeeminentialis neurons that project directly to the ventral molecular layer of the electrosensory lateral line lobe. The neurons studied were the stellate cells described by Sas and Maler (1983), and we found 2 physiological subtypes of these. These neurons typically had no spontaneous activity, but responded vigorously to either increased electric organ discharge amplitude on the contralateral side of the body (ST-E cells) or to decreased amplitude (ST-I cells). These neurons also responded to low-frequency sinusoidal electric organ discharge amplitude modulations (AM) but were inhibited by AMs having frequencies greater than about 16 Hz. These stellate neurons were unable to encode information about long-term changes in electric organ discharge amplitude, but they responded very well to moving electrolocation targets. The relatively long response latency of these neurons suggests that they receive inputs from higher centers in addition to those from the electrosensory lateral line lobe. It is suggested that these cells alter the sensitivity of restricted populations of output cells in the electrosensory lateral line lobe and process temporally and spatially restricted stimuli. They may act to increase the intensity of the neural representation of important stimuli.

  1. Neuronal projections from the Haller's organ and palp sensilla to the synganglion of Amblyomma americanum§.

    Science.gov (United States)

    Borges, Lígia Miranda Ferreira; Li, Andrew Yongsheng; Olafson, Pia Untalan; Renthal, Robert; Bauchan, Gary Roy; Lohmeyer, Kimberly Hutchison; León, Adalberto Angel Pérez de

    2016-06-14

    The present study was conducted to elucidate the neuronal pathways between peripheral olfactory and taste sensilla and the synganglion in an Ixodidae tick species. The tarsus of the front legs (olfactory nerves) and the fourth palpal segment (gustatory nerves) of unfed Amblyomma americanum males and females were excised. A neuronal tracer, dextran tetramethylrhodamine, was used for filling of the sensory neurons. The synganglion preparations were examined using a confocal microscope. Neuronal arborizations from the Haller's organ were confined to the olfactory lobes and the first pedal ganglion. The estimated number of olfactory glomeruli ranged from 16 to 22 per olfactory lobe in the females. The number of glomeruli was not counted in males because they were densely packed. Sensory neurons associated with sensilla at the distal end of the palpal organ projected into the palpal ganglion in the synganglion through the palpal nerve. Gustatory sensory neurons associated with palpal sensilla projected into a commissure with several bulges, which are confined in the palpal ganglion. The findings of distinct projection patterns of sensory neurons associated with the Haller's organ and palpal organ in the lone star tick from this study advanced our knowledge on mechanisms of sensory information processing in ticks.

  2. The expression of chemorepulsive guidance receptors and the regenerative abilities of spinal-projecting neurons after spinal cord injury.

    Science.gov (United States)

    Chen, Jie; Laramore, Cindy; Shifman, Michael I

    2017-01-26

    Spinal cord injury (SCI) in mammals leads to permanent loss of function because axons do not regenerate in the central nervous system (CNS). To date, treatments based on neutralizing inhibitory environmental cues, such as the myelin-associated growth inhibitors and chondroitin sulfate proteoglycans, or on adding neurotrophic factors, have had limited success in enhancing regeneration. Published studies suggested that multiple axon guidance cues (repulsive guidance molecule (RGM) family, semaphorins, ephrins, and netrins) persist in adult animals, and that their expression is upregulated after CNS injury. Moreover, many adult CNS neurons continue to express axon guidance receptors. We used the advantages of the lamprey CNS to test the hypotheses that the regenerative abilities of spinal-projecting neurons depend upon their expression of chemorepulsive guidance receptors. After complete spinal transection, lampreys recover behaviorally, and injured axons grow selectively in their correct paths. However, the large identified reticulospinal (RS) neurons in the lamprey brain are heterogeneous in their regenerative abilities - some are high regeneration capacity neurons (probability of axon regeneration >50%), others are low regeneration capacity neurons (regeneration capacity RS neurons that regenerate poorly, and that downregulation of Neogenin by morpholino antisense oligonucleotides enhances regeneration of RS axons after SCI. Moreover, lamprey CNS neurons co-express multiple guidance receptors (Neogenin, UNC5 and PlexinA), suggesting that the regenerative abilities of spinal-projecting neurons might reflect the summed influences of the chemorepulsive guidance receptors that they express. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  3. TALE-class homeodomain transcription factors, homothorax and extradenticle, control dendritic and axonal targeting of olfactory projection neurons in the Drosophila brain.

    Science.gov (United States)

    Ando, Mai; Totani, Yoko; Walldorf, Uwe; Furukubo-Tokunaga, Katsuo

    2011-10-01

    Precise neuronal connectivity in the nervous system depends on specific axonal and dendritic targeting of individual neurons. In the Drosophila brain, olfactory projection neurons convey odor information from the antennal lobe to higher order brain centers such as the mushroom body and the lateral horn. Here, we show that Homothorax (Hth), a TALE-class homeodomain transcription factor, is expressed in many of the antennal lobe neurons including projection neurons and local interneurons. In addition, HTH is expressed in the progenitors of the olfactory projection neurons, and the activity of hth is required for the generation of the lateral but not for the anterodorsal and ventral lineages. MARCM analyses show that the hth is essential for correct dendritic targeting of projection neurons in the antennal lobe. Moreover, the activity of hth is required for axonal fasciculation, correct routing and terminal branching of the projection neurons. We also show that another TALE-class homeodomain protein, Extradenticle (Exd), is required for the dendritic and axonal development of projection neurons. Mutation of exd causes projection neuron defects that are reminiscent of the phenotypes caused by the loss of the hth activity. Double immunostaining experiments show that Hth and Exd are coexpressed in olfactory projection neurons and their progenitors, and that the expressions of Hth and Exd require the activity of each other gene. These results thus demonstrate the functional importance of the TALE-class homeodomain proteins in cell-type specification and precise wiring of the Drosophila olfactory network.

  4. Drosophila olfactory local interneurons and projection neurons derive from a common neuroblast lineage specified by the empty spiracles gene

    Directory of Open Access Journals (Sweden)

    Ito Kei

    2008-12-01

    Full Text Available Abstract Background Encoding of olfactory information in insects occurs in the antennal lobe where the olfactory receptor neurons interact with projection neurons and local interneurons in a complex sensory processing circuitry. While several studies have addressed the developmental mechanisms involved in specification and connectivity of olfactory receptor neurons and projection neurons in Drosophila, the local interneurons are far less well understood. Results In this study, we use genetic marking techniques combined with antibody labelling and neuroblast ablation to analyse lineage specific aspects of local interneuron development. We find that a large set of local interneurons labelled by the GAL4-LN1 (NP1227 and GAL4-LN2 (NP2426 lines arise from the lateral neuroblast, which has also been shown to generate uniglomerular projection neurons. Moreover, we find that a remarkable diversity of local interneuron cell types with different glomerular innervation patterns and neurotransmitter expression derives from this lineage. We analyse the birth order of these two distinct neuronal types by generating MARCM (mosaic analysis with a repressible cell marker clones at different times during larval life. This analysis shows that local interneurons arise throughout the proliferative cycle of the lateral neuroblast beginning in the embryo, while uniglomerular projection neurons arise later during the second larval instar. The lateral neuroblast requires the function of the cephalic gap gene empty spiracles for the development of olfactory interneurons. In empty spiracles null mutant clones, most of the local interneurons and lateral projection neurons are lacking. These findings reveal similarities in the development of local interneurons and projection neurons in the olfactory system of Drosophila. Conclusion We find that the lateral neuroblast of the deutocerebrum gives rise to a large and remarkably diverse set of local interneurons as well as to

  5. Different correlation patterns of cholinergic and GABAergic interneurons with striatal projection neurons

    Directory of Open Access Journals (Sweden)

    Avital eAdler

    2013-09-01

    Full Text Available The striatum is populated by a single projection neuron group, the medium spiny neurons (MSNs, and several groups of interneurons. Two of the electrophysiologically well-characterized striatal interneuron groups are the tonically active neurons (TANs, which are presumably cholinergic interneurons, and the fast spiking interneurons (FSIs, presumably parvalbumin (PV expressing GABAergic interneurons. To better understand striatal processing it is thus crucial to define the functional relationship between MSNs and these interneurons in the awake and behaving animal. We used multiple electrodes and standard physiological methods to simultaneously record MSN spiking activity and the activity of TANs or FSIs from monkeys engaged in a classical conditioning paradigm. All three cell populations were highly responsive to the behavioral task. However, they displayed different average response profiles and a different degree of response synchronization (signal correlation. TANs displayed the most transient and synchronized response, MSNs the most diverse and sustained response and FSIs were in between on both parameters. We did not find evidence for direct monosynaptic connectivity between the MSNs and either the TANs or the FSIs. However, while the cross correlation histograms of TAN to MSN pairs were flat, those of FSI to MSN displayed positive asymmetrical broad peaks. The FSI-MSN correlogram profile implies that the spikes of MSNs follow those of FSIs and both are driven by a common, most likely cortical, input. Thus, the two populations of striatal interneurons are probably driven by different afferents and play complementary functional roles in the physiology of the striatal microcircuit.

  6. Morphogenetic Studies of the Drosophila DA1 Ventral Olfactory Projection Neuron.

    Science.gov (United States)

    Shen, Hung-Chang; Wei, Jia-Yi; Chu, Sao-Yu; Chung, Pei-Chi; Hsu, Tsai-Chi; Yu, Hung-Hsiang

    2016-01-01

    In the Drosophila olfactory system, odorant information is sensed by olfactory sensory neurons and relayed from the primary olfactory center, the antennal lobe (AL), to higher olfactory centers via olfactory projection neurons (PNs). A major portion of the AL is constituted with dendrites of four groups of PNs, anterodorsal PNs (adPNs), lateral PNs (lPNs), lateroventral PNs (lvPNs) and ventral PNs (vPNs). Previous studies have been focused on the development and function of adPNs and lPNs, while the investigation on those of lvPNs and vPNs received less attention. Here, we study the molecular and cellular mechanisms underlying the morphogenesis of a putative male-pheromone responding vPN, the DA1 vPN. Using an intersection strategy to remove background neurons labeled within a DA1 vPN-containing GAL4 line, we depicted morphological changes of the DA1 vPN that occurs at the pupal stage. We then conducted a pilot screen using RNA interference knock-down approach to identify cell surface molecules, including Down syndrome cell adhesion molecule 1 and Semaphorin-1a, that might play essential roles for the DA1 vPN morphogenesis. Taken together, by revealing molecular and cellular basis of the DA1 vPN morphogenesis, we should provide insights into future comprehension of how vPNs are assembled into the olfactory neural circuitry.

  7. Parvalbumin-positive projection neurons characterise the vocal premotor pathway in male, but not female, zebra finches.

    Science.gov (United States)

    Wild, J M; Williams, M N; Suthers, R A

    2001-11-02

    Parvalbumin (PV) and calbindin (CB) immunoreactivities were assessed in nucleus robustus archistriatalis (RA) of male and female zebra finches, together with retrograde labelling of RA neurons. The results of double and triple labelling experiments suggested that, in males, moderately and faintly PV-positive neurons were projection neurons, but that all intensely PV-positive cells were not. The latter, which are presumably interneurons, were also intensely CB-positive, and may correspond to the GABAergic inhibitory interneurons identified by others. In addition, the complete RA pathway and its terminal fields in the respiratory-vocal nuclei of the brainstem were strongly PV-positive. In female zebra finches, which do not sing, no evidence was found that PV-positive RA cells were projection neurons, yet the pattern of projections of RA neurons, as determined by anterograde transport of biotinylated dextran amine, was very similar to that of RA in males. Moreover, in females, RA neurons retrogradely labelled from injections of cholera toxin B-chain into the tracheosyringeal nucleus (XIIts) were abundant and included, in the lateral part of the nucleus, a population of cells that were as large as those in the male RA. Parvalbumin immunoreactivity was also present in RA and its projections in males of several other songbird species (northern cardinal, brown headed cowbird, canary) and in the female cardinal, which sings to some extent, but the labelling was not as intense as that in male zebra finches.

  8. Transient global ischemia in rats yields striatal projection neuron and interneuron loss resembling that in Huntington's disease.

    Science.gov (United States)

    Meade, C A; Figueredo-Cardenas, G; Fusco, F; Nowak, T S; Pulsinelli, W A; Reiner, A

    2000-12-01

    The various types of striatal projection neurons and interneurons show a differential pattern of loss in Huntington's disease (HD). Since striatal injury has been suggested to involve similar mechanisms in transient global brain ischemia and HD, we examined the possibility that the patterns of survival for striatal neurons after transient global ischemic damage to the striatum in rats resemble that in HD. The perikarya of specific types of striatal interneurons were identified by histochemical or immunohistochemical labeling while projection neuron abundance was assessed by cresyl violet staining. Projectionneuron survival was assessed by neurotransmitter immunolabeling of their efferent fibers in striatal target areas. The relative survival of neuron types was determined quantitatively within the region of ischemic damage, and the degree of fiber loss in striatal target areas was quantified by computer-assisted image analysis. We found that NADPHd(+) and cholinergic interneurons were largely unaffected, even in the striatal area of maximal damage. Parvalbumin interneurons, however, were as vulnerable as projection neurons. Among immunolabeled striatal projection systems, striatoentopeduncular fibers survived global ischemia better than did striatopallidal or striatonigral fibers. The order of vulnerability observed in this study among the striatal projection systems, and the resistance to damage shown by NADPHd(+) and cholinergic interneurons, is similar to that reported in HD. The high vulnerability of projection neurons and parvalbumin interneurons to global ischemia also resembles that seen in HD. Our results thus indicate that global ischemic damage to striatum in rat closely mimics HD in its neuronal selectivity, which supports the notion that the mechanisms of injury may be similar in both.

  9. Efficient Generation of Corticofugal Projection Neurons from Human Embryonic Stem Cells.

    Science.gov (United States)

    Zhu, Xiaoqing; Ai, Zongyong; Hu, Xintian; Li, Tianqing

    2016-06-27

    Efforts to study development and function of corticofugal projection neurons (CfuPNs) in the human cerebral cortex for health and disease have been limited by the unavailability of highly enriched CfuPNs. Here, we develop a robust, two-step process for generating CfuPNs from human embryonic stem cells (hESCs): directed induction of neuroepithelial stem cells (NESCs) from hESCs and efficient differentiation of NESCs to about 80% of CfuPNs. NESCs or a NESC faithfully maintain unlimitedly self-renewal and self-organized abilities to develop into miniature neural tube-like structures. NESCs retain a stable propensity toward neuronal differentiation over culture as fate-restricted progenitors of CfuPNs and interneurons. When grafted into mouse brains, NESCs successfully integrate into the host brains, differentiate into CfuPNs and effectively reestablish specific patterns of subcortical projections and synapse structures. Efficient generation of CfuPNs in vitro and in vivo will facilitate human cortex development and offer sufficient CfuPNs for cell therapy.

  10. Different corticostriatal integration in spiny projection neurons from direct and indirect pathways

    Directory of Open Access Journals (Sweden)

    Edén Flores-Barrera

    2010-06-01

    Full Text Available The striatum is the principal input structure of the basal ganglia (BG. Major glutamatergic afferents to the striatum come from the cerebral cortex and make monosynaptic contacts with medium spiny projection neurons (MSNs and interneurons. Despite differences in axonal projections, dopamine receptors expression and differences in excitability between MSNs from “direct” and “indirect” BG pathways, these neuronal classes have been thought as electrophysiologically very similar. Based on work with BAC transgenic mice, here it is shown that corticostriatal responses in D1- and D2-receptor expressing MSNs (D1- and D2-MSNs are radically different so as to establish an electrophysiological footprint that readily differentiates between them. Experiments in BAC mice allowed us to predict, with high probability (P>0.9, in rats or non-BAC mice, whether a recorded neuron, from rat or mouse, was going to be substance P or enkephalin immunoreactive. Responses are more prolonged and evoke more action potentials in D1-MSNs, while they are briefer and exhibit intrinsic autoregenerative responses in D2-MSNs. A main cause for these differences was the interaction of intrinsic properties with the inhibitory contribution in each response Inhibition always depressed corticostriatal depolarization in D2-MSNs, while it helped in sustaining prolonged depolarizations in D1-MSNs, in spite of depressing early discharge. Corticostriatal responses changed dramatically after striatal DA-depletion in 6-hydroxy-dopamine (6-OHDA lesioned animals: a response reduction was seen in SP+ MSNs whereas an enhanced response was seen in ENK+ MSNs. The end result was that differences in the responses were greatly diminished after DA depletion.

  11. Projection neurons in the cortex and hippocampus: differential effects of chronic khat and ethanol exposure in adult male rats

    Science.gov (United States)

    Alele, Paul E; Matovu, Daniel; Imanirampa, Lawrence; Ajayi, Abayomi M; Kasule, Gyaviira T

    2016-01-01

    Background Recent evidence suggests that many individuals who chew khat recreationally also drink ethanol to offset the stimulating effect of khat. The objective of this study was to describe the separate and interactive effects of chronic ethanol and khat exposure on key projection neurons in the cortex and hippocampus of young adult male rats. Methods Young adult male Sprague Dawley rats were divided into six treatment groups: 2 g/kg khat, 4 g/kg khat, 4 g/kg ethanol, combined khat and ethanol (4 g/kg each), a normal saline control, and an untreated group. Treatments were administered orally for 28 continuous days; brains were then harvested, sectioned, and routine hematoxylin–eosin staining was done. Following photomicrography, ImageJ® software captured data regarding neuron number and size. Results No differences occurred in counts of both granular and pyramidal projection neurons in the motor cortex and all four subfields of the hippocampal formation. Khat dose-dependently increased pyramidal neuron size in the motor cortex and the CA3 region, but had different effects on granular neuron size in the dentate gyrus and the motor cortex. Mean pyramidal neuron size for the ethanol-only treatment was larger than that for the 2 g/kg khat group, and the saline control group, in CA3 and in the motor cortex. Concomitant khat and ethanol increased granular neuron size in the motor cortex, compared to the 2 g/kg khat group, the 4 g/kg khat group, and the 4 g/kg ethanol group. In the CA3 region, the 4 g/kg ethanol group showed a larger mean pyramidal neuron size than the combined khat and ethanol group. Conclusion These results suggest that concomitant khat and ethanol exposure changes granular and pyramidal projection neuron sizes differentially in the motor cortex and hippocampus, compared to the effects of chronic exposure to these two drugs separately.

  12. Coexpression analysis of nine neuropeptides in the neurosecretory preoptic area of larval zebrafish

    Directory of Open Access Journals (Sweden)

    Ulrich eHerget

    2015-02-01

    Full Text Available The paraventricular nucleus (PVN of the hypothalamus in mammals coordinates neuroendocrine, autonomic and behavioral responses pivotal for homeostasis and the stress response. A large amount of studies in rodents has documented that the PVN contains diverse neuronal cell types which can be identified by the expression of distinct secretory neuropeptides. Interestingly, PVN cell types often coexpress multiple neuropeptides whose relative coexpression level are subject to environment-induced plasticity.Due to their small size and transparency, zebrafish larvae offer the possibility to comprehensively study the development and plasticity of the PVN in large groups of intact animals, yet important anatomical information about the larval zebrafish PVN-homologous region has been missing. Therefore we recently defined the location and borders of the larval neurosecretory preoptic area (NPO as the PVN-homologous region in larval zebrafish based on transcription factor expression and cell type clustering. To identify distinct cell types present in the larval NPO, we also generated a comprehensive 3D map of 9 zebrafish homologs of typical neuropeptides found in the mammalian PVN (arginine vasopressin, corticotropin-releasing hormone, proenkephalin a/b, neurotensin, oxytocin, vasoactive intestinal peptide, cholecystokinin, and somatostatin. Here we extend this chemoarchitectural map to include the degrees of coexpression of two neuropeptides in the same cell by performing systematic pairwise comparisons. Our results allowed the subclassification of NPO cell types, and differences in variability of coexpression profiles suggest potential targets of biochemical plasticity. Thus, this work provides an important basis for the analysis of the development, function, and plasticity of the primary neuroendocrine brain region in larval zebrafish.

  13. Exercise training normalizes an increased neuronal excitability of NTS-projecting neurons of the hypothalamic paraventricular nucleus in hypertensive rats.

    Science.gov (United States)

    Stern, Javier E; Sonner, Patrick M; Son, Sook Jin; Silva, Fabiana C P; Jackson, Keshia; Michelini, Lisete C

    2012-05-01

    Elevated sympathetic outflow and altered autonomic reflexes, including impaired baroreflex function, are common findings observed in hypertensive disorders. Although a growing body of evidence supports a contribution of preautonomic neurons in the hypothalamic paraventricular nucleus (PVN) to altered autonomic control during hypertension, the precise underlying mechanisms remain unknown. Here, we aimed to determine whether the intrinsic excitability and repetitive firing properties of preautonomic PVN neurons that innervate the nucleus tractus solitarii (PVN-NTS neurons) were altered in spontaneously hypertensive rats (SHR). Moreover, given that exercise training is known to improve and/or correct autonomic deficits in hypertensive conditions, we evaluated whether exercise is an efficient behavioral approach to correct altered neuronal excitability in hypertensive rats. Patch-clamp recordings were obtained from retrogradely labeled PVN-NTS neurons in hypothalamic slices obtained from sedentary (S) and trained (T) Wistar-Kyoto (WKY) and SHR rats. Our results indicate an increased excitability of PVN-NTS neurons in SHR-S rats, reflected by an enhanced input-output function in response to depolarizing stimuli, a hyperpolarizing shift in Na(+) spike threshold, and smaller hyperpolarizing afterpotentials. Importantly, we found exercise training in SHR rats to restore all these parameters back to those levels observed in WKY-S rats. In several cases, exercise evoked opposing effects in WKY-S rats compared with SHR-S rats, suggesting that exercise effects on PVN-NTS neurons are state dependent. Taken together, our results suggest that elevated preautonomic PVN-NTS neuronal excitability may contribute to altered autonomic control in SHR rats and that exercise training efficiently corrects these abnormalities.

  14. Electrical stimulation of the preoptic area in Eigenmannia: evoked interruptions in the electric organ discharge.

    Science.gov (United States)

    Wong, C J

    2000-01-01

    The functional role of the basal forebrain and preoptic regions in modulating the normally regular electric organ discharge was determined by focal brain stimulation in the weakly electric fish, Eigenmannia. The rostral preoptic area, which is connected with the diencephalic prepacemaker nucleus, was examined physiologically by electrical stimulation in a curarized fish. Electrical stimulation of the most rostral region of the preoptic area with trains of relatively low intensity current elicits discrete bursts of electric organ discharge interruptions in contrast to other forebrain loci. These responses were observed primarily as after-responses following the termination of the stimulus train and were relatively immune to variations in the stimulus parameters. As the duration and rate of these preoptic-evoked bursts of electric organ discharge interruptions (approximately 100 ms at 2 per s) are similar to duration and rate of natural interruptions, it is proposed that these bursts might be precursors to natural interruptions. These data suggest that the preoptic area, consistent with its role in controlling reproductive behaviors in vertebrates, may be influencing the occurrence of electric organ discharge courtship signals by either direct actions on the prepacemaker nucleus or through other regions that are connected with the diencephalic pre-pacemaker nucleus.

  15. Descending control of electroreception. I. Properties of nucleus praeeminentialis neurons projecting indirectly to the electrosensory lateral line lobe.

    Science.gov (United States)

    Bastian, J; Bratton, B

    1990-04-01

    The first-order CNS processing region within the electrosensory system, the electrosensory lateral line lobe, receives massive descending inputs from the nucleus praeeminentialis as well as the primary afferent projection. The n. praeeminentialis receives its input from the electrosensory lateral line lobe as well as from higher centers; hence this nucleus occupies an important position in a feedback loop within the electrosensory system. This report describes the physiological properties of a category of n. praeeminentialis neurons characterized by very high spontaneous firing frequency, but relatively poor sensitivity to electrolocation targets as compared to neurons in the electrosensory lateral line lobe. These neurons are specialized to encode long-term changes in electric organ discharge amplitude with high resolution. Intracellular recording and Lucifer yellow staining of these neurons show that they are the previously described multipolar neurons of the n. praeeminentialis, and they project bilaterally to the posterior eminentia granularis. Posterior eminentia granularis efferents project to the electrosensory lateral line lobe forming its dorsal molecular layer. Hence, these multipolar cells influence the electrosensory lateral line lobe circuitry indirectly. The information that the multipolar cells encode regarding the electric organ discharge amplitude may be needed for a gain control mechanism operative within the electrosensory lateral line lobe. Previous studies have shown that the indirect projection from the n. praeeminentialis to the electrosensory lateral line lobe must be intact for this gain control mechanism to operate.

  16. Spikes and bursts in two types of thalamic projection neurons differentially shape sleep patterns and auditory responses in a songbird.

    Science.gov (United States)

    Hahnloser, Richard H R; Wang, Claude Z-H; Nager, Aymeric; Naie, Katja

    2008-05-07

    In mammals, the thalamus plays important roles for cortical processing, such as relay of sensory information and induction of rhythmical firing during sleep. In neurons of the avian cerebrum, in analogy with cortical up and down states, complex patterns of regular-spiking and dense-bursting modes are frequently observed during sleep. However, the roles of thalamic inputs for shaping these firing modes are largely unknown. A suspected key player is the avian thalamic nucleus uvaeformis (Uva). Uva is innervated by polysensory input, receives indirect cerebral feedback via the midbrain, and projects to the cerebrum via two distinct pathways. Using pharmacological manipulation, electrical stimulation, and extracellular recordings of Uva projection neurons, we study the involvement of Uva in zebra finches for the generation of spontaneous activity and auditory responses in premotor area HVC (used as a proper name) and the downstream robust nucleus of the arcopallium (RA). In awake and sleeping birds, we find that single Uva spikes suppress and spike bursts enhance spontaneous and auditory-evoked bursts in HVC and RA neurons. Strong burst suppression is mediated mainly via tonically firing HVC-projecting Uva neurons, whereas a fast burst drive is mediated indirectly via Uva neurons projecting to the nucleus interface of the nidopallium. Our results reveal that cerebral sleep-burst epochs and arousal-related burst suppression are both shaped by sophisticated polysynaptic thalamic mechanisms.

  17. Zbtb20 defines a hippocampal neuronal identity through direct repression of genes that control projection neuron development in the isocortex.

    Science.gov (United States)

    Nielsen, Jakob V; Thomassen, Mads; Møllgård, Kjeld; Noraberg, Jens; Jensen, Niels A

    2014-05-01

    Hippocampal pyramidal neurons are important for encoding and retrieval of spatial maps and episodic memories. While previous work has shown that Zbtb20 is a cell fate determinant for CA1 pyramidal neurons, the regulatory mechanisms governing this process are not known. In this study, we demonstrate that Zbtb20 binds to genes that control neuronal subtype specification in the developing isocortex, including Cux1, Cux2, Fezf2, Foxp2, Mef2c, Rorb, Satb2, Sox5, Tbr1, Tle4, and Zfpm2. We show that Zbtb20 represses these genes during ectopic CA1 pyramidal neuron development in transgenic mice. These data reveal a novel regulatory mechanism by which Zbtb20 suppresses the acquisition of an isocortical fate during archicortical neurogenesis to ensure commitment to a CA1 pyramidal neuron fate. We further show that the expression pattern of Zbtb20 is evolutionary conserved in the fetal human hippocampus, where it is complementary to the expression pattern of the Zbtb20 target gene Tbr1. Therefore, the disclosed Zbtb20-mediated transcriptional repressor mechanism may be involved in development of the human archicortex.

  18. Empty spiracles is required for the development of olfactory projection neuron circuitry in Drosophila.

    Science.gov (United States)

    Lichtneckert, Robert; Nobs, Lionel; Reichert, Heinrich

    2008-08-01

    In both insects and mammals, second-order olfactory neurons receive input from olfactory receptor neurons and relay olfactory input to higher brain centers. In Drosophila, the wiring specificity of these olfactory projection neurons (PNs) is predetermined by their lineage identity and birth order. However, the genetic programs that control this wiring specificity are not well understood. The cephalic gap gene empty spiracles (ems) encodes a homeodomain transcription factor required for embryonic development of the antennal brain neuromere. Here we show that ems is expressed postembryonically in the progenitors of the two major olfactory PN lineages. Moreover, we show that ems has cell lineage-specific functions in postembryonic PN development. Thus, in the lateral PN lineage, transient ems expression is essential for development of the correct number of PNs; in ems mutants, the number of PNs in the lineage is dramatically reduced by apoptosis. By contrast, in the anterodorsal PN lineage, transient ems expression is necessary for precise targeting of PN dendrites to appropriate glomeruli; in ems mutants, these PNs fail to innervate correct glomeruli, innervate inappropriate glomeruli, or mistarget dendrites to other brain regions. Furthermore, in the anterodorsal PN lineage, ems controls the expression of the POU-domain transcription factor Acj6 in approximately half of the cells and, in at least one glomerulus, ems function in dendritic targeting is mediated through Acj6. The finding that Drosophila ems, like its murine homologs Emx1/2, is required for the formation of olfactory circuitry implies that conserved genetic programs control olfactory system development in insects and mammals.

  19. Different cortical projections from three subdivisions of the rat lateral posterior thalamic nucleus: a single-neuron tracing study with viral vectors.

    Science.gov (United States)

    Nakamura, Hisashi; Hioki, Hiroyuki; Furuta, Takahiro; Kaneko, Takeshi

    2015-05-01

    The lateral posterior thalamic nucleus (LP) is one of the components of the extrageniculate pathway in the rat visual system, and is cytoarchitecturally divided into three subdivisions--lateral (LPl), rostromedial (LPrm), and caudomedial (LPcm) portions. To clarify the differences in the dendritic fields and axonal arborisations among the three subdivisions, we applied a single-neuron labeling technique with viral vectors to LP neurons. The proximal dendrites of LPl neurons were more numerous than those of LPrm and LPcm neurons, and LPrm neurons tended to have wider dendritic fields than LPl neurons. We then analysed the axonal arborisations of LP neurons by reconstructing the axon fibers in the cortex. The LPl, LPrm and LPcm were different from one another in terms of the projection targets--the main target cortical regions of LPl and LPrm neurons were the secondary and primary visual areas, whereas those of LPcm neurons were the postrhinal and temporal association areas. Furthermore, the principal target cortical layers of LPl neurons in the visual areas were middle layers, but that of LPrm neurons was layer 1. This indicates that LPl and LPrm neurons can be categorised into the core and matrix types of thalamic neurons, respectively, in the visual areas. In addition, LPl neurons formed multiple axonal clusters within the visual areas, whereas the fibers of LPrm neurons were widely and diffusely distributed. It is therefore presumed that these two types of neurons play different roles in visual information processing by dual thalamocortical innervation of the visual areas.

  20. HERC 1 Ubiquitin Ligase Mutation Affects Neocortical, CA3 Hippocampal and Spinal Cord Projection Neurons: An Ultrastructural Study.

    Science.gov (United States)

    Ruiz, Rocío; Pérez-Villegas, Eva María; Bachiller, Sara; Rosa, José Luis; Armengol, José Angel

    2016-01-01

    The spontaneous mutation tambaleante is caused by the Gly483Glu substitution in the highly conserved N terminal RCC1-like domain of the HERC1 protein, which leads to the increase of mutated protein levels responsible for cerebellar Purkinje cell death by autophagy. Until now, Purkinje cells have been the only central nervous neurons reported as being targeted by the mutation, and their degeneration elicits an ataxic syndrome in adult mutant mice. However, the ultrastructural analysis performed here demonstrates that signs of autophagy, such as autophagosomes, lysosomes, and altered mitochondria, are present in neocortical pyramidal, CA3 hippocampal pyramidal, and spinal cord motor neurons. The main difference is that the reduction in the number of neurons affected in the tambaleante mutation in the neocortex, the hippocampus, and the spinal cord is not so evident as the dramatic loss of cerebellar Purkinje cells. Interestingly, signs of autophagy are absent in both interneurons and neuroglia cells. Affected neurons have in common that they are projection neurons which receive strong and varied synaptic inputs, and possess the highest degree of neuronal activity. Therefore, because the integrity of the ubiquitin-proteasome system is essential for protein degradation and hence, for normal protein turnover, it could be hypothesized that the deleterious effects of the misrouting of these pathways would depend directly on the neuronal activity.

  1. HERC 1 ubiquitin ligase mutation affects neocortical, CA3 hippocampal and spinal cord projection neurons. An ultrastructural study

    Directory of Open Access Journals (Sweden)

    Rocío eRuiz

    2016-04-01

    Full Text Available The spontaneous mutation tambaleante is caused by the Gly483Glu substitution in the highly conserved N terminal RCC1-like domain of the HERC1 protein, which leads to the increase of mutated protein levels responsible for cerebellar Purkinje cell death by autophagy. Until now, Purkinje cells have been the only central nervous neurons reported as being targeted by the mutation, and their degeneration elicits an ataxic syndrome in adult mutant mice. However, the ultrastructural analysis performed here demonstrates that signs of autophagy, such as autophagosomes, lysosomes, and altered mitochondria, are present in neocortical pyramidal, CA3 hippocampal pyramidal, and spinal cord motor neurons. The main difference is that the reduction in the number of neurons affected in the tambaleante mutation in the neocortex, the hippocampus, and the spinal cord is not so evident as the dramatic loss of cerebellar Purkinje cells. Interestingly, signs of autophagy are absent in both interneurons and neuroglia cells. Affected neurons have in common that they are projection neurons which receive strong and varied synaptic inputs, and possess the highest degree of neuronal activity. Therefore, because the integrity of the ubiquitin-proteasome system is essential for protein degradation and, hence, for normal protein turnover, it could be hypothesized that the deleterious effects of the misrouting of these pathways would depend directly on the neuronal activity.

  2. Hypothalamic neuron projection to autonomic preganglionic levels related with glucose metabolism: a fluorescent labelling study in the rat.

    Science.gov (United States)

    Portillo, F; Carrasco, M; Vallo, J J

    1996-06-01

    The location of hypothalamic paraventricular neurons projecting to sympathetic preganglionic levels and related to the autonomic regulation of various organs involved in glucose metabolism (OGM) was determined by ipsilateral injections of two fluorescent tracers, Diamidino Yellow into the left dorsal motor nucleus of the vagus and Fast Blue into the left intermediolateral cell column of the T8-T9 spinal cord. Hypothalamospinal neurons were mainly located in the dorsal part of the paraventricular hypothalamic nucleus (PVH) and the hypothalamobulbar neurons were most abundant in the ventral, medial and extreme lateral parts of the PVH. No double-labelled neurons were found in the hypothalamus. These results can help the knowledge of the neural hypothalamic network related with the autonomic hypothalamic control.

  3. Neurons in the lateral sacral cord of the cat project to periaqueductal grey, but not to thalamus

    NARCIS (Netherlands)

    Klop, EM; Mouton, LJ; Kuipers, R; Holstege, G; Klop, [No Value

    2005-01-01

    Previous work of our laboratory has shown that neurons in the lateral sacral cord in cat project heavily to the periaqueductal grey (PAG), in all likelihood conveying information from bladder and genital organs. In humans this information usually does not reach consciousness, which raises the questi

  4. Persistent activation of microglia is associated with neuronal dysfunction of callosal projecting pathways and multiple sclerosis-like lesions in relapsing--remitting experimental autoimmune encephalomyelitis

    DEFF Research Database (Denmark)

    Rasmussen, Stine; Wang, Yue; Kivisäkk, Pia

    2007-01-01

    callosal projecting neurons. There was significant impairment of retrograde labeling of NeuN-positive callosal projecting neurons and reduction in the labelling of their transcallosal axons. These data demonstrate a novel paradigm of cortical and callosal neuropathology in a mouse model of MS, perpetuated...

  5. Prospective separation and transcriptome analyses of cortical projection neurons and interneurons based on lineage tracing by Tbr2 (Eomes)-GFP/Dcx-mRFP reporters.

    Science.gov (United States)

    Liu, Jiancheng; Wu, Xiwei; Zhang, Heying; Qiu, Runxiang; Yoshikawa, Kazuaki; Lu, Qiang

    2016-06-01

    In the cerebral cortex, projection neurons and interneurons work coordinately to establish neural networks for normal cortical functions. While the specific mechanisms that control productions of projection neurons and interneurons are beginning to be revealed, a global characterization of the molecular differences between these two neuron types is crucial for a more comprehensive understanding of their developmental specifications and functions. In this study, using lineage tracing power of combining Tbr2(Eomes)-GFP and Dcx-mRFP reporter mice, we prospectively separated intermediate progenitor cell (IPC)-derived neurons (IPNs) from non-IPC-derived neurons (non-IPNs) of the embryonic cerebral cortex. Molecular characterizations revealed that IPNs and non-IPNs were enriched with projection neurons and interneurons, respectively. Expression profiling documented cell-specific genes including differentially expressed transcriptional regulators that might be involved in cellular specifications, for instance, our data found that SOX1 and SOX2, which were known for important functions in neural stem/progenitor cells, continued to be expressed by interneurons but not by projection neurons. Transcriptome analyses of cortical neurons isolated at different stages of neurogenesis revealed distinct temporal patterns of expression of genes involved in early-born or late-born neuron specification. These data present a resource useful for further investigation of the molecular regulations and functions of projection neurons and interneurons.

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

    Science.gov (United States)

    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.

  7. Development of the sexually dimorphic nucleus of the preoptic area and the influence of estrogen-like compounds.

    Science.gov (United States)

    He, Zhen; Ferguson, Sherry Ann; Cui, Li; Greenfield, Lazar John; Paule, Merle Gale

    2013-10-15

    One of the well-defined sexually dimorphic structures in the brain is the sexually dimorphic nucleus, a cluster of cells located in the preoptic area of the hypothalamus. The rodent sexually dimorphic nucleus of the preoptic area can be delineated histologically using conventional Nissl staining or immunohistochemically using calbindin D28K immunoreactivity. There is increasing use of the bindin D28K-delineated neural cluster to define the sexually dimorphic nucleus of the preoptic area in rodents. Several mechanisms are proposed to underlie the processes that contribute to the sexual dimorphism (size difference) of the sexually dimorphic nucleus of the preoptic area. Recent evidence indicates that stem cell activity, including proliferation and migration presumably from the 3(rd) ventricle stem cell niche, may play a critical role in the postnatal development of the sexually dimorphic nucleus of the preoptic area and its distinguishing sexually dimorphic feature: a signifi-cantly larger volume in males. Sex hormones and estrogen-like compounds can affect the size of the sexually dimorphic nucleus of the preoptic area. Despite considerable research, it remains un-clear whether estrogen-like compounds and/or sex hormones increase size of the sexually dimor-phic nucleus of the preoptic area via an increase in stem cell activity originating from the 3(rd) ventricle stem cell niche.

  8. Injection of Retrograde Beads into the Nucleus Accumbens (NAc) and Medial Prefronral Cortex (mPFC) to Isolate Projection-Specific Neurons in the Ventral Tegmental Area (VTA)

    OpenAIRE

    sprotocols

    2015-01-01

    Authors: Jessica Walsh, Allyson Friedman, Dipesh Chaudhury, Barbara Juarez, Stacy Ku & Ming-Hu Han ### Abstract Retrograde dyes, such as lumafluors, have been used as tracers to visualize neurons that project to a specific target region. Injection of these dyes provides an important method in being able to understand the functional role of projection-specific neurons. Lumafluors can be directly injected into a target brain region of a mouse and dye positive cells from the project...

  9. Spatial distribution of intermingling pools of projection neurons with distinct targets: A 3D analysis of the commissural ganglia in Cancer borealis.

    Science.gov (United States)

    Follmann, Rosangela; Goldsmith, Christopher John; Stein, Wolfgang

    2017-06-01

    Projection neurons play a key role in carrying long-distance information between spatially distant areas of the nervous system and in controlling motor circuits. Little is known about how projection neurons with distinct anatomical targets are organized, and few studies have addressed their spatial organization at the level of individual cells. In the paired commissural ganglia (CoGs) of the stomatogastric nervous system of the crab Cancer borealis, projection neurons convey sensory, motor, and modulatory information to several distinct anatomical regions. While the functions of descending projection neurons (dPNs) which control downstream motor circuits in the stomatogastric ganglion are well characterized, their anatomical distribution as well as that of neurons projecting to the labrum, brain, and thoracic ganglion have received less attention. Using cell membrane staining, we investigated the spatial distribution of CoG projection neurons in relation to all CoG neurons. Retrograde tracing revealed that somata associated with different axonal projection pathways were not completely spatially segregated, but had distinct preferences within the ganglion. Identified dPNs had diameters larger than 70% of CoG somata and were restricted to the most medial and anterior 25% of the ganglion. They were contained within a cluster of motor neurons projecting through the same nerve to innervate the labrum, indicating that soma position was independent of function and target area. Rather, our findings suggest that CoG neurons projecting to a variety of locations follow a generalized rule: for all nerve pathway origins, the soma cluster centroids in closest proximity are those whose axons project down that pathway. © 2017 Wiley Periodicals, Inc.

  10. Superficially projecting principal neurons in layer V of medial entorhinal cortex in the rat receive excitatory retrosplenial input.

    Science.gov (United States)

    Czajkowski, Rafał; Sugar, Jørgen; Zhang, Sheng-Jia; Couey, Jonathan J; Ye, Jing; Witter, Menno P

    2013-10-01

    Principal cells in layer V of the medial entorhinal cortex (MEC) have a nodal position in the cortical-hippocampal network. They are the main recipients of hippocampal output and receive inputs from several cortical areas, including a prominent one from the retrosplenial cortex (RSC), likely targeting basal dendrites of layer V neurons. The latter project to extrahippocampal structures but also relay information to the superficial layers of MEC, closing the hippocampal-entorhinal loop. In the rat, we electrophysiologically and morphologically characterized RSC input into MEC and conclude that RSC provides an excitatory input to layer V pyramidal cells. Ultrastructural analyses of anterogradely labeled RSC projections showed that RSC axons in layer V of MEC form predominantly asymmetrical, likely excitatory, synapses on dendritic spines (90%) or shafts (8%), with 2% symmetrical, likely inhibitory, synapses on shafts and spines. The overall excitatory nature of the RSC input was confirmed by an optogenetic approach. Patterned laser stimulation of channelrhodopsin-expressing presynaptic RSC axons evoked exclusively EPSPs in recorded postsynaptic layer V cells. All responding layer V pyramidal cells had an axon extending toward the white matter. Half of these neurons also sent an axon to superficial layers. Confocal imaging of RSC synapses onto MEC layer V neurons shown to project superficially by way of retrogradely labeling from superficial layers confirmed that proximal dendrites of superficially projecting cells are among the targets of inputs from RSC. The excitatory RSC input thus interacts with both entorhinal-cortical and entorhinal-hippocampal circuits.

  11. Castration modulates singing patterns and electrophysiological properties of RA projection neurons in adult male zebra finches

    Directory of Open Access Journals (Sweden)

    Songhua Wang

    2014-04-01

    Full Text Available Castration can change levels of plasma testosterone. Androgens such as testosterone play an important role in stabilizing birdsong. The robust nucleus of the arcopallium (RA is an important premotor nucleus critical for singing. In this study, we investigated the effect of castration on singing patterns and electrophysiological properties of projection neurons (PNs in the RA of adult male zebra finches. Adult male zebra finches were castrated and the changes in bird song assessed. We also recorded the electrophysiological changes from RA PNs using patch clamp recording. We found that the plasma levels of testosterone were significantly decreased, song syllable’s entropy was increased and the similarity of motif was decreased after castration. Spontaneous and evoked firing rates, membrane time constants, and membrane capacitance of RA PNs in the castration group were lower than those of the control and the sham groups. Afterhyperpolarization AHP time to peak of spontaneous action potential (AP was prolonged after castration.These findings suggest that castration decreases song stereotypy and excitability of RA PNs in male zebra finches.

  12. Pioneer neurons of the antennal nervous system project to protocerebral pioneers in the grasshopper Schistocerca gregaria.

    Science.gov (United States)

    Boyan, George; Ehrhardt, Erica

    2015-11-01

    The twin nerve tracts of the antenna of the grasshopper Schistocerca gregaria are established early in embryogenesis by sibling pairs of pioneers which delaminate from the epithelium into the lumen at the antennal tip. These cells can be uniquely identified via their co-expression of the neuronal labels horseradish peroxidase and the lipocalin Lazarillo. The apical pioneers direct axons toward the antennal base where they encounter guidepost-like cells called base pioneers which transiently express the same molecular labels as the apical pioneers. To what extent the pioneer growth cones then progress into the brain neuropil proper, and what their targets there might be, has remained unclear. In this study, we show that the apical antennal pioneers project centrally beyond the antennal base first into the deutocerebral, and then into the protocerebral brain neuropils. In the protocerebrum, we identify their target circuitry as being identified Lazarillo-positive cells which themselves pioneer the primary axon scaffold of the brain. The apical and base antennal pioneers therefore form part of a molecularly contiguous pathway from the periphery to an identified central circuit of the embryonic grasshopper brain.

  13. Local Circuits of V1 Layer 4B Neurons Projecting to V2 Thick Stripes Define Distinct Cell Classes and Avoid Cytochrome Oxidase Blobs.

    Science.gov (United States)

    Yarch, Jeff; Federer, Frederick; Angelucci, Alessandra

    2017-01-11

    Decades of anatomical studies on the primate primary visual cortex (V1) have led to a detailed diagram of V1 intrinsic circuitry, but this diagram lacks information about the output targets of V1 cells. Understanding how V1 local processing relates to downstream processing requires identification of neuronal populations defined by their output targets. In primates, V1 layers (L)2/3 and 4B send segregated projections to distinct cytochrome oxidase (CO) stripes in area V2: neurons in CO blob columns project to thin stripes while neurons outside blob columns project to thick and pale stripes, suggesting functional specialization of V1-to-V2 CO streams. However, the conventional diagram of V1 shows all L4B neurons, regardless of their soma location in blob or interblob columns, as projecting selectively to CO blobs in L2/3, suggesting convergence of blob/interblob information in L2/3 blobs and, possibly, some V2 stripes. However, it is unclear whether all L4B projection neurons show similar local circuitries. Using viral-mediated circuit tracing, we have identified the local circuits of L4B neurons projecting to V2 thick stripes in macaque. Consistent with previous studies, we found the somata of this L4B subpopulation to reside predominantly outside blob columns; however, unlike previous descriptions of local L4B circuits, these cells consistently projected outside CO blob columns in all layers. Thus, the local circuits of these L4B output neurons, just like their extrinsic projections to V2, preserve CO streams. Moreover, the intra-V1 laminar patterns of axonal projections identify two distinct neuron classes within this L4B subpopulation, including a rare novel neuron type, suggestive of two functionally specialized output channels.

  14. Subpallial origin of a population of projecting pioneer neurons during corticogenesis

    OpenAIRE

    Morante-Oria, Javier; Carleton, Alan; Ortino, Barbara; Eric J. Kremer; Fairén, Alfonso; Lledo, Pierre-Marie

    2003-01-01

    Pyramidal neurons of the mammalian cerebral cortex are generated in the ventricular zone of the pallium whereas the subpallium provides the cortex with inhibitory interneurons. The marginal zone contains a subpial stream of migratory interneurons and two different classes of transient neurons, the pioneer neurons provided with corticofugal axons, and the reelin-expressing Cajal–Retzius cells. We found in cultured slices that the medial ganglionic eminence provides the reelin-negative pioneer ...

  15. Hypoxia-excited neurons in NTS send axonal projections to Kölliker-Fuse/parabrachial complex in dorsolateral pons.

    Science.gov (United States)

    Song, G; Xu, H; Wang, H; Macdonald, S M; Poon, C-S

    2011-02-23

    Hypoxic respiratory and cardiovascular responses in mammals are mediated by peripheral chemoreceptor afferents which are relayed centrally via the solitary tract nucleus (NTS) in dorsomedial medulla to other cardiorespiratory-related brainstem regions such as ventrolateral medulla (VLM). Here, we test the hypothesis that peripheral chemoafferents could also be relayed directly to the Kölliker-Fuse/parabrachial complex in dorsolateral pons, an area traditionally thought to subserve pneumotaxic and cardiovascular regulation. Experiments were performed on adult Sprague-Dawley rats. Brainstem neurons with axons projecting to the dorsolateral pons were retrogradely labeled by microinjection with choleras toxin subunit B (CTB). Neurons involved in peripheral chemoreflex were identified by hypoxia-induced c-Fos expression. We found that double-labeled neurons (i.e. immunopositive to both CTB and c-Fos) were localized mostly in the commissural and medial subnuclei of NTS and to a lesser extent in the ventrolateral NTS subnucleus, VLM and ventrolateral pontine A5 region. Extracellular recordings from the commissural and medial NTS subnuclei revealed that some hypoxia-excited NTS neurons could be antidromically activated by electrical stimulations at the dorsolateral pons. These findings demonstrate that hypoxia-activated afferent inputs are relayed to the Kölliker-Fuse/parabrachial complex directly via the commissural and medial NTS and indirectly via the ventrolateral NTS subnucleus, VLM and A5 region. These pontine-projecting peripheral chemoafferent inputs may play an important role in the modulation of cardiorespiratory regulation by dorsolateral pons.

  16. Three Types of A11 Neurons Project to the Rat Spinal Cord.

    Science.gov (United States)

    Ozawa, Hidechika; Yamaguchi, Tsuyoshi; Hamaguchi, Shinsuke; Yamaguchi, Shigeki; Ueda, Shuichi

    2017-03-16

    The A11 dopaminergic cell group is the only group among the A8-A16 dopaminergic cell groups that includes neurons innervating the spinal cord, and a decrease in dopaminergic transmission at the spinal cord is thought to contribute to the pathogenesis of restless legs syndrome. However, the mechanisms regulating the neuronal activity of A11 dopaminergic neurons remain to be elucidated. Unraveling the neuronal composition, distribution and connectivity of A11 neurons would provide insights into the mechanisms regulating the spinal dopaminergic system. To address this, we performed immunohistochemistry for calcium-binding proteins such as calbindin (Calb) and parvalbumin (PV), in combination with the retrograde tracer Fluorogold (FG) injected into the spinal cord. Immunohistochemistry for Calb, PV, or tyrosine hydroxylase (TH), a marker for dopaminergic neurons, revealed that there were at least three types of neurons in the A11 region: neurons expressing Calb, TH, or both TH and Calb, whereas there were no PV-immunoreactive (IR) cell bodies. Both Calb- and PV-IR processes were found throughout the entire A11 region, extending in varied directions depending on the level relative to bregma. We found retrogradely labeled FG-positive neurons expressing TH, Calb, or both TH and Calb, as well as FG-positive neurons lacking both TH and Calb. These findings indicate that the A11 region is composed of a variety of neurons that are distinct in their neurochemical properties, and suggest that the diencephalospinal dopamine system may be regulated at the A11region by both Calb-IR and PV-IR processes, and at the terminal region of the spinal cord by Calb-IR processes derived from the A11 region.

  17. Inositol 1,4,5-Triphosphate Drives Glutamatergic and Cholinergic Inhibition Selectively in Spiny Projection Neurons in the Striatum

    OpenAIRE

    Clements, Michael A; Swapna, Immani; Morikawa, Hitoshi

    2013-01-01

    The striatum is critically involved in the selection of appropriate actions in a constantly changing environment. The spiking activity of striatal spiny projection neurons (SPNs), driven by extrinsic glutamatergic inputs, is shaped by local GABAergic and cholinergic networks. For example, it is well established that different types of GABAergic interneurons, activated by extrinsic glutamatergic and local cholinergic inputs, mediate powerful feedforward inhibition of SPN activity. In this stud...

  18. Human embryonic stem cell-derived neurons establish region-specific, long-range projections in the adult brain.

    Science.gov (United States)

    Steinbeck, Julius A; Koch, Philipp; Derouiche, Amin; Brüstle, Oliver

    2012-02-01

    While the availability of pluripotent stem cells has opened new prospects for generating neural donor cells for nervous system repair, their capability to integrate with adult brain tissue in a structurally relevant way is still largely unresolved. We addressed the potential of human embryonic stem cell-derived long-term self-renewing neuroepithelial stem cells (lt-NES cells) to establish axonal projections after transplantation into the adult rodent brain. Transgenic and species-specific markers were used to trace the innervation pattern established by transplants in the hippocampus and motor cortex. In vitro, lt-NES cells formed a complex axonal network within several weeks after the initiation of differentiation and expressed a composition of surface receptors known to be instrumental in axonal growth and pathfinding. In vivo, these donor cells adopted projection patterns closely mimicking endogenous projections in two different regions of the adult rodent brain. Hippocampal grafts placed in the dentate gyrus projected to both the ipsilateral and contralateral pyramidal cell layers, while axons of donor neurons placed in the motor cortex extended via the external and internal capsule into the cervical spinal cord and via the corpus callosum into the contralateral cortex. Interestingly, acquisition of these region-specific projection profiles was not correlated with the adoption of a regional phenotype. Upon reaching their destination, human axons established ultrastructural correlates of synaptic connections with host neurons. Together, these data indicate that neurons derived from human pluripotent stem cells are endowed with a remarkable potential to establish orthotopic long-range projections in the adult mammalian brain.

  19. SK channels modulate the excitability and firing precision of projection neurons in the robust nucleus of the arcopallium in adult male zebra finches

    Institute of Scientific and Technical Information of China (English)

    Guo-Qiang Hou; Xuan Pan; Cong-Shu Liao; Song-Hua Wang; Dong-Feng Li

    2012-01-01

    [Objective] Motor control is encoded by neuronal activity.Small conductance Ca2+-activated Kˉ channels (SK channels) maintain the regularity and precision of firing by contributing to the afterhyperpolarization (AHP) of the action potential in mammals.However,it is not clear how SK channels regulate the output of the vocal motor system in songbirds.The premotor robust nucleus of the arcopallium (RA) in the zebra finch is responsible for the output of song information.The temporal pattern of spike bursts in RA projection neurons is associated with the timing of the acoustic features of birdsong.[Methods] The firing properties of RA projection neurons were analyzed using patch clamp wholecell and cell-attached recording techniques.[Results] SK channel blockade by apamin decreased the AHP amplitude and increased the evoked firing rate in RA projection neurons.It also caused reductions in the regularity and precision of firing.RA projection neurons displayed regular spontaneous action potentials,while apamin caused irregular spontaneous firing but had no effect on the firing rate.In the absence of synaptic inputs,RA projection neurons still had spontaneous firing,and apamin had an evident effect on the firing rate,but caused no significant change in the firing regularity,compared with apamin application in the presence of synaptic inputs.[Conclusion]SK channels contribute to the maintenance of firing regularity in RA projection neurons whichrequires synaptic activity,and consequently ensures the precision of song encoding.

  20. The Order and Place of Neuronal Differentiation Establish the Topography of Sensory Projections and the Entry Points within the Hindbrain.

    Science.gov (United States)

    Zecca, Andrea; Dyballa, Sylvia; Voltes, Adria; Bradley, Roger; Pujades, Cristina

    2015-05-13

    Establishing topographical maps of the external world is an important but still poorly understood feature of the vertebrate sensory system. To study the selective innervation of hindbrain regions by sensory afferents in the zebrafish embryo, we mapped the fine-grained topographical representation of sensory projections at the central level by specific photoconversion of sensory neurons. Sensory ganglia located anteriorly project more medially than do ganglia located posteriorly, and this relates to the order of sensory ganglion differentiation. By single-plane illumination microscopy (SPIM) in vivo imaging, we show that (1) the sequence of arrival of cranial ganglion inputs predicts the topography of central projections, and (2) delaminated neuroblasts differentiate in close contact with the neural tube, and they never loose contact with the neural ectoderm. Afferent entrance points are established by plasma membrane interactions between primary differentiated peripheral sensory neurons and neural tube border cells with the cooperation of neural crest cells. These first contacts remain during ensuing morphological growth to establish pioneer axons. Neural crest cells and repulsive slit1/robo2 signals then guide axons from later-differentiating neurons toward the neural tube. Thus, this study proposes a new model by which the topographical representation of cranial sensory ganglia is established by entrance order, with the entry points determined by cell contact between the sensory ganglion cell bodies and the hindbrain.

  1. Overexpression of GAP-43 in thalamic projection neurons of transgenic mice does not enable them to regenerate axons through peripheral nerve grafts.

    Science.gov (United States)

    Mason, M R; Campbell, G; Caroni, P; Anderson, P N; Lieberman, A R

    2000-09-01

    It is well established that some populations of neurons of the adult rat central nervous system (CNS) will regenerate axons into a peripheral nerve implant, but others, including most thalamocortical projection neurons, will not. The ability to regenerate axons may depend on whether neurons can express growth-related genes such as GAP-43, whose expression correlates with axon growth during development and with competence to regenerate. Thalamic projection neurons which fail to regenerate into a graft also fail to upregulate GAP-43. We have tested the hypothesis that the absence of strong GAP-43 expression by the thalamic projection neurons prevents them from regenerating their axons, using transgenic mice which overexpress GAP-43. Transgene expression was mapped by in situ hybridization with a digoxigenin-labeled RNA probe and by immunohistochemistry with a monoclonal antibody against the GAP-43 protein produced by the transgene. Many CNS neurons were found to express the mRNA and protein, including neurons of the mediodorsal and ventromedial thalamic nuclei, which rarely regenerate axons into peripheral nerve grafts. Grafts were implanted into the region of these nuclei in the brains of transgenic animals. Although these neurons strongly expressed the transgene mRNA and protein and transported the protein to their axon terminals, they did not regenerate axons into the graft, suggesting that lack of GAP-43 expression is not the only factor preventing thalamocortical neurons regenerating their axons. Copyright 2000 Academic Press.

  2. Differentiation of pluripotent stem cells into striatal projection neurons: a pure MSN fate may not be sufficient

    Directory of Open Access Journals (Sweden)

    Amy eReddington

    2014-12-01

    Full Text Available Huntington’s disease (HD is an autosomal dominant inherited disorder leading to the loss of DARPP-32 medium spiny projection neurons (‘MSNs’ in the striatum. The relative specificity of cell loss early in HD has made cell replacement by neural transplantation an attractive therapeutic possibility. Transplantation of human fetal striatal precursors has shown ‘proof-of-principle’ in clinical trials; however, the practical and ethical difficulty associated with sourcing fetal tissue has stimulated the need to identify alternative sources of donor cells that are more readily available and suitable for standardisation. The first generation of protocols to generate DARPP-32 positive MSN-like neurons from pluripotent stem cells are now available and have been successfully grafted in animal models of HD. However, whether these grafts can provide stable functional recovery to the level that can regularly be achieved with primary fetal striatal grafts remains to be demonstrated. Of particular concern, primary fetal striatal grafts are not homogeneous; they contain not only the MSN subpopulation of striatal projection neurons but also include diverse neuronal and glia cell types of the mature striatum that certainly contribute to normal striatal function. By contrast, present protocols for pluripotent stem cell differentiation just target specifying neurons of an MSN lineage, and evidence for functional integration of stem-cell derived grafts is correspondingly limited. Indeed, consideration of the features of full striatal reconstruction that is achieved with primary fetal striatal grafts suggests that effective stem cell-based therapy in HD will require that graft protocols be developed to allow inclusion of multiple striatal cell types, including interneurons and striatal glia. A rational solution to this technical challenge requires that we re-address the underlying question – what constitutes a functional striatal graft?

  3. Modulation of the activity of vasopressinergic neurons by estrogen in rats refed with normal or sodium-free food after fasting.

    Science.gov (United States)

    Lucio-Oliveira, F; Traslaviña, G A A; Borges, B D B; Franci, C R

    2015-01-22

    Feeding increases plasma osmolality and ovarian steroids may influence the balance of fluids. Vasopressin (AVP) neurons in the paraventricular nucleus (PVN) and supraoptic nucleus (SON) express estrogen receptor type β (ERβ), but not estrogen receptor type α (ERα). The circumventricular organs express ERα and project efferent fibers to the PVN and SON. Our aim was to assess whether interactions exist between food state-related osmolality changes and the action of estrogen on AVP neuron activity and estrogen receptor expression. We assessed plasma osmolality and AVP levels; fos-coded protein (FOS)- and AVP-immunoreactivity (-IR) and FOS-IR and ERα-IR in the median preoptic nucleus (MnPO) and organ vasculosum lamina terminalis (OVLT) in estrogen-primed and unprimed ovariectomized rats under the provision of ad libitum food, 48h of fasting, and subsequent refeeding with standard chow or sodium-free food. Refeeding with standard chow increased plasma osmolality and AVP as well as the co-expression of FOS-IR/AVP-IR in the PVN and SON. These responses were not altered by estrogen, with the exception of the decreases in FOS-IR/AVP-IR in the lateral PVN. During refeeding, estrogen modulates only a subpopulation of AVP neurons in the lateral PVN. FOS-ERα co-expression in the ventral median preoptic nucleus (vMnPO) was reduced by estrogen and increased after refeeding with standard chow following fasting. It appears that estrogen may indirectly modulate the activity of AVP neurons, which are involved in the mechanism affected by hyperosmolality-induced refeeding after fasting. This indirect action of estrogen can be at least in part via ERα in the vMnPO.

  4. Integration of stress and leptin signaling by CART producing neurons in the rodent midbrain centrally projecting Edinger-Westphal nucleus.

    Science.gov (United States)

    Xu, Lu; Janssen, Donny; van der Knaap, Noortje; Roubos, Eric W; Leshan, Rebecca L; Myers, Martin G; Gaszner, Balázs; Kozicz, Tamás

    2014-01-01

    Leptin targets the brain to regulate feeding, neuroendocrine function and metabolism. The leptin receptor is present in hypothalamic centers controlling energy metabolism as well as in the centrally projecting Edinger-Westphal nucleus (EWcp), a region implicated in the stress response and in various aspects of stress-related behaviors. We hypothesized that the stress response by cocaine- and amphetamine-regulated transcript (CART)-producing EWcp-neurons would depend on the animal's energy state. To test this hypothesis, we investigated the effects of changes in energy state (mimicked by low, normal and high leptin levels, which were achieved by 24 h fasting, normal chow and leptin injection, respectively) on the response of CART neurons in the EWcp of rats subjected or not to acute restraint stress. Our data show that leptin treatment alone significantly increases CART mRNA expression in the rat EWcp and that in leptin receptor deficient (db/db) mice, the number of CART producing neurons in this nucleus is reduced. This suggests that leptin has a stimulatory effect on the production of CART in the EWcp under non-stressed condition. Under stressed condition, however, leptin blunts stress-induced activation of EWcp neurons and decreases their CART mRNA expression. Interestingly, fasting, does not influence the stress-induced activation of EWcp-neurons, and specifically EWcp-CART neurons are not activated. These results suggest that the stress response by the EWcp depends to some degree on the animal's energy state, a mechanism that may contribute to a better understanding of the complex interplay between obesity and stress.

  5. Integration of stress and leptin signaling by CART producing neurons in the rodent midbrain centrally projecting Edinger-Westphal nucleus

    Directory of Open Access Journals (Sweden)

    Lu eXu

    2014-03-01

    Full Text Available Leptin targets the brain to regulate feeding, neuroendocrine function and metabolism. The leptin receptor is present in hypothalamic centers controlling energy metabolism as well as in the centrally projecting Edinger-Westphal nucleus (EWcp, a region implicated in the stress response and in various aspects of stress-related behaviors. We hypothesized that the stress response by cocaine- and amphetamine-regulated transcript (CART-producing EWcp-neurons would depend on the animal’s energy state. To test this hypothesis, we investigated the effects of changes in energy state (mimicked by low, normal and high leptin levels, which were achieved by 24h fasting, normal chow and leptin injection, respectively on the response of CART neurons in the EWcp of rats subjected or not to acute restraint stress. Our data show that leptin treatment alone significantly increases CART mRNA expression in the rat EWcp and that in leptin receptor deficient (db/db mice, the number of CART producing neurons in this nucleus is reduced. This suggests that leptin has a stimulatory effect on the production of CART in the EWcp under non-stressed condition. Under stressed condition, however, leptin blunts stress-induced activation of EWcp neurons and decreases their CART mRNA expression. Interestingly, fasting, does not influence the stress-induced activation of EWcp-neurons, and specifically EWcp-CART neurons are not activated. These results suggest that the stress response by the EWcp depends to some degree on the animal’s energy state, a mechanism that may contribute to a better understanding of the complex interplay between obesity and stress.

  6. Cultured networks of excitatory projection neurons and inhibitory interneurons for studying human cortical neurotoxicity.

    Science.gov (United States)

    Xu, Jin-Chong; Fan, Jing; Wang, Xueqing; Eacker, Stephen M; Kam, Tae-In; Chen, Li; Yin, Xiling; Zhu, Juehua; Chi, Zhikai; Jiang, Haisong; Chen, Rong; Dawson, Ted M; Dawson, Valina L

    2016-04-06

    Translating neuroprotective treatments from discovery in cell and animal models to the clinic has proven challenging. To reduce the gap between basic studies of neurotoxicity and neuroprotection and clinically relevant therapies, we developed a human cortical neuron culture system from human embryonic stem cells or human inducible pluripotent stem cells that generated both excitatory and inhibitory neuronal networks resembling the composition of the human cortex. This methodology used timed administration of retinoic acid to FOXG1(+) neural precursor cells leading to differentiation of neuronal populations representative of the six cortical layers with both excitatory and inhibitory neuronal networks that were functional and homeostatically stable. In human cortical neuronal cultures, excitotoxicity or ischemia due to oxygen and glucose deprivation led to cell death that was dependent on N-methyl-D-aspartate (NMDA) receptors, nitric oxide (NO), and poly(ADP-ribose) polymerase (PARP) (a cell death pathway called parthanatos that is distinct from apoptosis, necroptosis, and other forms of cell death). Neuronal cell death was attenuated by PARP inhibitors that are currently in clinical trials for cancer treatment. This culture system provides a new platform for the study of human cortical neurotoxicity and suggests that PARP inhibitors may be useful for ameliorating excitotoxic and ischemic cell death in human neurons.

  7. Overexpression of 5-HT1B mRNA in nucleus accumbens shell projection neurons differentially affects microarchitecture of initiation and maintenance of ethanol consumption

    OpenAIRE

    Furay, AR; Neumaier, JF; Mullenix, AT; Kaiyala, KK; Sandygren, N; Hoplight, BJ

    2010-01-01

    Serotonin 1B (5-HT1B) heteroreceptors on nucleus accumbens shell (NAcSh) projection neurons have been shown to enhance the voluntary consumption of alcohol by rats, presumably by modulating the activity of the mesolimbic reward pathway. The present study examined whether increasing 5-HT1B receptors expressed on NAcSh projection neurons via viral mediated gene transfer enhances ethanol consumption during the initiation or maintenance phase of drinking and alters the temporal pattern of drinkin...

  8. Glial cells modulate the synaptic transmission of NTS neurons sending projections to ventral medulla of Wistar rats.

    Science.gov (United States)

    Accorsi-Mendonça, Daniela; Zoccal, Daniel B; Bonagamba, Leni G H; Machado, Benedito H

    2013-09-01

    There is evidence that sympathoexcitatory and respiratory responses to chemoreflex activation involve ventrolateral medulla-projecting nucleus tractus solitarius (NTS) neurons (NTS-VLM neurons) and also that ATP modulates this neurotransmission. Here, we evaluated whether or not astrocytes is the source of endogenous ATP modulating the synaptic transmission in NTS-VLM neurons. Synaptic activities of putative astrocytes or NTS-VLM neurons were recorded using whole cell patch clamp. Tractus solitarius (TS) stimulation induced TS-evoked excitatory postsynaptic currents (TS-eEPSCs) in NTS-VLM neurons as well in NTS putative astrocytes, which were also identified by previous labeling. Fluoracetate (FAC), an inhibitor of glial metabolism, reduced TS-eEPSCs amplitude (-85.6 ± 16 vs. -39 ± 7.1 pA, n = 12) and sEPSCs frequency (2.8 ± 0.5 vs. 1.8 ± 0.46 Hz, n = 10) in recorded NTS-VLM neurons, indicating a gliomodulation of glutamatergic currents. To verify the involvement of endogenous ATP a purinergic antagonist was used, which reduced the TS-eEPSCs amplitude (-207 ± 50 vs. -149 ± 50 pA, n = 6), the sEPSCs frequency (1.19 ± 0.2 vs. 0.62 ± 0.11 Hz, n = 6), and increased the paired-pulse ratio (PPR) values (∼20%) in NTS-VLM neurons. Simultaneous perfusion of Pyridoxalphosphate-6-azophenyl-2',5'-disulfonic acid (iso-PPADS) and FAC produced reduction in TS-eEPSCs similar to that observed with iso-PPADS or FAC alone, indicating that glial cells are the source of ATP released after TS stimulation. Extracellular ATP measurement showed that FAC reduced evoked and spontaneous ATP release. All together these data show that putative astrocytes are the source of endogenous ATP, which via activation of presynaptic P2X receptors, facilitates the evoked glutamate release and increases the synaptic transmission efficacy in the NTS-VLM neurons probably involved with the peripheral chemoreflex pathways.

  9. Endogenous GLP-1 acts on paraventricular nucleus to suppress feeding: projection from nucleus tractus solitarius and activation of corticotropin-releasing hormone, nesfatin-1 and oxytocin neurons.

    Science.gov (United States)

    Katsurada, Kenichi; Maejima, Yuko; Nakata, Masanori; Kodaira, Misato; Suyama, Shigetomo; Iwasaki, Yusaku; Kario, Kazuomi; Yada, Toshihiko

    2014-08-22

    Glucagon-like peptide-1 (GLP-1) receptor agonists have been used to treat type 2 diabetic patients and shown to reduce food intake and body weight. The anorexigenic effects of GLP-1 and GLP-1 receptor agonists are thought to be mediated primarily via the hypothalamic paraventricular nucleus (PVN). GLP-1, an intestinal hormone, is also localized in the nucleus tractus solitarius (NTS) of the brain stem. However, the role of endogenous GLP-1, particularly that in the NTS neurons, in feeding regulation remains to be established. The present study examined whether the NTS GLP-1 neurons project to PVN and whether the endogenous GLP-1 acts on PVN to restrict feeding. Intra-PVN injection of GLP-1 receptor antagonist exendin (9-39) increased food intake. Injection of retrograde tracer into PVN combined with immunohistochemistry for GLP-1 in NTS revealed direct projection of NTS GLP-1 neurons to PVN. Moreover, GLP-1 evoked Ca(2+) signaling in single neurons isolated from PVN. The majority of GLP-1-responsive neurons were immunoreactive predominantly to corticotropin-releasing hormone (CRH) and nesfatin-1, and less frequently to oxytocin. These results indicate that endogenous GLP-1 targets PVN to restrict feeding behavior, in which the projection from NTS GLP-1 neurons and activation of CRH and nesfatin-1 neurons might be implicated. This study reveals a neuronal basis for the anorexigenic effect of endogenous GLP-1 in the brain.

  10. Do sensory calcitonin gene-related peptide nerve fibres in the rat pelvic plexus supply autonomic neurons projecting to the uterus and cervix?

    Science.gov (United States)

    Houdeau, E; Barranger, E; Rossano, B

    2002-10-25

    Sensory nerve fibres containing calcitonin gene-related peptide (CGRP) innervate neurons of the paracervical ganglion (PCG) in the female rat pelvic plexus. We have combined retrograde tracing with immunocytochemistry to investigate whether CGRP-immunoreactive (-IR) fibres supply neurons targeting the genital tract. Of the total neurons projecting to either the uterine horns or the cervix, 38 and 41% received CGRP-IR innervation, respectively. All these neurons displayed choline acetyltransferase-IR, thus are cholinergic. They were found throughout the PCG and other pelvic plexus ganglia, namely accessory ganglia (AG) and hypogastric plexus (HP). Pelvic nerve section showed that afferent fibres in these nerves provided most of the CGRP-IR fibres supplying uterine- or cervical-related neurons in the PCG/AG, none in HP. It is suggested that such sensory-motor network may provide a local pathway for reflex control of genital tract activity, acting through cholinergic nerve projections.

  11. Disinhibition of neurons of the nucleus of solitary tract that project to the superior salivatory nucleus causes choroidal vasodilation: Implications for mechanisms underlying choroidal baroregulation.

    Science.gov (United States)

    Li, Chunyan; Fitzgerald, Malinda E C; Del Mar, Nobel; Reiner, Anton

    2016-10-28

    Preganglionic neurons in the superior salivatory nucleus (SSN) that mediate parasympathetic vasodilation of choroidal blood vessels receive a major excitatory input from the baroresponsive part of the nucleus of the solitary tract (NTS). This input appears likely to mediate choroidal vasodilation during systemic hypotension, which prevents decreases in choroidal blood flow (ChBF) due to reduced perfusion pressure. It is uncertain, however, how low blood pressure signals to NTS from the aortic depressor nerve (ADN), which fires at a low rate during systemic hypotension, could yield increased firing in the NTS output to SSN. The simplest hypothesis is that SSN-projecting NTS neurons are under the inhibitory control of ADN-receptive GABAergic NTS neurons. As part of evaluating this hypothesis, we assessed if SSN-projecting NTS neurons, in fact, receive prominent inhibitory input and if blocking GABAergic modulation of them increases ChBF. We found that SSN-projecting NTS neuronal perikarya identified by retrograde labeling are densely coated with GABAergic terminals, but lightly coated with excitatory terminals. We also found that, infusion of the GABA-A receptor antagonist GABAzine into NTS increased ChBF. Our results are consistent with the possibility that low blood pressure signals from the ADN produce vasodilation in choroid by causing diminished activity in ADN-receptive NTS neurons that tonically suppress SSN-projecting NTS neurons.

  12. Whole-brain Mapping of the Direct Inputs and Axonal Projections of Pro-opiomelanocortin(POMC and Agouti-related peptide(AgRP Neurons

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    Daqing ewang

    2015-03-01

    Full Text Available Pro-opiomelanocortin (POMC neurons in the arcuate nucleus (ARC of the hypothalamus and nucleus tractus solitarius (NTS of the brainstem play important roles in suppressing food intake and maintaining energy homeostasis. Previous tract-tracing studies have revealed the axonal connection patterns of these two brain areas, but the intermingling of POMC neurons with other neuron types has made it challenging to precisely identify the inputs and outputs of POMC neurons. In this study, we used the modified rabies virus to map the brain areas that provide direct inputs to the POMC neurons in the ARC and NTS as well as the inputs to the ARC AgRP neurons for comparison. ARC POMC neurons receive inputs from dozens of discrete structures throughout the forebrain and brainstem. The brain areas containing the presynaptic partners of ARC POMC neurons largely overlap with those of ARC AgRP neurons, although POMC neurons receive relatively broader, denser inputs. Furthermore, POMC neurons in the NTS receive direct inputs predominantly from the brainstem and show very different innervation patterns for POMC neurons in the ARC. By selectively expressing fluorescent markers in the ARC and NTS POMC neurons, we found that almost all of their major presynaptic partners are innervated by POMC neurons in the two areas, suggesting that there are strong reciprocal projections among the major POMC neural pathways. By comprehensively chartering the whole-brain connections of the central melanocortin system in a cell-type-specific manner, this study lays the foundation for dissecting the roles and underlying circuit mechanisms of specific neural pathways in regulating energy homeostasis.

  13. Neurons Containing Orexin or Melanin Concentrating Hormone Reciprocally Regulate Wake and Sleep

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    Roda Rani eKonadhode

    2015-01-01

    Full Text Available There is considerable amount of data on arousal neurons whereas there is a paucity of knowledge regarding neurons that make us fall asleep. Indeed, current network models of sleep-wake regulation list many arousal neuronal populations compared to only one sleep group located in the preoptic area. There are neurons outside the preoptic area that are active during sleep, but they have never been selectively manipulated. Indeed, none of the sleep-active neurons have been selectively stimulated. To close this knowledge gap we used optogenetics to selectively manipulate neurons containing melanin concentrating hormone (MCH. The MCH neurons are located in the posterior hypothalamus intermingled with the orexin arousal neurons. Our data indicated that optogenetic stimulation of MCH neurons in wildtype mice (J Neuroscience, 2013 robustly increased both non-REM and REM sleep. MCH neuron stimulation increased sleep during the animal’s normal active period, which is compelling evidence that stimulation of MCH neurons has a powerful effect in counteracting the strong arousal signal from all of the arousal neurons. The MCH neurons represent the only group of sleep-active neurons that when selectively stimulated induce sleep. From a translational perspective this is potentially useful in sleep disorders, such as insomnia, where sleep needs to be triggered against a strong arousal drive. Our studies indicate that the MCH neurons belong within an overall model of sleep-wake regulation.

  14. Bcl-2 enhances the formation of newborn striatal long-projection neurons in adult rat brain after a transient ischemic stroke

    Institute of Scientific and Technical Information of China (English)

    Jian-Jun Guo; Fang Liu; Xiao Sun; Jun-Jie Huang; Ming Xu; Feng-Yan Sun

    2012-01-01

    Objective It has been reported that B-cell lymphoma 2 (Bcl-2) enhances neurogenesis as well as supporting axonal growth after injury.In the present study,we investigated whether Bcl-2 overexpression plays a role in the formation of newborn striatonigral projection neurons in the adult rat brain after transient middle cerebral artery occlusion (MCAO).Methods We infused human Bcl-2-expressing plasmid (pBcl-2) into the lateral ventricle immediately after 30 min of MCAO,injected 5'-bromodeoxyuridine (BrdU) intraperitoneally to label proliferative cells,and microinjected fluorogold (FG) into the substantia nigra at 11 weeks of reperfusion followed by multiple immunostaining of striatonigral projection neurons at 12 weeks.Results We found that pBcl-2 treatment significantly increased the number of newborn neurons (BrdU+-NeuN+) in the striatum ipsilateral to the MCAO.We further detected newborn striatonigral projection neurons (BrdU+-FG+-NeuN+) in the ipsilateral striatum at 12 weeks.More interestingly,the number of newborn striatonigral projection neurons (BrdU+-FG+) was significantly increased by pBcl-2 treatment compared to that by pEGFP,a control plasmid.Conclusion Taken together,we found that Bcl-2 overexpression in the brain enhanced the generation of newborn striatonigral projection neurons.This provides a potential strategy for promoting the reestablishment of neural networks and brain repair after ischemic injury.

  15. Anatomical distribution of estrogen target neurons in turtle brain

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    Kim, Y.S.; Stumpf, W.E.; Sar, M. (North Carolina Univ., Chapel Hill (USA))

    1981-12-28

    Autoradiographic studies with (/sup 3/H)estradiol-17..beta.. in red-eared turtle (Pseudemys scripta elegans) show concentration and retention of radioactivity in nuclei of neurons in certain regions. Accumulations of estrogen target neurons exist in the periventricular brain with relationships to ventral extensions of the forebrain ventricles, including parolfactory, amygdaloid, septal, preoptic, hypothalamic and thalamic areas, as well as the dorsal ventricular ridge, the piriform cortex, and midbrain-pontine periaqueductal structures. The general anatomical pattern of distribution of estrogen target neurons corresponds to those observed not only in another reptile (Anolis carolinensis), but also in birds and mammals, as well as in teleosts and cyclostomes. In Pseudemys, which appears to display an intermediate degree of phylogenetic differentiation, the amygdaloid-septal-preoptic groups of estrogen target neurons constitute a continuum. In phylogenetic ascendency, e.g. in mammals, these cell populations are increasingly separated and distinct, while in phylogenetic descendency, e.g. in teleosts and cyclostomes, an amygdaloid group appears to be absent or contained within the septal-preoptic target cell population.

  16. Activation of organum vasculosum of lamina terminalis, median preoptic nucleus, and medial preoptic area in anticipation of nursing in rabbit pups.

    Science.gov (United States)

    Moreno, María Luisa; Meza, Enrique; Morgado, Elvira; Juárez, Claudia; Ramos-Ligonio, Angel; Ortega, Arturo; Caba, Mario

    2013-12-01

    Rhythmic feeding in rabbit pups is a natural model to study food entrainment because, similar to rodents under a schedule of food restriction, these animals show food-anticipatory activity (FAA) prior to daily nursing. In rodents, several brain systems, including the orexinergic system, shift their activity to the restricted feeding schedule, and remain active when subjects are hungry. As the lamina terminalis and regions of the preoptic area participate in the control of behavioral arousal, it was hypothesized that these brain regions are also activated during FAA. Thus, the effects of daily milk ingestion on FOS protein expression in the organum vasculosum of lamina terminalis (OVLT), median preoptic nucleus (MnPO), and medial preoptic area (MPOA) were examined using immunohistochemistry before and after scheduled time of nursing in nursed and fasted subjects. Additionally, FOS expression was explored in orexin (ORX) cells in the lateral hypothalamic area and in the supraoptic nucleus (SON) because of their involvement in arousal and fluid ingestion, respectively. Pups were entrained by daily nursing, as indicated by a significant increase in locomotor behavior before scheduled time of nursing in both nursed and fasted subjects. FOS was significantly higher in the OVLT, MnPO, and MPOA at the time of nursing, and decreased 8 h later in nursed pups. In fasted subjects, this effect persisted in the OVLT, whereas in the MnPO and MPOA, values did not drop at 8 h later, but remained at the same level or higher than those at the time of scheduled nursing. In addition, FOS was significantly higher in ORX cells during FAA in nursed pups in comparison with 8 h later, but in fasted subjects it remained high during most fasting time points. Additionally, OVLT, SON, and ORX cells were activated 1.5 h after nursing. We conclude that the OVLT, MnPO, and MPOA, but not SON, may participate in FAA, as they show activation before suckling of periodic milk ingestion, and that

  17. Collateral projections of neurons in laminae I, III, and IV of rat spinal cord to thalamus, periaqueductal gray matter, and lateral parabrachial area.

    Science.gov (United States)

    Al-Khater, Khulood M; Todd, Andrew J

    2009-08-20

    Projection neurons in lamina I, together with those in laminae III-IV that express the neurokinin 1 receptor (NK1r), form a major route through which nociceptive information reaches the brain. Axons of these cells innervate various targets, including thalamus, periaqueductal gray matter (PAG), and lateral parabrachial area (LPb), and many cells project to more than one target. The aims of this study were to quantify projections from cervical enlargement to PAG and LPb, to determine the proportion of spinothalamic neurons at lumbar and cervical levels that were labelled from PAG and LPb, and to investigate morphological differences between projection populations. The C7 segment contained fewer lamina I spinoparabrachial cells than L4, but a similar number of spino-PAG cells. Virtually all spinothalamic lamina I neurons at both levels were labelled from LPb and between one-third and one-half from PAG. This suggests that significant numbers project to all three targets. Spinothalamic lamina I neurons differed from those labelled only from LPb in that they were generally larger, were more often multipolar, and (in cervical enlargement) had stronger NK1r immunoreactivity. Most lamina III/IV NK1r cells at both levels projected to LPb, but few were labelled from PAG. The great majority of these cells in C7 and over one-fourth of those in L4 were spinothalamic, and at each level some projected to both thalamus and LPb. These results confirm that neurons in these laminae have extensive collateral projections and suggest that different neuronal subpopulations in lamina I have characteristic patterns of supraspinal projection.

  18. Monosynaptic convergence of somatic and visceral C-fiber afferents on projection and local circuit neurons in lamina I: a substrate for referred pain.

    Science.gov (United States)

    Luz, Liliana L; Fernandes, Elisabete C; Sivado, Miklos; Kokai, Eva; Szucs, Peter; Safronov, Boris V

    2015-10-01

    Referred pain is a phenomenon of feeling pain at a site other than the site of the painful stimulus origin. It arises from a pathological mixing of nociceptive processing pathways for visceral and somatic inputs. Despite numerous studies based on unit recordings from spinal and supraspinal neurons, the exact mechanism and site of this mixing within the central nervous system are not known. Here, we selectively recorded from lamina I neurons, using a visually guided patch-clamp technique, in thoracic spinal cord preparation with preserved intercostal (somatic) and splanchnic (visceral) nerves. We show that somatic and visceral C fibers converge monosynaptically onto a group of lamina I neurons, which includes both projection and local circuit neurons. Other groups of lamina I neurons received inputs from either somatic or visceral afferents. We have also identified a population of lamina I local circuit neurons showing overall inhibitory responses upon stimulation of both nerves. Thus, the present data allow us to draw two major conclusions. First, lamina I of the spinal cord is the first site in the central nervous system where somatic and visceral pathways directly converge onto individual projection and local circuit neurons. Second, the mechanism of somatovisceral convergence is complex and based on functional integration of monosynaptic and polysynaptic excitatory as well as inhibitory inputs in specific groups of neurons. This complex pattern of convergence provides a substrate for alterations in the balance between visceral and somatic inputs causing referred pain.

  19. Parallel olfactory processing in the honey bee brain: odor learning and generalization under selective lesion of a projection neuron tract

    Directory of Open Access Journals (Sweden)

    Julie eCarcaud

    2016-01-01

    Full Text Available The function of parallel neural processing is a fundamental problem in Neuroscience, as it is found across sensory modalities and evolutionary lineages, from insects to humans. Recently, parallel processing has attracted increased attention in the olfactory domain, with the demonstration in both insects and mammals that different populations of second-order neurons encode and/or process odorant information differently. Among insects, Hymenoptera present a striking olfactory system with a clear neural dichotomy from the periphery to higher-order centers, based on two main tracts of second-order (projection neurons: the medial and lateral antennal lobe tracts (m-ALT and l-ALT. To unravel the functional role of these two pathways, we combined specific lesions of the m-ALT tract with behavioral experiments, using the classical conditioning of the proboscis extension response (PER conditioning. Lesioned and intact bees had to learn to associate an odorant (1-nonanol with sucrose. Then the bees were subjected to a generalization procedure with a range of odorants differing in terms of their carbon chain length or functional group. We show that m-ALT lesion strongly affects acquisition of an odor-sucrose association. However, lesioned bees that still learned the association showed a normal gradient of decreasing generalization responses to increasingly dissimilar odorants. Generalization responses could be predicted to some extent by in vivo calcium imaging recordings of l-ALT neurons. The m-ALT pathway therefore seems necessary for normal classical olfactory conditioning performance.

  20. Parallel Olfactory Processing in the Honey Bee Brain: Odor Learning and Generalization under Selective Lesion of a Projection Neuron Tract.

    Science.gov (United States)

    Carcaud, Julie; Giurfa, Martin; Sandoz, Jean Christophe

    2015-01-01

    The function of parallel neural processing is a fundamental problem in Neuroscience, as it is found across sensory modalities and evolutionary lineages, from insects to humans. Recently, parallel processing has attracted increased attention in the olfactory domain, with the demonstration in both insects and mammals that different populations of second-order neurons encode and/or process odorant information differently. Among insects, Hymenoptera present a striking olfactory system with a clear neural dichotomy from the periphery to higher-order centers, based on two main tracts of second-order (projection) neurons: the medial and lateral antennal lobe tracts (m-ALT and l-ALT). To unravel the functional role of these two pathways, we combined specific lesions of the m-ALT tract with behavioral experiments, using the classical conditioning of the proboscis extension response (PER conditioning). Lesioned and intact bees had to learn to associate an odorant (1-nonanol) with sucrose. Then the bees were subjected to a generalization procedure with a range of odorants differing in terms of their carbon chain length or functional group. We show that m-ALT lesion strongly affects acquisition of an odor-sucrose association. However, lesioned bees that still learned the association showed a normal gradient of decreasing generalization responses to increasingly dissimilar odorants. Generalization responses could be predicted to some extent by in vivo calcium imaging recordings of l-ALT neurons. The m-ALT pathway therefore seems necessary for normal classical olfactory conditioning performance.

  1. Molecular pathways underlying projection neuron production and migration during cerebral cortical development

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    Chiaki eOhtaka-Maruyama

    2015-12-01

    Full Text Available Glutamatergic neurons of the mammalian cerebral cortex originate from the radial glia (RG progenitors in the ventricular zone (VZ. During corticogenesis, neuroblasts migrate toward the pial surface using two different migration modes. One is multipolar (MP migration with random directional movement, and the other is locomotion, which is a unidirectional movement guided by the RG fiber. After reaching their final destination, the neurons finalize their migration by terminal translocation, which is followed by maturation via dendrite extension to initiate synaptogenesis and thereby complete neural circuit formation. This switching of migration modes during cortical development is unique in mammals, which suggests that the RG-guided locomotion mode may contribute to the evolution of the mammalian neocortical 6-layer structure. Many factors have been reported to be involved in the regulation of this radial neuronal migration process. In general, the radial migration can be largely divided into four steps; (1 maintenance and departure from the VZ of neural progenitor cells, (2 MP migration and transition to bipolar cells, (3 RG-guided locomotion, and (4 terminal translocation and dendrite maturation. Among these, many different gene mutations or knockdown effects have resulted in failure of the MP to bipolar transition (step 2, suggesting that it is a critical step, particularly in radial migration. Moreover, this transition occurs at the subplate layer. In this review, we summarize recent advances in our understanding of the molecular mechanisms underlying each of these steps. Finally, we discuss the evolutionary aspects of neuronal migration in corticogenesis.

  2. Neuronal projections from the Haller's organ and palp sensilla to the synganglion of Amblyomma americanum

    Science.gov (United States)

    The present study was conducted to elucidate the neuronal pathways between peripheral olfactory and taste sensilla and the synganglion in an Ixodidae tick species. The tarsus of the front legs (olfactory nerves) and the fourth palpal segment (gustatory nerves) of unfed Amblyomma americanum males and...

  3. Fate-mapping the mammalian hindbrain: segmental origins of vestibular projection neurons assessed using rhombomere-specific Hoxa2 enhancer elements in the mouse embryo.

    Science.gov (United States)

    Pasqualetti, Massimo; Díaz, Carmen; Renaud, Jean-Sébastien; Rijli, Filippo M; Glover, Joel C

    2007-09-05

    As a step toward generating a fate map of identified neuron populations in the mammalian hindbrain, we assessed the contributions of individual rhombomeres to the vestibular nuclear complex, a major sensorimotor area that spans the entire rhombencephalon. Transgenic mice harboring either the lacZ or the enhanced green fluorescent protein reporter genes under the transcriptional control of rhombomere-specific Hoxa2 enhancer elements were used to visualize rhombomere-derived domains. We labeled functionally identifiable vestibular projection neuron groups retrogradely with conjugated dextran-amines at successive embryonic stages and obtained developmental fate maps through direct comparison with the rhombomere-derived domains in the same embryos. The fate maps show that each vestibular neuron group derives from a unique rostrocaudal domain that is relatively stable developmentally, suggesting that anteroposterior migration is not a major contributor to the rostrocaudal patterning of the vestibular system. Most of the groups are multisegmental in origin, and each rhombomere is fated to give rise to two or more vestibular projection neuron types, in a complex pattern that is not segmentally iterated. Comparison with studies in the chicken embryo shows that the rostrocaudal patterning of identified vestibular projection neuron groups is generally well conserved between avians and mammalians but that significant species-specific differences exist in the rostrocaudal limits of particular groups. This mammalian hindbrain fate map can be used as the basis for targeting genetic manipulation to specific subpopulations of vestibular projection neurons.

  4. Rapid mapping of visual receptive fields by filtered back projection: application to multi-neuronal electrophysiology and imaging.

    Science.gov (United States)

    Johnston, Jamie; Ding, Huayu; Seibel, Sofie H; Esposti, Federico; Lagnado, Leon

    2014-11-15

    Neurons in the visual system vary widely in the spatiotemporal properties of their receptive fields (RFs), and understanding these variations is key to elucidating how visual information is processed. We present a new approach for mapping RFs based on the filtered back projection (FBP), an algorithm used for tomographic reconstructions. To estimate RFs, a series of bars were flashed across the retina at pseudo-random positions and at a minimum of five orientations. We apply this method to retinal neurons and show that it can accurately recover the spatial RF and impulse response of ganglion cells recorded on a multi-electrode array. We also demonstrate its utility for in vivo imaging by mapping the RFs of an array of bipolar cell synapses expressing a genetically encoded Ca(2+) indicator. We find that FBP offers several advantages over the commonly used spike-triggered average (STA): (i) ON and OFF components of a RF can be separated; (ii) the impulse response can be reconstructed at sample rates of 125 Hz, rather than the refresh rate of a monitor; (iii) FBP reveals the response properties of neurons that are not evident using STA, including those that display orientation selectivity, or fire at low mean spike rates; and (iv) the FBP method is fast, allowing the RFs of all the bipolar cell synaptic terminals in a field of view to be reconstructed in under 4 min. Use of the FBP will benefit investigations of the visual system that employ electrophysiology or optical reporters to measure activity across populations of neurons.

  5. Non-peptidergic primary afferents are presynaptic to neurokinin-1 receptor immunoreactive lamina I projection neurons in rat spinal cord

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    Saeed Abeer W

    2012-09-01

    Full Text Available Abstract Background Pain-related (nociceptive information is carried from the periphery to the dorsal horn of the spinal cord mostly by two populations of small diameter primary afferents, the peptidergic and the non-peptidergic. The peptidergic population expresses neuropeptides, such as substance P and calcitonin gene-related peptide, while the non-peptidergic fibers are devoid of neuropeptides, express the purinergic receptor P2X3, and bind the isolectin B4 (IB4. Although it has been known for some time that in rat the peptidergic afferents terminate mostly in lamina I and outer lamina II and non-peptidergic afferents in inner lamina II, the extent of the termination of the latter population in lamina I was never investigated as it was considered as very minor. Because our preliminary evidence suggested otherwise, we decided to re-examine the termination of non-peptidergic afferents in lamina I, in particular with regards to their innervation of projection neurons expressing substance P receptors (NK-1r. We used retrograde labeling of neurons from the parabrachial nucleus combined with lectin IB4 binding and immunocytochemistry. Samples were examined by confocal and electron microscopy. Results By confocal microscopy, we studied the termination of non-peptidergic afferents in lamina I using IB4 binding and P2X3 immunoreactivity as markers, in relation to CGRP immunoreactivy, a marker of peptidergic afferents. The number of IB4 or P2X3-labeled fibers in lamina I was higher than previously thought, although they were less abundant than CGRP-labeled afferents. There were very few fibers double-labeled for CGRP and either P2X3 or IB4. We found a considerable number of IB4-positive fiber varicosities in close apposition to NK-1r-positive lamina I projection neurons, which were distinct from peptidergic varicosities. Furthermore, we confirmed at the ultrastructural level that there were bona fide synapses between P2X3-immunoreactive non

  6. Cell type-specific plasticity of striatal projection neurons in parkinsonism and L-DOPA-induced dyskinesia

    Science.gov (United States)

    Fieblinger, Tim; Graves, Steven M.; Sebel, Luke E.; Alcacer, Cristina; Plotkin, Joshua L.; Gertler, Tracy S.; Chan, C. Savio; Heiman, Myriam; Greengard, Paul; Cenci, M. Angela; Surmeier, D. James

    2015-01-01

    Summary The striatum is widely viewed as the fulcrum of pathophysiology in Parkinson's disease (PD) and L-DOPA-induced dyskinesia (LID). In these disease states, the balance in activity of striatal direct pathway spiny projection neurons (dSPNs) and indirect pathway spiny projection neurons (iSPNs) is disrupted, leading to aberrant action selection. However, it is unclear whether countervailing mechanisms are engaged in these states. Here we report that iSPN intrinsic excitability and excitatory corticostriatal synaptic connectivity were lower in PD models than normal; L-DOPA treatment restored these properties. Conversely, dSPN intrinsic excitability was elevated in tissue from PD models and suppressed in LID models. Although the synaptic connectivity of dSPNs did not change in PD models, it fell with L-DOPA treatment. In neither case, however, was the strength of corticostriatal connections globally scaled. Thus, SPNs manifested homeostatic adaptations in intrinsic excitability and in the number but not strength of excitatory corticostriatal synapses. PMID:25360704

  7. Ethanol affects striatal interneurons directly and projection neurons through a reduction in cholinergic tone.

    Science.gov (United States)

    Blomeley, Craig P; Cains, Sarah; Smith, Richard; Bracci, Enrico

    2011-04-01

    The acute effects of ethanol on the neurons of the striatum, a basal ganglia nucleus crucially involved in motor control and action selection, were investigated using whole-cell recordings. An intoxicating concentration of ethanol (50 mM) produced inhibitory effects on striatal large aspiny cholinergic interneurons (LAIs) and low-threshold spike interneurons (LTSIs). These effects persisted in the presence of tetrodotoxin and were because of an increase in potassium currents, including those responsible for medium and slow afterhyperpolarizations. In contrast, fast-spiking interneurons (FSIs) were directly excited by ethanol, which depolarized these neurons through the suppression of potassium currents. Medium spiny neurons (MSNs) became hyperpolarized in the presence of ethanol, but this effect did not persist in the presence of tetrodotoxin and was mimicked and occluded by application of the M1 muscarinic receptor antagonist telenzepine. Ethanol effects on MSNs were also abolished by 100 μM barium. This showed that the hyperpolarizations observed in MSNs were because of decreased tonic activation of M1 muscarinic receptors, resulting in an increase in Kir2 conductances. Evoked GABAergic responses of MSNs were reversibly decreased by ethanol with no change in paired-pulse ratio. Furthermore, ethanol impaired the ability of thalamostriatal inputs to inhibit a subsequent corticostriatal glutamatergic response in MSNs. These results offer the first comprehensive description of the highly cell type-specific effects of ethanol on striatal neurons and provide a cellular basis for the interpretation of ethanol influence on a brain area crucially involved in the motor and decisional impairment caused by this drug.

  8. Optogenetic manipulation of Ventral Tegmental Area (VTA) Neurons that project to the Nucleus Accumbens (NAc) and medial Prefrontal Cortex (mPFC)

    OpenAIRE

    sprotocols

    2015-01-01

    Authors: Jessica Walsh, Dipesh Chaudhury, Allyson Friedman, Barbara Juarez, Stacy Ku, Mary Kay Lobo & Ming-Hu Han ### Abstract Optogenetics has evolved to be a critical technique used to manipulate the firing activity of specific subsets of neurons. Through the use of specific firing parameters, it has become possible to control the behavior of freely moving animals. Here we have established a system to control projection pathway-specific neurons from a particular brain region thr...

  9. Oxytocin receptors are expressed on dopamine and glutamate neurons in the mouse ventral tegmental area that project to nucleus accumbens and other mesolimbic targets.

    Science.gov (United States)

    Peris, Joanna; MacFadyen, Kaley; Smith, Justin A; de Kloet, Annette D; Wang, Lei; Krause, Eric G

    2017-04-01

    The mesolimbic dopamine (DA) circuitry determines which behaviors are positively reinforcing and therefore should be encoded in the memory to become a part of the behavioral repertoire. Natural reinforcers, like food and sex, activate this pathway, thereby increasing the likelihood of further consummatory, social, and sexual behaviors. Oxytocin (OT) has been implicated in mediating natural reward and OT-synthesizing neurons project to the ventral tegmental area (VTA) and nucleus accumbens (NAc); however, direct neuroanatomical evidence of OT regulation of DA neurons within the VTA is sparse. To phenotype OT-receptor (OTR) expressing neurons originating within the VTA, we delivered Cre-inducible adeno-associated virus that drives the expression of fluorescent marker into the VTA of male mice that had Cre-recombinase driven by OTR gene expression. OTR-expressing VTA neurons project to NAc, prefrontal cortex, the extended amygdala, and other forebrain regions but less than 10% of these OTR-expressing neurons were identified as DA neurons (defined by tyrosine hydroxylase colocalization). Instead, almost 50% of OTR-expressing cells in the VTA were glutamate (GLU) neurons, as indicated by expression of mRNA for the vesicular GLU transporter (vGluT). About one-third of OTR-expressing VTA neurons did not colocalize with either DA or GLU phenotypic markers. Thus, OTR expression by VTA neurons implicates that OT regulation of reward circuitry is more complex than a direct action on DA neurotransmission. J. Comp. Neurol. 525:1094-1108, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  10. Projection patterns of lateral hypothalamic, cocaine- and amphetamine-regulated transcript (CART) neurons to the dorsal raphe and/or the locus coeruleus in the rat.

    Science.gov (United States)

    Yoon, Ye S; Lee, Hyun S

    2013-02-04

    The present study was designed to reveal the projection patterns of lateral hypothalamic (LH), cocaine- and amphetamine-regulated transcript (CART) neurons to the dorsal raphe (DR) and/or the locus coeruleus (LC) in the rat. After the injection of Red or Green Retrobeads into the DR or LC, LH sections were immunostained for CART and/or melanin-concentrating hormone (MCH). First, CART-immunoreactive axon terminals formed close appositions to the DR (or LC) neuronal profiles. Second, a subpopulation of CART neurons containing MCH projected to the monoaminergic nuclei; the majority of labeled neurons were observed in the dorsal hypothalamic area, the dorsal part of the posterior hypothalamic area, and the zona incerta. Cells were also observed in the perifornical part of the LH, the dorsomedial hypothalamic nucleus, the peduncular and the magnocellular parts of the LH. Of the total population of DR (or LC)-projecting cells, CART/MCH co-containing neurons were 9.5% ± 1.6% (or 10.8% ± 1.3% for LC). Finally, a subset of CART (or MCH) neurons provided divergent axon collaterals to the DR and the LC. Of the entire CART (or MCH) cell population, 3.9% ± 0.8% (or 5.6% ± 1.0% for MCH) sent axon collaterals to the DR/LC. CART/MCH co-containing neurons projecting to the DR or LC might be involved in the feeding-related regulation of arousal, stress-related responses, and emotional behaviors. Thus, CART (or MCH) cells that send divergent axon collaterals to the DR/LC might have a simultaneous (and possibly more efficient) way to exert their specific influences on the aminergic nuclei.

  11. Projections and neurochemical coding of motor neurones to the circular and longitudinal muscle of the guinea pig gastric corpus.

    Science.gov (United States)

    Michel, K; Reiche, D; Schemann, M

    2000-07-01

    The present study identified projection and neurochemical coding patterns of intrinsic circular (CMN) and longitudinal muscle motor neurones (LMN) in the guinea pig stomach by using the retrograde tracer DiI (1,1'-didodecyl-3,3,3',3'-tetramethylindocarbocya-nine perchlorate) in combination with the immunohistochemical demonstration of choline acetyltransferase (ChAT), enkephalin (ENK), neuropeptide Y (NPY), nitric oxide synthase (NOS) and substance P (SP). Populations of LMN and CMN had similar neurochemical coding and a clear polarity of projection. Taking all DiI-labeled cell bodies as 100%, ascending pathways exhibited the coding ChAT/- (CMN:14.7%/LMN: 18.3%), ChAT/ENK (15.7%/10.1%), ChAT/SP/+/-ENK (19.2%/16.4%), or ChAT/NPY (4.4%/7.6%); descending pathways had the coding NOS/- (13.8%/16.9%), NOS/NPY (9.9%/17%), NOS/ENK (4.4%/1.2%) or NOS/NPY/ENK (13.0%/5.5%). The relative contributions of these populations were not different between CMN and LMN. However, target-specific projection patterns were revealed: most LMN (82%) had longitudinal whereas most CMN (58%) had circumferential projection preferences. The results indicate that gastric circular and longitudinal muscle layers are innervated by ascending excitatory and descending inhibitory pathways in the myenteric plexus. The projection patterns of CMN and LMN were different and followed the orientation of the muscle layers. It is suggested that the specific muscle motor pathways in the gastric myenteric plexus coordinate the reflex-mediated phasic and tonic activity of gastric muscle layers.

  12. A Population of Projection Neurons that Inhibits the Lateral Horn but Excites the Antennal Lobe through Chemical Synapses in Drosophila

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    Kazumichi Shimizu

    2017-05-01

    Full Text Available In the insect olfactory system, odor information is transferred from the antennal lobe (AL to higher brain areas by projection neurons (PNs in multiple AL tracts (ALTs. In several species, one of the ALTs, the mediolateral ALT (mlALT, contains some GABAergic PNs; in the Drosophila brain, the great majority of ventral PNs (vPNs are GABAergic and project through this tract to the lateral horn (LH. Most excitatory PNs (ePNs, project through the medial ALT (mALT to the mushroom body (MB and the LH. Recent studies have shown that GABAergic vPNs play inhibitory roles at their axon terminals in the LH. However, little is known about the properties and functions of vPNs at their dendritic branches in the AL. Here, we used optogenetic and patch clamp techniques to investigate the functional roles of vPNs in the AL. Surprisingly, our results show that specific activation of vPNs reliably elicits strong excitatory postsynaptic potentials (EPSPs in ePNs. Moreover, the connections between vPNs and ePNs are mediated by direct chemical synapses. Neither pulses of GABA, nor pharmagological, or genetic blockade of GABAergic transmission gave results consistent with the involvement of GABA in vPN-ePN excitatory transmission. These unexpected results suggest new roles for the vPN population in olfactory information processing.

  13. Lobula-specific visual projection neurons are involved in perception of motion-defined second-order motion in Drosophila.

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    Zhang, Xiaonan; Liu, He; Lei, Zhengchang; Wu, Zhihua; Guo, Aike

    2013-02-01

    A wide variety of animal species including humans and fruit flies see second-order motion although they lack coherent spatiotemporal correlations in luminance. Recent electrophysiological recordings, together with intensive psychophysical studies, are bringing to light the neural underpinnings of second-order motion perception in mammals. However, where and how the higher-order motion signals are processed in the fly brain is poorly understood. Using the rich genetic tools available in Drosophila and examining optomotor responses in fruit flies to several stimuli, we revealed that two lobula-specific visual projection neurons, specifically connecting the lobula and the central brain, are involved in the perception of motion-defined second-order motion, independent of whether the second-order feature is moving perpendicular or opposite to the local first-order motion. By contrast, blocking these neurons has no effect on first-order and flicker-defined second-order stimuli in terms of response delay. Our results suggest that visual neuropils deep in the optic lobe and the central brain, whose functional roles in motion processing were previously unclear, may be specifically required for motion-defined motion processing.

  14. Postsynaptic odorant concentration dependent inhibition controls temporal properties of spike responses of projection neurons in the moth antennal lobe.

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    Fujiwara, Terufumi; Kazawa, Tomoki; Haupt, Stephan Shuichi; Kanzaki, Ryohei

    2014-01-01

    Although odorant concentration-response characteristics of olfactory neurons have been widely investigated in a variety of animal species, the effect of odorant concentration on neural processing at circuit level is still poorly understood. Using calcium imaging in the silkmoth (Bombyx mori) pheromone processing circuit of the antennal lobe (AL), we studied the effect of odorant concentration on second-order projection neuron (PN) responses. While PN calcium responses of dendrites showed monotonic increases with odorant concentration, calcium responses of somata showed decreased responses at higher odorant concentrations due to postsynaptic inhibition. Simultaneous calcium imaging and electrophysiology revealed that calcium responses of PN somata but not dendrites reflect spiking activity. Inhibition shortened spike response duration rather than decreasing peak instantaneous spike frequency (ISF). Local interneurons (LNs) that were specifically activated at high odorant concentrations at which PN responses were suppressed are the putative source of inhibition. Our results imply the existence of an intraglomerular mechanism that preserves time resolution in olfactory processing over a wide odorant concentration range.

  15. Postsynaptic odorant concentration dependent inhibition controls temporal properties of spike responses of projection neurons in the moth antennal lobe.

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    Terufumi Fujiwara

    Full Text Available Although odorant concentration-response characteristics of olfactory neurons have been widely investigated in a variety of animal species, the effect of odorant concentration on neural processing at circuit level is still poorly understood. Using calcium imaging in the silkmoth (Bombyx mori pheromone processing circuit of the antennal lobe (AL, we studied the effect of odorant concentration on second-order projection neuron (PN responses. While PN calcium responses of dendrites showed monotonic increases with odorant concentration, calcium responses of somata showed decreased responses at higher odorant concentrations due to postsynaptic inhibition. Simultaneous calcium imaging and electrophysiology revealed that calcium responses of PN somata but not dendrites reflect spiking activity. Inhibition shortened spike response duration rather than decreasing peak instantaneous spike frequency (ISF. Local interneurons (LNs that were specifically activated at high odorant concentrations at which PN responses were suppressed are the putative source of inhibition. Our results imply the existence of an intraglomerular mechanism that preserves time resolution in olfactory processing over a wide odorant concentration range.

  16. Expression and function of nr4a2, lmx1b, and pitx3 in zebrafish dopaminergic and noradrenergic neuronal development

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    Willaredt Marc

    2007-12-01

    Full Text Available Abstract Background: Dopaminergic neurons form in diverse areas of the vertebrate di- and mesencephalon to constitute several major neuromodulatory systems. While much is known about mammalian mesencephalic dopaminergic neuron development, little is known about the specification of the diencephalic dopaminergic groups. The transcription factors Pitx3 and Lmx1b play an important role in mammalian mesencephalic dopaminergic specification, and Nurr1/Nr4a2 has been shown to contribute to specification of the dopaminergic neurotransmitter phenotype. We use zebrafish to analyze potentially evolutionarily conserved roles of these transcription factors in a vertebrate brain that lacks a mesencephalic dopaminergic system, but has an ascending dopaminergic system in the ventral diencephalon. Results: We use a combination of fluorescent in situ hybridization and immunohistochemistry to determine whether nr4a2, lmx1b, and pitx3 genes are expressed in mature dopaminergic neurons or in potential precursor populations. We identify a second nr4a2 paralogue, nr4a2a, and find it co-expressed with Tyrosine hydroxylase in preoptic, pretectal and retinal amacrine dopaminergic neurons, while nr4a2b is only expressed in preoptic and retinal dopaminergic neurons. Both zebrafish nr4a2 paralogues are not expressed in ventral diencephalic dopaminergic neurons with ascending projections. Combined morpholino antisense oligo mediated knock-down of both nr4a2a and nr4a2b transcripts reveals that all zebrafish dopaminergic neurons expressing nr4a2a depend on Nr4a2 activity for tyrosine hydroxylase and dopamine transporter expression. Zebrafish lmx1b.1 is expressed in noradrenergic neurons of the locus coeruleus and medulla oblongata, but knock-down reveals that it is specifically required for tyrosine hydroxylase expression only in the medulla oblongata area postrema noradrenergic neurons. Both lmx1b genes and pitx3 are not expressed in dopaminergic neurons, but in a

  17. Semaphorin-1a prevents Drosophila olfactory projection neuron dendrites from mis-targeting into select antennal lobe regions.

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    Shen, Hung-Chang; Chu, Sao-Yu; Hsu, Tsai-Chi; Wang, Chun-Han; Lin, I-Ya; Yu, Hung-Hsiang

    2017-04-01

    Elucidating how appropriate neurite patterns are generated in neurons of the olfactory system is crucial for comprehending the construction of the olfactory map. In the Drosophila olfactory system, projection neurons (PNs), primarily derived from four neural stem cells (called neuroblasts), populate their cell bodies surrounding to and distribute their dendrites in distinct but overlapping patterns within the primary olfactory center of the brain, the antennal lobe (AL). However, it remains unclear whether the same molecular mechanisms are employed to generate the appropriate dendritic patterns in discrete AL glomeruli among PNs produced from different neuroblasts. Here, by examining a previously explored transmembrane protein Semaphorin-1a (Sema-1a) which was proposed to globally control initial PN dendritic targeting along the dorsolateral-to-ventromedial axis of the AL, we discover a new role for Sema-1a in preventing dendrites of both uni-glomerular and poly-glomerular PNs from aberrant invasion into select AL regions and, intriguingly, this Sema-1a-deficient dendritic mis-targeting phenotype seems to associate with the origins of PNs from which they are derived. Further, ectopic expression of Sema-1a resulted in PN dendritic mis-projection from a select AL region into adjacent glomeruli, strengthening the idea that Sema-1a plays an essential role in preventing abnormal dendritic accumulation in select AL regions. Taken together, these results demonstrate that Sema-1a repulsion keeps dendrites of different types of PNs away from each other, enabling the same types of PN dendrites to be sorted into destined AL glomeruli and permitting for functional assembly of olfactory circuitry.

  18. The neuroanatomical organization of projection neurons associated with different olfactory bulb pathways in the sea lamprey, Petromyzon marinus.

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    Warren W Green

    Full Text Available Although there is abundant evidence for segregated processing in the olfactory system across vertebrate taxa, the spatial relationship between the second order projection neurons (PNs of olfactory subsystems connecting sensory input to higher brain structures is less clear. In the sea lamprey, there is tight coupling between olfaction and locomotion via PNs extending to the posterior tuberculum from the medial region of the olfactory bulb. This medial region receives peripheral input predominantly from the accessory olfactory organ. However, the axons from olfactory sensory neurons residing in the main olfactory epithelium extend to non-medial regions of the olfactory bulb, and the non-medial bulbar PNs extend their axons to the lateral pallium. It is not known if the receptive fields of the PNs in the two output pathways overlap; nor has the morphology of these PNs been investigated. In this study, retrograde labelling was utilized to investigate the PNs belonging to medial and non-medial projections. The dendrites and somata of the medial PNs were confined to medial glomerular neuropil, and dendrites of non-medial PNs did not enter this territory. The cell bodies and dendrites of the non-medial PNs were predominantly located below the glomeruli (frequently deeper in the olfactory bulb. While PNs in both locations contained single or multiple primary dendrites, the somal size was greater for medial than for non-medial PNs. When considered with the evidence-to-date, this study shows different neuroanatomical organization for medial olfactory bulb PNs extending to locomotor control centers and non-medial PNs extending to the lateral pallium in this vertebrate.

  19. The neuroanatomical organization of projection neurons associated with different olfactory bulb pathways in the sea lamprey, Petromyzon marinus.

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    Green, Warren W; Basilious, Alfred; Dubuc, Réjean; Zielinski, Barbara S

    2013-01-01

    Although there is abundant evidence for segregated processing in the olfactory system across vertebrate taxa, the spatial relationship between the second order projection neurons (PNs) of olfactory subsystems connecting sensory input to higher brain structures is less clear. In the sea lamprey, there is tight coupling between olfaction and locomotion via PNs extending to the posterior tuberculum from the medial region of the olfactory bulb. This medial region receives peripheral input predominantly from the accessory olfactory organ. However, the axons from olfactory sensory neurons residing in the main olfactory epithelium extend to non-medial regions of the olfactory bulb, and the non-medial bulbar PNs extend their axons to the lateral pallium. It is not known if the receptive fields of the PNs in the two output pathways overlap; nor has the morphology of these PNs been investigated. In this study, retrograde labelling was utilized to investigate the PNs belonging to medial and non-medial projections. The dendrites and somata of the medial PNs were confined to medial glomerular neuropil, and dendrites of non-medial PNs did not enter this territory. The cell bodies and dendrites of the non-medial PNs were predominantly located below the glomeruli (frequently deeper in the olfactory bulb). While PNs in both locations contained single or multiple primary dendrites, the somal size was greater for medial than for non-medial PNs. When considered with the evidence-to-date, this study shows different neuroanatomical organization for medial olfactory bulb PNs extending to locomotor control centers and non-medial PNs extending to the lateral pallium in this vertebrate.

  20. Antisense mRNA for NPY-Y1 receptor in the medial preoptic area increases prolactin secretion

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    N.A. Silveira

    1999-09-01

    Full Text Available We investigated the participation of neuropeptide Y-Y1 receptors within the medial preoptic area in luteinizing hormone, follicle-stimulating hormone and prolactin release. Four bilateral microinjections of sense (control or antisense 18-base oligonucleotides of messenger ribonucleic acid (mRNA (250 ng corresponding to the NH2-terminus of the neuropeptide Y1 receptor were performed at 12-h intervals for two days into the medial preoptic area of ovariectomized Wistar rats (N = 16, weighing 180 to 200 g, treated with estrogen (50 µg and progesterone (25 mg two days before the experiments between 8.00 and 10:00 a.m. Blockade of Y1 receptor synthesis in the medial preoptic area by the antisense mRNA did not change plasma luteinizing hormone or follicle-stimulating hormone but did increase prolactin from 19.6 ± 5.9 ng/ml in the sense group to 52.9 ± 9.6 ng/ml in the antisense group. The plasma hormones were measured by radioimmunoassay and the values are reported as mean ± SEM. These data suggest that endogenous neuropeptide Y in the medial preoptic area has an inhibitory action on prolactin secretion through Y1 receptors.

  1. Origin and central projections of rat dorsal penile nerve: possible direct projection to autonomic and somatic neurons by primary afferents of nonmuscle origin.

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    Núñez, R; Gross, G H; Sachs, B D

    1986-05-22

    Cell number, size, and somatotopic arrangement within the spinal ganglia of the cells of origin of the rat dorsal penile nerve (DPN), and their spinal cord projections, were studied by loading the proximal stump of the severed DPN with horseradish peroxidase (HRP). The DPN sensory cells were located entirely in the sixth lumbar (L6) dorsal root ganglia (DRG), in which a mean of 468 +/- 78 cells per side were observed, measuring 26.7 +/- 0.8 microns in their longest axis (range 10-65 microns) and distributed apparently randomly within the ganglia. Within the spinal cord, no retrograde label was found, i.e., no motoneurons were labeled, indicating that in the rat the DPN is formed exclusively of sensory nerve fibers. Although labeled fibers entered the cord only through L6, transganglionically transported HRP was evident in all spinal segments examined, i.e., T13-S2. Labeled fibers projected along the inner edge of the dorsal horn (medial pathway) throughout their extensive craniosacral distribution. However, laminar distribution varied with spinal segment. In the dorsal horn, terminals or preterminal axons were found in the dorsal horn marginal zone (lamina I), the substantia gelatinosa (lamina II), the nucleus proprius (laminae III and IV--the most consistent projection), Clarke's column (lamina VI), and the dorsal gray commissure. In the ventral horn, terminals were found in lamina VII and lamina IX. Label apposed to cell somas and dendrites in lamina VII may represent direct primary afferent projections onto sympathetic autonomic neurons. In lamina IX, labeled terminals delineated the somas and dendrites of cells that appeared to be motoneurons. This is the first description of an apparently monosynaptic contact onto motoneurons by a primary afferent of nonmuscle origin.

  2. Integration of the antennal lobe glomeruli and three projection neurons in the standard brain atlas of the moth Heliothis virescens

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    Bjarte B Løfaldli

    2010-02-01

    Full Text Available Digital three dimensional standard brain atlases are valuable tools for integrating neuroimaging data of different preparations. In insects, standard brain atlases of five species are available, including the atlas of the female Heliothis virescens moth brain. Like for the other species, the antennal lobes of the moth brain atlas were integrated as one material identity without internal structures. Different from the others, the H. virescens standard brain atlas exclusively included the glomerular layer of the antennal lobe. This was an advantage in the present study for performing a direct registration of the glomerular layer of individual preparations into the standard brain. We here present the H. virescens female standard brain atlas with a new model of the antennal lobe glomeruli integrated into the atlas, i.e. with each of the 66 glomeruli identified and labelled with a specific number. The new model differs from the previous H. virescens antennal lobe model both in respect to the number of glomeruli and the numbering system; the latter according to the system used for the antennal lobe atlases of two other heliothine species. For identifying female specific glomeruli comparison with the male antennal lobe was necessary. This required a new male antennal lobe atlas, included in this paper. As demonstrated by the integration of three antennal lobe projection neurons of different preparations, the new standard brain atlas with the integrated glomruli is a helpful tool for determining the glomeruli innervated as well as the relative position of the axonal projections in the protocerebrum.

  3. The effects of nitric oxide-cGMP pathway stimulation on dopamine in the medial preoptic area and copulation in DHT-treated castrated male rats.

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    Sato, Satoru M; Wersinger, Scott R; Hull, Elaine M

    2007-08-01

    Dopamine (DA) in the medial preoptic area (MPOA) provides important facilitative influence on male rat copulation. We have shown that the nitric oxide-cGMP (NO-cGMP) pathway modulates MPOA DA levels and copulation. We have also shown that systemic estradiol (E(2)) maintains neuronal NO synthase (nNOS) immunoreactivity in the MPOA of castrates, as well as relatively normal DA levels. This effect of E(2) on nNOS probably accounts for at least some of the previously demonstrated behavioral facilitation by intra-MPOA E(2) administration in castrates. Therefore, we hypothesized that stimulation of the MPOA NO-cGMP pathway in dihydrotestosterone (DHT)-treated castrates should restore DA levels and copulatory behaviors. Reverse-dialysis of a NO donor, sodium nitroprusside (SNP), increased extracellular DA in the MPOA of DHT-treated castrates and restored the ability to copulate to ejaculation in half of the animals. A cGMP analog, 8-Br-cGMP, also increased extracellular DA, though not as robustly, but did not restore copulatory ability. The effectiveness of the NO donor in restoring copulation and MPOA DA levels is consistent with our hypothesis. However, the lack of behavioral effects of 8-Br-cGMP, despite its increase in MPOA DA, suggests that NO may have additional mediators in the MPOA in the regulation of copulation. Furthermore, the suboptimal copulation seen in the NO donor-treated animals suggests the importance of extra-MPOA systems in the regulation of copulation.

  4. Activity of basal forebrain neurons in the rat during motivated behaviors.

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    Mink, J W; Sinnamon, H M; Adams, D B

    1983-04-01

    The activity of single neurons in the basal forebrain was recorded in the freely-moving rat with moveable fine-wire electrodes. Neural activity was observed while the water-deprived male rat was exposed to three different types of motivating stimuli that elicit locomotion in a running wheel: an estrous female rat; a drinking tube containing water; and grasping and lifting by the experimenter. The neural activity was also observed when the subject was presented with standardized sensory tests and during single pulse stimulation of other brain structures. A majority of the 76 neurons recorded in the forebrain changed their firing rate during orienting and/or locomotion in general (23 neurons) or during behavior related to only one of the specific motivational contexts: the conspecific female (4 neurons); water (7 neurons); or grasp by the experimenter (8 neurons). Whereas the neurons related to orienting and/or locomotion in general were scattered through various brain structures, those neurons related to specific motivational contexts were concentrated in specific areas: the sexually dimorphic nucleus of the medial preoptic area (conspecific female); lateral septum (water); and lateral preoptic area (water and grasp). The present results, although based on relatively few neurons, are consonant with results of research using other techniques. This indicates that analyses at the level of the single neuron promise to be useful for understanding the role of the basal forebrain in motivational systems.

  5. Inositol 1,4,5-triphosphate drives glutamatergic and cholinergic inhibition selectively in spiny projection neurons in the striatum.

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    Clements, Michael A; Swapna, Immani; Morikawa, Hitoshi

    2013-02-06

    The striatum is critically involved in the selection of appropriate actions in a constantly changing environment. The spiking activity of striatal spiny projection neurons (SPNs), driven by extrinsic glutamatergic inputs, is shaped by local GABAergic and cholinergic networks. For example, it is well established that different types of GABAergic interneurons, activated by extrinsic glutamatergic and local cholinergic inputs, mediate powerful feedforward inhibition of SPN activity. In this study, using mouse striatal slices, we show that glutamatergic and cholinergic inputs exert direct inhibitory regulation of SPN activity via activation of metabotropic glutamate receptors (mGluRs) and muscarinic acetylcholine receptors. While pressure ejection of the group I mGluR (mGluR1/5) agonist DHPG [(S)-3,5-dihydroxyphenylglycine] equally engages both mGluR1 and mGluR5 subtypes, the mGluR-dependent component of IPSCs elicited by intrastriatal electrical stimulation is almost exclusively mediated by the mGluR1 subtype. Ca(2+) release from intracellular stores specifically through inositol 1,4,5-triphospahte receptors (IP(3)Rs) and not ryanodine receptors (RyRs) mediates this form of inhibition by gating two types of Ca(2+)-activated K(+) channels (i.e., small-conductance SK channels and large-conductance BK channels). Conversely, spike-evoked Ca(2+) influx triggers Ca(2+) release solely through RyRs to generate SK-dependent slow afterhyperpolarizations, demonstrating functional segregation of IP(3)Rs and RyRs. Finally, IP(3)-induced Ca(2+) release is uniquely observed in SPNs and not in different types of interneurons in the striatum. These results demonstrate that IP(3)-mediated activation of SK and BK channels provides a robust mechanism for glutamatergic and cholinergic inputs to selectively suppress striatal output neuron activity.

  6. The chromatin remodeling factor Bap55 functions through the TIP60 complex to regulate olfactory projection neuron dendrite targeting

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    Luo Liqun

    2011-02-01

    Full Text Available Abstract Background The Drosophila olfactory system exhibits very precise and stereotyped wiring that is specified predominantly by genetic programming. Dendrites of olfactory projection neurons (PNs pattern the developing antennal lobe before olfactory receptor neuron axon arrival, indicating an intrinsic wiring mechanism for PN dendrites. These wiring decisions are likely determined through a transcriptional program. Results We find that loss of Brahma associated protein 55 kD (Bap55 results in a highly specific PN mistargeting phenotype. In Bap55 mutants, PNs that normally target to the DL1 glomerulus mistarget to the DA4l glomerulus with 100% penetrance. Loss of Bap55 also causes derepression of a GAL4 whose expression is normally restricted to a small subset of PNs. Bap55 is a member of both the Brahma (BRM and the Tat interactive protein 60 kD (TIP60 ATP-dependent chromatin remodeling complexes. The Bap55 mutant phenotype is partially recapitulated by Domino and Enhancer of Polycomb mutants, members of the TIP60 complex. However, distinct phenotypes are seen in Brahma and Snf5-related 1 mutants, members of the BRM complex. The Bap55 mutant phenotype can be rescued by postmitotic expression of Bap55, or its human homologs BAF53a and BAF53b. Conclusions Our results suggest that Bap55 functions through the TIP60 chromatin remodeling complex to regulate dendrite wiring specificity in PNs. The specificity of the mutant phenotypes suggests a position for the TIP60 complex at the top of a regulatory hierarchy that orchestrates dendrite targeting decisions.

  7. A mammalian conserved element derived from SINE displays enhancer properties recapitulating Satb2 expression in early-born callosal projection neurons.

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    Kensuke Tashiro

    Full Text Available Short interspersed repetitive elements (SINEs are highly repeated sequences that account for a significant proportion of many eukaryotic genomes and are usually considered "junk DNA". However, we previously discovered that many AmnSINE1 loci are evolutionarily conserved across mammalian genomes, suggesting that they may have acquired significant functions involved in controlling mammalian-specific traits. Notably, we identified the AS021 SINE locus, located 390 kbp upstream of Satb2. Using transgenic mice, we showed that this SINE displays specific enhancer activity in the developing cerebral cortex. The transcription factor Satb2 is expressed by cortical neurons extending axons through the corpus callosum and is a determinant of callosal versus subcortical projection. Mouse mutants reveal a crucial function for Sabt2 in corpus callosum formation. In this study, we compared the enhancer activity of the AS021 locus with Satb2 expression during telencephalic development in the mouse. First, we showed that the AS021 enhancer is specifically activated in early-born Satb2(+ neurons. Second, we demonstrated that the activity of the AS021 enhancer recapitulates the expression of Satb2 at later embryonic and postnatal stages in deep-layer but not superficial-layer neurons, suggesting the possibility that the expression of Satb2 in these two subpopulations of cortical neurons is under genetically distinct transcriptional control. Third, we showed that the AS021 enhancer is activated in neurons projecting through the corpus callosum, as described for Satb2(+ neurons. Notably, AS021 drives specific expression in axons crossing through the ventral (TAG1(-/NPY(+ portion of the corpus callosum, confirming that it is active in a subpopulation of callosal neurons. These data suggest that exaptation of the AS021 SINE locus might be involved in enhancement of Satb2 expression, leading to the establishment of interhemispheric communication via the corpus callosum

  8. Seasonal changes in RFamide-related peptide-3 neurons in the hypothalamus of a seasonally breeding marsupial species, the brushtail possum (Trichosurus vulpecula).

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    Harbid, Anan A; McLeod, Bernie J; Caraty, Alain; Anderson, Greg M

    2013-09-01

    RFamide-related peptide-3 (RFRP-3) neurons have been shown to inhibit gonadotropin-releasing hormone (GnRH) neuronal activity and hence reproduction in birds and eutherian mammals. They have also been proposed to have a direct hypophysiotropic effect on pituitary gonadotropin release. We used a new RFRP-3 antibody to characterize the cell body distribution and fiber projections of RFRP-3 neurons in the adult female brushtail possum brain. RFRP-3-immunoreactive cell bodies were found scattered within the dorsomedial hypothalamus and the dorsomedial half of the ventromedial hypothalamus, while GnRH neurons were observed scattered rostrocaudally along the lateral septum, rostral to the medial septum. There was a significant 2-fold increase in the RFRP-3 cell body number during the nonbreeding season (summer) compared to the breeding season (winter). Immunoreactive RFRP-3 fibers were distributed throughout the thalamus, preoptic area, and hypothalamus. Very few fibers were observed in the median eminence, especially in the external zone. Intraperitoneal injection of the retrograde tracer Fluoro-Gold resulted in the labeling of 40% of hypophysiotropic tuberoinfundibular dopaminergic (tyrosine hydroxylase-positive) neurons; however, <10% of zona incerta dopaminergic neurons (which are not hypophysiotropic) or RFRP-3 neurons were labeled with this tracer. These observations suggest that RFRP-3 exhibits a seasonal fluctuation in cell numbers, as seen in sheep and birds, which is consistent with an increased inhibitory tone during the nonbreeding season. The lack of RFRP-3 fibers in the median eminence and of Fluoro-Gold uptake from the periphery imply that the actions of this peptide occur primarily centrally rather than at the anterior pituitary gland.

  9. Retrograde study of CART- or NPY-neuronal projection from the hypothalamic arcuate nucleus to the dorsal raphe and/or the locus coeruleus in the rat.

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    Yoon, Ye S; Lee, Ji S; Lee, Hyun S

    2013-06-26

    The present study was designed to reveal cocaine- and amphetamine-regulated transcript (CART)- or neuropeptide Y (NPY)-immunoreactive neuronal projections from the hypothalamic arcuate nucleus (Arc) to the dorsal raphe (DR) and/or the locus coeruleus (LC) in the rat. Our results demonstrated that CART or NPY axon terminals formed close appositions to the neuronal profiles in the DR and the LC. Thus, arcuate sections were immunostained for the CART or NPY after the injections of green RetroBeads(™) into the DR and red tracer into the LC (or vice versa). First, retrogradely-labeled CART cells were mainly observed in the lateral Arc without colchicine. Of the total population of arcuate CART neurons, DR- and LC-projecting cells were 5.7% ± 0.9% and 6.6% ± 0.7%, respectively. In addition, a subset (3.3% ± 0.7%) of CART neurons provided divergent axon collaterals to the DR and the LC. Second, retrogradely-labeled NPY cells were observed in lateral or ventral borders of the medial Arc only after colchicine injection. Of the entire NPY cell population, DR- and LC-projecting neurons were 1.5% ± 0.3% and 1.3% ± 0.3%, respectively. Only a scanty proportion (0.1% ± 0.0%) sent axon collaterals to the DR and the LC. These observations suggested that arcuate CART or NPY system might have a potential influence on the brainstem monoaminergic nuclei, modulating their roles in feeding, nociception, emotional behaviors, arousal, and stress responses. Furthermore, a portion of arcuate CART neurons (along with only a few NPY cells) sending divergent axon collaterals to the DR/LC might have a simultaneous (and possibly more efficient) way to exert their specific influences on the monoaminergic nuclei.

  10. Dorsal border periaqueductal gray neurons project to the area directly adjacent to the central canal ependyma of the C4-T8 spinal cord in the cat.

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    Mouton, L J; Kerstens, L; Van der Want, J; Holstege, G

    1996-11-01

    In a previous study horseradish peroxidase (HRP) injections in the upper thoracic and cervical spinal cord revealed some faintly labeled small neurons at the dorsal border of the periaqueductal gray (PAG). The present light microscopic and electronmicroscopic tracing study describes the precise location of these dorsal border PAG-spinal neurons and their terminal organization. Wheat germ agglutinin-conjugated HRP (WGA-HRP) injections into cervical and upper thoracic spinal segments resulted in several hundreds of small retrogradely labeled neurons at the dorsal border of the ipsilateral caudal PAG. These neurons were not found after injections in more caudal segments. WGA-HRP injections in the dorsal border PAG region surprisingly resulted in anterogradely labeled fibers terminating in the area dorsally and laterally adjoining the central canal ependyma of the C4-T8 spinal cord. No anterogradely labeled fibers were found more caudal in the spinal cord. The labeled fibers found in the upper cervical cord were not located in the area immediately adjoining the ependymal layer of the central canal, but in the lateral part of laminae VI, VII and VIII and in area X bilaterally. Electronmicroscopic results of one case show that the dorsal border PAG-spinal neurons terminate in the neuropil of the subependymal area and in the vicinity of the basal membranes of capillaries located laterally to the central canal. The terminal profiles contain electron-lucent and densecored vesicles, suggesting a heterogeneity of possible transmitters. A striking observation was the lack of synaptic contacts, suggesting nonsynaptic release from the profiles. The function of the dorsal border PAG-spinal projection is unknown, but considering the termination pattern of the dorsal border PAG neurons on the capillaries the intriguing similarity between this projection system and the hypothalamohypophysial system is discussed.

  11. Bcl11a (Ctip1) Controls Migration of Cortical Projection Neurons through Regulation of Sema3c.

    Science.gov (United States)

    Wiegreffe, Christoph; Simon, Ruth; Peschkes, Katharina; Kling, Carolin; Strehle, Michael; Cheng, Jin; Srivatsa, Swathi; Liu, Pentao; Jenkins, Nancy A; Copeland, Neal G; Tarabykin, Victor; Britsch, Stefan

    2015-07-15

    During neocortical development, neurons undergo polarization, oriented migration, and layer-type-specific differentiation. The transcriptional programs underlying these processes are not completely understood. Here, we show that the transcription factor Bcl11a regulates polarity and migration of upper layer neurons. Bcl11a-deficient late-born neurons fail to correctly switch from multipolar to bipolar morphology, resulting in impaired radial migration. We show that the expression of Sema3c is increased in migrating Bcl11a-deficient neurons and that Bcl11a is a direct negative regulator of Sema3c transcription. In vivo gain-of-function and rescue experiments demonstrate that Sema3c is a major downstream effector of Bcl11a required for the cell polarity switch and for the migration of upper layer neurons. Our data uncover a novel Bcl11a/Sema3c-dependent regulatory pathway used by migrating cortical neurons.

  12. The median preoptic nucleus exhibits circadian regulation and is involved in food anticipatory activity in rabbit pups.

    Science.gov (United States)

    Moreno, María Luisa; Meza, Enrique; Ortega, Arturo; Caba, Mario

    2014-05-01

    Rabbit pups are a natural model to study food anticipatory activity (FAA). Recently, we reported that three areas in the forebrain - the organum vasculosum of lamina terminalis, median preoptic nucleus (MnPO) and medial preoptic area - exhibit activation during FAA. Here, we examined the PER1 protein profile of these three forebrain regions in both nursed and fasted subjects. We found robust PER1 oscillations in the MnPO in nursed subjects, with high PER1 levels during FAA that persisted in fasted subjects. In conclusion, our data indicate that periodic nursing is a strong signal for PER1 oscillations in MnPO and future experiments are warranted to explore the specific role of this area in FAA.

  13. Early histone modifications in the ventromedial hypothalamus and preoptic area following oestradiol administration.

    Science.gov (United States)

    Gagnidze, K; Weil, Z M; Faustino, L C; Schaafsma, S M; Pfaff, D W

    2013-10-01

    Expression of the primary female sex behaviour, lordosis, in laboratory animals depends on oestrogen-induced expression of progesterone receptor (PgR) within a defined cell group in the ventrolateral portion of the ventromedial nucleus of the hypothalamus (VMH). The minimal latency from oestradiol administration to lordosis is 18 h. During that time, ligand-bound oestrogen receptors (ER), members of a nuclear receptor superfamily, recruit transcriptional coregulators, which induce covalent modifications of histone proteins, thus leading to transcriptional activation or repression of target genes. The present study aimed to investigate the early molecular epigenetic events underlying oestrogen-regulated transcriptional activation of the Pgr gene in the VMH of female mice. Oestradiol (E₂) administration induced rapid and transient global histone modifications in the VMH of ovariectomised female mice. Histone H3 N-terminus phosphorylation (H3S10phK14Ac), acetylation (H3Ac) and methylation (H3K4me3) exhibited distinct temporal patterns facilitative to the induction of transcription. A transcriptional repressive (H3K9me3) modification showed a different temporal pattern. Collectively, this should create a permissive environment for the transcriptional activity necessary for lordosis, within 3-6 h after E₂ treatment. In the VMH, changes in the H3Ac and H3K4me3 levels of histone H3 were also detected at the promoter region of the Pgr gene within the same time window, although they were delayed in the preoptic area. Moreover, examination of histone modifications associated with the promoter of another ER-target gene, oxytocin receptor (Oxtr), revealed gene- and brain-region specific effects of E₂ treatment. In the VMH of female mice, E₂ treatment resulted in the recruitment of ERα to the oestrogen-response-elements-containing putative enhancer site of Pgr gene, approximately 200 kb upstream of the transcription start site, although it failed to increase ER

  14. The transcriptional repressor Zbtb20 is essential for specification of hippocampal projection neurons and territory in mice

    DEFF Research Database (Denmark)

    Rosenthal, Eva Helga

    for specification of both hippocampal pyramidal neurons and territory in a mouse knockout model. Homozygous Zbtb20-/- mice are viable at birth, but display dwarfism and die during the first month of postnatal life. Characterization of the Zbtb20-/- brain phenotype reveals a small vestigial hippocampus...... as an essential regulator of various aspects of neuronal development and corticogenesis in the hippocampus....

  15. Morphology, projection pattern, and neurochemical identity of Cajal's "centrifugal neurons": the cells of origin of the tectoventrogeniculate pathway in pigeon (Columba livia) and chicken (Gallus gallus).

    Science.gov (United States)

    Vega-Zuniga, Tomas; Mpodozis, Jorge; Karten, Harvey J; Marín, Gonzalo; Hain, Sarah; Luksch, Harald

    2014-07-01

    The nucleus geniculatus lateralis pars ventralis (GLv) is a prominent retinal target in all amniotes. In birds, it is in receipt of a dense and topographically organized retinal projection. The GLv is also the target of substantial and topographically organized projections from the optic tectum and the visual wulst (hyperpallium). Tectal and retinal afferents terminate homotopically within the external GLv-neuropil. Efferents from the GLv follow a descending course through the tegmentum and can be traced into the medial pontine nucleus. At present, the cells of origin of the Tecto-GLv projection are only partially described. Here we characterized the laminar location, morphology, projection pattern, and neurochemical identity of these cells by means of neural tracer injections and intracellular fillings in slice preparations and extracellular tracer injections in vivo. The Tecto-GLv projection arises from a distinct subset of layer 10 bipolar neurons, whose apical dendrites show a complex transverse arborization at the level of layer 7. Axons of these bipolar cells arise from the apical dendrites and follow a course through the optic tract to finally form very fine and restricted terminal endings inside the GLv-neuropil. Double-label experiments showed that these bipolar cells were choline acetyltransferase (ChAT)-immunoreactive. Our results strongly suggest that Tecto-GLv neurons form a pathway by which integrated tectal activity rapidly feeds back to the GLv and exerts a focal cholinergic modulation of incoming retinal inputs.

  16. Type 1 cannabinoid receptor ligands display functional selectivity in a cell culture model of striatal medium spiny projection neurons.

    Science.gov (United States)

    Laprairie, Robert B; Bagher, Amina M; Kelly, Melanie E M; Dupré, Denis J; Denovan-Wright, Eileen M

    2014-09-05

    Modulation of type 1 cannabinoid receptor (CB1) activity has been touted as a potential means of treating addiction, anxiety, depression, and neurodegeneration. Different agonists of CB1 are known to evoke varied responses in vivo. Functional selectivity is the ligand-specific activation of certain signal transduction pathways at a receptor that can signal through multiple pathways. To understand cannabinoid-specific functional selectivity, different groups have examined the effect of individual cannabinoids on various signaling pathways in heterologous expression systems. In the current study, we compared the functional selectivity of six cannabinoids, including two endocannabinoids (2-arachidonyl glycerol (2-AG) and anandamide (AEA)), two synthetic cannabinoids (WIN55,212-2 and CP55,940), and two phytocannabinoids (cannabidiol (CBD) and Δ(9)-tetrahydrocannabinol (THC)) on arrestin2-, Gα(i/o)-, Gβγ-, Gα(s)-, and Gα(q)-mediated intracellular signaling in the mouse STHdh(Q7/Q7) cell culture model of striatal medium spiny projection neurons that endogenously express CB1. In this system, 2-AG, THC, and CP55,940 were more potent mediators of arrestin2 recruitment than other cannabinoids tested. 2-AG, AEA, and WIN55,212-2, enhanced Gα(i/o) and Gβγ signaling, with 2-AG and AEA treatment leading to increased total CB1 levels. 2-AG, AEA, THC, and WIN55,212-2 also activated Gα(q)-dependent pathways. CP55,940 and CBD both signaled through Gα(s). CP55,940, but not CBD, activated downstream Gα(s) pathways via CB1 targets. THC and CP55,940 promoted CB1 internalization and decreased CB1 protein levels over an 18-h period. These data demonstrate that individual cannabinoids display functional selectivity at CB1 leading to activation of distinct signaling pathways. To effectively match cannabinoids with therapeutic goals, these compounds must be screened for their signaling bias.

  17. Differential changes in thalamic and cortical excitatory synapses onto striatal spiny projection neurons in a Huntington disease mouse model.

    Science.gov (United States)

    Kolodziejczyk, Karolina; Raymond, Lynn A

    2016-02-01

    Huntington disease (HD), a neurodegenerative disorder caused by CAG repeat expansion in the gene encoding huntingtin, predominantly affects the striatum, especially the spiny projection neurons (SPN). The striatum receives excitatory input from cortex and thalamus, and the role of the former has been well-studied in HD. Here, we report that mutated huntingtin alters function of thalamostriatal connections. We used a novel thalamostriatal (T-S) coculture and an established corticostriatal (C-S) coculture, generated from YAC128 HD and WT (FVB/NJ background strain) mice, to investigate excitatory neurotransmission onto striatal SPN. SPN in T-S coculture from WT mice showed similar mini-excitatory postsynaptic current (mEPSC) frequency and amplitude as in C-S coculture; however, both the frequency and amplitude were significantly reduced in YAC128 T-S coculture. Further investigation in T-S coculture showed similar excitatory synapse density in WT and YAC128 SPN dendrites by immunostaining, suggesting changes in total dendritic length or probability of release as possible explanations for mEPSC frequency changes. Synaptic N-methyl-D-aspartate receptor (NMDAR) current was similar, but extrasynaptic current, associated with cell death signaling, was enhanced in YAC128 SPN in T-S coculture. Employing optical stimulation of cortical versus thalamic afferents and recording from striatal SPN in brain slice, we found increased glutamate release probability and reduced AMPAR/NMDAR current ratios in thalamostriatal synapses, most prominently in YAC128. Enhanced extrasynaptic NMDAR current in YAC128 SPN was apparent with both cortical and thalamic stimulation. We conclude that thalamic afferents to the striatum are affected early, prior to an overt HD phenotype; however, changes in NMDAR localization in SPN are independent of the source of glutamatergic input.

  18. Brainstem projections of neurons located in various subdivisions of the dorsolateral hypothalamic area – an anterograde tract-tracing study

    Directory of Open Access Journals (Sweden)

    Rege Sugárka Papp

    2014-05-01

    Full Text Available The projections from the dorsolateral hypothalamic area (DLH to the lower brainstem have been investigated by using biotinylated dextran amine (BDA, an anterograde tracer in rats. The DLH can be divided into 3 areas (dorsomedial hypothalamus, perifornical area, lateral hypothalamic area, and further subdivided into 8 subdivisions. After unilateral stereotaxic injections of BDA into individual DLH subdivisions, the correct sites of injections were controlled histologically, and the distribution patterns of BDA-positive fibers were mapped on serial sections between the hypothalamus and spinal cord in 22 rats. BDA-labeled fibers were observable over 100 different brainstem areas, nuclei or subdivisions. Injections into the 8 DLH subdivisions established distinct topographical patterns. In general, the density of labeled fibers was low in the lower brainstem. High density of fibers was seen only 4 of the 116 areas: in the lateral and ventrolateral parts of the periaqueductal gray, the Barrington’s and the pedunculopontine tegmental nuclei. All of the biogenic amine cell groups in the lower brainstem (9 noradrenaline, 3 adrenaline and 9 serotonin cell groups received labeled fibers, some of them from all, or at least 7 DLH subdivisions, mainly from perifornical and ventral lateral hypothalamic neurons. Some of the tegmental nuclei and nuclei of the reticular formation were widely innervated, although the density of the BDA-labeled fibers was generally low. No definitive descending BDA-positive pathway, but long-run solitaire BDA-labeled fibers were seen in the lower brainstem. These descending fibers joined some of the large tracts or fasciculi in the brainstem. The distribution pattern of BDA-positive fibers of DLH origin throughout the lower brainstem was comparable to patterns of previously published orexin- or melanin-concentrating hormone-immunoreactive fibers with somewhat differences.

  19. Hypoxia-induced hypothermia mediated by the glutamatergic transmission in the lateral preoptic area.

    Science.gov (United States)

    Osaka, T

    2012-12-13

    Hypoxia evokes a regulated decrease in the body core temperature, which response is mediated, at least in part, by noradrenaline (NA) and nitric oxide (NO) in the rostromedial preoptic area (POA) of the hypothalamus. In the accompanying paper, it was shown that glutamatergic activation of the lateral POA also evokes hypothermic responses. Here, I tested the hypothesis that the glutamatergic transmission in the lateral POA is critically involved in the neural mechanism of hypoxia-induced hypothermia. Hypoxic ventilation (10% O(2)-90% N(2), 5 min) as well as a single microinjection of NA (50 pmol) or the NO donor sodium nitroprusside (8.4 nmol) into the rostromedial POA evoked an increase in the tail skin temperature and a decrease in the colonic temperature in urethane-chloralose-anesthetized, neuromuscularly blocked, artificially ventilated rats. All of these responses were greatly attenuated by pretreatment with multiple microinjections of kynurenic acid (10 nmol, four locations), a nonselective glutamate receptor antagonist, but not by those with saline solution, in the bilateral rostral and central parts of the lateral POA. These results suggest that the NA- and NO-sensitive structure in the rostromedial POA activated the glutamatergic transmission in the lateral POA to mediate hypoxia-induced hypothermia.

  20. Alterations to dendritic spine morphology, but not dendrite patterning, of cortical projection neurons in Tc1 and Ts1Rhr mouse models of Down syndrome.

    Directory of Open Access Journals (Sweden)

    Matilda A Haas

    Full Text Available Down Syndrome (DS is a highly prevalent developmental disorder, affecting 1/700 births. Intellectual disability, which affects learning and memory, is present in all cases and is reflected by below average IQ. We sought to determine whether defective morphology and connectivity in neurons of the cerebral cortex may underlie the cognitive deficits that have been described in two mouse models of DS, the Tc1 and Ts1Rhr mouse lines. We utilised in utero electroporation to label a cohort of future upper layer projection neurons in the cerebral cortex of developing mouse embryos with GFP, and then examined neuronal positioning and morphology in early adulthood, which revealed no alterations in cortical layer position or morphology in either Tc1 or Ts1Rhr mouse cortex. The number of dendrites, as well as dendrite length and branching was normal in both DS models, compared with wildtype controls. The sites of projection neuron synaptic inputs, dendritic spines, were analysed in Tc1 and Ts1Rhr cortex at three weeks and three months after birth, and significant changes in spine morphology were observed in both mouse lines. Ts1Rhr mice had significantly fewer thin spines at three weeks of age. At three months of age Tc1 mice had significantly fewer mushroom spines--the morphology associated with established synaptic inputs and learning and memory. The decrease in mushroom spines was accompanied by a significant increase in the number of stubby spines. This data suggests that dendritic spine abnormalities may be a more important contributor to cognitive deficits in DS models, rather than overall neuronal architecture defects.

  1. Effects of neonatal exposure to anti-nerve growth factor on the number and size distribution of trigeminal neurones projecting to the molar dental pulp in rats.

    Science.gov (United States)

    Qian, X B; Naftel, J P

    1996-04-01

    The first aim of the present study was to determine whether depletion of endogenous nerve growth factor (NGF) during early postnatal development results in a long-term deficit in the number of trigeminal ganglion cells and axons projecting to the molar pulp. The second aim was to identify selectivity of the effects of NGF deprivation for any specific size group among pulp neurones. Newborn Sprague-Dawley rats were given subcutaneous injections of either rabbit anti-mouse-NGF serum or non-immune (control) rabbit serum for a period of 1 month. At age 4 months, Fluoro-gold (FG) was applied to the pulp chamber of the right maxillary first molar. One week later the animals were perfusion-fixed, and the trigeminal ganglia were removed and serially sectioned with a cryostat. Labelled neurones were seen only in the trigeminal ganglia ipsilateral to the injected teeth. The area of every labelled cell profile was measured, and from these data, estimates of the true number and size distribution of FG-labelled cells were obtained by recursive translation. Ganglia of control animals had a mean of 197 labelled neurones, all in the maxillary division, and most of the somas were of medium or large diameter. NGF-deprived animals had significantly fewer (mean = 145) FG-labelled cells in the trigeminal ganglion ipsilateral to the injected tooth. Neurones with somas of less than 30 microns dia were most strikingly subnormal in anti-NGF treated animals (64% of controls). In accordance with the greater susceptibility of small neurones to anti-NGF exposure, deficits in apical nerve fibres of the mandibular first molar were greater in degree and duration for unmyelinated axons than for myelinated axons. It is concluded that NGF is an important mediator in regulation of postnatal development of the sensory innervation of the dental pulp. The results also indicate that postnatal development of at least one class of larger pulpal afferent neurones is regulated by factors other than NGF.

  2. Moxd1 Is a Marker for Sexual Dimorphism in the Medial Preoptic Area, Bed Nucleus of the Stria Terminalis and Medial Amygdala

    Science.gov (United States)

    Tsuneoka, Yousuke; Tsukahara, Shinji; Yoshida, Sachine; Takase, Kenkichi; Oda, Satoko; Kuroda, Masaru; Funato, Hiromasa

    2017-01-01

    The brain shows various sex differences in its structures. Various mammalian species exhibit sex differences in the sexually dimorphic nucleus of the preoptic area (SDN-POA) and parts of the extended amygdala such as the principal nucleus of the bed nucleus of the stria terminalis (BNSTpr) and posterodorsal part of the medial amygdala (MePD). The SDN-POA and BNSTpr are male-biased sexually dimorphic nuclei, and characterized by the expression of calbindin D-28K (calbindin 1). However, calbindin-immunoreactive cells are not restricted to the SDN-POA, but widely distributed outside of the SDN-POA. To find genes that are more specific to sexually dimorphic nuclei, we selected candidate genes by searching the Allen brain atlas and examined the detailed expressions of the candidate genes using in situ hybridization. We found that the strong expression of monooxygenase DBH-like 1 (Moxd1) was restricted to the SDN-POA, BNSTpr and MePD. The numbers of Moxd1-positive cells in the SDN-POA, BNSTpr and MePD in male mice were larger than those in female mice. Most of the Moxd1-positive cells in the SDN-POA and BNSTpr expressed calbindin. Neonatal castration of male mice reduced the number of Moxd1-positive cells in the SDN-POA, whereas gonadectomy in adulthood did not change the expression of the Moxd1 gene in the SDN-POA in both sexes. These results suggest that the Moxd1 gene is a suitable marker for sexual dimorphic nuclei in the POA, BNST and amygdala, which enables us to manipulate sexually dimorphic neurons to examine their roles in sex-biased physiology and behaviors.

  3. Ageing and Chronic Administration of Serotonin-Selective Reuptake Inhibitor Citalopram Upregulate Sirt4 Gene Expression in the Preoptic Area of Male Mice

    Directory of Open Access Journals (Sweden)

    Wong eDutt Way

    2015-09-01

    Full Text Available Sexual dysfunction and cognitive deficits are markers of the ageing process. Mammalian sirtuins (SIRT, encoded by sirt 1-7 genes, are known as ageing molecules which are sensitive to serotonin (5-hydroxytryptamine, 5-HT. Whether the 5-HT system regulates SIRT in the preoptic area (POA, which could affect reproduction and cognition has not been examined. Therefore, this study was designed to examine the effects of citalopram (CIT, 10mg/kg for 4 weeks, wk, a potent selective-serotonin reuptake inhibitor and ageing on SIRT expression in the POA of male mice using real-time PCR and immunocytochemistry. Age-related increases of sirt1, sirt4, sirt5, and sirt7 mRNA levels were observed in the POA of 52 wk old mice. Furthermore, 4 wk of chronic CIT treatment started at 8 wk of age also increased sirt2 and sirt4 mRNA expression in the POA. Moreover, the number of SIRT4 immuno-reactive neurons increased with ageing in the medial septum area (12 wk = 1.00±0.15 vs 36 wk = 1.68±0.14 vs 52 wk = 1.54±0.11, p<0.05. In contrast, the number of sirt4-immunopositive cells did not show a statistically significant change with CIT treatment, suggesting that the increase in sirt4 mRNA levels may occur in cells in which sirt4 is already being expressed. Taken together, these studies suggest that CIT treatment and the process of ageing utilize the serotonergic system to up-regulate SIRT4 in the POA as a common pathway to deregulate social cognitive and reproductive functions.

  4. Segmental distribution and morphometric features of primary sensory neurons projecting to the tibial periosteum in the rat.

    Directory of Open Access Journals (Sweden)

    Tadeusz Cichocki

    2004-07-01

    Full Text Available Previous reports have demonstrated very rich innervation pattern in the periosteum. Most of the periosteal fibers were found to be sensory in nature. The aim of this study was to identify the primary sensory neurons that innervate the tibial periosteum in the adult rat and to describe the morphometric features of their perikarya. To this end, an axonal fluorescent carbocyanine tracer, DiI, was injected into the periosteum on the medial surface of the tibia. The perikarya of the sensory fibers were traced back in the dorsal root ganglia (DRG L1-L6 by means of fluorescent microscopy on cryosections. DiI-containing neurons were counted in each section and their segmental distribution was determined. Using PC-assisted image analysis system, the size and shape of the traced perikarya were analyzed. DiI-labeled sensory neurons innervating the periosteum of the tibia were located in the DRG ipsilateral to the injection site, with the highest distribution in L3 and L4 (57% and 23%, respectively. The majority of the traced neurons were of small size (area < 850 microm2, which is consistent with the size distribution of CGRP- and SP-containing cells, regarded as primary sensory neurons responsible for perception of pain and temperature. A small proportion of labeled cells had large perikarya and probably supplied corpuscular sense receptors observed in the periosteum. No differences were found in the shape distribution of neurons belonging to different size classes.

  5. Cold-induced thermogenesis mediated by GABA in the preoptic area of anesthetized rats.

    Science.gov (United States)

    Osaka, Toshimasa

    2004-08-01

    Bilateral microinjections of GABA (300 mM, 100 nl) or the GABA(A) receptor agonist muscimol (100 microM, 100 nl) into the preoptic area (POA) of the hypothalamus increased the rate of whole body O(2) consumption (VO(2)) and the body core (colonic) temperature of urethane-chloralose-anesthetized, artificially ventilated rats. The most sensitive site was the dorsomedial POA at the level of the anterior commissure. The GABA-induced thermogenesis was accompanied by a tachycardic response and electromyographic (EMG) activity recorded from the femoral or neck muscles. Pretreatment with muscle relaxants (1 mg/kg pancuronium bromide + 4 mg/kg vecuronium bromide i.v.) prevented GABA-induced EMG activity but had no significant effect on GABA-induced thermogenesis. However, pretreatment with the beta-adrenoceptor propranolol (5 mg/kg i.v.) greatly attenuated the GABA-induced increase in VO(2) and tachycardic responses. Accordingly, the GABA-induced increase in VO(2) reflected mainly nonshivering thermogenesis. On the other hand, cooling of the shaved back of the rat by contact with a plastic bag containing 28 degrees C water also elicited thermogenic, tachycardic, and EMG responses. Bilateral microinjections of the GABA(A) receptor antagonist bicuculline (500 microM, 100 nl), but not the vehicle saline, into the POA blocked these skin cooling-induced responses. These results suggest that GABA and GABA(A) receptors in the POA mediate cold information arising from the skin for eliciting cold-induced thermogenesis.

  6. Effect of Physical Exercise on the Febrigenic Signaling is Modulated by Preoptic Hydrogen Sulfide Production

    Science.gov (United States)

    Nogueira, Jonatas E.; Soriano, Renato N.; Fernandez, Rodrigo A. R.; Francescato, Heloísa D. C.; Saia, Rafael S.; Coimbra, Terezila M.; Antunes-Rodrigues, José; Branco, Luiz G. S.

    2017-01-01

    We tested the hypothesis that the neuromodulator hydrogen sulfide (H2S) in the preoptic area (POA) of the hypothalamus modulates the febrigenic signaling differently in sedentary and trained rats. Besides H2S production rate and protein expressions of H2S-related synthases cystathionine β-synthase (CBS), 3-mercaptopyruvate sulfurtransferase (3-MPST) and cystathionine γ-lyase (CSE) in the POA, we also measured deep body temperature (Tb), circulating plasma levels of cytokines and corticosterone in an animal model of systemic inflammation. Rats run on a treadmill before receiving an intraperitoneal injection of lipopolysaccharide (LPS, 100 μg/kg) or saline. The magnitude of changes of Tb during the LPS-induced fever was found to be similar between sedentary and trained rats. In sedentary rats, H2S production was not affected by LPS. Conversely, in trained rats LPS caused a sharp increase in H2S production rate that was accompanied by an increased CBS expression profile, whereas 3-MPST and CSE expressions were kept relatively constant. Sedentary rats showed a significant LPS-induced release of cytokines (IL-1β, IL-6, and TNF-α) which was virtually abolished in the trained animals. Correlation between POA H2S and IL-6 as well as TNF-α was observed. Corticosterone levels were augmented after LPS injection in both groups. We found correlations between H2S and corticosterone, and corticosterone and IL-1β. These data are consistent with the notion that the responses to systemic inflammation are tightly regulated through adjustments in POA H2S production which may play an anti-inflammatory role downmodulating plasma cytokines levels and upregulating corticosterone release. PMID:28118407

  7. Effect of Physical Exercise on the Febrigenic Signaling is Modulated by Preoptic Hydrogen Sulfide Production.

    Science.gov (United States)

    Nogueira, Jonatas E; Soriano, Renato N; Fernandez, Rodrigo A R; Francescato, Heloísa D C; Saia, Rafael S; Coimbra, Terezila M; Antunes-Rodrigues, José; Branco, Luiz G S

    2017-01-01

    We tested the hypothesis that the neuromodulator hydrogen sulfide (H2S) in the preoptic area (POA) of the hypothalamus modulates the febrigenic signaling differently in sedentary and trained rats. Besides H2S production rate and protein expressions of H2S-related synthases cystathionine β-synthase (CBS), 3-mercaptopyruvate sulfurtransferase (3-MPST) and cystathionine γ-lyase (CSE) in the POA, we also measured deep body temperature (Tb), circulating plasma levels of cytokines and corticosterone in an animal model of systemic inflammation. Rats run on a treadmill before receiving an intraperitoneal injection of lipopolysaccharide (LPS, 100 μg/kg) or saline. The magnitude of changes of Tb during the LPS-induced fever was found to be similar between sedentary and trained rats. In sedentary rats, H2S production was not affected by LPS. Conversely, in trained rats LPS caused a sharp increase in H2S production rate that was accompanied by an increased CBS expression profile, whereas 3-MPST and CSE expressions were kept relatively constant. Sedentary rats showed a significant LPS-induced release of cytokines (IL-1β, IL-6, and TNF-α) which was virtually abolished in the trained animals. Correlation between POA H2S and IL-6 as well as TNF-α was observed. Corticosterone levels were augmented after LPS injection in both groups. We found correlations between H2S and corticosterone, and corticosterone and IL-1β. These data are consistent with the notion that the responses to systemic inflammation are tightly regulated through adjustments in POA H2S production which may play an anti-inflammatory role downmodulating plasma cytokines levels and upregulating corticosterone release.

  8. Dual projections of single orexin- or CART-immunoreactive, lateral hypothalamic neurons to the paraventricular thalamic nucleus and nucleus accumbens shell in the rat: Light microscopic study.

    Science.gov (United States)

    Lee, Eun Y; Lee, Hyun S

    2016-03-01

    The paraventricular thalamic nucleus (PVT) is a major relay station to the limbic forebrain areas such as the nucleus accumbens shell (AcbSh). Both PVT and AcbSh are known to receive feeding/arousal-related peptidergic fibers including orexin (ORX) and cocaine- and amphetamine-regulated transcript (CART) peptide. In the first series of experiments, we examined the peptidergic fiber distribution in the AcbSh; the density of ORX (or CART) fibers in the AcbSh was substantially lower than that in the PVT. At the light microscopic level, ORX (or CART) terminals formed close appositions to choline acetyltransferase (ChAT)-, glutamate decarboxylase (GAD)-, or enkephalin (Enk)-immunoreactive neuronal elements in the AcbSh. In the second series of experiments, we addressed the question of whether single ORX (or CART) cells in the hypothalamus provided divergent axon collaterals to the PVT and AcbSh. ORX neurons with dual projections were found in the medial, central, and lateral subdivisions of the lateral hypothalamus (LH), which amounted to an average of 1.6% of total ORX cells. CART neurons with divergent axon collaterals were observed in the LH, zona incerta, dorsal hypothalamic area, and retrochiasmatic nucleus, which represented a mean of 2.5% of total CART cells. None of arcuate CART cells sent dual projections. These data suggested that a portion of ORX (or CART) neurons in the hypothalamus, via divergent axon collaterals, might concurrently modulate the activity of PVT and AcbSh cells to affect feeding and drug-seeking behaviors.

  9. 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.

  10. Striated perineal muscles: location of autonomic, sensory, and somatic neurons projecting to the male pig bulbospongiosus muscle.

    Science.gov (United States)

    Botti, Maddalena; Ragionieri, Luisa; Gazza, Ferdinando; Acone, Franca; Bo Minelli, Luisa; Panu, Rino

    2009-11-01

    The location, number, and size of the neurons innervating the bulbospongiosus muscle (BSM) were studied in male pigs, by means of Fast Blue (FB) retrograde transport. After injection of FB into the left BSM, labeled neurons were found bilaterally in the L2-S4 sympathetic trunk ganglia (STGs), in the caudal mesenteric ganglia (CMGs), in the microganglia of the pelvic plexus (PGs), in a dorsolateral area with respect to the central canal of S1-S3 segments of the spinal cord (SC) and in the S1-S4 ipsilateral and S2-S3 contralateral spinal ganglia (SGs). The mean number of labeled FB cells was 3,122 +/- 1,968 in STGs, 979 +/- 667 in CMGs, 108 +/- 104 in PGs, 89 +/- 39 in SC and 77 +/- 23 in SGs. The area of the multipolar neurons was 852 +/- 22 microm(2) in the STGs, 878 +/- 23 microm(2) in the CMGs and 922 +/- 31 microm(2) in the PGs. The multipolar SC neurons had an area of 1,057 +/- 38 microm(2), while pseudounipolar SG cells had dimensions of 2,281 +/- 129 microm(2). Our research enables us to highlight two peculiarities regarding the innervation of the boar BSM: the very high number of labeled autonomic neurons and the particular localization of the motor somatic nucleus.

  11. Effects of gamma-aminobutyric acid A-receptor antagonist on sleep-wakefulness cycles following lesion to the ventrolateral preoptic area in rats

    Institute of Scientific and Technical Information of China (English)

    Xin Zhang; Yina Sun; Peng Xie; Xuguang Yang; Yiping Hou

    2009-01-01

    BACKGROUND: Neurons expressing gamma-aminobutyric acid (GABA) play an important role in the regulation of wakefulness to sleep, as well as the maintenance of sleep. However, the role of GABAergic neurons in the tuberomammillary nucleus (TMn), with regard to the sleep-wakefulness cycle, is poorly understood.OBJECTIVE: To investigate the effects of GABAergic neurons in the TMn on the sleep-wakefulness cycle.DESIGN, TIME AND SETTING: Randomized controlled study, performed at the Laboratory of Neurobiology, Department of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Lanzhou University from July 2007 to February 2008.MATERIALS: Fifteen healthy, adult, male, Sprague Dawley rats were randomly divided into three groups(n = 5): control, ventrolateral preoptic area (VLPO) lesion, and VLPO lesion plus GABAA receptor antagonist-treated. Ibotenic acid and bicuculline were provided by Sigma (St. Louis, USA). METHODS: Four electroencephalogram screw electrodes were implanted into the skull at a frontal region (two) and parietal bones (two) on each side. Three flexible electromyogram wire electrodes were placed into the nuchal muscles. On day 8, a fine glass micropipette (10-20 mm tip diameter) containing ibotenic acid solution (10 nmol/L) was injected into the VLPO in both hemispheres following bone wax removal under anesthesia. One week after the second surgery, sleep-wakefulness states were recorded in rats from the VLPO lesion group. On day 10 after VLPO lesion, bicuculline (10 nmol/L), a GABAA-receptor antagonist, was microinjected into the TMn and sleep-wakefulness states were recorded for 24 hours.MAIN OUTCOME MEASURES: Duration of the sleep-wakefulness cycle in each group using a Data acquisition unit (Micro1 401 mk2) and Data collection software (Spike Ⅱ). RESULTS: VLPO lesion induced an increased duration of wakefulness (W, 13.17%) and light slow-wave sleep (SWS1, 28.9%), respectively. Deep slow-wave sleep (SWS2, 43.74%) and paradoxical sleep (PS

  12. Overexpression of 5-HT(1B) mRNA in nucleus accumbens shell projection neurons differentially affects microarchitecture of initiation and maintenance of ethanol consumption.

    Science.gov (United States)

    Furay, Amy R; Neumaier, John F; Mullenix, Andrew T; Kaiyala, Karl K; Sandygren, Nolan K; Hoplight, Blair J

    2011-02-01

    Serotonin 1B (5-HT(1B)) heteroreceptors on nucleus accumbens shell (NAcSh) projection neurons have been shown to enhance the voluntary consumption of alcohol by rats, presumably by modulating the activity of the mesolimbic reward pathway. The present study examined whether increasing 5-HT(1B) receptors expressed on NAcSh projection neurons by means of virus-mediated gene transfer enhances ethanol consumption during the initiation or maintenance phase of drinking and alters the temporal pattern of drinking behavior. Animals received stereotaxic injections of viral vectors expressing either 5-HT(1B) receptor and green fluorescent protein (GFP) or GFP alone. Home cages equipped with a three-bottle (water and 6 and 12% ethanol) lickometer system recorded animals' drinking behaviors continuously, capturing either initiation or maintenance of drinking behavior patterns. Overexpression of 5-HT(1B) receptors during initiation increased consumption of 12% ethanol during both forced-access and free-choice consumption. There was a shift in drinking pattern for 6% ethanol with an increase in number of drinking bouts per day, although the total number of drinking bouts for 12% ethanol was not different. Finally, increased 5-HT(1B) expression induced more bouts with very high-frequency licking from the ethanol bottle sippers. During the maintenance phase of drinking, there were no differences between groups in total volume of ethanol consumed; however, there was a shift toward drinking bouts of longer duration, especially for 12% ethanol. This suggests that during maintenance drinking, increased 5-HT(1B) receptors facilitate longer drinking bouts of more modest volumes. Taken together, these results indicate that 5-HT(1B) receptors expressed on NAcSh projection neurons facilitate ethanol drinking, with different effects during initiation and maintenance of ethanol-drinking behavior. Copyright © 2011 Elsevier Inc. All rights reserved.

  13. Distribution of Endomorphin-like-immunoreactive neurones in the brain of the cichlid fish Oreochromis mossambicus.

    Science.gov (United States)

    Vijayalaxmi; Ganesh, C B

    2017-02-08

    Endomorphins are tetrapeptides involved in pain and neuroendocrine responses with high affinity for mu opioid receptors in mammals. In the present investigation, we studied the distribution of endomorphin-like-immunoreactive (EM-L-ir) neurones in the brain of the cichlid fish Oreochromis mossambicus. Application of antisera against endomorphin 1 and 2 (EM-1-2) revealed the presence of EM-L-ir somata and fibres throughout the different subdivisions of the olfactory bulb such as the olfactory nerve layer and the granule cell layer. While the extensions of EM-L-ir fibres were seen along the medial olfactory tract, intensely labeled EM-L-ir somata were found in different subdivisions of the telencephalon. In the diencephalon, intensely stained EM-L-ir neurones were noticed in the preoptic area, the nucleus preopticus pars magnocellularis, the suprachiasmatic nucleus, the nucleus lateralis tuberis pars lateralis (NLTl) and the nucleus lateralis tuberis pars medialis (NLTm) regions, whereas projections of EM-L-ir fibres were also seen along the hypothalamo-hypophyseal tract suggested a possible hypophysiotrophic role for these neurones. Intense to moderately stained EM-L-ir neurones were noticed in different subdivisions of thalamic nucleus such as the dorsal posterior thalamic nucleus, commissura posterior, ventromedial thalamic nucleus, nucleus posterior tuberis, ventrolateral thalamic nucleus and medial preglomerular nucleus. Numerous intensely stained perikarya and axonal fibres were also noticed throughout the inferior lobe, along the periventricular margin of the reccessus lateralis, and in the nucleus recesus lateralis regions. In addition, numerous moderately labeled EM-like neuronal populations were found in the secondary gustatory nucleus and rostral spinal cord. The widespread distribution of EM-L-ir neurones throughout the brain and spinal cord indicate diverse roles for these cells in neuroendocrine and neuromodulatory responses for the first time in fish

  14. Diverse Short-Term Dynamics of Inhibitory Synapses Converging on Striatal Projection Neurons: Differential Changes in a Rodent Model of Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Janet Barroso-Flores

    2015-01-01

    Full Text Available Most neurons in the striatum are projection neurons (SPNs which make synapses with each other within distances of approximately 100 µm. About 5% of striatal neurons are GABAergic interneurons whose axons expand hundreds of microns. Short-term synaptic plasticity (STSP between fast-spiking (FS interneurons and SPNs and between SPNs has been described with electrophysiological and optogenetic techniques. It is difficult to obtain pair recordings from some classes of interneurons and due to limitations of actual techniques, no other types of STSP have been described on SPNs. Diverse STSPs may reflect differences in presynaptic release machineries. Therefore, we focused the present work on answering two questions: Are there different identifiable classes of STSP between GABAergic synapses on SPNs? And, if so, are synapses exhibiting different classes of STSP differentially affected by dopamine depletion? Whole-cell voltage-clamp recordings on SPNs revealed three classes of STSPs: depressing, facilitating, and biphasic (facilitating-depressing, in response to stimulation trains at 20 Hz, in a constant ionic environment. We then used the 6-hydroxydopamine (6-OHDA rodent model of Parkinson’s disease to show that synapses with different STSPs are differentially affected by dopamine depletion. We propose a general model of STSP that fits all the dynamics found in our recordings.

  15. Diverse Short-Term Dynamics of Inhibitory Synapses Converging on Striatal Projection Neurons: Differential Changes in a Rodent Model of Parkinson's Disease

    Science.gov (United States)

    Herrera-Valdez, Marco A.; Lopez-Huerta, Violeta Gisselle; Galarraga, Elvira

    2015-01-01

    Most neurons in the striatum are projection neurons (SPNs) which make synapses with each other within distances of approximately 100 µm. About 5% of striatal neurons are GABAergic interneurons whose axons expand hundreds of microns. Short-term synaptic plasticity (STSP) between fast-spiking (FS) interneurons and SPNs and between SPNs has been described with electrophysiological and optogenetic techniques. It is difficult to obtain pair recordings from some classes of interneurons and due to limitations of actual techniques, no other types of STSP have been described on SPNs. Diverse STSPs may reflect differences in presynaptic release machineries. Therefore, we focused the present work on answering two questions: Are there different identifiable classes of STSP between GABAergic synapses on SPNs? And, if so, are synapses exhibiting different classes of STSP differentially affected by dopamine depletion? Whole-cell voltage-clamp recordings on SPNs revealed three classes of STSPs: depressing, facilitating, and biphasic (facilitating-depressing), in response to stimulation trains at 20 Hz, in a constant ionic environment. We then used the 6-hydroxydopamine (6-OHDA) rodent model of Parkinson's disease to show that synapses with different STSPs are differentially affected by dopamine depletion. We propose a general model of STSP that fits all the dynamics found in our recordings. PMID:26167304

  16. The transcriptional repressor Zbtb20 is essential for specification of hippocampal projection neurons and territory in mice

    DEFF Research Database (Denmark)

    Rosenthal, Eva Helga

    for specification of both hippocampal pyramidal neurons and territory in a mouse knockout model. Homozygous Zbtb20-/- mice are viable at birth, but display dwarfism and die during the first month of postnatal life. Characterization of the Zbtb20-/- brain phenotype reveals a small vestigial hippocampus...

  17. Projections of medullary and pontine noradrenergic neurons to the horizontal limb of the nucleus of diagonal band in the rat.

    Science.gov (United States)

    Senatorov, V V; Renaud, L P

    1999-01-01

    Recent investigations in the rat have implicated a noradrenergic innervation to the horizontal nucleus of the diagonal band of Broca as a critical link in a neural circuit that conveys baroreceptor information centrally to inhibit the firing of vasopressin-secreting neurons in the hypothalamic supraoptic nucleus. In this study we used small intra-diagonal band injections of a retrograde tracer, rhodamine latex microspheres, in combination with tyrosine hydroxylase histochemistry to identify brainstem noradrenergic cells contributing to this innervation. In three cases where tracer injections were limited to the horizontal limb of the diagonal band, we observed 20-50 double-labelled neurons ipsilaterally in the dorsal part of the locus coeruleus (A6) and the caudal nucleus tractus solitarius (A2), and bilaterally in the caudal ventrolateral medulla (A1). Double-labelled neurons were also noted in the ventral tegmental area (dopaminergic A10 cell group). Although all major brainstem noradrenergic cell groups contribute fibers to the horizontal limb of the nucleus of diagonal band, data from physiological studies suggest that the noradrenergic A2 neurons in the nucleus tractus solitarius are the most likely pathway through which it receives this baroreceptor information.

  18. High-frequency stimulation-induced peptide release synchronizes arcuate kisspeptin neurons and excites GnRH neurons

    Science.gov (United States)

    Qiu, Jian; Nestor, Casey C; Zhang, Chunguang; Padilla, Stephanie L; Palmiter, Richard D

    2016-01-01

    Kisspeptin (Kiss1) and neurokinin B (NKB) neurocircuits are essential for pubertal development and fertility. Kisspeptin neurons in the hypothalamic arcuate nucleus (Kiss1ARH) co-express Kiss1, NKB, dynorphin and glutamate and are postulated to provide an episodic, excitatory drive to gonadotropin-releasing hormone 1 (GnRH) neurons, the synaptic mechanisms of which are unknown. We characterized the cellular basis for synchronized Kiss1ARH neuronal activity using optogenetics, whole-cell electrophysiology, molecular pharmacology and single cell RT-PCR in mice. High-frequency photostimulation of Kiss1ARH neurons evoked local release of excitatory (NKB) and inhibitory (dynorphin) neuropeptides, which were found to synchronize the Kiss1ARH neuronal firing. The light-evoked synchronous activity caused robust excitation of GnRH neurons by a synaptic mechanism that also involved glutamatergic input to preoptic Kiss1 neurons from Kiss1ARH neurons. We propose that Kiss1ARH neurons play a dual role of driving episodic secretion of GnRH through the differential release of peptide and amino acid neurotransmitters to coordinate reproductive function. DOI: http://dx.doi.org/10.7554/eLife.16246.001 PMID:27549338

  19. Commissurally projecting inhibitory interneurons of the rat hippocampal dentate gyrus: a colocalization study of neuronal markers and the retrograde tracer Fluoro-gold.

    Science.gov (United States)

    Zappone, C A; Sloviter, R S

    2001-12-24

    Improved methods for detecting neuronal markers and the retrograde tracer Fluoro-Gold (FG) were used to identify commissurally projecting neurons of the rat hippocampus. In addition to the dentate hilar mossy cells and CA3 pyramidal cells shown previously to transport retrograde tracers after injection into the dorsal hippocampus, FG-positive interneurons of the dentate granule cell layer and hilus were detected in numbers greater than previously reported. FG labeling of interneurons was variable among animals, but was as high as 96% of hilar somatostatin-positive interneurons, 84% of parvalbumin-positive cells of the granule cell layer and hilus combined, and 33% of hilar calretinin-positive cells. By comparison, interneurons of the dentate molecular layer and all hippocampal subregions were conspicuously FG-negative. Whereas hilar mossy cells and CA3 pyramidal cells were FG-labeled throughout the longitudinal axis, FG-positive interneurons exhibited a relatively homotopic distribution. "Control" injections of FG into the neocortex, septum, and ventral hippocampus demonstrated that the homotopic labeling of dentate interneurons was injection site-specific, and that the CA1-CA3 interneurons unlabeled by contralateral hippocampal FG injection were nonetheless able to transport FG from the septum. These data suggest a hippocampal organizing principle according to which virtually all commissurally projecting hippocampal neurons share the property of being monosynaptic targets of dentate granule cells. Because granule cells innervate their exclusively ipsilateral target cells in a highly lamellar pattern, these results suggest that focal granule cell excitation may result in commissural inhibition of the corresponding "twin" granule cell lamella, thereby lateralizing and amplifying the influence of the initiating discharge.

  20. Separate populations of neurons within the paraventricular hypothalamic nucleus of the rat project to vagal and thoracic autonomic preganglionic levels and express c-Fos protein induced by lithium chloride.

    Science.gov (United States)

    Portillo, F; Carrasco, M; Vallo, J J

    1998-03-01

    The role of different hypothalamic nuclei, particularly the paraventricular nucleus (PVN), in the control of food intake and feeding behaviour is well known. It is also well established that lithium chloride (LiCl) causes various disorders in feeding behaviour. In this study, we analyzed the precise distribution of hypothalamic neurons activated by i.p. LiCl administration (LCA neurons) and compared it to that of hypothalamic neurons which project to autonomic preganglionic levels (HAP neurons). We also analysed the possibility that some neurons belong to both populations of nerve cells. To this end, a multiple-labelling technique, using two retrograde fluorescent tracers together with c-Fos-like immunohistochemistry, was performed. Fast Blue was injected in the dorsal motor nucleus of the vagus and Fluorogold (FG) in the thoracic intermedial-lateral cell column, to trace parasympathetic and sympathetic pathways, respectively. LiCl was used as stimulus for c-Fos-like immunohistochemistry. HAP neurons were located mainly in the dorsal, ventral and lateral regions of the parvocellular PVN, while LCA neurons were observed predominantly in the magnocellular region of the PVN rostrally to HAP neurons. A significant number of FG/Fos double-labelled neurons were located in the dorsal parvocellular subnucleus of the PVN (dp) in the LiCl-stimulated rats. We concluded that there is a clear segregation of LCA neurons from HAP neurons within the PVN. The presence of FG/Fos double-labelled neurons in the dp suggests that this nucleus could mediate a sympathetic response after LiCl administration.

  1. The ventromedial hypothalamic nucleus in the zebra finch (Taeniopygia guttata): Afferent and efferent projections in relation to the control of reproductive behavior.

    Science.gov (United States)

    Wild, J Martin

    2017-08-15

    Sex-specific mating behaviors occur in a variety of mammals, with the medial preoptic nucleus (POM) and the ventromedial hypothalamic nucleus (VMH) mediating control of male and female sexual behavior, respectively. In birds, likewise, POM is predominantly involved in the control of male reproductive behavior, but the degree to which VMH is involved in female reproductive behavior is unclear. Here, in male and female zebra finches, a combination of aromatase immunohistochemistry and conventional tract tracing facilitated the definition of two separate but adjacent nuclei in the basal hypothalamus: an oblique band of aromatase-positive (AR+) neurons, and ventromedial to this, an ovoid, aromatase-negative (AR-) nucleus. The AR- nucleus, but not the AR+ nucleus, was here shown to receive a projection from rostral parts of the thalamic auditory nucleus ovoidalis and from the nucleus of the tractus ovoidalis. The AR- nucleus also receives an overlapping, major projection from previously uncharted regions of the medial arcopallium and a minor projection from the caudomedial nidopallium. Both the AR- and the AR+ nuclei project to the intercollicular nucleus of the midbrain. No obvious sex differences in either the pattern of AR immunoreactivity or of the afferent projections to the AR- nucleus were observed. The significance of these results in terms of the acoustic control of avian reproductive behavior is discussed, and a comparison with the organization of VMH afferents in lizards suggests a homologous similarity of the caudal telencephalon in sauropsids. © 2017 Wiley Periodicals, Inc.

  2. The Memory-Impairing Effects of Septal GABA Receptor Activation Involve GABAergic Septo-Hippocampal Projection Neurons

    Science.gov (United States)

    Krebs-Kraft, Desiree L.; Wheeler, Marina G.; Parent, Marise B.

    2007-01-01

    Septal infusions of the [gamma]-aminobutyric acid (GABA)[subscript A] agonist muscimol impair memory, and the effect likely involves the hippocampus. GABA[subscript A] receptors are present on the perikarya of cholinergic and GABAergic septo-hippocampal (SH) projections. The current experiments determined whether GABAergic SH projections are…

  3. Corticotrigeminal Projections from the Insular Cortex to the Trigeminal Caudal Subnucleus Regulate Orofacial Pain after Nerve Injury via Extracellular Signal-Regulated Kinase Activation in Insular Cortex Neurons.

    Science.gov (United States)

    Wang, Jian; Li, Zhi-Hua; Feng, Ban; Zhang, Ting; Zhang, Han; Li, Hui; Chen, Tao; Cui, Jing; Zang, Wei-Dong; Li, Yun-Qing

    2015-01-01

    Cortical neuroplasticity alterations are implicated in the pathophysiology of chronic orofacial pain. However, the relationship between critical cortex excitability and orofacial pain maintenance has not been fully elucidated. We recently demonstrated a top-down corticospinal descending pain modulation pathway from the anterior cingulate cortex (ACC) to the spinal dorsal horn that could directly regulate nociceptive transmission. Thus, we aimed to investigate possible corticotrigeminal connections that directly influence orofacial nociception in rats. Infraorbital nerve chronic constriction injury (IoN-CCI) induced significant orofacial nociceptive behaviors as well as pain-related negative emotions such as anxiety/depression in rats. By combining retrograde and anterograde tract tracing, we found powerful evidence that the trigeminal caudal subnucleus (Vc), especially the superficial laminae (I/II), received direct descending projections from granular and dysgranular parts of the insular cortex (IC). Extracellular signal-regulated kinase (ERK), an important signaling molecule involved in neuroplasticity, was significantly activated in the IC following IoN-CCI. Moreover, in IC slices from IoN-CCI rats, U0126, an inhibitor of ERK activation, decreased both the amplitude and the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) and reduced the paired-pulse ratio (PPR) of Vc-projecting neurons. Additionally, U0126 also reduced the number of action potentials in the Vc-projecting neurons. Finally, intra-IC infusion of U0126 obviously decreased Fos expression in the Vc, accompanied by the alleviation of both nociceptive behavior and negative emotions. Thus, the corticotrigeminal descending pathway from the IC to the Vc could directly regulate orofacial pain, and ERK deactivation in the IC could effectively alleviate neuropathic pain as well as pain-related negative emotions in IoN-CCI rats, probably through this top-down pathway. These findings may help

  4. Evidence that gonadal steroids modulate nitric oxide efflux in the medial preoptic area: effects of N-methyl-D-aspartate and correlation with luteinizing hormone secretion.

    Science.gov (United States)

    Pu, S; Xu, B; Kalra, S P; Kalra, P S

    1996-05-01

    Several lines of evidence suggest that nitric oxide (NO) is involved in the neuroendocrine control of reproductive function. This study was undertaken to determine 1) NO activity in the medial preoptic area (MPOA) where LHRH- and NO synthase-containing neurons are coextensive; 2) whether N-methyl-D-aspartate (NMDA) receptor activation, which stimulates LHRH release, augments NO activity in the MPOA; and 3) whether NO activation in the MPOA underlies the steroid dependency of NMDA-induced pituitary LH release. As extracellular levels of cGMP in discrete brain sites are a reliable index of basal and stimulated activity of NO, extracellular cGMP levels in the MPOA of freely moving, awake rats were measured by microdialysis in the current study. In the first experiment, the MPOA of intact and castrated male rats were microdialyzed with artificial cerebrospinal fluid at a rate of 5 microliters/min. The basal level of cGMP efflux was determined from the initial seven samples collected at 20-min intervals. The NO response to a single i.v. injection of NMDA (10 mg/kg) or saline was assessed in the next five samples. In the second experiment, the basal and NMDA-evoked NO effluxes in the MPOA of ovariectomized (ovx) and estrogen-treated ovx rats were examined. Results showed that in both sexes, the absence of gonadal steroids resulted in significantly lower basal cGMP levels. Additionally, the cGMP response to NMDA was steroid dependent. Whereas in castrated rats it failed to affect cGMP efflux, NMDA in intact male rats promptly raised cGMP levels at 20 min, and these elevated levels were maintained through the duration of the experiment. This NMDA-induced cGMP response, observed selectively in intact rats, was also associated with stimulation of plasma LH levels. In female rats, NMDA similarly enhanced MPOA cGMP efflux and pituitary LH secretion in estradiol benzoate-treated, but not in oil-treated, ovx rats. The NMDA receptor antagonist D,L-amino-5-phosphoropentanoic acid

  5. Kappe neurons, a novel population of olfactory sensory neurons

    Science.gov (United States)

    Ahuja, Gaurav; Nia, Shahrzad Bozorg; Zapilko, Veronika; Shiriagin, Vladimir; Kowatschew, Daniel; Oka, Yuichiro; Korsching, Sigrun I.

    2014-02-01

    Perception of olfactory stimuli is mediated by distinct populations of olfactory sensory neurons, each with a characteristic set of morphological as well as functional parameters. Beyond two large populations of ciliated and microvillous neurons, a third population, crypt neurons, has been identified in teleost and cartilaginous fishes. We report here a novel, fourth olfactory sensory neuron population in zebrafish, which we named kappe neurons for their characteristic shape. Kappe neurons are identified by their Go-like immunoreactivity, and show a distinct spatial distribution within the olfactory epithelium, similar to, but significantly different from that of crypt neurons. Furthermore, kappe neurons project to a single identified target glomerulus within the olfactory bulb, mdg5 of the mediodorsal cluster, whereas crypt neurons are known to project exclusively to the mdg2 glomerulus. Kappe neurons are negative for established markers of ciliated, microvillous and crypt neurons, but appear to have microvilli. Kappe neurons constitute the fourth type of olfactory sensory neurons reported in teleost fishes and their existence suggests that encoding of olfactory stimuli may require a higher complexity than hitherto assumed already in the peripheral olfactory system.

  6. Origin and neurochemical properties of bulbospinal neurons projecting to the rat lumbar spinal cord via the medal longitudinal fasciculus and caudal ventrolateral medulla

    Directory of Open Access Journals (Sweden)

    Zilli eHuma

    2014-04-01

    Full Text Available Bulbospinal systems (BS originate from various regions of the brainstem and influence spinal neurons by classical synaptic and modulatory mechanisms. Our aim was to determine the brainstem locations of cells of origin of BS pathways passing through the medial longitudinal fasciculus (MLF and the caudal ventrolateral medulla (CVLM. We also examined the transmitter content of spinal terminations of the CVLM pathway. Six adult rats received Fluorogold (FG injections to the right intermediate grey matter of the lumbar cord (L1-L2 and the b-subunit of cholera toxin (CTb was injected either into the MLF or the right CVLM (3 animals each. Double-labelled cells were identified within brainstem structures with confocal microscopy and mapped onto brainstem diagrams. An additional 3 rats were injected with CTb in the CVLM to label axon terminals in the lumbar spinal cord. Double-labelled cells projecting via the MLF or CVLM were found principally in reticular regions of the medulla and pons but small numbers of cells were also located within the midbrain. CVLM projections to the lumbar cord were almost exclusively ipsilateral and concentrated within the intermediate grey matter. Most (62% of terminals were immunoreactive for the vesicular glutamate transporter 2 while 23% contained the vesicular GABA transporter. The inhibitory subpopulation was glycinergic, GABAergic or contained both transmitters. The proportions of excitatory and inhibitory axons projecting via the CVLM to the lumbar cord are similar to those projecting via the MLF. Unlike the MLF pathway, CVLM projections are predominantly ipsilateral and concentrated within intermediate grey but do not extend into motor nuclei or laminia VIII. Terminations of the CVLM pathway are located in a region of the grey matter that is rich in premotor interneurons; thus its primary function may be to coordinate activity of premotor networks.

  7. Neuroanatomical evidence that kisspeptin directly regulates isotocin and vasotocin neurons.

    Directory of Open Access Journals (Sweden)

    Shinji Kanda

    Full Text Available Neuropeptide kisspeptin has been suggested to be an essential central regulator of reproduction in response to changes in serum gonadal steroid concentrations. However, in spite of wide kisspeptin receptor distribution in the brain, especially in the preoptic area and hypothalamus, the research focus has mostly been confined to the kisspeptin regulation on GnRH neurons. Here, by using medaka whose kisspeptin (kiss1 neurons have been clearly demonstrated to be regulated by sex steroids, we analyzed the anatomical distribution of kisspeptin receptors Gpr54-1 and Gpr54-2. Because the both receptors were shown to be activated by kisspeptins (Kiss1 and Kiss2, we analyzed the anatomical distribution of the both receptors by in situ hybridization. They were mainly expressed in the ventral telencephalon, preoptic area, and hypothalamus, which have been suggested to be involved in homeostatic functions including reproduction. First, we found gpr54-2 mRNA expression in nucleus preopticus pars magnocellularis and demonstrated that vasotocin and isotocin (Vasopressin and Oxytocin ortholog, respectively neurons express gpr54-2 by dual in situ hybridization. Given that kisspeptin administration increases serum oxytocin and vasopressin concentration in mammals, the present finding are likely to be vertebrate-wide phenomenon, although direct regulation has not yet been demonstrated in mammals. We then analyzed co-expression of kisspeptin receptors in three types of GnRH neurons. It was clearly demonstrated that gpr54-expressing cells were located adjacent to GnRH1 neurons, although they were not GnRH1 neurons themselves. In contrast, there was no gpr54-expressing cell in the vicinities of neuromodulatory GnRH2 or GnRH3 neurons. From these results, we suggest that medaka kisspeptin neurons directly regulate some behavioral and neuroendocrine functions via vasotocin/isotocin neurons, whereas they do not regulate hypophysiotropic GnRH1 neurons at least in a direct

  8. A Simple and Efficient In Vivo Non-viral RNA Transfection Method for Labeling the Whole Axonal Tree of Individual Adult Long-Range Projection Neurons.

    Science.gov (United States)

    Porrero, César; Rodríguez-Moreno, Javier; Quetglas, José I; Smerdou, Cristian; Furuta, Takahiro; Clascá, Francisco

    2016-01-01

    We report a highly efficient, simple, and non-infective method for labeling individual long-range projection neurons (LRPNs) in a specific location with enough sparseness and intensity to allow complete and unambiguous reconstructions of their entire axonal tree. The method is based on the "in vivo" transfection of a large RNA construct that drives the massive expression of green fluorescent protein. The method combines two components: injection of a small volume of a hyperosmolar NaCl solution containing the Pal-eGFP-Sindbis RNA construct (Furuta et al., 2001), followed by the application of high-frequency electric current pulses through the micropipette tip. We show that, although each component alone increases transfection efficacy, compared to simple volume injections of standard RNA solution, the highest efficacy (85.7%) is achieved by the combination of both components. In contrast with the infective viral Sindbis vector, RNA transfection occurs exclusively at the position of the injection micropipette tip. This method simplifies consistently labeling one or a few isolated neurons per brain, a strategy that allows unambiguously resolving and quantifying the brain-wide and often multi-branched monosynaptic circuits created by LRPNs.

  9. Columnar organization of estrogen receptor-alpha immunoreactive neurons in the periaqueductal gray projecting to the nucleus para-retroambiguus in the caudal brainstem of the female golden hamster.

    Science.gov (United States)

    Gerrits, P O; Krukerink, M; Veening, J G

    2009-06-30

    In the hamster brainstem estrogen receptor-alpha-immunoreactive neurons (ER-alpha-IR) are present in the nucleus para-retroambiguus (NPRA), located in the caudal ventrolateral medulla (CVLM) ventrolaterally to the nucleus retroambiguus (NRA). NPRA neurons project mainly to the thoracic and upper lumbar cord and are probably involved in the autonomic adaptations during the estrous cycle. The periaqueductal gray (PAG), projecting to the CVLM, also contains ER-alpha-IR neurons. This raises the questions: how are these projections organized and are ER-alpha-IR neurons in PAG and NPRA linked directly? Combined retro- and anterograde tracing techniques, using wheat germ agglutinin-horseradish peroxidase (WGA-HRP), were carried out to demonstrate neuronal relationships between PAG and NPRA and/or NRA. Finally, a double-label immunostaining was performed in ovariectomized hamsters combining anti-ER-alpha antibody immunocytochemistry with cholera toxin B injections into the CVLM, to differentiate between ER-alpha-IR projections from the PAG to either NRA or NPRA. The experiments showed that retrograde labeling from the NRA mainly occurred in the rostral and intermediate ipsilateral PAG, while injections involving both NRA and NPRA resulted in numerous labeled neurons in the ipsilateral rostral, intermediate and especially the caudal PAG. The anterograde tracing studies confirmed these projections: from the rostral PAG almost exclusively to the NRA and from the caudal PAG to the NPRA, while the intermediate lateral PAG projects to both NPRA and NRA. Our double-immunostudies revealed that ER-alpha-IR projections descend only towards the NPRA and mainly originate from the ipsilateral caudal PAG. Retrogradely labeled ER-alpha-IR neurons in the PAG were observed in two separate columns, laterally and ventrolaterally in the caudal half of the PAG. The results provide evidence for the existence of differentiated PAG-CVLM projections to NRA and NPRA, respectively, originating from

  10. Sexual phenotype differences in zic2 mRNA abundance in the preoptic area of a protogynous teleost, Thalassoma bifasciatum.

    Science.gov (United States)

    McCaffrey, Katherine; Hawkins, Mary Beth; Godwin, John

    2011-01-01

    The highly conserved members of the zic family of zinc-finger transcription factors are primarily known for their roles in embryonic signaling pathways and regulation of cellular proliferation and differentiation. This study describes sexual phenotype differences in abundances of zic2 mRNA in the preoptic area of the hypothalamus, a region strongly implicated in sexual behavior and function, in an adult teleost, Thalassoma bifasciatum. The bluehead wrasse (Thalassoma bifasciatum) is a valuable model for studying neuroendocrine processes because it displays two discrete male phenotypes, initial phase (IP) males and territorial, terminal phase (TP) males, and undergoes socially-controlled protogynous sex change. Previously generated microarray-based comparisons suggested that zic2 was upregulated in the brains of terminal phase males relative to initial phase males. To further explore this difference, we cloned a 727 bp sequence for neural zic2 from field-collected animals. Riboprobe-based in situ hybridization was employed to localize zic2 signal in adult bluehead brains and assess the relative abundance of brain zic2 mRNA across sexual phenotypes. We found zic2 mRNA expression was extremely abundant in the granular cells of the cerebellum and widespread in other brain regions including in the thalamus, hypothalamus, habenula, torus semicircularis, torus longitudinalis, medial longitudinal fascicle and telencephalic areas. Quantitative autoradiography and phosphorimaging showed zic2 mRNA hybridization signal in the preoptic area of the hypothalamus was significantly higher in terminal phase males relative to both initial phase males and females, and silver grain analysis confirmed this relationship between phenotypes. No significant difference in abundance was found in zic2 signal across phenotypes in the habenula, a brain region not implicated in the control of sexual behavior, or cerebellum.

  11. Sexual phenotype differences in zic2 mRNA abundance in the preoptic area of a protogynous teleost, Thalassoma bifasciatum.

    Directory of Open Access Journals (Sweden)

    Katherine McCaffrey

    Full Text Available The highly conserved members of the zic family of zinc-finger transcription factors are primarily known for their roles in embryonic signaling pathways and regulation of cellular proliferation and differentiation. This study describes sexual phenotype differences in abundances of zic2 mRNA in the preoptic area of the hypothalamus, a region strongly implicated in sexual behavior and function, in an adult teleost, Thalassoma bifasciatum. The bluehead wrasse (Thalassoma bifasciatum is a valuable model for studying neuroendocrine processes because it displays two discrete male phenotypes, initial phase (IP males and territorial, terminal phase (TP males, and undergoes socially-controlled protogynous sex change. Previously generated microarray-based comparisons suggested that zic2 was upregulated in the brains of terminal phase males relative to initial phase males. To further explore this difference, we cloned a 727 bp sequence for neural zic2 from field-collected animals. Riboprobe-based in situ hybridization was employed to localize zic2 signal in adult bluehead brains and assess the relative abundance of brain zic2 mRNA across sexual phenotypes. We found zic2 mRNA expression was extremely abundant in the granular cells of the cerebellum and widespread in other brain regions including in the thalamus, hypothalamus, habenula, torus semicircularis, torus longitudinalis, medial longitudinal fascicle and telencephalic areas. Quantitative autoradiography and phosphorimaging showed zic2 mRNA hybridization signal in the preoptic area of the hypothalamus was significantly higher in terminal phase males relative to both initial phase males and females, and silver grain analysis confirmed this relationship between phenotypes. No significant difference in abundance was found in zic2 signal across phenotypes in the habenula, a brain region not implicated in the control of sexual behavior, or cerebellum.

  12. Representation of pheromones, interspecific signals, and plant odors in higher olfactory centers; mapping physiologically identified antennal-lobe projection neurons in the male heliothine moth

    Directory of Open Access Journals (Sweden)

    Xin-Cheng eZhao

    2014-10-01

    Full Text Available In the primary olfactory centre of the moth brain, for example, a few enlarged glomeruli situated dorsally, at the entrance of the antennal nerve, are devoted to information about female-produced substances whereas a set of more numerous ordinary glomeruli receives input about general odorants. Heliothine moths are particularly suitable for studying central chemosensory mechanisms not only because of their anatomically separated systems for plant odours and pheromones but also due to their use of female-produced substances in communication across the species. Thus, the male-specific system of heliothine moths includes two sub arrangements, one ensuring attraction and mating behavior by carrying information about pheromones released by conspecifics, and the other reproductive isolation via signal information emitted from heterospecifics. Based on previous tracing experiments, a general chemotopic organization of the male-specific glomeruli has been demonstrated in a number of heliothine species. As compared to the well explored organization of the moth antennal lobe, demonstrating a non-overlapping representation of the biologically relevant stimuli, less is known about the neural arrangement residing at the following synaptic level, i.e. the mushroom body calyces and the lateral horn. In the study presented here, we have labelled physiologically characterized antennal-lobe projection neurons in males of the two heliothine species, Heliothis virescens and Helicoverpa assulta, for the purpose of mapping their target regions in the protocerebrum. In order to compare the representation of plant odours, pheromones, and interspecific signals in the higher brain regions of each species, we have created standard brain atlases and registered three-dimensional models of distinct uniglomerular projection neuron types into the relevant atlas.

  13. Dual nitrergic/cholinergic control of short-term plasticity of corticostriatal inputs to striatal projection neurons

    Directory of Open Access Journals (Sweden)

    Craig Peter Blomeley

    2015-11-01

    Full Text Available The ability of nitric oxide and acetylcholine to modulate the short-term plasticity of corticostriatal inputs was investigated using current-clamp recordings in BAC mouse brain slices. Glutamatergic responses were evoked by stimulation of corpus callosum in D1 and D2 dopamine receptor-expressing medium spiny neurons (D1-MSNs and D2-MSN, respectively. Paired-pulse stimulation (50 ms intervals evoked depressing or facilitating responses in subgroups of both D1-MSNs and D2 MSNs. In both neuronal types, glutamatergic responses of cells that displayed paired-pulse depression were not significantly affected by the nitric oxide donor S-nitroso-N-acetylpenicillamine (SNAP; 100 µM. Conversely, in D1-MSNs and D2-MSNs that displayed paired-pulse facilitation, SNAP did not affect the first evoked response, but significantly reduced the amplitude of the second evoked EPSP, converting paired-pulse facilitation into paired-pulse depression. SNAP also strongly excited cholinergic interneurons and increased their cortical glutamatergic responses acting through a presynaptic mechanism. The effects of SNAP on glutamatergic response of D1-MSNs and D2-MSN were mediated by acetylcholine. The broad-spectrum muscarinic receptor antagonist atropine (25 µM did not affect paired-pulse ratios and did not prevent the effects of SNAP. Conversely, the broad-spectrum nicotinic receptor antagonist tubocurarine (10 µM fully mimicked and occluded the effects of SNAP. We concluded that phasic acetylcholine release mediates feedforward facilitation in MSNs through activation of nicotinic receptors on glutamatergic terminals and that nitric oxide, while increasing cholinergic interneurons’ firing, functionally impairs their ability to modulate glutamatergic inputs of MSNs. These results show that nitrergic and cholinergic transmission control the short-term plasticity of glutamatergic inputs in the striatum and reveal a novel cellular mechanism underlying paired

  14. Whole-brain mapping of afferent projections to the bed nucleus of the stria terminalis in tree shrews.

    Science.gov (United States)

    Ni, Rong-Jun; Luo, Peng-Hao; Shu, Yu-Mian; Chen, Ju-Tao; Zhou, Jiang-Ning

    2016-10-01

    The bed nucleus of the stria terminalis (BST) plays an important role in integrating and relaying input information to other brain regions in response to stress. The cytoarchitecture of the BST in tree shrews (Tupaia belangeri chinensis) has been comprehensively described in our previous publications. However, the inputs to the BST have not been described in previous reports. The aim of the present study was to investigate the sources of afferent projections to the BST throughout the brain of tree shrews using the retrograde tracer Fluoro-Gold (FG). The present results provide the first detailed whole-brain mapping of BST-projecting neurons in the tree shrew brain. The BST was densely innervated by the prefrontal cortex, entorhinal cortex, ventral subiculum, amygdala, ventral tegmental area, and parabrachial nucleus. Moreover, moderate projections to the BST originated from the medial preoptic area, supramammillary nucleus, paraventricular thalamic nucleus, pedunculopontine tegmental nucleus, dorsal raphe nucleus, locus coeruleus, and nucleus of the solitary tract. Afferent projections to the BST are identified in the ventral pallidum, nucleus of the diagonal band, ventral posteromedial thalamic nucleus, posterior complex of the thalamus, interfascicular nucleus, retrorubral field, rhabdoid nucleus, intermediate reticular nucleus, and parvicellular reticular nucleus. In addition, the different densities of BST-projecting neurons in various regions were analyzed in the tree shrew brains. In summary, whole-brain mapping of direct inputs to the BST is delineated in tree shrews. These brain circuits are implicated in the regulation of numerous physiological and behavioral processes including stress, reward, food intake, and arousal.

  15. Integration of stress and leptin signaling by CART producing neurons in the rodent midbrain centrally projecting Edinger-Westphal nucleus

    NARCIS (Netherlands)

    Xu, L.; Janssen, D.; Knaap, N.J.F. van der; Roubos, E.W.; Leshan, R.L.; Myers, M.G.; Gaszner, B.; Kozicz, T.L.

    2014-01-01

    Leptin targets the brain to regulate feeding, neuroendocrine function and metabolism. The leptin receptor is present in hypothalamic centers controlling energy metabolism as well as in the centrally projecting Edinger-Westphal nucleus (EWcp), a region implicated in the stress response and in various

  16. Neuronal networks: enhanced feedback feeds forward.

    Science.gov (United States)

    Calabrese, Ronald L

    2012-09-25

    Modulatory projection neurons gate neuronal networks, such as those comprising motor central pattern generators; in turn, they receive feedback from the networks they gate. A recent study has shown that, in the crab stomatogastric ganglion, this feedback is also subject to modulation: the enhanced feedback feeds forward through the projection neurons to modify circuit output.

  17. Kv3.1-Kv3.2 channels underlie a high-voltage-activating component of the delayed rectifier K+ current in projecting neurons from the globus pallidus.

    Science.gov (United States)

    Hernández-Pineda, R; Chow, A; Amarillo, Y; Moreno, H; Saganich, M; Vega-Saenz de Miera, E C; Hernández-Cruz, A; Rudy, B

    1999-09-01

    The globus pallidus plays central roles in the basal ganglia circuitry involved in movement control as well as in cognitive and emotional functions. There is therefore great interest in the anatomic and electrophysiological characterization of this nucleus. Most pallidal neurons are GABAergic projecting cells, a large fraction of which express the calcium binding protein parvalbumin (PV). Here we show that PV-containing pallidal neurons coexpress Kv3. 1 and Kv3.2 K+ channel proteins and that both Kv3.1 and Kv3.2 antibodies coprecipitate both channel proteins from pallidal membrane extracts solubilized with nondenaturing detergents, suggesting that the two channel subunits are forming heteromeric channels. Kv3.1 and Kv3.2 channels have several unusual electrophysiological properties when expressed in heterologous expression systems and are thought to play special roles in neuronal excitability including facilitating sustained high-frequency firing in fast-spiking neurons such as interneurons in the cortex and the hippocampus. Electrophysiological analysis of freshly dissociated pallidal neurons demonstrates that these cells have a current that is nearly identical to the currents expressed by Kv3.1 and Kv3.2 proteins in heterologous expression systems, including activation at very depolarized membrane potentials (more positive than -10 mV) and very fast deactivation rates. These results suggest that the electrophysiological properties of native channels containing Kv3.1 and Kv3.2 proteins in pallidal neurons are not significantly affected by factors such as associated subunits or postranslational modifications that result in channels having different properties in heterologous expression systems and native neurons. Most neurons in the globus pallidus have been reported to fire sustained trains of action potentials at high-frequency. Kv3.1-Kv3.2 voltage-gated K+ channels may play a role in helping maintain sustained high-frequency repetitive firing as they probably do

  18. Whole-Cell Properties of Cerebellar Nuclei Neurons In Vivo

    NARCIS (Netherlands)

    Canto, Cathrin B; Witter, L.; De Zeeuw, C.I.

    2016-01-01

    Cerebellar nuclei neurons integrate sensorimotor information and form the final output of the cerebellum, projecting to premotor brainstem targets. This implies that, in contrast to specialized neurons and interneurons in cortical regions, neurons within the nuclei encode and integrate complex

  19. Corticospinal mirror neurons.

    Science.gov (United States)

    Kraskov, A; Philipp, R; Waldert, S; Vigneswaran, G; Quallo, M M; Lemon, R N

    2014-01-01

    Here, we report the properties of neurons with mirror-like characteristics that were identified as pyramidal tract neurons (PTNs) and recorded in the ventral premotor cortex (area F5) and primary motor cortex (M1) of three macaque monkeys. We analysed the neurons' discharge while the monkeys performed active grasp of either food or an object, and also while they observed an experimenter carrying out a similar range of grasps. A considerable proportion of tested PTNs showed clear mirror-like properties (52% F5 and 58% M1). Some PTNs exhibited 'classical' mirror neuron properties, increasing activity for both execution and observation, while others decreased their discharge during observation ('suppression mirror-neurons'). These experiments not only demonstrate the existence of PTNs as mirror neurons in M1, but also reveal some interesting differences between M1 and F5 mirror PTNs. Although observation-related changes in the discharge of PTNs must reach the spinal cord and will include some direct projections to motoneurons supplying grasping muscles, there was no EMG activity in these muscles during action observation. We suggest that the mirror neuron system is involved in the withholding of unwanted movement during action observation. Mirror neurons are differentially recruited in the behaviour that switches rapidly between making your own movements and observing those of others.

  20. Delayed post-treatment with bone marrow-derived mesenchymal stem cells is neurorestorative of striatal medium-spiny projection neurons and improves motor function after neonatal rat hypoxia-ischemia.

    Science.gov (United States)

    Cameron, Stella H; Alwakeel, Amr J; Goddard, Liping; Hobbs, Catherine E; Gowing, Emma K; Barnett, Elizabeth R; Kohe, Sarah E; Sizemore, Rachel J; Oorschot, Dorothy E

    2015-09-01

    Perinatal hypoxia-ischemia is a major cause of striatal injury and may lead to cerebral palsy. This study investigated whether delayed administration of bone marrow-derived mesenchymal stem cells (MSCs), at one week after neonatal rat hypoxia-ischemia, was neurorestorative of striatal medium-spiny projection neurons and improved motor function. The effect of a subcutaneous injection of a high-dose, or a low-dose, of MSCs was investigated in stereological studies. Postnatal day (PN) 7 pups were subjected to hypoxia-ischemia. At PN14, pups received treatment with either MSCs or diluent. A subset of high-dose pups, and their diluent control pups, were also injected intraperitoneally with bromodeoxyuridine (BrdU), every 24h, on PN15, PN16 and PN17. This permitted tracking of the migration and survival of neuroblasts originating from the subventricular zone into the adjacent injured striatum. Pups were euthanized on PN21 and the absolute number of striatal medium-spiny projection neurons was measured after immunostaining for DARPP-32 (dopamine- and cAMP-regulated phosphoprotein-32), double immunostaining for BrdU and DARPP-32, and after cresyl violet staining alone. The absolute number of striatal immunostained calretinin interneurons was also measured. There was a statistically significant increase in the absolute number of DARPP-32-positive, BrdU/DARPP-32-positive, and cresyl violet-stained striatal medium-spiny projection neurons, and fewer striatal calretinin interneurons, in the high-dose mesenchymal stem cell (MSC) group compared to their diluent counterparts. A high-dose of MSCs restored the absolute number of these neurons to normal uninjured levels, when compared with previous stereological data on the absolute number of cresyl violet-stained striatal medium-spiny projection neurons in the normal uninjured brain. For the low-dose experiment, in which cresyl violet-stained striatal medium-spiny neurons alone were measured, there was a lower statistically

  1. Kölliker–Fuse neurons send collateral projections to multiple hypoxia-activated and nonactivated structures in rat brainstem and spinal cord.

    Science.gov (United States)

    Song, Gang; Wang, Hui; Xu, Hui; Poon, Chi-Sang

    2012-10-01

    The Kölliker–Fuse nucleus (KFN) in dorsolateral pons has been implicated in many physiological functions via its extensive efferent connections. Here, we combine iontophoretic anterograde tracing with posthypoxia c-Fos immunohistology to map KFN axonal terminations among hypoxia-activated/nonactivated brain stem and spinal structures in rats. Using a set of stringent inclusion/exclusion criteria to align visualized axons across multiple coronal brain sections, we were able to unequivocally trace axonal trajectories over a long rostrocaudal distance perpendicular to the coronal plane. Structures that were both richly innervated by KFN axonal projections and immunopositive to c-Fos included KFN (contralateral side), ventrolateral pontine area, areas ventral to rostral compact/subcompact ambiguus nucleus, caudal (lateral) ambiguus nucleus, nucleus retroambiguus, and commissural–medial subdivisions of solitary tract nucleus. The intertrigeminal nucleus, facial and hypoglossal nuclei, retrotrapezoid nucleus, parafacial region and spinal cord segment 5 were also richly innervated by KFN axonal projections but were only weakly (or not) immunopositive to c-Fos. The most striking finding was that some descending axons from KFN sent out branches to innervate multiple (up to seven) pontomedullary target structures including facial nucleus, trigeminal sensory nucleus, and various parts of ambiguus nucleus and its surrounding areas. The extensive axonal fan-out from single KFN neurons to multiple brainstem and spinal cord structures("one-to-many relationship"’) provides anatomical evidence that KFN may coordinate diverse physiological functions including hypoxic and hypercapnic respiratory responses, respiratory pattern generation and motor output,diving reflex, modulation of upper airways patency,coughing and vomiting abdominal expiratory reflex, as well as cardiovascular regulation and cardiorespiratory coupling.

  2. [Efferent projections of "classical" peptidergic neurons of the neurosecretory system of the telencephalon in reptiles (Scincus scincus L. and Chalcides ocellatus Forskal; Lacertilia, Squamata].

    Science.gov (United States)

    Hoheisel, G; Petter, H

    1990-01-01

    In both species of lacertilian reptiles investigated, the peptidergic hypothalamic supraoptic and paraventricular nucleus project with efferents to the telencephalon, to caudal parts of the brain, and to the spinal cord. The marked system of efferents of the "classic" peptidergic neurosecretory nuclei to the telencephalon was mapped. The unlabeled peroxidase-antiperoxidase immunocytochemical procedure revealed at the light microscopical level neurophysin- respectively mesotocin- or vasotocin-containing exohypothalamic fibres in the septal area, in subcortical regions (ventral striatum and hypopallium), and in all layers of the cortical areas (medial, dorsal and lateral cortex). Within the different parts of the brain, there seems to be a characteristically quantitative ratio of the mesotocin and vasotocin fibres. The terminals of the exohypothalamic fibres contact perikarya and processes of neurons of the target regions intimately. In a selected area, peptidergic synapses could be demonstrated at the electron microscopical level using an ultrahistochemical method. It is assumed that the nonapeptides mentioned are released from the fibre terminals and then act as neurotransmitters/neuromodulators influencing different brain functions.

  3. Activation of angiotensin II type 1 receptors in the median preoptic nucleus induces a diuretic and natriuretic response in rats

    Institute of Scientific and Technical Information of China (English)

    Yuan Gao; Lei Luo; Hong Liu

    2009-01-01

    Objective: To investigate the effect of activation of angiotensin II (AngII) type 1 (ATI) receptors in the median preoptic nucleus (MnPO) of rats on renal sodium excretion. Methods: After anesthesia, the rats were injected into the MnPO via an implanted cannula. Urine samples were collected via a bladder cannula, and the urine sodium concentration was assayed with flame spectrophotometry. The serum level of endogenous digitalis-like factor (EDLF) and Na+,K+-ATPase activity in the renal cortex tissue were assayed respectively with a radioimmunoassay and with an ammonium molybdophosphate-based kit. Results: Both the urinary volume and the sodium excretion peaked 60 min after Angll was administered into the MnPO. The responses were accompanied by an increase in serum EDLF and a decrease in Na+,K+-ATPase activity in the renal cortex. The responses of diuresis and natriuresis, as well as an increase in serum EDLF and a decrease in Na+,K+-ATPase activity in the renal cortex induced by MnPO adminstration with AngII were inhibited by pior treatment with the AngII receptor blocking agent losartan into the MnPO. Conclusion: These results suggest that activation of ATI receptors in the MnPO of rat induces diuretic and natriuretic responses. The responses are associated with an increase release of EDLF and with the inhibition of Na+,K+-ATPase activity in renal cortex tissue.

  4. GFAP expression in astrocytes of suprachiasmatic nucleus and medial preoptic area are differentially affected by malnutrition during rat brain development.

    Science.gov (United States)

    Mendonça, João Esmeraldo Frota; Vilela, Maria Cristina Ramos; Bittencourt, Heitor; Lapa, Raíssa Maria; Oliveira, Francisco Gilberto; Alessio, Maria Luíza Martins; Guedes, Rubem Carlos Araújo; De Oliveira Costa, Miriam Stela Maris; Da Costa, Belmira Lara da Silveira Andrade

    2004-08-01

    The aim of the present study was investigate, in young rats, the effects of malnutrition on astrocyte distribution of two hypothalamic regions, the circadian pacemaker suprachiasmatic nucleus (SCN) and the medial preoptic area (MPA). Control rats were born from mothers fed on commercial diet since gestation and malnourished rats from mothers fed on multideficient diet, from the beginning of gestation (GLA group) or from the onset of lactation (LA group). After weaning, pups received ad libitum the same diet as their mothers, and were maintained under a 12/12 h light/dark cycle. The animals were analyzed either at 30-33, or 60-63 days of life. Brain coronal sections (50 microm) were processed to visualize glial fibrillary acidic protein (GFAP) immunoreactivity. Compared to control rats, both malnourished groups of 30 and 60 days exhibited a reduced number of GFAP-immunoreactive astrocytes in the SCN. The total GFAP-immunoreactive area in the SCN of the GLA group differed from the control group at both age ranges analyzed. The GFAP expression as measured by the relative optical density (ROD) exhibited a 50-60% reduction in the MPA in both malnourished groups, compared to controls. The results suggest that malnutrition early in life leads to alterations in gliogenesis or glial cell proliferation in both nuclei, being these alterations greater in the MPA. Compensatory plasticity mechanisms in the GFAP-expression seem to be developed in the astrocyte differentiation process in the SCN, especially when the malnutrition is installed from the lactation.

  5. Exposure to an open-field arena increases c-Fos expression in a subpopulation of neurons in the dorsal raphe nucleus, including neurons projecting to the basolateral amygdaloid complex

    DEFF Research Database (Denmark)

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

    2008-01-01

    Serotonergic systems in the dorsal raphe nucleus are thought to play an important role in the regulation of anxiety states. To investigate responses of neurons in the dorsal raphe nucleus to a mild anxiety-related stimulus, we exposed rats to an open-field, under low-light or high-light conditions....... Treatment effects on c-Fos expression in serotonergic and non-serotonergic cells in the midbrain raphe nuclei were determined 2 h following open-field exposure or home cage control (CO) conditions. Rats tested under both light conditions responded with increases in c-Fos expression in serotonergic neurons...... within subdivisions of the midbrain raphe nuclei compared with CO rats. However, the total numbers of serotonergic neurons involved were small suggesting that exposure to the open-field may affect a subpopulation of serotonergic neurons. To determine if exposure to the open-field activates a subset...

  6. Nanoresolution radiology of neurons

    Energy Technology Data Exchange (ETDEWEB)

    Wu, H.R.; Chen, S.T.; Chu, Y.S.; Conley, R.; Bouet, N.; Chien, C.C.; Chen, H.H.; Lin, C.H.; Tung, H.T.; Chen, Y.S.; Margaritondo, G.; Je, J.H.; Hwu, Y. (IP-Taiwan); (Ecole); (BNL); (POSTECH)

    2013-04-08

    We report recent advances in hard-x-ray optics - including record spatial resolution - and in staining techniques that enable synchrotron microradiology to produce neurobiology images of quality comparable to electron and visible microscopy. In addition, microradiology offers excellent penetration and effective three-dimensional detection as required for many neuron studies. Our tests include tomographic reconstruction based on projection image sets.

  7. Neurons derived from human embryonic stem cells extend long–distance axonal projections through growth along host white matter tracts after intra-cerebral transplantation.

    Directory of Open Access Journals (Sweden)

    Mark eDenham

    2012-03-01

    Full Text Available Human pluripotent stem cells have the capacity for directed differentiation into a wide variety of neuronal subtypes that may be useful for brain repair. While a substantial body of research has lead to a detailed understanding of the ability of neurons in fetal tissue grafts to structurally and functionally integrate after intra-cerebral transplantation, we are only just beginning to understand the in vivo properties of neurons derived from human pluripotent stem cells. Here we have utilised the human embryonic stem (ES cell line Envy, which constitutively expresses green fluorescent protein (GFP, in order to study the in vivo properties of neurons derived from human ES cells. Rapid and efficient neural induction, followed by differentiation as neurospheres resulted in a GFP+ neural precursor population with traits of neuroepithelial and dorsal forebrain identity. Ten weeks after transplantation into neonatal rats, GFP+ fibre patterns revealed extensive axonal growth in the host brain, particularly along host white matter tracts, although innervation of adjacent nuclei was limited. The grafts were composed of a mix of neural cell types including differentiated neurons and glia, but also dividing neural progenitors and migrating neuroblasts, indicating an incomplete state of maturation at 10 weeks. This was reflected in patch-clamp recordings showing stereotypical properties appropriate for mature functional neurons, including the ability to generate action potentials, as well profiles consistent for more immature neurons. These findings illustrate the intrinsic capacity for neurons derived from human ES cells to integrate at a structural and functional level following transplantation.

  8. Projections from estrogen receptor-alpha immunoreactive neurons in the periaqueductal gray to the lateral medulla oblongata in the rhesus monkey

    NARCIS (Netherlands)

    Vanderhorst, VGJM; Terasawa, E; Ralston, HJ

    2004-01-01

    The periaqueductal gray (PAG) contains numerous estrogen receptor-alpha immunoreactive (ER-alpha IR) neurons that are distributed in a species-specific way. These neurons might modulate different types of behavior that are mediated by the PAG such as active and passive coping responses, analgesia,

  9. Lack of dystrophin leads to the selective loss of superior cervical ganglion neurons projecting to muscular targets in genetically dystrophic mdx mice.

    Science.gov (United States)

    De Stefano, M Egle; Leone, Lucia; Lombardi, Loredana; Paggi, Paola

    2005-12-01

    Autonomic imbalance is a pathological aspect of Duchenne muscular dystrophy. Here, we show that the sympathetic superior cervical ganglion (SCG) of mdx mice, which lack dystrophin (Dp427), has 36% fewer neurons than that of wild-type animals. Cell loss occurs around P10 and affects those neurons innervating muscular targets (heart and iris), which, differently from the submandibular gland (non-muscular target), are precociously damaged by the lack of Dp427. In addition, although we reveal altered axonal defasciculation in the submandibular gland and reduced terminal sprouting in all SCG target organs, poor adrenergic innervation is observed only in the heart and iris. These alterations, detected as early as P5, when neuronal loss has not yet occurred, suggest that in mdx mice the absence of Dp427 directly impairs the axonal growth and terminal sprouting of sympathetic neurons. However, when these intrinsic alterations combine with structural and/or functional damages of muscular targets, neuronal death occurs.

  10. Galanin neurons in the intermediate nucleus (InM) of the human hypothalamus in relation to sex, age, and gender identity.

    Science.gov (United States)

    Garcia-Falgueras, Alicia; Ligtenberg, Lisette; Kruijver, Frank P M; Swaab, Dick F

    2011-10-15

    The intermediate nucleus (InM) in the preoptic area of the human brain, also known as the sexually dimorphic nucleus of the preoptic area (SDN-POA) and the interstitial nucleus of the anterior hypothalamus-1 (INAH-1) is explored here. We investigated its population of galanin-immunoreactive (Gal-Ir) neurons in relation to sex, age, and gender identity in the postmortem brain of 77 subjects. First we compared the InM volume and number of Gal-Ir neurons of 22 males and 22 females in the course of aging. In a second experiment, we compared for the first time the InM volume and the total and Gal-Ir neuron number in 43 subjects with different gender identities: 14 control males (M), 11 control females (F), 10 male-to-female (MtF) transsexual people, and 5 men who were castrated because of prostate cancer (CAS). In the first experiment we found a sex difference in the younger age group ( 45 years. In the second experiment the MtF transsexual group presented an intermediate value for the total InM neuron number and volume that did not seem different in males and females. Because the CAS group did not have total neuron numbers that were different from the intact males, the change in adult circulating testosterone levels does not seem to explain the intermediate values in the MtF group. Organizational and activational hormone effects on the InM are discussed.

  11. The medial preoptic nucleus as a site of the thermogenic and metabolic actions of melanotan II in male rats.

    Science.gov (United States)

    Monge-Roffarello, Boris; Labbe, Sebastien M; Lenglos, Christophe; Caron, Alexandre; Lanfray, Damien; Samson, Pierre; Richard, Denis

    2014-07-15

    The present study was designed to investigate the role of the medial preoptic nucleus (MPO) as a site of the thermogenic and metabolic effects of the α-melanocyte-stimulating hormone analog melanotan II (MTII). We also assessed the involvement of the dorsomedial hypothalamic nucleus (DMH) by investigating the effects of the MPO infusion of MTII in rats with DMH lesions produced by kainic acid. Infusion of MTII in the MPO led to increases in interscapular brown adipose tissue (iBAT) temperature and iBAT uptake of 14C-bromopalmitate. Both increases were blocked by DMH lesions. iBAT temperature increase (area under curve) and 14C-bromopalmitate uptake emerged as two correlated variables (r = 0.63, P < 0.001). DMH lesions also blocked MTII-induced expression of mRNAs coding for proteins involved in 1) thermogenesis [type II iodothyronine deiodinase (Dio2) and peroxisome proliferator-activated receptor gamma coactivator 1-α (Pgc1α)], 2) lipolysis [hormone-sensitive lipase (Hsl)], and 3) lipogenesis [diacylglycerol-O-acyltransferase 2 (Dgat2), fatty acid synthase (Fas)], in iBAT of rats killed 1 h after MPO infusion of MTII. MTII also stimulated expression of genes in iWAT but only in rats with DMH lesions. These genes included glucose transporter member 4 (Glut4), glycerol-3-phosphate acyltransferase 3 (Gpat3), Dgat1, Dgat2, triglyceride lipase (Atgl), Hsl, and carnitine palmitoyltransferase 1β (Cpt1β). Altogether, the present results reveal the MPO as a site of the thermogenic and metabolic actions of MTII. They also contribute to establish the MPO-DMH duet as a significant target for melanocortins to modulate energy homeostasis.

  12. Serotonin promotes feminization of the sexually dimorphic nucleus of the preoptic area, but not the calbindin cell group.

    Science.gov (United States)

    Madden, Amanda M K; Paul, Alexandria T; Pritchard, Rory A; Michel, Rebecca; Zup, Susan L

    2016-11-01

    Testosterone and its metabolites masculinize the brain during a critical perinatal window, including the relative volume of sexually dimorphic brain areas such as the sexually dimorphic nucleus of the preoptic area (SDN), which is larger in males than females. Serotonin (5HT) may mediate this hormone action, since 5HT given during the second week of life decreases (i.e., feminizes) SDN volume in males and testosterone-treated females. Although previous work indicates that the 5HT2A/2C receptor is sufficient to induce feminization, it is unclear whether other serotonin receptors are required and which subpopulation(s) of SDN cells are specifically organized by 5HT. Therefore, we injected male and female Sprague-Dawley rat pups with saline, a nonselective 5HTR agonist, a 5HT2A/2C agonist, or a 5HT2A/2C antagonist over several timecourses in early life, and measured the Nissl-SDN as well as a calbindin+ subdivision of the SDN, the CALB-SDN. When examined on postnatal day 18 or early adulthood, the size of the Nissl-SDN was feminized in males treated with any of the serotonergic drugs, eliminating the typical sex difference. In contrast, the sex difference in CALB-SDN size was maintained regardless of serotoninergic drug treatment. This pattern suggests that although gonadal hormones shape the whole SDN, individual cellular phenotypes respond to different intermediary signals to become sexually dimorphic. Specifically, 5HT mediates sexual differentiation of non-calbindin population(s) within the SDN. The results also caution against using measurement of the CALB-SDN in isolation, as the absence of an effect on the CALB-SDN does not preclude an effect on the overall nucleus. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 76: 1241-1253, 2016. © 2016 Wiley Periodicals, Inc.

  13. Coordination of distinct but interacting rhythmic motor programs by a modulatory projection neuron using different co-transmitters in different ganglia

    Science.gov (United States)

    Kwiatkowski, Molly A.; Gabranski, Emily R.; Huber, Kristen E.; Chapline, M. Christine; Christie, Andrew E.; Dickinson, Patsy S.

    2013-01-01

    SUMMARY While many neurons are known to contain multiple neurotransmitters, the specific roles played by each co-transmitter within a neuron are often poorly understood. Here, we investigated the roles of the co-transmitters of the pyloric suppressor (PS) neurons, which are located in the stomatogastric nervous system (STNS) of the lobster Homarus americanus. The PS neurons are known to contain histamine; using RT-PCR, we identified a second co-transmitter as the FMRFamide-like peptide crustacean myosuppressin (Crust-MS). The modulatory effects of Crust-MS application on the gastric mill and pyloric patterns, generated in the stomatogastric ganglion (STG), closely resembled those recorded following extracellular PS neuron stimulation. To determine whether histamine plays a role in mediating the effects of the PS neurons in the STG, we bath-applied histamine receptor antagonists to the ganglion. In the presence of the antagonists, the histamine response was blocked, but Crust-MS application and PS stimulation continued to modulate the gastric and pyloric patterns, suggesting that PS effects in the STG are mediated largely by Crust-MS. PS neuron stimulation also excited the oesophageal rhythm, produced in the commissural ganglia (CoGs) of the STNS. Application of histamine, but not Crust-MS, to the CoGs mimicked this effect. Histamine receptor antagonists blocked the ability of both histamine and PS stimulation to excite the oesophageal rhythm, providing strong evidence that the PS neurons use histamine in the CoGs to exert their effects. Overall, our data suggest that the PS neurons differentially utilize their co-transmitters in spatially distinct locations to coordinate the activity of three independent networks. PMID:23393282

  14. Caloric restriction reduces cell loss and maintains estrogen receptor-alpha immunoreactivity in the pre-optic hypothalamus of female B6D2F1 mice.

    Science.gov (United States)

    Yaghmaie, Farzin; Saeed, Omar; Garan, Steven A; Freitag, Warren; Timiras, Paola S; Sternberg, Hal

    2005-06-01

    Life-long calorie restriction (CR) remains the most robust and reliable means of extending life span in mammals. Among the several theories to explain CR actions, one variant of the neuroendocrine theories of aging postulates that changing hypothalamic sensitivity to endocrine feedback is the clock that times phenotypic change over the life span. If the feedback sensitivity hypothesis is correct, CR animals should display a significantly different pattern of hormone-sensitive cell density and distribution in the hypothalamus. Of the many endocrine signal receptors that may be involved in maintaining hypothalamic feedback sensitivity, our study has selected to begin mapping those for estrogen (E). Altered hypothalamic sensitivity to E is known to schedule reproductive maturation and influence reproductive senescence. Taking estrogen receptor-alpha (ERalpha) immunoreactivity as an index of sensitivity to E, we counted ERalpha immunoreactive and non-immunoreactive cells in the pre-optic hypothalamus of young (6 weeks), ad-libitum (Old-AL) fed old (22 months), and calorie restricted (Old-CR) old (22 months) female B6D2F1 mice. An automated imaging microscopy system (AIMS) was used to generate cell counts for each sampled section of pre-optic hypothalamus. Results show a 38% reduction in ERalpha immunoreactive cells and an 18% reduction in total cell numbers in AL-old mice in comparison to young mice. However, CR mice only show a 19% reduction in ERalpha immunoreactive cells and a 13% reduction in total cell numbers in comparison to young mice. This indicates CR prevents age-related cell loss and maintains estrogen sensitivity in the pre-optic hypothalamus of old female B6D2F1 mice.

  15. Suckling induces a daily rhythm in the preoptic area and lateral septum but not in the bed nucleus of the stria terminalis in lactating rabbit does.

    Science.gov (United States)

    Meza, Enrique; Aguirre, Juan; Waliszewski, Stefan; Caba, Mario

    2015-01-01

    Maternal behavior in the rabbit is restricted to a brief nursing period every day. Previously, we demonstrated that this event induces daily rhythms of Period1 (PER1) protein, the product of the clock gene Per1, in oxytocinergic and dopaminergic populations in the hypothalamus of lactating rabbit does. This is significant for the periodic production and ejection of milk, but the activation of other areas of the brain has not been explored. Here, we hypothesised that daily suckling would induce a rhythm in the preoptic area, lateral septum, and bed nucleus of the stria terminalis, which are important areas for the expression of maternal behavior in mammals, including the rabbit. To this end, we analysed PER1 expression in those areas through a complete 24-h cycle at lactation day 7. Does were scheduled to nurse during either the day at 10:00 h [zeitgeber time (ZT)03] or the night at 02:00 h (ZT19). Non-pregnant, non-lactating females were used as controls. In contrast to control females, lactating does showed a clear, significant rhythm of PER1 that shifted in parallel with the timing of nursing in the preoptic area and lateral septum. We determined that the maximal expression of PER1 at 8 h after scheduled nursing decreased significantly at 24 and 48 h after the absence of suckling. This effect was more pronounced in the lateral septum than in the preoptic area. We conclude that daily suckling is a powerful stimulus inducing rhythmic activity in brain structures in the rabbit that appear to form part of a maternal entrainable circuit. © 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  16. Isotocin neuronal phenotypes differ among social systems in cichlid fishes

    Science.gov (United States)

    O'Connor, Constance M.; Nesjan, Erin; Cameron, Jason; Hellmann, Jennifer K.; Ligocki, Isaac Y.; Marsh-Rollo, Susan E.; Hamilton, Ian M.; Wylie, Douglas R.; Hurd, Peter L.; Balshine, Sigal

    2017-01-01

    Social living has evolved numerous times across a diverse array of animal taxa. An open question is how the transition to a social lifestyle has shaped, and been shaped by, the underlying neurohormonal machinery of social behaviour. The nonapeptide neurohormones, implicated in the regulation of social behaviours, are prime candidates for the neuroendocrine substrates of social evolution. Here, we examined the brains of eight cichlid fish species with divergent social systems, comparing the number and size of preoptic neurons that express the nonapeptides isotocin and vasotocin. While controlling for the influence of phylogeny and body size, we found that the highly social cooperatively breeding species (n = 4) had fewer parvocellular isotocin neurons than the less social independently breeding species (n = 4), suggesting that the evolutionary transition to group living and cooperative breeding was associated with a reduction in the number of these neurons. In a complementary analysis, we found that the size and number of isotocin neurons significantly differentiated the cooperatively breeding from the independently breeding species. Our results suggest that isotocin is related to sociality in cichlids and may provide a mechanistic substrate for the evolution of sociality. PMID:28573041

  17. A Quantitative Analysis of the Distribution of CRH Neurons in Whole Mouse Brain

    Directory of Open Access Journals (Sweden)

    Jie Peng

    2017-07-01

    Full Text Available Corticotropin-releasing hormone (CRH, with widespread expression in the brain, plays a key role in modulating a series of behaviors, including anxiety, arousal, motor function, learning and memory. Previous studies have focused on some brain regions with densely distributed CRH neurons such as paraventricular hypothalamic nucleus (PVH and bed nuclei of the stria terminalis (BST and revealed some basic structural and functional knowledge of CRH neurons. However, there is no systematic analysis of brain-wide distribution of CRH neurons. Here, we performed a comprehensive study of CRH neurons in CRH-IRES-Cre;Ai3 mice via automatic imaging and stereoscopic cell counting in a whole mouse brain. We acquired four datasets of the CRH distributions with co-localized cytoarchitecture at a voxel resolution of 0.32 μm × 0.32 μm × 2 μm using brain-wide positioning system (BPS. Next, we precisely located and counted the EYFP-labeled neurons in different regions according to propidium iodide counterstained anatomical reference using Neuronal Global Position System. In particular, dense EYFP expression was found in piriform area, BST, central amygdalar nucleus, PVH, Barrington’s nucleus, and inferior olivary complex. Considerable CRH neurons were also found in main olfactory bulb, medial preoptic nucleus, pontine gray, tegmental reticular nucleus, external cuneate nucleus, and midline thalamus. We reconstructed and compared the soma morphology of CRH neurons in 11 brain regions. The results demonstrated that CRH neurons had regional diversities of both cell distribution and soma morphology. This anatomical knowledge enhances the current understanding of the functions of CRH neurons. These results also demonstrated the ability of our platform to accurately orient, reconstruct and count neuronal somas in three-dimension for type-specific neurons in the whole brain, making it feasible to answer the fundamental neuroscience question of exact numbers of

  18. A Quantitative Analysis of the Distribution of CRH Neurons in Whole Mouse Brain.

    Science.gov (United States)

    Peng, Jie; Long, Ben; Yuan, Jing; Peng, Xue; Ni, Hong; Li, Xiangning; Gong, Hui; Luo, Qingming; Li, Anan

    2017-01-01

    Corticotropin-releasing hormone (CRH), with widespread expression in the brain, plays a key role in modulating a series of behaviors, including anxiety, arousal, motor function, learning and memory. Previous studies have focused on some brain regions with densely distributed CRH neurons such as paraventricular hypothalamic nucleus (PVH) and bed nuclei of the stria terminalis (BST) and revealed some basic structural and functional knowledge of CRH neurons. However, there is no systematic analysis of brain-wide distribution of CRH neurons. Here, we performed a comprehensive study of CRH neurons in CRH-IRES-Cre;Ai3 mice via automatic imaging and stereoscopic cell counting in a whole mouse brain. We acquired four datasets of the CRH distributions with co-localized cytoarchitecture at a voxel resolution of 0.32 μm × 0.32 μm × 2 μm using brain-wide positioning system (BPS). Next, we precisely located and counted the EYFP-labeled neurons in different regions according to propidium iodide counterstained anatomical reference using Neuronal Global Position System. In particular, dense EYFP expression was found in piriform area, BST, central amygdalar nucleus, PVH, Barrington's nucleus, and inferior olivary complex. Considerable CRH neurons were also found in main olfactory bulb, medial preoptic nucleus, pontine gray, tegmental reticular nucleus, external cuneate nucleus, and midline thalamus. We reconstructed and compared the soma morphology of CRH neurons in 11 brain regions. The results demonstrated that CRH neurons had regional diversities of both cell distribution and soma morphology. This anatomical knowledge enhances the current understanding of the functions of CRH neurons. These results also demonstrated the ability of our platform to accurately orient, reconstruct and count neuronal somas in three-dimension for type-specific neurons in the whole brain, making it feasible to answer the fundamental neuroscience question of exact numbers of various neurons in the

  19. Parvalbumin+ Neurons and Npas1+ Neurons Are Distinct Neuron Classes in the Mouse External Globus Pallidus

    Science.gov (United States)

    Hernández, Vivian M.; Hegeman, Daniel J.; Cui, Qiaoling; Kelver, Daniel A.; Fiske, Michael P.; Glajch, Kelly E.; Pitt, Jason E.; Huang, Tina Y.; Justice, Nicholas J.

    2015-01-01

    Compelling evidence suggests that pathological activity of the external globus pallidus (GPe), a nucleus in the basal ganglia, contributes to the motor symptoms of a variety of movement disorders such as Parkinson's disease. Recent studies have challenged the idea that the GPe comprises a single, homogenous population of neurons that serves as a simple relay in the indirect pathway. However, we still lack a full understanding of the diversity of the neurons that make up the GPe. Specifically, a more precise classification scheme is needed to better describe the fundamental biology and function of different GPe neuron classes. To this end, we generated a novel multicistronic BAC (bacterial artificial chromosome) transgenic mouse line under the regulatory elements of the Npas1 gene. Using a combinatorial transgenic and immunohistochemical approach, we discovered that parvalbumin-expressing neurons and Npas1-expressing neurons in the GPe represent two nonoverlapping cell classes, amounting to 55% and 27% of the total GPe neuron population, respectively. These two genetically identified cell classes projected primarily to the subthalamic nucleus and to the striatum, respectively. Additionally, parvalbumin-expressing neurons and Npas1-expressing neurons were distinct in their autonomous and driven firing characteristics, their expression of intrinsic ion conductances, and their responsiveness to chronic 6-hydroxydopamine lesion. In summary, our data argue that parvalbumin-expressing neurons and Npas1-expressing neurons are two distinct functional classes of GPe neurons. This work revises our understanding of the GPe, and provides the foundation for future studies of its function and dysfunction. SIGNIFICANCE STATEMENT Until recently, the heterogeneity of the constituent neurons within the external globus pallidus (GPe) was not fully appreciated. We addressed this knowledge gap by discovering two principal GPe neuron classes, which were identified by their nonoverlapping

  20. GDNF secreting human neural progenitor cells protect dying motor neurons, but not their projection to muscle, in a rat model of familial ALS.

    Directory of Open Access Journals (Sweden)

    Masatoshi Suzuki

    Full Text Available BACKGROUND: Amyotrophic lateral sclerosis (ALS is a fatal, progressive neurodegenerative disease characterized by rapid loss of muscle control and eventual paralysis due to the death of large motor neurons in the brain and spinal cord. Growth factors such as glial cell line derived neurotrophic factor (GDNF are known to protect motor neurons from damage in a range of models. However, penetrance through the blood brain barrier and delivery to the spinal cord remains a serious challenge. Although there may be a primary dysfunction in the motor neuron itself, there is also increasing evidence that excitotoxicity due to glial dysfunction plays a crucial role in disease progression. Clearly it would be of great interest if wild type glial cells could ameliorate motor neuron loss in these models, perhaps in combination with the release of growth factors such as GDNF. METHODOLOGY/PRINCIPAL FINDINGS: Human neural progenitor cells can be expanded in culture for long periods and survive transplantation into the adult rodent central nervous system, in some cases making large numbers of GFAP positive astrocytes. They can also be genetically modified to release GDNF (hNPC(GDNF and thus act as long-term 'mini pumps' in specific regions of the rodent and primate brain. In the current study we genetically modified human neural stem cells to release GDNF and transplanted them into the spinal cord of rats over-expressing mutant SOD1 (SOD1(G93A. Following unilateral transplantation into the spinal cord of SOD1(G93A rats there was robust cellular migration into degenerating areas, efficient delivery of GDNF and remarkable preservation of motor neurons at early and end stages of the disease within chimeric regions. The progenitors retained immature markers, and those not secreting GDNF had no effect on motor neuron survival. Interestingly, this robust motor neuron survival was not accompanied by continued innervation of muscle end plates and thus resulted in no

  1. Localization of tyrosine hydroxylase immunoreactive neurons in the forebrain of the guppy Poecilia reticulata.

    Science.gov (United States)

    Parafati, M; Senatori, O; Nicotra, A

    2009-10-01

    The current study reports for the first time the distribution of tyrosine hydroxylase immunoreactive (TH-ir) neurons in the forebrain of the guppy Poecilia reticulata. Numerous small TH-ir neurons were observed in the olfactory bulbs, located mainly in the periphery of the bulbs. The TH-ir telencephalic neurons are localized in the ventral telencephalic area where they are grouped in three distinct nuclei (Vv,Vd and Vp) composed of a small number of cells forming a continuous strip. The largest number of forebrain TH-ir neurons was observed in the diencephalon where both small and larger neurons are present. Diencephalic TH-ir neurons are subdivided in large nuclei located in the preoptic region (nSC, nPOp and nPOm), the thalamus (nDM), the pretectal region (nPPv and nAP), the hypothalamus (nPP and nRP) and the posterior tuberculum (nPT). Many diencephalic nuclei are distributed in periventricular regions and no TH-ir cells were observed in the paraventricular organ. A comparative analysis indicates that the present observations are consistent with the general pattern of TH-ir neurons distribution reported for the forebrain of other teleosts, but with some interspecies variability present, mainly in the diencephalon. This paper also provides valuable neuroanatomical information for P. reticulata, a teleost frequently used in toxicological tests, for future studies investigating the effects of environmental pollutants on the catecholaminergic system.

  2. Inhibitory Interneurons That Express GFP in the PrP-GFP Mouse Spinal Cord Are Morphologically Heterogeneous, Innervated by Several Classes of Primary Afferent and Include Lamina I Projection Neurons among Their Postsynaptic Targets.

    Science.gov (United States)

    Ganley, Robert P; Iwagaki, Noboru; del Rio, Patricia; Baseer, Najma; Dickie, Allen C; Boyle, Kieran A; Polgár, Erika; Watanabe, Masahiko; Abraira, Victoria E; Zimmerman, Amanda; Riddell, John S; Todd, Andrew J

    2015-05-13

    The superficial dorsal horn of the spinal cord contains numerous inhibitory interneurons, which regulate the transmission of information perceived as touch, pain, or itch. Despite the importance of these cells, our understanding of their roles in the neuronal circuitry is limited by the difficulty in identifying functional populations. One group that has been identified and characterized consists of cells in the mouse that express green fluorescent protein (GFP) under control of the prion protein (PrP) promoter. Previous reports suggested that PrP-GFP cells belonged to a single morphological class (central cells), received inputs exclusively from unmyelinated primary afferents, and had axons that remained in lamina II. However, we recently reported that the PrP-GFP cells expressed neuronal nitric oxide synthase (nNOS) and/or galanin, and it has been shown that nNOS-expressing cells are more diverse in their morphology and synaptic connections. We therefore used a combined electrophysiological, pharmacological, and anatomical approach to reexamine the PrP-GFP cells. We provide evidence that they are morphologically diverse (corresponding to "unclassified" cells) and receive synaptic input from a variety of primary afferents, with convergence onto individual cells. We also show that their axons project into adjacent laminae and that they target putative projection neurons in lamina I. This indicates that the neuronal circuitry involving PrP-GFP cells is more complex than previously recognized, and suggests that they are likely to have several distinct roles in regulating the flow of somatosensory information through the dorsal horn.

  3. 三种新发现的脊髓背角双投射神经元的特征与意义%Characteristics and implications of the three newly discovered double projection spinal dorsal horn neurons

    Institute of Scientific and Technical Information of China (English)

    吕国蔚; 李菁锦

    2002-01-01

    1980年来,我室用解剖学和(或)生理学方法鉴定出了脊颈束/背索突触后(sCT/DCPS),脊孤束/背索突触后(SST/DCPS)和脊颈束/脊孤束(SCT/SST)等三种脊髓背角神经元.这些神经元以经其各自的分叉轴突分别向两个靶核投射为特征.它们的另一特征是具有会聚性躯体-内脏觉传入输入.部分神经元除通过分叉初级传入从外周接受躯体-内脏感觉输入外,还从中枢神经系统各自的靶核接受躯体-内脏觉输入.这些发现对牵涉痛和针刺镇痛的发生机制提供新的理解.%Three neuronal populations, spinocervical tract / dorsal column postsynaptic (SCT/DCPS) , spinosolitarytract / dorsal column postsynaptic (SST/DCPS) and spinocervical tract / spinosolitary tract (SCT/SST) neurons, havebeen anatomically and/or physiologically identified in the spinal dorsal horn by our group since the 1980s. These newlyidentified neurons are characterized by their divergent projections to two target nuclei via their branched axons. These neu-rons are also characterized by having convergent viscero-somatic afferent inputs. Some of these neurons receive viscero-so-matic sensory inputs from both. the periphery via, in part, dichotomized primary afferents and their own target nuclei in thecentral nervous system. These findings put an new insight into mechanisms of referred pain and acupuncture.

  4. Water versus salty taste and Iontophoretic ANGII responses of septopreoptic neurons in dehydrated and euhydrated awake rats.

    Science.gov (United States)

    Mousseau, M C; Thornton, S N; Liénard, F; Martial, F P; Nicolaïdis, S

    1996-01-01

    Little is known of the influence of gustatory, particularly salt, input on neurons of the forebrain and if the same neurons are sensitive to hydromineral balance humoral stimuli. In awake, nonpremedicated rats we recorded the activity of spontaneously active neurons in the preoptic/anterior hypothalamic area of dehydrated and euhydrated rats while allowing them to ingest water or a hypertonic salt solution (1.6% NaCl) administered to the tongue. The hormones angiotensin and aldosterone, both implicated in hydromineral balance, were applied by iontophoresis to the same neurons. In the dehydrated rats, 27% (15/55) of the spontaneously active neurons responded to a liquid (either water or the NaCl) applied to the tongue; in the euhydrated rats 23% (18/78) responded to the same stimuli. In the dehydrated rats, however, 33% (5/15) of the responding neurons were inhibited when the NaCl solution was applied to the tongue compared with only 5% (1/18) in the euhydrated rats. Iontophoretic application of angiotensin increased the spontaneous activity in 21% of those neurons tested that responded to taste. These results suggest that the state of hydration of an animal is able to change the neuronal response to substances applied to the tongue. Furthermore, it appears that these gustatory-sensitive neurons may also be related to hydromineral balance regulation since they are able to respond to angiotensin.

  5. Mirror neurons

    National Research Council Canada - National Science Library

    Rubia Vila, Francisco José

    2011-01-01

    Mirror neurons were recently discovered in frontal brain areas of the monkey. They are activated when the animal makes a specific movement, but also when the animal observes the same movement in another animal...

  6. A New Population of Parvocellular Oxytocin Neurons Controlling Magnocellular Neuron Activity and Inflammatory Pain Processing.

    Science.gov (United States)

    Eliava, Marina; Melchior, Meggane; Knobloch-Bollmann, H Sophie; Wahis, Jérôme; da Silva Gouveia, Miriam; Tang, Yan; Ciobanu, Alexandru Cristian; Triana del Rio, Rodrigo; Roth, Lena C; Althammer, Ferdinand; Chavant, Virginie; Goumon, Yannick; Gruber, Tim; Petit-Demoulière, Nathalie; Busnelli, Marta; Chini, Bice; Tan, Linette L; Mitre, Mariela; Froemke, Robert C; Chao, Moses V; Giese, Günter; Sprengel, Rolf; Kuner, Rohini; Poisbeau, Pierrick; Seeburg, Peter H; Stoop, Ron; Charlet, Alexandre; Grinevich, Valery

    2016-03-16

    Oxytocin (OT) is a neuropeptide elaborated by the hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei. Magnocellular OT neurons of these nuclei innervate numerous forebrain regions and release OT into the blood from the posterior pituitary. The PVN also harbors parvocellular OT cells that project to the brainstem and spinal cord, but their function has not been directly assessed. Here, we identified a subset of approximately 30 parvocellular OT neurons, with collateral projections onto magnocellular OT neurons and neurons of deep layers of the spinal cord. Evoked OT release from these OT neurons suppresses nociception and promotes analgesia in an animal model of inflammatory pain. Our findings identify a new population of OT neurons that modulates nociception in a two tier process: (1) directly by release of OT from axons onto sensory spinal cord neurons and inhibiting their activity and (2) indirectly by stimulating OT release from SON neurons into the periphery.

  7. Brainstem neurons projecting to the rostral ventral respiratory group (VRG) in the medulla oblongata of the rat revealed by co-application of NMDA and biocytin

    DEFF Research Database (Denmark)

    Zheng, Y; Riche, D; Rekling, J C;

    1998-01-01

    axonal arborizations were seen in the same regions where retrogradely filled neurons were found as well as in a few other motor nuclei (the dorsal vagal motor nucleus and XII nucleus). Moreover, in the NTS and the PB/KF, efferent terminal varicosities were seen closely apposed to the soma and proximal...

  8. Dorsal border periaqueductal gray neurons project to the area directly adjacent to the central canal ependyma of the C4-T8 spinal cord in the cat

    NARCIS (Netherlands)

    Mouton, LJ; Kerstens, L; VanderWant, J; Holstege, G

    1996-01-01

    In a previous study horseradish peroxidase (HRP) injections in the upper thoracic and cervical spinal cord revealed some faintly labeled small neurons at the dorsal border of the periaqueductal gray (PAG). The present light microscopic and electronmicroscopic tracing study describes the precise loca

  9. CNS CELL GROUPS PROJECTING TO THE SUBMANDIBULAR PARASYMPATHETIC PREGANGLIONIC NEURONS IN THE RAT - A RETROGRADE TRANSNEURONAL VIRAL CELL BODY LABELING STUDY

    NARCIS (Netherlands)

    JANSEN, ASP; TERHORST, GJ; METTENLEITER, TC; LOEWY, AD

    1992-01-01

    The retrograde transneuronal viral tracing method was used to study the CNS nuclei that innervate the parasympathetic preganglionic neurons controlling the submandibular gland in the rat. A genetically engineered beta-galactosidase expressing Bartha strain of pseudorabies virus (PRV) was injected in

  10. Lonicera japonica-induced inhibition of interleukin-1 beta thermogenesis and E-type prostaglandin receptor-3 expression in the preoptic area of rabbits

    Institute of Scientific and Technical Information of China (English)

    Jun Dong; Rongbo Tu; Rui Pan; Xinhua Xie

    2008-01-01

    BACKGROUND:It has been shown that interleukin-1β(IL-I β)can induce fever by activating vascular endothelial cells and macrophages of the supraoptic crest to generate prostaglandin E2,which binds with receptors of the thermo-sensitive hypothalamic neurons.Lonicera japonica is one of the medicinal plants used widely in Asia for its antipyretic properties.However,these mechanisms have not yet been intensively studied.OBJECTIVE:To investigate the antipyretic effect and mechanisms of Lonicera japonica on IL-1 β-induced febrile New Zealand rabbits by observing expression changes of E-type prostaglandin receptor-3 (EP3)mRNA in the preoptic anterior hypothalamus(POAH). DESIGN:A randomized controlled study. SETTING:Electrophysiological Laboratory at the Department of Pathophysiology,Medical College of Jinan University; Department of Orthopaedics,First Hospital Affiliated to Medical College of Jinan University. MATERIALS:The experiment was performed from April to December 2005,using a total of 32 New Zealand white rabbits of both sexes,weighing 1.5-2.0 kg.All the animal experiments were performed according to the internationally accepted ethical guidelines.Lonicera japonica injection was purchased from Huanghe pharmaceutical factory of Xi'an,China.IL-1 β was purchased from Sigma,USA.METHODS:A total of 32 rabbits were divided randomly into four groups:①Normal saline(NS)control group; ②Lonicerajaponica treatment group;③IL-1 β treatment group; and ④Lonicerajaponica plus IL-1 β treatment group.In the first 3 groups,the rabbits were given separate intravenous(I.v.)injections of 1 mL NS,1 mL l.Lonicera japonica,and 100 ng IL-1 β(dissolved in 0.9% NS without pyrogen).In the lonicera japonica plus IL-I βgroup each rabbit was given I.v.injections of l mL NS and,30 minutes later, 100 ng IL-I β. MAIN OUTCOME MEASURES:Colonic temperature of each rabbit was measured at 0,10,20,30,40,50, 60,and 70 minutes after injection and the maximum temperature rise( △ T)and the

  11. Ventromedial and medial preoptic hypothalamic ibotenic acid lesions potentiate systemic morphine analgesia in female, but not male rats.

    Science.gov (United States)

    Cataldo, Giuseppe; Lovric, Jelena; Chen, Chia-Chien; Pytte, Carolyn L; Bodnar, Richard J

    2010-12-25

    Sex differences in systemic morphine analgesia occur with male rodents displaying significantly greater analgesic magnitudes and potencies than females. Neonatal androgenization, and to a lesser degree, adult ovariectomy enhance systemic morphine analgesia in female rats, implicating both organizational and activational effects of gonadal hormones. The neuroanatomical circuits sensitive to sex-related hormones by which females display a smaller opiate analgesic effect is not clear, but the ventromedial (VMH) and medial preoptic (MPOA) hypothalamic nuclei are critical in the monitoring of estradiol and other sex hormone levels. To assess the contribution of these nuclei to sex and adult gonadectomy differences in systemic morphine analgesia, intact male, intact female and adult ovariectomized (OVEX) female rats received bilateral saline (SAL) or ibotenic acid (IBO) microinjections into either the VMH or MPOA. Following surgeries, baseline tail-flick latencies over 120 minutes (min) were assessed over 4 days in all nine groups with intact females tested in the estrus phase of their cycle. All animals then received an ascending series of morphine (1.0, 2.5, 5.0, 7.5, 10.0mg/kg) injections 30min prior to the tail-flick test time course with 8-12 day inter-injection intervals between doses. Baseline latencies failed to differ between SAL-treated intact males and females, but were significantly higher in SAL-treated OVEX females. Both VMH IBO and MPOA IBO lesions increased baseline latencies in intact male and female rats, but not in OVEX females. SAL-treated intact males (ED(50)=4.0mg/kg) and SAL-treated OVEX females (ED(50)=3.5mg/kg) displayed significantly greater potencies of systemic morphine analgesia than SAL-treated intact females (ED(50)=6.3mg/kg), confirming previous gender and gonadectomy differences. Neither VMH IBO (ED(50)=3.7 mg/kg) nor MPOA IBO (ED(50)=4.1mg/kg) males differed from SAL-treated males in the potency of systemic morphine analgesia. In

  12. [Mirror neurons].

    Science.gov (United States)

    Rubia Vila, Francisco José

    2011-01-01

    Mirror neurons were recently discovered in frontal brain areas of the monkey. They are activated when the animal makes a specific movement, but also when the animal observes the same movement in another animal. Some of them also respond to the emotional expression of other animals of the same species. These mirror neurons have also been found in humans. They respond to or "reflect" actions of other individuals in the brain and are thought to represent the basis for imitation and empathy and hence the neurobiological substrate for "theory of mind", the potential origin of language and the so-called moral instinct.

  13. The Influence of Antral Ulcers on Intramural Gastric Nerve Projections Supplying the Pyloric Sphincter in the Pig (Sus scrofa domestica-Neuronal Tracing Studies.

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    Michal Zalecki

    Full Text Available Gastric ulcerations in the region of antrum pylori represent a serious medical problem in humans and animals. Such localization of ulcers can influence the intrinsic descending nerve supply to the pyloric sphincter. The pyloric function is precisely regulated by intrinsic and extrinsic nerves. Impaired neural regulation could result in pyloric sphincter dysfunction and gastric emptying malfunction. The aim of the study was to determine the effect of gastric antral ulcerations on the density and distribution of intramural gastric descending neurons supplying the pyloric sphincter in pigs.The experiment was performed on 2 groups of pigs: healthy gilts (n=6 and gilts with experimentally induced peptic ulcers in the region of antrum pylori (n=6. Gastric neurons supplying pyloric sphincter were labeled using the retrograde neuronal tracing technique (20μl of Fast Blue tracer injected into the pyloric sphincter muscle. After a week survival period the animals were sacrificed and the stomachs were collected. Then, the stomach wall was cross-cut into 0.5cm thick sections taken in specified intervals (section I - 1.5cm; section II - 3.5cm; section III - 5.5cm; section IV - 7.5cm starting from the sphincter. Consecutive microscopic slices prepared from each section were analyzed under fluorescent microscope to count traced neurons. Obtained data were statistically analyzed. The total number of FB-positive perikarya observed within all studied sections significantly decreased from 903.3 ± 130.7 in control to 243.8 ± 67.3 in experimental animals. In healthy pigs 76.1 ± 6.7% of labeled neurons were observed within the section I, 23.53 ± 6.5% in section II and only occasional cells in section III. In experimental animals, as many as 93.8 ± 2.1% of labeled cells were observed within the section I and only 6.2 ± 2.2% in section II, while section III was devoid of such neurons. There were no traced perikarya in section IV observed in both groups of pigs

  14. A single-neuron tracing study of arkypallidal and prototypic neurons in healthy rats.

    Science.gov (United States)

    Fujiyama, Fumino; Nakano, Takashi; Matsuda, Wakoto; Furuta, Takahiro; Udagawa, Jun; Kaneko, Takeshi

    2016-12-01

    The external globus pallidus (GP) is known as a relay nucleus of the indirect pathway of the basal ganglia. Recent studies in dopamine-depleted and healthy rats indicate that the GP comprises two main types of pallidofugal neurons: the so-called "prototypic" and "arkypallidal" neurons. However, the reconstruction of complete arkypallidal neurons in healthy rats has not been reported. Here we visualized the entire axonal arborization of four single arkypallidal neurons and six single prototypic neurons in rat brain using labeling with a viral vector expressing membrane-targeted green fluorescent protein and examined the distribution of axon boutons in the target nuclei. Results revealed that not only the arkypallidal neurons but nearly all of the prototypic neurons projected to the striatum with numerous axon varicosities. Thus, the striatum is a major target nucleus for pallidal neurons. Arkypallidal and prototypic GP neurons located in the calbindin-positive and calbindin-negative regions mainly projected to the corresponding positive and negative regions in the striatum. Because the GP and striatum calbindin staining patterns reflect the topographic organization of the striatopallidal projection, the striatal neurons in the sensorimotor and associative regions constitute the reciprocal connection with the GP neurons in the corresponding regions.

  15. Population Encoding With Hodgkin-Huxley Neurons.

    Science.gov (United States)

    Lazar, Aurel A

    2010-02-01

    The recovery of (weak) stimuli encoded with a population of Hodgkin-Huxley neurons is investigated. In the absence of a stimulus, the Hodgkin-Huxley neurons are assumed to be tonically spiking. The methodology employed calls for 1) finding an input-output (I/O) equivalent description of the Hodgkin-Huxley neuron and 2) devising a recovery algorithm for stimuli encoded with the I/O equivalent neuron(s). A Hodgkin-Huxley neuron with multiplicative coupling is I/O equivalent with an Integrate-and-Fire neuron with a variable threshold sequence. For bandlimited stimuli a perfect recovery of the stimulus can be achieved provided that a Nyquist-type rate condition is satisfied. A Hodgkin-Huxley neuron with additive coupling and deterministic conductances is first-order I/O equivalent with a Project-Integrate-and-Fire neuron that integrates a projection of the stimulus on the phase response curve. The stimulus recovery is formulated as a spline interpolation problem in the space of finite length bounded energy signals. A Hodgkin-Huxley neuron with additive coupling and stochastic conductances is shown to be first-order I/O equivalent with a Project-Integrate-and-Fire neuron with random thresholds. For stimuli modeled as elements of Sobolev spaces the reconstruction algorithm minimizes a regularized quadratic optimality criterion. Finally, all previous recovery results of stimuli encoded with Hodgkin-Huxley neurons with multiplicative and additive coupling, and deterministic and stochastic conductances are extended to stimuli encoded with a population of Hodgkin-Huxley neurons.

  16. Dcc regulates asymmetric outgrowth of forebrain neurons in zebrafish.

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    Jingxia Gao

    Full Text Available The guidance receptor DCC (deleted in colorectal cancer ortholog UNC-40 regulates neuronal asymmetry development in Caenorhabditis elegans, but it is not known whether DCC plays a role in the specification of neuronal polarity in vertebrates. To examine the roles of DCC in neuronal asymmetry regulation in vertebrates, we studied zebrafish anterior dorsal telencephalon (ADt neuronal axons. We generated transgenic zebrafish animals expressing the photo-convertible fluorescent protein Kaede in ADt neurons and then photo-converted Kaede to label specifically the ADt neuron axons. We found that ADt axons normally project ventrally. Knock down of Dcc function by injecting antisense morpholino oligonucleotides caused the ADt neurons to project axons dorsally. To examine the axon projection pattern of individual ADt neurons, we labeled single ADt neurons using a forebrain-specific promoter to drive fluorescent protein expression. We found that individual ADt neurons projected axons dorsally or formed multiple processes after morpholino knock down of Dcc function. We further found that knock down of the Dcc ligand, Netrin1, also caused ADt neurons to project axons dorsally. Knockdown of Neogenin1, a guidance receptor closely related to Dcc, enhanced the formation of aberrant dorsal axons in embryos injected with Dcc morpholino. These experiments provide the first evidence that Dcc regulates polarized axon initiation and asymmetric outgrowth of forebrain neurons in vertebrates.

  17. Motor Neurons

    DEFF Research Database (Denmark)

    Hounsgaard, Jorn

    2017-01-01

    Motor neurons translate synaptic input from widely distributed premotor networks into patterns of action potentials that orchestrate motor unit force and motor behavior. Intercalated between the CNS and muscles, motor neurons add to and adjust the final motor command. The identity and functional...... properties of this facility in the path from synaptic sites to the motor axon is reviewed with emphasis on voltage sensitive ion channels and regulatory metabotropic transmitter pathways. The catalog of the intrinsic response properties, their underlying mechanisms, and regulation obtained from motoneurons...... in in vitro preparations is far from complete. Nevertheless, a foundation has been provided for pursuing functional significance of intrinsic response properties in motoneurons in vivo during motor behavior at levels from molecules to systems....

  18. The neuronal soma trait of trigeminal nerve branch projecting to dental pulp in rat trigeminal ganglia%大鼠牙髓神经胞体在三叉神经节内分布特点

    Institute of Scientific and Technical Information of China (English)

    肖芳莉; 李国超; 马腾飞; 黄姗姗; 徐文华; 王烈成; 王元银

    2016-01-01

    目的 了解正常及三叉神经痛( TN)模型大鼠的牙髓神经胞体在三叉神经节( TG)内分布情况及其投射关系,为临床通过TG治疗TN提供解剖学依据. 方法 本实验分为模型组和假手术组,在两组大鼠不同牙髓腔内注入逆行荧光探针,用荧光显微镜观察 TG 中荧光标记神经元的分布情况. 结果 两组大鼠分别在右下及左上中切牙髓腔内注入绿色荧光探针Fast DiO 72 h后,分别在右侧TG后外侧区、左侧TG中段区观察到数个、成簇分布带有绿色荧光标记神经元;将两组大鼠右下及左上中切牙髓腔内分别注入 Fast DiO、Fast DiI两种荧光探针,72 h后在其同侧TG的后外侧区和中间区分别观察到成簇分布的带有绿色和红色荧光的神经元;两组大鼠左侧上中切牙及下颌第一磨牙髓腔内分别注入荧光探针Fast DiI和Fast DiO,72 h后在同侧TG的后外侧区和中段区分别观察到成簇分布带有绿色和红色荧光的神经元. 经统计学比较,两组之间相应牙髓神经胞体在TG内分布区域、数量及荧光强度没有明显区别. 结论 三叉神经上、下颌支神经胞体投射于同侧TG,并有一定区域性;TN产生不改变TG内神经元数量及投射联系,其可能与三叉神经功能活动改变有关.%Objective To observe the position relationship of neuronal somas in trigeminal ganglia ( TG ) , which projects from different dental pulps in the normal and trigeminal neuralgia( TN) model rats, and provides anatomi-cal theoretical guidance for the clinical treatment of TN. Methods Those experiments were divided into model group and control group. The retrograde fluorescent probes were injected into the different dental pulp cavities of rats in the two groups, and fluorescent microscope was used to observe distribution of fluorescence labeled neurons in TG. Results Green fluorescent probes Fast DiO were injected into right lower and left upper central incisor of rats in the two

  19. Synaptic Circuit Organization of Motor Corticothalamic Neurons

    Science.gov (United States)

    Yamawaki, Naoki

    2015-01-01

    Corticothalamic (CT) neurons in layer 6 constitute a large but enigmatic class of cortical projection neurons. How they are integrated into intracortical and thalamo-cortico-thalamic circuits is incompletely understood, especially outside of sensory cortex. Here, we investigated CT circuits in mouse forelimb motor cortex (M1) using multiple circuit-analysis methods. Stimulating and recording from CT, intratelencephalic (IT), and pyramidal tract (PT) projection neurons, we found strong CT↔ CT and CT↔ IT connections; however, CT→IT connections were limited to IT neurons in layer 6, not 5B. There was strikingly little CT↔ PT excitatory connectivity. Disynaptic inhibition systematically accompanied excitation in these pathways, scaling with the amplitude of excitation according to both presynaptic (class-specific) and postsynaptic (cell-by-cell) factors. In particular, CT neurons evoked proportionally more inhibition relative to excitation (I/E ratio) than IT neurons. Furthermore, the amplitude of inhibition was tuned to match the amount of excitation at the level of individual neurons; in the extreme, neurons receiving no excitation received no inhibition either. Extending these studies to dissect the connectivity between cortex and thalamus, we found that M1-CT neurons and thalamocortical neurons in the ventrolateral (VL) nucleus were remarkably unconnected in either direction. Instead, VL axons in the cortex excited both IT and PT neurons, and CT axons in the thalamus excited other thalamic neurons, including those in the posterior nucleus, which additionally received PT excitation. These findings, which contrast in several ways with previous observations in sensory areas, illuminate the basic circuit organization of CT neurons within M1 and between M1 and thalamus. PMID:25653383

  20. Brainstem neurons with descending projections to the spinal cord of two elasmobranch fishes: thornback guitarfish, Platyrhinoidis triseriata, and horn shark, Heterodontus francisci.

    Science.gov (United States)

    Cruce, W L; Stuesse, S L; Northcutt, R G

    1999-01-25

    We studied two cartilaginous fishes and described their brainstem supraspinal projections because most nuclei in the reticular formation can be identified that way. A retrogradely transported tracer, horseradish peroxidase or Fluoro-Gold, was injected into the spinal cord of Platyrhinoidis triseriata (thornback guitarfish) or Heterodontus fransisci (horn shark). We described labeled reticular cells by their position, morpohology, somatic orientation, dendritic processes, and laterality of spinal projections. Nineteen reticular nuclei have spinal projections: reticularis (r.) dorsalis, r. ventralis pars alpha and beta, r. gigantocellularis, r. magnocellularis, r. parvocellularis, r. paragigantocellularis lateralis and dorsalis, r. pontis caudalis pars alpha and beta, r. pontis oralis pars medialis and lateralis, r. subcuneiformis, r. peduncularis pars compacta, r. subcoeruleus pars alpha, raphe obscurus, raphe pallidus, raphe magnus, and locus coeruleus. Twenty nonreticular nuclei have spinal projections: descending trigeminal, retroambiguus, solitarius, posterior octaval, descending octaval, magnocellular octaval, ruber, Edinger-Westphal, nucleus of the medial longitudinal fasciculus, interstitial nucleus of Cajal, latral mesencephalic complex, periventricularis pretectalis pars dorsalis, central pretectal, ventromedial thalamic, posterior central thalamic, posterior dorsal thalamic, the posterior tuberculum, and nuclei B, F, and J. The large number of distinct reticular nuclei with spinal projections corroborates the hypothesis that the reticular formation of elasmobranches is complexly organized into many of the same nuclei that are found in frogs, reptiles, birds, and mammals.

  1. Cerebellar projections to the red nucleus and inferior olive originate from separate populations of neurons in the rat: A non-fluorescent double labeling study

    NARCIS (Netherlands)

    T.M. Teune (Thea); J. van der Burg (Johannes); T.J.H. Ruigrok (Tom)

    1995-01-01

    textabstractIn the rat, the extent of collateralization of projections from the cerebellar nuclei to the red nucleus and inferior olive was investigated using a retrograde double labeling technique. The combination of tracers selected, cholera toxin-β-subunit and WGA-BSA-gold, not only enabled the u

  2. Hypothalamic leptin-neurotensin-hypocretin neuronal networks in zebrafish.

    Science.gov (United States)

    Levitas-Djerbi, Talia; Yelin-Bekerman, Laura; Lerer-Goldshtein, Tali; Appelbaum, Lior

    2015-04-01

    Neurotensin (NTS) is a 13 amino acid neuropeptide that is expressed in the hypothalamus. In mammals, NTS-producing neurons that express leptin receptor (LepRb) regulate the function of hypocretin/orexin (HCRT) and dopamine neurons. Thus, the hypothalamic leptin-NTS-HCRT neuronal network orchestrates key homeostatic output, including sleep, feeding, and reward. However, the intricate mechanisms of the circuitry and the unique role of NTS-expressing neurons remain unclear. We studied the NTS neuronal networks in zebrafish and cloned the genes encoding the NTS neuropeptide and receptor (NTSR). Similar to mammals, the ligand is expressed primarily in the hypothalamus, while the receptor is expressed widely throughout the brain in zebrafish. A portion of hypothalamic nts-expressing neurons are inhibitory and some coexpress leptin receptor (lepR1). As in mammals, NTS and HCRT neurons are localized adjacently in the hypothalamus. To track the development and axonal projection of NTS neurons, the NTS promoter was isolated. Transgenesis and double labeling of NTS and HCRT neurons showed that NTS axons project toward HCRT neurons, some of which express ntsr. Moreover, another target of NTS neurons is ntsr-expressing dopaminergeric neurons. These findings suggest structural circuitry between leptin, NTS, and hypocretinergic or dopaminergic neurons and establish the zebrafish as a model to study the role of these neuronal circuits in the regulation of feeding, sleep, and reward.

  3. Linking neuronal ensembles by associative synaptic plasticity.

    Directory of Open Access Journals (Sweden)

    Qi Yuan

    Full Text Available Synchronized activity in ensembles of neurons recruited by excitatory afferents is thought to contribute to the coding information in the brain. However, the mechanisms by which neuronal ensembles are generated and modified are not known. Here we show that in rat hippocampal slices associative synaptic plasticity enables ensembles of neurons to change by incorporating neurons belonging to different ensembles. Associative synaptic plasticity redistributes the composition of different ensembles recruited by distinct inputs such as to specifically increase the similarity between the ensembles. These results show that in the hippocampus, the ensemble of neurons recruited by a given afferent projection is fluid and can be rapidly and persistently modified to specifically include neurons from different ensembles. This linking of ensembles may contribute to the formation of associative memories.

  4. 腹外侧视前区微量注射组胺对大鼠睡眠-觉醒周期的影响%Effects of Microinjection of Histamine in Ventrolateral Preoptic Area on Rat Sleep-Wakefulness Cycle

    Institute of Scientific and Technical Information of China (English)

    刘宇炜; 若剑; 陈晓青; 易卉玲; 黄丹

    2015-01-01

    Objective To study the effect of histamine in rat ventrolateral preoptic area on sleep-wakeful⁃ness cycle. Methods Histamine was microinjected into ventrolateral preoptic area through stereotaxic technique,sleeping and waking time phases were recorded and analyzed by electroencephalograph. Results Microinjection of 50 μmol/L histamine had no significant effect ,but 100 μmol/L histamine de⁃creased sleeping time and increased waking time significantly. Conclusion Histamine is involved in reg⁃ulation of sleep-waking cycle and promotes wakefulness significantly in the ventrolateral preoptic area.%目的:研究组胺作用于腹外侧视前区对大鼠睡眠-觉醒周期的影响。方法通过脑立体定位、腹外侧视前区微量注射组胺,脑电图仪记录及分析睡眠、觉醒时相。结果微量注射50μmol/L组胺无明显影响,而100μmol/L组胺显著减少大鼠睡眠,增加觉醒。结论组胺在腹外侧视前区对大鼠睡眠-觉醒周期发挥重要的调节作用,具有明显的促觉醒作用。

  5. Differential regulation of the zebrafish orthopedia1 gene during fate determination of diencephalic neurons

    Directory of Open Access Journals (Sweden)

    Tarallo Raffaella

    2006-10-01

    Full Text Available Abstract Background The homeodomain transcription factor Orthopedia (Otp is essential in restricting the fate of multiple classes of secreting neurons in the neuroendocrine hypothalamus of vertebrates. However, there is little information on the intercellular factors that regulate Otp expression during development. Results Here, we identified two otp orthologues in zebrafish (otp1 and otp2 and explored otp1 in the context of the morphogenetic pathways that specify neuroectodermal regions. During forebrain development, otp1 is expressed in anterior groups of diencephalic cells, positioned in the preoptic area (PO (anterior alar plate and the posterior tuberculum (PT (posterior basal plate. The latter structure is characterized by Tyrosine Hydroxylase (TH-positive cells, suggesting a role for otp1 in the lineage restriction of catecholaminergic (CA neurons. Disruptions of Hedgehog (HH and Fibroblast Growth Factor (FGF pathways point to the ability of SHH protein to trigger otp1 expression in PO presumptive neuroblasts, with the attenuating effect of Dzip1 and FGF8. In addition, our data disclose otp1 as a determinant of CA neurons in the PT, where otp1 activity is strictly dependent on Nodal signaling and it is not responsive to SHH and FGF. Conclusion In this study, we pinpoint the evolutionary importance of otp1 transcription factor in cell states of the diencephalon anlage and early neuronal progenitors. Furthermore, our data indicate that morphogenetic mechanisms differentially regulate otp1 expression in alar and basal plates.

  6. Characterization of GABAergic neurons in the mouse lateral septum: a double fluorescence in situ hybridization and immunohistochemical study using tyramide signal amplification.

    Directory of Open Access Journals (Sweden)

    Changjiu Zhao

    Full Text Available Gamma-aminobutyric acid (GABA neurotransmission in the lateral septum (LS is implicated in modulating various behavioral processes, including emotional reactivity and maternal behavior. However, identifying the phenotype of GABAergic neurons in the CNS has been hampered by the longstanding inability to reliably detect somal immunoreactivity for GABA or glutamic acid decarboxylase (GAD, the enzyme that produces GABA. In this study, we designed unique probes for both GAD65 (GAD2 and GAD67 (GAD1, and used fluorescence in Situ hybridization (FISH with tyramide signal amplification (TSA to achieve unequivocal detection of cell bodies of GABAergic neurons by GAD mRNAs. We quantitatively characterized the expression and chemical phenotype of GABAergic neurons across each subdivision of LS and in cingulate cortex (Cg and medial preoptic area (MPOA in female mice. Across LS, almost all GAD65 mRNA-expressing neurons were found to contain GAD67 mRNA (approximately 95-98%, while a small proportion of GAD67 mRNA-containing neurons did not express GAD65 mRNA (5-14%. Using the neuronal marker NeuN, almost every neuron in LS (> 90% was also found to be GABA-positive. Interneuron markers using calcium-binding proteins showed that LS GABAergic neurons displayed immunoreactivity for calbindin (CB or calretinin (CR, but not parvalbumin (PV; almost all CB- or CR-immunoreactive neurons (98-100% were GABAergic. The proportion of GABAergic neurons immunoreactive for CB or CR varied depending on the subdivisions examined, with the highest percentage of colocalization in the caudal intermediate LS (LSI (approximately 58% for CB and 35% for CR. These findings suggest that the vast majority of GABAergic neurons within the LS have the potential for synthesizing GABA via the dual enzyme systems GAD65 and GAD67, and each subtype of GABAergic neurons identified by distinct calcium-binding proteins may exert unique roles in the physiological function and neuronal circuitry of

  7. Seasonal changes of androgen receptor, estrogen receptors and aromatase expression in the medial preoptic area of the wild male ground squirrels (Citellus dauricus Brandt

    Directory of Open Access Journals (Sweden)

    F. Zhang

    2016-05-01

    Full Text Available The wild ground squirrel is a typical seasonal breeder. In this study, using RT-PCR, western blot and immunohistochemistry, we investigated the mRNA and protein expressions of androgen receptor (AR, estrogen receptors α and β (ERα and ERβ and aromatase cytochrome P450 (P450arom in the medial preoptic area (MPOA of hypothalamus of the wild male ground squirrel during the breeding season (April, the non-breeding season (June and pre-hibernation (September. AR, ERα, ERβ and P450arom protein/mRNA were present in the MPOA of all seasons detected. The immunostaining of AR and ERα showed no significant changes in different periods, whereas ERβ and P450arom had higher immunoreactivities during the breeding season and pre-hibernation when compared to those of the non-breeding season. Consistently, both the protein and mRNA levels of P450arom and ERβ were higher in the MPOA of pre-hibernation and the breeding season than in the non-breeding season, whereas no significant difference amongst the three periods was observed for AR and ERα levels. These findings suggested that the MPOA of hypothalamus may be a direct target of androgen and estrogen. Androgen may play important regulatory roles through its receptor and/or the aromatized estrogen in the MPOA of hypothalamus of the wild male ground squirrels.

  8. Effects of NMDA and non-NMDA ionotropic glutamate receptors in the medial preoptic area on body temperature in awake rats.

    Science.gov (United States)

    Sengupta, Trina; Jaryal, Ashok Kumar; Mallick, Hruda Nanda

    2016-10-01

    Glutamate when microinjected at the medial preoptic area (mPOA) influences brain temperature (Tbr) and body temperature (Tb) in rats. Glutamate and its various receptors are present at the mPOA. The aim of this study was to identify the contribution of each of the ionotropic glutamatergic receptors at the mPOA on changes in Tbr and Tb in freely moving rats. Adult male Wistar rats (n=40) were implanted with bilateral guide cannula with indwelling styli above the mPOA. A telemetric transmitter was implanted at the peritoneum to record Tb and locomotor activity (LMA). A precalibrated thermocouple wire implanted near the hypothalamus was used to assess Tbr. Specific agonist for each ionotropic glutamate receptor was microinjected into the mPOA and its effects on temperature and LMA were measured in the rats. The rats were also microinjected with the respective ionotropic receptor antagonists, 15min prior to the microinjection of each agonist. Amongst amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), N-methyl-d-aspartate (NMDA) and kainic acid, AMPA increased Tb and LMA when injected at the mPOA. Specific antagonists for AMPA receptors was able to attenuate this increase (ptemperature.

  9. Effects of electrical lesions of the medial preoptic area and the ventral pallidum on mate-dependent paternal behavior in mice.

    Science.gov (United States)

    Akther, Shirin; Fakhrul, Azam A K M; Higashida, Haruhiro

    2014-06-06

    In laboratory animals, less is known about the neural circuits that mediate paternal behavior than those that influence maternal behavior. In mice, we recently reported that when sires are separated with their mate dams from their pups, ultrasound and pheromonal signals from the dams can evoke and initiate maternal-like retrieval behavior in the sires upon reunion with the offspring; this is termed mate-dependent paternal care. We used electrolytic brain lesion (EBL) methods to identify the potential roles of the medial preoptic area (mPOA) and ventral pallidum (VP) regions in regulating paternal care, areas known to be critical for the expression of maternal behavior. Electrolytic lesions of the mPOA or VP disrupted mate-dependent paternal care; latencies to initiate pup retrieval, grooming and crouching were longer in the EBL-treated sires relative to the sham-operated mice. The number of grooming episodes and duration of crouching were also lower in sires with the EBL in both areas. These results indicate that the mPOA and VP regions are essential for mate-dependent paternal care in mice.

  10. Effects of photoperiod on kisspeptin neuronal populations of the ewe diencephalon in connection with reproductive function.

    Science.gov (United States)

    Chalivoix, S; Bagnolini, A; Caraty, A; Cognié, J; Malpaux, B; Dufourny, L

    2010-02-01

    Kisspeptin (Kiss) is a key regulator of reproductive function in both prepubertal and adult mammals. Its expression appears to vary throughout the year in seasonal species. We aimed to determine the impact of a change of photoperiod on the size of Kiss neuronal populations found in the preoptic area (POA) and arcuate nucleus (ARC) of the ewe brain. Using immunocytochemistry, we first examined the proportion of neurones expressing Kiss, using HuC/D as a neuronal marker, at different time-points after transition from long days (LD; 16 : 8 h light/dark cycle) to short days (SD; 8 : 16 h light/dark cycle). Luteinising hormone (LH) secretion was measured in ovariectomised oestradiol replaced ewes from the month preceding the transition to SD until the sacrifice of the animals at days 0, 45 and 112 from this photoperiodic transition. High LH levels were only observed in animals killed at day 112. The number of Kiss neurones/mm(2) doubled in the caudal ARC at day 112. The percentage of neurones showing Kiss immunoreactivity increased significantly in both the POA and ARC in the day 112 group. In a second experiment, ewes kept in LD received an i.c.v. injection of colchicine 20 h before sacrifice. Colchicine treatment increased the number and the percentage of neurones with Kiss in both the POA and caudal ARC. The data obtained suggest that the increase in Kiss neurones detected in the POA and caudal ARC after transition to SD stemmed from an increase in Kiss synthesis. This up-regulation of Kiss content under the shorter day condition appears to be a late event within the cascade activated by a longer secretion of melatonin, which is a critical factor in switching gonadotrophin-releasing hormone secretion to a breeding season profile.

  11. Sexual differentiation of the brain requires perinatal kisspeptin-GnRH neuron signaling.

    Science.gov (United States)

    Clarkson, Jenny; Busby, Ellen R; Kirilov, Milen; Schütz, Günther; Sherwood, Nancy M; Herbison, Allan E

    2014-11-12

    Sex differences in brain function underlie robust differences between males and females in both normal and disease states. Although alternative mechanisms exist, sexual differentiation of the male mammalian brain is initiated predominantly by testosterone secreted by the testes during the perinatal period. Despite considerable advances in understanding how testosterone and its metabolite estradiol sexually differentiate the brain, little is known about the mechanism that generates the male-specific perinatal testosterone surge. In mice, we show that a male-specific activation of GnRH neurons occurs 0-2 h following birth and that this correlates with the male-specific surge of testosterone occurring up to 5 h after birth. The necessity of GnRH signaling for the sexually differentiating effects of the perinatal testosterone surge was demonstrated by the persistence of female-like brain characteristics in adult male, GnRH receptor knock-out mice. Kisspeptin neurons have recently been identified to be potent, direct activators of GnRH neurons. We demonstrate that a population of kisspeptin neurons appears in the preoptic area of only the male between E19 and P1. The importance of kisspeptin inputs to GnRH neurons for the process of sexual differentiation was demonstrated by the lack of a normal neonatal testosterone surge, and disordered brain sexual differentiation of male mice in which the kisspeptin receptor was deleted selectively from GnRH neurons. These observations demonstrate the necessity of perinatal GnRH signaling for driving brain sexual differentiation and indicate that kisspeptin inputs to GnRH neurons are essential for this process to occur.

  12. Neuroanatomical organization of gonadotropin-releasing hormone neurons during the oestrus cycle in the ewe

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    Malpaux Benoît

    2004-11-01

    Full Text Available Abstract Background During the preovulatory surge of gonadotropin-releasing hormone (GnRH, a very large amount of the peptide is released in the hypothalamo-hypophyseal portal blood for 24-36H00. To study whether this release is linked to a modification of the morphological organization of the GnRH-containing neurons, i.e. morphological plasticity, we conducted experiments in intact ewes at 4 different times of the oestrous cycle (before the expected LH surge, during the LH surge, and on day 8 and day 15 of the subsequent luteal phase. The cycle stage was verified by determination of progesterone and LH concentrations in the peripheral blood samples collected prior to euthanasia. Results The distribution of GnRH-containing neurons throughout the preoptic area around the vascular organ of the lamina terminalis was studied following visualisation using immunohistochemistry. No difference was observed in the staining intensity for GnRH between the different groups. Clusters of GnRH-containing neurons (defined as 2 or more neurons being observed in close contact were more numerous during the late follicular phase (43 ± 7 than during the luteal phase (25 ± 6, and the percentage of clusters was higher during the beginning of the follicular phase than during the luteal phase. There was no difference in the number of labelled neurons in each group. Conclusions These results indicate that the morphological organization of the GnRH-containing neurons in ewes is modified during the follicular phase. This transitory re-organization may contribute to the putative synchronization of these neurons during the surge. The molecular signal inducing this plasticity has not yet been identified, but oestradiol might play an important role, since in sheep it is the only signal which initiates the GnRH preovulatory surge.

  13. The origin of cortical neurons

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    J.G. Parnavelas

    2002-12-01

    Full Text Available Neurons of the mammalian cerebral cortex comprise two broad classes: pyramidal neurons, which project to distant targets, and the inhibitory nonpyramidal cells, the cortical interneurons. Pyramidal neurons are generated in the germinal ventricular zone, which lines the lateral ventricles, and migrate along the processes of radial glial cells to their positions in the developing cortex in an `inside-out' sequence. The GABA-containing nonpyramidal cells originate for the most part in the ganglionic eminence, the primordium of the basal ganglia in the ventral telencephalon. These cells follow tangential migratory routes to enter the cortex and are in close association with the corticofugal axonal system. Once they enter the cortex, they move towards the ventricular zone, possibly to obtain positional information, before they migrate radially in the direction of the pial surface to take up their positions in the developing cortex. The mechanisms that guide interneurons throughout these long and complex migratory routes are currently under investigation.

  14. L-DOPA Oppositely Regulates Synaptic Strength and Spine Morphology in D1 and D2 Striatal Projection Neurons in Dyskinesia

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    Suarez, Luz M; Solis, Oscar; Aguado, Carolina; Lujan, Rafael; Moratalla, Rosario

    2016-01-01

    Dopamine depletion in Parkinson's disease (PD) produces dendritic spine loss in striatal medium spiny neurons (MSNs) and increases their excitability. However, the synaptic changes that occur in MSNs in PD, in particular those induced by chronic L-3,4-dihydroxyphenylalanine (L-DOPA) treatment, are still poorly understood. We exposed BAC-transgenic D1-tomato and D2-eGFP mice to PD and dyskinesia model paradigms, enabling cell type-specific assessment of changes in synaptic physiology and morphology. The distinct fluorescence markers allowed us to identify D1 and D2 MSNs for analysis using intracellular sharp electrode recordings, electron microscopy, and 3D reconstructions with single-cell Lucifer Yellow injections. Dopamine depletion induced spine pruning in both types of MSNs, affecting mushroom and thin spines equally. Dopamine depletion also increased firing rate in both D1- and D2-MSNs, but reduced evoked-EPSP amplitude selectively in D2-MSNs. L-DOPA treatment that produced dyskinesia differentially affected synaptic properties in D1- and D2-MSNs. In D1-MSNs, spine density remained reduced but the remaining spines were enlarged, with bigger heads and larger postsynaptic densities. These morphological changes were accompanied by facilitation of action potential firing triggered by synaptic inputs. In contrast, although L-DOPA restored the number of spines in D2-MSNs, it resulted in shortened postsynaptic densities. These changes in D2-MSNs correlated with a decrease in synaptic transmission. Our findings indicate that L-DOPA-induced dyskinesia is associated with abnormal spine morphology, modified synaptic transmission, and altered EPSP-spike coupling, with distinct effects in D1- and D2-MSNs. PMID:27613437

  15. L-DOPA Oppositely Regulates Synaptic Strength and Spine Morphology in D1 and D2 Striatal Projection Neurons in Dyskinesia.

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    Suarez, Luz M; Solis, Oscar; Aguado, Carolina; Lujan, Rafael; Moratalla, Rosario

    2016-10-17

    Dopamine depletion in Parkinson's disease (PD) produces dendritic spine loss in striatal medium spiny neurons (MSNs) and increases their excitability. However, the synaptic changes that occur in MSNs in PD, in particular those induced by chronic L-3,4-dihydroxyphenylalanine (L-DOPA) treatment, are still poorly understood. We exposed BAC-transgenic D1-tomato and D2-eGFP mice to PD and dyskinesia model paradigms, enabling cell type-specific assessment of changes in synaptic physiology and morphology. The distinct fluorescence markers allowed us to identify D1 and D2 MSNs for analysis using intracellular sharp electrode recordings, electron microscopy, and 3D reconstructions with single-cell Lucifer Yellow injections. Dopamine depletion induced spine pruning in both types of MSNs, affecting mushroom and thin spines equally. Dopamine depletion also increased firing rate in both D1- and D2-MSNs, but reduced evoked-EPSP amplitude selectively in D2-MSNs. L-DOPA treatment that produced dyskinesia differentially affected synaptic properties in D1- and D2-MSNs. In D1-MSNs, spine density remained reduced but the remaining spines were enlarged, with bigger heads and larger postsynaptic densities. These morphological changes were accompanied by facilitation of action potential firing triggered by synaptic inputs. In contrast, although L-DOPA restored the number of spines in D2-MSNs, it resulted in shortened postsynaptic densities. These changes in D2-MSNs correlated with a decrease in synaptic transmission. Our findings indicate that L-DOPA-induced dyskinesia is associated with abnormal spine morphology, modified synaptic transmission, and altered EPSP-spike coupling, with distinct effects in D1- and D2-MSNs. © The Author 2016. Published by Oxford University Press.

  16. Activation of Pedunculopontine Glutamate Neurons Is Reinforcing.

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    Yoo, Ji Hoon; Zell, Vivien; Wu, Johnathan; Punta, Cindy; Ramajayam, Nivedita; Shen, Xinyi; Faget, Lauren; Lilascharoen, Varoth; Lim, Byung Kook; Hnasko, Thomas S

    2017-01-04

    Dopamine transmission from midbrain ventral tegmental area (VTA) neurons underlies behavioral processes related to motivation and drug addiction. The pedunculopontine tegmental nucleus (PPTg) is a brainstem nucleus containing glutamate-, acetylcholine-, and GABA-releasing neurons with connections to basal ganglia and limbic brain regions. Here we investigated the role of PPTg glutamate neurons in reinforcement, with an emphasis on their projections to VTA dopamine neurons. We used cell-type-specific anterograde tracing and optogenetic methods to selectively label and manipulate glutamate projections from PPTg neurons in mice. We used anatomical, electrophysiological, and behavioral assays to determine their patterns of connectivity and ascribe functional roles in reinforcement. We found that photoactivation of PPTg glutamate cell bodies could serve as a direct positive reinforcer on intracranial self-photostimulation assays. Further, PPTg glutamate neurons directly innervate VTA; photostimulation of this pathway preferentially excites VTA dopamine neurons and is sufficient to induce behavioral reinforcement. These results demonstrate that ascending PPTg glutamate projections can drive motivated behavior, and PPTg to VTA synapses may represent an important target relevant to drug addiction and other mental health disorders. Uncovering brain circuits underlying reward-seeking is an important step toward understanding the circuit bases of drug addiction and other psychiatric disorders. The dopaminergic system emanating from the ventral tegmental area (VTA) plays a key role in regulating reward-seeking behaviors. We used optogenetics to demonstrate that the pedunculopontine tegmental nucleus sends glutamatergic projections to VTA dopamine neurons, and that stimulation of this circuit promotes behavioral reinforcement. The findings support a critical role for pedunculopontine tegmental nucleus glutamate neurotransmission in modulating VTA dopamine neuron activity and

  17. Novel oxytocin gene expression in the hindbrain is induced by alcohol exposure: transgenic zebrafish enable visualization of sensitive neurons.

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    Caitrín M Coffey

    Full Text Available BACKGROUND: Fetal Alcohol Spectrum Disorders (FASD are a collection of disorders resulting from fetal ethanol exposure, which causes a wide range of physical, neurological and behavioral deficits including heightened susceptibility for alcoholism and addictive disorders. While a number of mechanisms have been proposed for how ethanol exposure disrupts brain development, with selective groups of neurons undergoing reduced proliferation, dysfunction and death, the induction of a new neurotransmitter phenotype by ethanol exposure has not yet been reported. PRINCIPAL FINDINGS: The effects of embryonic and larval ethanol exposure on brain development were visually monitored using transgenic zebrafish expressing cell-specific green fluorescent protein (GFP marker genes. Specific subsets of GFP-expressing neurons were highly sensitive to ethanol exposure, but only during defined developmental windows. In the med12 mutant, which affects the Mediator co-activator complex component Med12, exposure to lower concentrations of ethanol was sufficient to reduce GFP expression in transgenic embryos. In transgenic embryos and larva containing GFP driven by an oxytocin-like (oxtl promoter, ethanol exposure dramatically up-regulated GFP expression in a small group of hindbrain neurons, while having no effect on expression in the neuroendocrine preoptic area. CONCLUSIONS: Alcohol exposure during limited embryonic periods impedes the development of specific, identifiable groups of neurons, and the med12 mutation sensitizes these neurons to the deleterious effects of ethanol. In contrast, ethanol exposure induces oxtl expression in the hindbrain, a finding with profound implications for understanding alcoholism and other addictive disorders.

  18. Developmental specification of forebrain cholinergic neurons.

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    Allaway, Kathryn C; Machold, Robert

    2017-01-01

    Striatal cholinergic interneurons and basal forebrain cholinergic projection neurons, which together comprise the forebrain cholinergic system, regulate attention, memory, reward pathways, and motor activity through the neuromodulation of multiple brain circuits. The importance of these neurons in the etiology of neurocognitive disorders has been well documented, but our understanding of their specification during embryogenesis is still incomplete. All forebrain cholinergic projection neurons and interneurons appear to share a common developmental origin in the embryonic ventral telencephalon, a region that also gives rise to GABAergic projection neurons and interneurons. Significant progress has been made in identifying the key intrinsic and extrinsic factors that promote a cholinergic fate in this precursor population. However, how cholinergic interneurons and projection neurons differentiate from one another during development, as well as how distinct developmental programs contribute to heterogeneity within those two classes, is not yet well understood. In this review we summarize the transcription factors and signaling molecules known to play a role in the specification and early development of striatal and basal forebrain cholinergic neurons. We also discuss the heterogeneity of these populations and its possible developmental origins. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. [Neuronal network].

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    Langmeier, M; Maresová, D

    2005-01-01

    Function of the central nervous system is based on mutual relations among the nerve cells. Description of nerve cells and their processes, including their contacts was enabled by improvement of optical features of the microscope and by the development of impregnation techniques. It is associated with the name of Antoni van Leeuwenhoek (1632-1723), J. Ev. Purkyne (1787-1869), Camillo Golgi (1843-1926), and Ramón y Cajal (1852-1934). Principal units of the neuronal network are the synapses. The term synapse was introduced into neurophysiology by Charles Scott Sherrington (1857-1952). Majority of the interactions between nerve cells is mediated by neurotransmitters acting at the receptors of the postsynaptic membrane or at the autoreceptors of the presynaptic part of the synapse. Attachment of the vesicles to the presynaptic membrane and the release of the neurotransmitter into the synaptic cleft depend on the intracellular calcium concentration and on the presence of several proteins in the presynaptic element.

  20. Regeneration and rewiring of rodent olfactory sensory neurons.

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    Yu, C Ron; Wu, Yunming

    2017-01-01

    The olfactory sensory neurons are the only neurons in the mammalian nervous system that not only regenerate naturally and in response to injury, but also project to specific targets in the brain. The stem cells in the olfactory epithelium commit to both neuronal and non-neuronal lineages depending on the environmental conditions. They provide a continuous supply of new neurons. A newly generated neuron must express a specific odorant receptor gene and project to a central target consist of axons expressing the same receptor type. Recent studies have provided insights into this highly regulated, complex process. However, the molecular mechanisms that determine the regenerative capacity of stem cells, and the ability of newly generated neurons in directing their axons toward specific targets, remain elusive. Here we review progresses and controversies in the field and offer testable models. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Distribution of type 1 cannabinoid receptor-expressing neurons in the septal-hypothalamic region of the mouse: colocalization with GABAergic and glutamatergic markers.

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    Hrabovszky, Erik; Wittmann, Gábor; Kalló, Imre; Füzesi, Tamás; Fekete, Csaba; Liposits, Zsolt

    2012-04-01

    Type 1 cannabinoid receptor (CB1) is the principal mediator of retrograde endocannabinoid signaling in the brain. In this study, we addressed the topographic distribution and amino acid neurotransmitter phenotype of endocannabinoid-sensitive hypothalamic neurons in mice. The in situ hybridization detection of CB1 mRNA revealed high levels of expression in the medial septum (MS) and the diagonal band of Broca (DBB), moderate levels in the preoptic area and the hypothalamic lateroanterior (LA), paraventricular (Pa), ventromedial (VMH), lateral mammillary (LM), and ventral premammillary (PMV) nuclei, and low levels in many other hypothalamic regions including the suprachiasmatic (SCh) and arcuate (Arc) nuclei. This regional distribution pattern was compared with location of γ-aminobutyric acid (GABA)ergic and glutamatergic cell groups, as identified by the expression of glutamic acid decarboxylase 65 (GAD65) and type 2 vesicular glutamate transporter (VGLUT2) mRNAs, respectively. The MS, DBB, and preoptic area showed overlaps between GABAergic and CB1-expressing neurons, whereas hypothalamic sites with moderate CB1 signals, including the LA, Pa, VMH, LM, and PMV, were dominated by glutamatergic neurons. Low CB1 mRNA levels were also present in other glutamatergic and GABAergic regions. Dual-label in situ hybridization experiments confirmed the cellular co-expression of CB1 with both glutamatergic and GABAergic markers. In this report we provide a detailed anatomical map of hypothalamic glutamatergic and GABAergic systems whose neurotransmitter release is controlled by retrograde endocannabinoid signaling from hypothalamic and extrahypothalamic target neurons. This neuroanatomical information contributes to an understanding of the role that the endocannabinoid system plays in the regulation of endocrine and metabolic functions.

  2. Multiple embryonic origins of nitric oxide synthase-expressing GABAergic neurons of the neocortex

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    Lorenza eMagno

    2012-09-01

    Full Text Available Cortical GABAergic interneurons in rodents originate in three subcortical regions: the medial ganglionic eminence (MGE, the lateral/caudal ganglionic eminence (LGE/CGE and the preoptic area (POA. Each of these neuroepithelial precursor domains contributes different interneuron subtypes to the cortex. nNOS-expressing neurons represent a heterogenous population of cortical interneurons. We examined the development of these cells in the mouse embryonic cortex and their abundance and distribution in adult animals. Using genetic lineage tracing in transgenic mice we find that nNOS type I cells originate only in the MGE whereas type II cells have a triple origin in the MGE, LGE/CGE and POA. The two populations are born at different times during development, occupy different layers in the adult cortex and have distinct neurochemical profiles. nNOS neurons are more numerous in the adult cortex than previously reported and constitute a significant proportion of the cortical interneuron population. Our data suggest that the heterogeneity of nNOS neurons in the cortex can be attributed to their multiple embryonic origins which likely impose distinct genetic specification programs.

  3. RFRP neurons are critical gatekeepers for the photoperiodic control of reproduction

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    Valerie eSimonneaux

    2012-12-01

    Full Text Available Seasonally-breeding mammals rely on the photoperiodic signal to restrict their fertility to a certain time of the year. The photoperiodic information is translated in the brain via the pineal hormone melatonin, and it is now well established that it is the variation in the duration of the nocturnal peak of melatonin which synchronises reproduction with the seasons. The Syrian hamster is a long day breeder, and sexual activity is therefore promoted by exposure to a long day photoperiod and inhibited by exposure to a short day photoperiod. Interestingly, in this species electrolytic lesion of the mediobasal hypothalamus abolishes the short day-induced gonadal regression. We have shown that the expression of a recently discovered neuronal population, namely RFamide-related peptide (rfrp neurons, present in the mediobasal hypothalamus, is strongly down-regulated by melatonin in short day conditions, but not altered by circulating levels of sex steroids. The role of rfrp and its product RFRP-3 in the regulation of reproductive activity has been extensively studied in mammals, and our recent findings indicate that this peptide is a potent stimulator of the reproductive axis in the Syrian hamster. It induces a marked increase in GnRH neuron activity and gonadotrophin secretion, and it is able to rescue reproductive activity in short day sexually inactive hamsters. Little is known about the localisation of the RFRP-3 receptor, GPR147, in the rodent brain. Accumulating evidence suggests that RFRP-3 could be acting via two intermediates, the GnRH neurons in the preoptic area and the Kiss1 neurons in the arcuate nucleus, but future studies should aim at describing the localisation of Gpr147 in the Syrian hamster brain. Altogether our data indicate that the rfrp neuronal population within the mediobasal hypothalamus might be a serious candidate in mediating the photoperiodic effects of melatonin on the regulation of the reproductive axis.

  4. Over-Expression of Copper/Zinc Superoxide Dismutase in the Median Preoptic Nucleus Attenuates Chronic Angiotensin II-Induced Hypertension in the Rat

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    John P. Collister

    2014-12-01

    Full Text Available The brain senses circulating levels of angiotensin II (AngII via circumventricular organs, such as the subfornical organ (SFO, and is thought to adjust sympathetic nervous system output accordingly via this neuro-hormonal communication. However, the cellular signaling mechanisms involved in these communications remain to be fully understood. Previous lesion studies of either the SFO, or the downstream median preoptic nucleus (MnPO have shown a diminution of the hypertensive effects of chronic AngII, without providing a clear explanation as to the intracellular signaling pathway(s involved. Additional studies have reported that over-expressing copper/zinc superoxide dismutase (CuZnSOD, an intracellular superoxide (O2·− scavenging enzyme, in the SFO attenuates chronic AngII-induced hypertension. Herein, we tested the hypothesis that overproduction of O2·− in the MnPO is an underlying mechanism in the long-term hypertensive effects of chronic AngII. Adenoviral vectors encoding human CuZnSOD (AdCuZnSOD or control vector (AdEmpty were injected directly into the MnPO of rats implanted with aortic telemetric transmitters for recording of arterial pressure. After a 3 day control period of saline infusion, rats were intravenously infused with AngII (10 ng/kg/min for ten days. Rats over-expressing CuZnSOD (n = 7 in the MnPO had a blood pressure increase of only 6 ± 2 mmHg after ten days of AngII infusion while blood pressure increased 21 ± 4 mmHg in AdEmpty-infected rats (n = 9. These results support the hypothesis that production of O2·− in the MnPO contributes to the development of chronic AngII-dependent hypertension.

  5. Muscarinic Receptors Types 1 and 2 in the Preoptic-Anterior Hypothalamic Areas Regulate Ovulation Unequally in the Rat Oestrous Cycle

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    Yadira L. López-Ramírez

    2017-01-01

    Full Text Available Muscarinic receptors types 1 (m1AChR and 2 (m2AChR in the preoptic and anterior hypothalamus areas (POA-AHA were counted, and the effects of blocking these receptors on spontaneous ovulation were analysed throughout the rat oestrous cycle. Rats in each phase of the oestrous cycle were assigned to the following experiments: (1 an immunohistochemical study of the number of cells expressing m1AChR or m2AChR in the POA-AHA and (2 analysis of the effects of the unilateral blockade of the m1AChR (pirenzepine, PZP or m2AChR (methoctramine, MTC on either side of the POA-AHA on the ovulation rate. The number of m2AChR-immunoreactive cells was significantly higher at 09:00 h on each day of the oestrous cycle in the POA-AHA region, while no changes in the expression profile of m1AChR protein were observed. The ovulation rate in rats treated with PZP on the oestrous day was lower than that in the vehicle group. Animals treated on dioestrous-1 with PZP or MTC had a higher ovulation rate than those in the vehicle group. In contrast, on dioestrous-2, the MTC treatment decreased the ovulation rate. These results suggest that m1AChR or m2AChR in the POA-AHA could participate in the regulation of spontaneous ovulation in rats.

  6. Colocalization of Mating-Induced Fos and D2-Like Dopamine Receptors in the Medial Preoptic Area: Influence of Sexual Experience

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    Victoria L Nutsch

    2016-04-01

    Full Text Available Dopamine in the medial preoptic area (mPOA stimulates sexual activity in males. This is evidenced by microdialysis and microinjection experiments revealing that dopamine receptor antagonists in the mPOA inhibit sexual activity, whereas agonists facilitate behavior. Microdialysis experiments similarly show a facilitative role for dopamine, as levels of dopamine in the mPOA increase with mating. While the majority of evidence suggests an important role for dopamine receptors in the mPOA in the regulation of male sexual behaviors, whether sexual activity or sexual experience influence dopamine receptor function in the mPOA has not been previously shown. Here, we used immunohistochemical assays to determine whether varying levels of sexual activity or experience influence the number of cells containing Fos or D2 receptor immunoreactivity. Results show that sexual experience facilitated subsequent behavior, namely experience decreased latencies. Moreover, the number of cells with immunoreactivity for Fos or D2 correlated with levels of sexual experience and sexual activity. Sexual activity increased Fos immunoreactivity. Sexually experienced animals also had significantly more D2-positive cells. Sexually inexperienced animals copulating for the first time had a larger percentage of D2-positive cells containing Fos, when compared to sexually experienced animals. Finally, regardless of experience, animals that had sex prior to sacrifice had significantly more D2-positive cells that contained Fos, versus animals that did not copulate. These findings are noteworthy because sexually experienced animals display increased sexual efficiency. The differences in activation of D2 and changes in receptor density may play a role in this efficiency and other behavioral changes across sexual experience.

  7. Reward associated with singing behavior correlates with opioid-related gene expression in the medial preoptic nucleus in male European starlings.

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    Lauren V Riters

    Full Text Available Birdsong consists of species-specific learned vocal sequences that are used primarily to attract mates and to repel competitors during the breeding season. However, many birds continue to sing at times when vocal production has no immediate or obvious impact on conspecific behavior. The mechanisms that ensure that animals produce important behaviors in contexts in which the function of these behaviors is not immediate or obvious are not known. One possibility is that animals engage in such behaviors because they are associated with pleasure. Here we examined the hypothesis that male European starlings sing outside of the breeding season in part because the act of singing in this context is facilitated and/or maintained by opioid-mediated reward. We measured song-associated reward using a conditioned place preference (CPP test in male starlings producing fall, non-breeding season-typical song. We used quantitative real time PCR to measure expression of the enkephalin opioid precursor preproenkephalin (PENK and mu opioid receptors (MOR in the medial preoptic nucleus (POM; a region in which opioids are implicated in both reward and starling fall song and additionally the song control region HVC as a control. Starlings developed a strong preference for a place that had been paired previously with the act of producing fall-typical song, indicating that fall song production was associated with a positive affective state. Both PENK and MOR mRNA expression in the POM, but not HVC, correlated positively with both individual reward state (as reflected in CPP and undirected singing behavior. These results suggest that singing induces opioid receptor and enkephalin expression in the POM and consequent reward, and/or that opioid release in the POM induced by individual or environmental factors (e.g., the presence of food, safety of a flock or the absence of predators induces a positive affective state which then facilitates singing behavior.

  8. Effects of ghrelin on Kisspeptin mRNA expression in the hypothalamic medial preoptic area and pulsatile luteinising hormone secretion in the female rat.

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    Forbes, Sarah; Li, Xiao Feng; Kinsey-Jones, James; O'Byrne, Kevin

    2009-08-28

    The orexigenic gut peptide ghrelin negatively modulates the hypothalamic-pituitary-gonadal (HPG) axis. Hyperghrelinaemia results during negative energy balance, a state often associated with delayed puberty and disrupted fertility, whilst exogenous ghrelin suppresses pulsatile luteinising hormone (LH) secretion. The recent identification of kisspeptin (Kiss1) and its G protein-coupled receptor (GPR)54 (Kiss1r) as an essential component of the HPG axis controlling gonadotrophin secretion raises the possibility that kisspeptin-Kiss1r signalling may play a critical role in the transduction of ghrelin-induced suppression of LH. Ovariectomised oestrogen-replaced rats were implanted with intravenous catheters and blood samples collected for detection of LH pulses prior to and after intravenous administration of ghrelin (3nM/250 microl) or saline (250 microl) during ad libitum feeding or after overnight fasting. Quantitative RT-PCR was used to determine Kiss1 and Kiss1r mRNA levels in brain punches of the key hypothalamic sites regulating gonadotrophin secretion, the medial preoptic area (mPOA) and arcuate nucleus (ARC), collected 6h following administration of ghrelin. Ghrelin significantly lowered LH pulse frequency in fed rats, an effect significantly enhanced by food deprivation. Fasting, ghrelin or their combination down-regulated Kiss1, without affecting Kiss1r, expression in the mPOA, and affected the expression of neither in the ARC. Considering the pivotal role for kisspeptin signalling in the activation of the HPG axis, the ability of ghrelin to down-regulate Kiss1 expression in mPOA may be a contributing factor in ghrelin-related suppression of pulsatile LH secretion.

  9. Statistical Mechanics Characterization of Neuronal Mosaics

    CERN Document Server

    Costa, Luciano da Fontoura; de Lima, Silene Maria Araujo

    2005-01-01

    The spatial distribution of neuronal cells is an important requirement for achieving proper neuronal function in several parts of the nervous system of most animals. For instance, specific distribution of photoreceptors and related neuronal cells, particularly the ganglion cells, in mammal's retina is required in order to properly sample the projected scene. This work presents how two concepts from the areas of statistical mechanics and complex systems, namely the \\emph{lacunarity} and the \\emph{multiscale entropy} (i.e. the entropy calculated over progressively diffused representations of the cell mosaic), have allowed effective characterization of the spatial distribution of retinal cells.

  10. General artificial neuron

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    Degeratu, Vasile; Schiopu, Paul; Degeratu, Stefania

    2007-05-01

    In this paper the authors present a model of artificial neuron named the general artificial neuron. Depending on application this neuron can change self number of inputs, the type of inputs (from excitatory in inhibitory or vice versa), the synaptic weights, the threshold, the type of intensifying functions. It is achieved into optoelectronic technology. Also, into optoelectronic technology a model of general McCulloch-Pitts neuron is showed. The advantages of these neurons are very high because we have to solve different applications with the same neural network, achieved from these neurons, named general neural network.

  11. Projections from the 'cingular' vocalization area in the squirrel monkey.

    Science.gov (United States)

    Müller-Preuss, P; Jürgens, U

    1976-02-13

    In 5 squirrel monkeys the anatomical projections from the 'cingular' vocalization area were studied by the autoradiographic tracing technique. The 'cingular' vocalization area lies around the sulcus cinguli at the level of the genu of the corpus callosum; its electrical stimulation yields purring and cackling calls. The following efferent connections were found: corticocortical fibers could be traced into the orbital cortex (areas 10 and 11), dorsomedial frontal cortex (areas 9, 8 and 6), limbic cortex (areas 25, 24 and 23), Broca's area (area 44), frontal operculum (area 50), insula (areas 13 and 14), and auditory association cortex (area 22). Subcortical terminal fields within the telencephalon were found in the nucleus caudatus, putamen, claustrum, globus pallidus, olfactory tubercle, preoptic region and nucleus centralis and basolateralis amygdalae. Fibers reached most of these structures along different trajectories. In the diencephalon terminal fields lay in the dorsal hypothalamus, the subthalamus, lateral habenular nucleus, and the following thalamic nuclei: nucleus reticularis, ventralis anterior, centralis medialis, centralis superior lateralis, centralis inferior, submedius, medialis dorsalis and centrum medianum. In the midbrain, the periaqueductal gray was the only projection area, extending into the parabrachial nuclei at the pontomesencephalic transition. The most caudal terminal field was found in the medial pontine gray. No terminals were detected in the nucleus ambiguus, nucleus n. hypoglossi or in any other cranial motor nucleus involved in phonation processes. A comparison of this projection system with the whole of structures producing vocalization when electrically stimulated yielded only partial overlap. Not all vocalization areas lie within the 'cingular' projection system, and inversely, not the whole projection system yielded vocalization. Overlap took place in the anterior limbic cortex, preoptic region, central amygdaloid nucleus

  12. Embryonic transcription factor expression in mice predicts medial amygdala neuronal identity and sex-specific responses to innate behavioral cues

    Science.gov (United States)

    Lischinsky, Julieta E; Sokolowski, Katie; Li, Peijun; Esumi, Shigeyuki; Kamal, Yasmin; Goodrich, Meredith; Oboti, Livio; Hammond, Timothy R; Krishnamoorthy, Meera; Feldman, Daniel; Huntsman, Molly; Liu, Judy; Corbin, Joshua G

    2017-01-01

    The medial subnucleus of the amygdala (MeA) plays a central role in processing sensory cues required for innate behaviors. However, whether there is a link between developmental programs and the emergence of inborn behaviors remains unknown. Our previous studies revealed that the telencephalic preoptic area (POA) embryonic niche is a novel source of MeA destined progenitors. Here, we show that the POA is comprised of distinct progenitor pools complementarily marked by the transcription factors Dbx1 and Foxp2. As determined by molecular and electrophysiological criteria this embryonic parcellation predicts postnatal MeA inhibitory neuronal subtype identity. We further find that Dbx1-derived and Foxp2+ cells in the MeA are differentially activated in response to innate behavioral cues in a sex-specific manner. Thus, developmental transcription factor expression is predictive of MeA neuronal identity and sex-specific neuronal responses, providing a potential developmental logic for how innate behaviors could be processed by different MeA neuronal subtypes. DOI: http://dx.doi.org/10.7554/eLife.21012.001 PMID:28244870

  13. Prospects for replacement of auditory neurons by stem cells.

    Science.gov (United States)

    Shi, Fuxin; Edge, Albert S B

    2013-03-01

    Sensorineural hearing loss is caused by degeneration of hair cells or auditory neurons. Spiral ganglion cells, the primary afferent neurons of the auditory system, are patterned during development and send out projections to hair cells and to the brainstem under the control of largely unknown guidance molecules. The neurons do not regenerate after loss and even damage to their projections tends to be permanent. The genesis of spiral ganglion neurons and their synapses forms a basis for regenerative approaches. In this review we critically present the current experimental findings on auditory neuron replacement. We discuss the latest advances with a focus on (a) exogenous stem cell transplantation into the cochlea for neural replacement, (b) expression of local guidance signals in the cochlea after loss of auditory neurons, (c) the possibility of neural replacement from an endogenous cell source, and (d) functional changes from cell engraftment. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. Juvenil neuronal ceroid lipofuscinosis

    DEFF Research Database (Denmark)

    Ostergaard, J R; Hertz, Jens Michael

    1998-01-01

    Neuronal ceroid-lipofuscinosis is a group of neurodegenerative diseases which are characterized by an abnormal accumulation of lipopigment in neuronal and extraneuronal cells. The diseases can be differentiated into several subgroups according to age of onset, the clinical picture...

  15. Multiple telencephalic and extratelencephalic embryonic domains contribute neurons to the medial extended amygdala.

    Science.gov (United States)

    Bupesh, Munisamy; Legaz, Isabel; Abellán, Antonio; Medina, Loreta

    2011-06-01

    Dysfunctions in emotional control and social behavior are behind human neuropsychiatric disorders, some of which are associated with an alteration of amygdalar development. The medial extended amygdala is a key telencephalic center for control of social behavior, but very little is known about its development. We used in vitro migration assays for analyzing the origin of the neurons of the medial extended amygdala in mouse embryos (E13.5-E16.5). We compared the migration assays with immunofluorescence/immunohistochemistry for calbindin and radial glial fibers and with mRNA expression of several genetic markers of distinct forebrain subdivisions. We provide experimental evidence for multiple embryonic origins of the principal neurons of the medial extended amygdala. In particular, we provide novel evidence indicating that a major part of the neurons derives from a caudoventral pallidal subdivision (previously called or included as part of the anterior peduncular area), forming a cell corridor with similar molecular features (expression of Lhx6 and calbindin), connectivity, and function, which relates to reproductive behavior. We also provide novel experimental evidence indicating that the ventral pallium produces some neurons for the medial amygdala, which correlates with data from Lhx9 expression. Our results also confirm that some neurons of the medial extended amygdala originate in the preoptic area (our results indicate that these cells specifically originate in its commissural subdivision) and the supraoptoparaventricular domain of the hypothalamus. Our study helps to set up the foundations for a better understanding of medial amygdalar control of behavior in normal and abnormal conditions.

  16. NEURON and Python

    OpenAIRE

    Michael Hines; Davison, Andrew P.; Eilif Muller

    2009-01-01

    The NEURON simulation program now allows Python to be used, alone or in combination with NEURON's traditional Hoc interpreter. Adding Python to NEURON has the immediate benefit of making available a very extensive suite of analysis tools written for engineering and science. It also catalyzes NEURON software development by offering users a modern programming tool that is recognized for its flexibility and power to create and maintain complex programs. At the same time, nothing is lost because ...

  17. A Neuron-Based Model of Sleep-Wake Cycles

    Science.gov (United States)

    Postnova, Svetlana; Peters, Achim; Braun, Hans

    2008-03-01

    In recent years it was discovered that a neuropeptide orexin/hypocretin plays a main role in sleep processes. This peptide is produced by the neurons in the lateral hypothalamus, which project to almost all brain areas. We present a computational model of sleep-wake cycles, which is based on the Hodgkin-Huxley type neurons and considers reciprocal glutaminergic projections between the lateral hypothalamus and the prefrontal cortex. Orexin is released as a neuromodulator and is required to keep the neurons firing, which corresponds to the wake state. When orexin is depleted the neurons are getting silent as observed in the sleep state. They can be reactivated by the circadian signal from the suprachiasmatic nucleus and/or external stimuli (alarm clock). Orexin projections to the thalamocortical neurons also can account for their transition from tonic firing activity during wakefulness to synchronized burst discharges during sleep.

  18. Glutamate and GABA in Vestibulo-Sympathetic Pathway Neurons.

    Science.gov (United States)

    Holstein, Gay R; Friedrich, Victor L; Martinelli, Giorgio P

    2016-01-01

    The vestibulo-sympathetic reflex (VSR) actively modulates blood pressure during changes in posture. This reflex allows humans to stand up and quadrupeds to rear or climb without a precipitous decline in cerebral perfusion. The VSR pathway conveys signals from the vestibular end organs to the caudal vestibular nuclei. These cells, in turn, project to pre-sympathetic neurons in the rostral and caudal ventrolateral medulla (RVLM and CVLM, respectively). The present study assessed glutamate- and GABA-related immunofluorescence associated with central vestibular neurons of the VSR pathway in rats. Retrograde FluoroGold tract tracing was used to label vestibular neurons with projections to RVLM or CVLM, and sinusoidal galvanic vestibular stimulation (GVS) was employed to activate these pathways. Central vestibular neurons of the VSR were identified by co-localization of FluoroGold and cFos protein, which accumulates in some vestibular neurons following galvanic stimulation. Triple-label immunofluorescence was used to co-localize glutamate- or GABA- labeling in the identified VSR pathway neurons. Most activated projection neurons displayed intense glutamate immunofluorescence, suggestive of glutamatergic neurotransmission. To support this, anterograde tracer was injected into the caudal vestibular nuclei. Vestibular axons and terminals in RVLM and CVLM co-localized the anterograde tracer and vesicular glutamate transporter-2 signals. Other retrogradely-labeled cFos-positive neurons displayed intense GABA immunofluorescence. VSR pathway neurons of both phenotypes were present in the caudal medial and spinal vestibular nuclei, and projected to both RVLM and CVLM. As a group, however, triple-labeled vestibular cells with intense glutamate immunofluorescence were located more rostrally in the vestibular nuclei than the GABAergic neurons. Only the GABAergic VSR pathway neurons showed a target preference, projecting predominantly to CVLM. These data provide the first

  19. Glutamate and GABA in vestibulo-sympathetic pathway neurons

    Directory of Open Access Journals (Sweden)

    Gay R Holstein

    2016-02-01

    Full Text Available The vestibulo-sympathetic reflex actively modulates blood pressure during changes in posture. This reflex allows humans to stand up and quadrupeds to rear or climb without a precipitous decline in cerebral perfusion. The vestibulo-sympathetic reflex pathway conveys signals from the vestibular end organs to the caudal vestibular nuclei. These cells, in turn, project to pre-sympathetic neurons in the rostral and caudal ventrolateral medulla (RVLM and CVLM, respectively. The present study assessed glutamate- and GABA-related immunofluorescence associated with central vestibular neurons of the vestibulo-sympathetic reflex pathway in rats. Retrograde FluoroGold tract tracing was used to label vestibular neurons with projections to RVLM or CVLM, and sinusoidal galvanic vestibular stimulation was employed to activate these pathways. Central vestibular neurons of the vestibulo-sympathetic reflex were identified by co-localization of FluoroGold and cFos protein, which accumulates in some vestibular neurons following galvanic stimulation. Triple-label immunofluorescence was used to co-localize glutamate- or GABA- labeling in the identified vestibulo-sympathetic reflex pathway neurons. Most activated projection neurons displayed intense glutamate immunofluorescence, suggestive of glutamatergic neurotransmission. To support this, anterograde tracer was injected into the caudal vestibular nuclei. Vestibular axons and terminals in RVLM and CVLM co-localized the anterograde tracer and vesicular glutamate transporter-2 signals. Other retrogradely-labeled cFos-positive neurons displayed intense GABA immunofluorescence. Vestibulo-sympathetic reflex pathway neurons of both phenotypes were present in the caudal medial and spinal vestibular nuclei, and projected to both RVLM and CVLM. As a group, however, triple-labeled vestibular cells with intense glutamate immunofluorescence were located more rostrally in the vestibular nuclei than the GABAergic neurons. Only the

  20. Neuronal Rac1 is required for learning-evoked neurogenesis

    DEFF Research Database (Denmark)

    Haditsch, Ursula; Anderson, Matthew P; Freewoman, Julia

    2013-01-01

    neurons for normal synaptic plasticity in vivo, and here we show that selective loss of neuronal Rac1 also impairs the learning-evoked increase in neurogenesis in the adult mouse hippocampus. Earlier work has indicated that experience elevates the abundance of adult-born neurons in the hippocampus...... primarily by enhancing the survival of neurons produced just before the learning event. Loss of Rac1 in mature projection neurons did reduce learning-evoked neurogenesis but, contrary to our expectations, these effects were not mediated by altering the survival of young neurons in the hippocampus. Instead......, loss of neuronal Rac1 activation selectively impaired a learning-evoked increase in the proliferation and accumulation of neural precursors generated during the learning event itself. This indicates that experience-induced alterations in neurogenesis can be mechanistically resolved into two effects: (1...

  1. Control of abdominal muscles by brain stem respiratory neurons in the cat

    Science.gov (United States)

    Miller, Alan D.; Ezure, Kazuhisa; Suzuki, Ichiro

    1985-01-01

    The nature of the control of abdominal muscles by the brain stem respiratory neurons was investigated in decerebrate unanesthetized cats. First, it was determined which of the brain stem respiratory neurons project to the lumbar cord (from which the abdominal muscles receive part of their innervation), by stimulating the neurons monopolarly. In a second part of the study, it was determined if lumbar-projecting respiratory neurons make monosynaptic connections with abdominal motoneurons; in these experiments, discriminate spontaneous spikes of antidromically acivated expiratory (E) neurons were used to trigger activity from both L1 and L2 nerves. A large projection was observed from E neurons in the caudal ventral respiratory group to the contralateral upper lumber cord. However, cross-correlation experiments found only two (out of 47 neuron pairs tested) strong monosynaptic connections between brain stem neurons and abdominal motoneurons.

  2. Brain-derived neurotrophic factor is required for axonal growth of selective groups of neurons in the arcuate nucleus

    Directory of Open Access Journals (Sweden)

    Guey-Ying Liao

    2015-06-01

    Conclusion: This study shows that the majority of TrkB neurons in the ARH are distinct from known neuronal populations and that BDNF plays a critical role in directing projections from these neurons to the DMH and PVH. We propose that hyperphagic obesity due to BDNF deficiency is in part attributable to impaired axonal growth of TrkB-expressing ARH neurons.

  3. Flybrain neuron database: a comprehensive database system of the Drosophila brain neurons.

    Science.gov (United States)

    Shinomiya, Kazunori; Matsuda, Keiji; Oishi, Takao; Otsuna, Hideo; Ito, Kei

    2011-04-01

    The long history of neuroscience has accumulated information about numerous types of neurons in the brain of various organisms. Because such neurons have been reported in diverse publications without controlled format, it is not easy to keep track of all the known neurons in a particular nervous system. To address this issue we constructed an online database called Flybrain Neuron Database (Flybrain NDB), which serves as a platform to collect and provide information about all the types of neurons published so far in the brain of Drosophila melanogaster. Projection patterns of the identified neurons in diverse areas of the brain were recorded in a unified format, with text-based descriptions as well as images and movies wherever possible. In some cases projection sites and the distribution of the post- and presynaptic sites were determined with greater detail than described in the original publication. Information about the labeling patterns of various antibodies and expression driver strains to visualize identified neurons are provided as a separate sub-database. We also implemented a novel visualization tool with which users can interactively examine three-dimensional reconstruction of the confocal serial section images with desired viewing angles and cross sections. Comprehensive collection and versatile search function of the anatomical information reported in diverse publications make it possible to analyze possible connectivity between different brain regions. We analyzed the preferential connectivity among optic lobe layers and the plausible olfactory sensory map in the lateral horn to show the usefulness of such a database.

  4. Neurochemistry of neurons in the ventrolateral medulla activated by hypotension: Are the same neurons activated by glucoprivation?

    Science.gov (United States)

    Parker, Lindsay M; Le, Sheng; Wearne, Travis A; Hardwick, Kate; Kumar, Natasha N; Robinson, Katherine J; McMullan, Simon; Goodchild, Ann K

    2017-06-15

    Previous studies have demonstrated that a range of stimuli activate neurons, including catecholaminergic neurons, in the ventrolateral medulla. Not all catecholaminergic neurons are activated and other neurochemical content is largely unknown hence whether stimulus specific populations exist is unclear. Here we determine the neurochemistry (using in situ hybridization) of catecholaminergic and noncatecholaminergic neurons which express c-Fos immunoreactivity throughout the rostrocaudal extent of the ventrolateral medulla, in Sprague Dawley rats treated with hydralazine or saline. Distinct neuronal populations containing PPCART, PPPACAP, and PPNPY mRNAs, which were largely catecholaminergic, were activated by hydralazine but not saline. Both catecholaminergic and noncatecholaminergic neurons containing preprotachykinin and prepro-enkephalin (PPE) mRNAs were also activated, with the noncatecholaminergic population located in the rostral C1 region. Few GlyT2 neurons were activated. A subset of these data was then used to compare the neuronal populations activated by 2-deoxyglucose evoked glucoprivation (Brain Structure and Function (2015) 220:117). Hydralazine activated more neurons than 2-deoxyglucose but similar numbers of catecholaminergic neurons. Commonly activated populations expressing PPNPY and PPE mRNAs were defined. These likely include PPNPY expressing catecholaminergic neurons projecting to vasopressinergic and corticotrophin releasing factor neurons in the paraventricular nucleus, which when activated result in elevated plasma vasopressin and corticosterone. Stimulus specific neurons included noncatecholaminergic neurons and a few PPE positive catecholaminergic neuron but neurochemical codes were largely unidentified. Reasons for the lack of identification of stimulus specific neurons, readily detectable using electrophysiology in anaesthetized preparations and for which neural circuits can be defined, are discussed. © 2017 Wiley Periodicals, Inc.

  5. Study of a new neuron

    CERN Document Server

    Adler, Stephen Louis; Weckel, J D

    1994-01-01

    We study a modular neuron alternative to the McCulloch-Pitts neuron that arises naturally in analog devices in which the neuron inputs are represented as coherent oscillatory wave signals. Although the modular neuron can compute XOR at the one neuron level, it is still characterized by the same Vapnik-Chervonenkis dimension as the standard neuron. We give the formulas needed for constructing networks using the new neuron and training them using back-propagation. A numerical study of the modular neuron on two data sets is presented, which demonstrates that the new neuron performs at least as well as the standard neuron.

  6. Cajal bodies in neurons.

    Science.gov (United States)

    Lafarga, Miguel; Tapia, Olga; Romero, Ana M; Berciano, Maria T

    2016-09-14

    Cajal is commonly regarded as the father of modern neuroscience in recognition of his fundamental work on the structure of the nervous system. But Cajal also made seminal contributions to the knowledge of nuclear structure in the early 1900s, including the discovery of the "accessory body" later renamed "Cajal body" (CB). This important nuclear structure has emerged as a center for the assembly of ribonucleoproteins (RNPs) required for splicing, ribosome biogenesis and telomere maintenance. The modern era of CB research started in the 1990s with the discovery of coilin, now known as a scaffold protein of CBs, and specific probes for small nuclear RNAs (snRNAs). In this review, we summarize what we have learned in the recent decades concerning CBs in post-mitotic neurons, thereby ruling out dynamic changes in CB functions during the cell cycle. We show that CBs are particularly prominent in neurons, where they frequently associate with the nucleolus. Neuronal CBs are transcription-dependent nuclear organelles. Indeed, their number dynamically accommodates to support the high neuronal demand for splicing and ribosome biogenesis required for sustaining metabolic and bioelectrical activity. Mature neurons have canonical CBs enriched in coilin, survival motor neuron protein and snRNPs. Disruption and loss of neuronal CBs associate with severe neuronal dysfunctions in several neurological disorders such as motor neuron diseases. In particular, CB depletion in motor neurons seems to reflect a perturbation of transcription and splicing in spinal muscular atrophy, the most common genetic cause of infant mortality.

  7. Intrinsic and integrative properties of substantia nigra pars reticulata neurons

    Science.gov (United States)

    Zhou, Fu-Ming; Lee, Christian R.

    2011-01-01

    The GABA projection neurons of the substantia nigra pars reticulata (SNr) are output neurons for the basal ganglia and thus critical for movement control. Their most striking neurophysiological feature is sustained, spontaneous high frequency spike firing. A fundamental question is: what are the key ion channels supporting the remarkable firing capability in these neurons? Recent studies indicate that these neurons express tonically active TRPC3 channels that conduct a Na-dependent inward current even at hyperpolarized membrane potentials. When the membrane potential reaches −60 mV, a voltage-gated persistent sodium current (INaP) starts to activate, further depolarizing the membrane potential. At or slightly below −50 mV, the large transient voltage-activated sodium current (INaT) starts to activate and eventually triggers the rapid rising phase of action potentials. SNr GABA neurons have a higher density of (INaT), contributing to the faster rise and larger amplitude of action potentials, compared with the slow-spiking dopamine neurons. INaT also recovers from inactivation more quickly in SNr GABA neurons than in nigral dopamine neurons. In SNr GABA neurons, the rising phase of the action potential triggers the activation of high-threshold, inactivation-resistant Kv3-like channels that can rapidly repolarize the membrane. These intrinsic ion channels provide SNr GABA neurons with the ability to fire spontaneous and sustained high frequency spikes. Additionally, robust GABA inputs from direct pathway medium spiny neurons in the striatum and GABA neurons in the globus pallidus may inhibit and silence SNr GABA neurons, whereas glutamate synaptic input from the subthalamic nucleus may induce burst firing in SNr GABA neurons. Thus, afferent GABA and glutamate synaptic inputs sculpt the tonic high frequency firing of SNr GABA neurons and the consequent inhibition of their targets into an integrated motor control signal that is further fine-tuned by neuromodulators

  8. The neuronal organization of horizontal semicircular canalactivated inhibitory vestibulocollic neurons in the cat.

    Science.gov (United States)

    Isu, N; Sakuma, A; Hiranuma, K; Uchino, H; Sasaki, S; Imagawa, M; Uchino, Y

    1991-01-01

    1. The somatic location and axonal projections of inhibitory vestibular nucleus neurons activated by the horizontal semicircular canal nerve (HCN) were studied in anesthetized cats. Cats were anesthetized with ketamine hydrochloride and pentobarbital sodium. 2. Intracellular recordings were obtained from 11 neck extensor motoneurons which were identified by antidromic activation from the dosal rami (DR) in the C1 segment. Stimulation of the ipsilateral (i-) HCN and the ipsilateral abducens (AB) nucleus evoked IPSPs in the motoneurons. These IPSPs were fully or partially occluded when they were evoked simultaneously. 3. Intracellular recordings were obtained from 8 AB motoneurons. Stimulation of the i-HCN and the i-C1DR motoneuron pool evoked IPSPs in the AB motoneurons. These IPSPs were also partially occluded when they were evoked simultaneously, which implied that some HCN-activated neurons inhibit both i-AB motoneurons and ipsilateral neck motoneurons. 4. Unit activity was extracellularly recorded from 30 vestibular neurons that were activated monosynaptically by i-HCN stimulation. Their axonal projections were determined by stimulating the i-AB nucleus and the i-C1DR motoneuron pool. Eight neurons were activated by both stimuli, and were termed vestibulooculo-collic (VOC) neurons. Their axonal branching was examined by means of local stimulation in and around the i-AB nucleus and the i-C1DR motoneuron pool. Eighteen neurons were antidromically activated from the i-C1DR motoneuron pool but not from the i-AB nucleus. These were termed vestibulo-collic (VC) neurons. Four neurons were activated from the i-AB nucleus but not from the ventral funiculus in the C1 segment, and were termed vestibulo-ocular (VO) neurons.(ABSTRACT TRUNCATED AT 250 WORDS)

  9. Noise and Neuronal Heterogeneity

    CERN Document Server

    Barber, Michael J

    2010-01-01

    We consider signal transaction in a simple neuronal model featuring intrinsic noise. The presence of noise limits the precision of neural responses and impacts the quality of neural signal transduction. We assess the signal transduction quality in relation to the level of noise, and show it to be maximized by a non-zero level of noise, analogous to the stochastic resonance effect. The quality enhancement occurs for a finite range of stimuli to a single neuron; we show how to construct networks of neurons that extend the range. The range increases more rapidly with network size when we make use of heterogeneous populations of neurons with a variety of thresholds, rather than homogeneous populations of neurons all with the same threshold. The limited precision of neural responses thus can have a direct effect on the optimal network structure, with diverse functional properties of the constituent neurons supporting an economical information processing strategy that reduces the metabolic costs of handling a broad...

  10. GABAergic neurons in K(o)lliker-Fuse nucleus and B(o)tzinger complex with axons projecting to phrenic nucleus%KF核及B(o)tzinger复合体内GABA能神经元向膈神经核的投射

    Institute of Scientific and Technical Information of China (English)

    宋刚; 李勤; 邵凤之

    2000-01-01

    实验在6只成年猫上进行.将WGA-HRP微量注入C5膈神经核内, 通过逆行追踪及GABA免疫组织化学FITC荧光双重标记方法, 研究了脑干内GABA能神经元向膈神经核的投射.结果在脑桥KF核和面神经后核周围区(即B(o)tzinger复合体)观察到GABA-HRP双标神经元.另外, 在中缝大核、旁巨细胞外侧核及前庭神经核也观察到双标神经元.本实验结果表明: 发自上述脑干神经核团, 特别是KF核及B(o)tzinger复合体的GABA能神经元的轴突可投射到膈神经核.%Experiments were made on 6 adult cats. Brainstem neurons that project to the phrenic nucleus were retrogradely labeled by microinjection of WGA-HRP into phrenic nucleus. The brainstem sections were doubly processed for HRP histochemical staining with the TMB-Co-DAB method, and GABA immunohistochemical staining with anti-GABA primary antibody and FITC conjugated immunofluorescent secondary antibody. HRP-FITC double-labeled neurons were observed in the pontine K(o)lliker-Fuse nucleus and areas around the retrofacial nucleus (B(o)tzinger complex). Double-labeled neurons were also observed in the raphe nucleus, the lateral paragigantocellular nucleus, and the vestibular nucleus. The results show that brainstem GABAergic neurons in these structures, especially those in the K(o)lliker-Fuse nucleus and the B(o)t.C, send axonal projections to the phrenic nucleus.

  11. Three-dimensional distribution of sensory stimulation-evoked neuronal activity of spinal dorsal horn neurons analyzed by in vivo calcium imaging.

    Science.gov (United States)

    Nishida, Kazuhiko; Matsumura, Shinji; Taniguchi, Wataru; Uta, Daisuke; Furue, Hidemasa; Ito, Seiji

    2014-01-01

    The spinal dorsal horn comprises heterogeneous populations of interneurons and projection neurons, which form neuronal circuits crucial for processing of primary sensory information. Although electrophysiological analyses have uncovered sensory stimulation-evoked neuronal activity of various spinal dorsal horn neurons, monitoring these activities from large ensembles of neurons is needed to obtain a comprehensive view of the spinal dorsal horn circuitry. In the present study, we established in vivo calcium imaging of multiple spinal dorsal horn neurons by using a two-photon microscope and extracted three-dimensional neuronal activity maps of these neurons in response to cutaneous sensory stimulation. For calcium imaging, a fluorescence resonance energy transfer (FRET)-based calcium indicator protein, Yellow Cameleon, which is insensitive to motion artifacts of living animals was introduced into spinal dorsal horn neurons by in utero electroporation. In vivo calcium imaging following pinch, brush, and heat stimulation suggests that laminar distribution of sensory stimulation-evoked neuronal activity in the spinal dorsal horn largely corresponds to that of primary afferent inputs. In addition, cutaneous pinch stimulation elicited activities of neurons in the spinal cord at least until 2 spinal segments away from the central projection field of primary sensory neurons responsible for the stimulated skin point. These results provide a clue to understand neuronal processing of sensory information in the spinal dorsal horn.

  12. Three-dimensional distribution of sensory stimulation-evoked neuronal activity of spinal dorsal horn neurons analyzed by in vivo calcium imaging.

    Directory of Open Access Journals (Sweden)

    Kazuhiko Nishida

    Full Text Available The spinal dorsal horn comprises heterogeneous populations of interneurons and projection neurons, which form neuronal circuits crucial for processing of primary sensory information. Although electrophysiological analyses have uncovered sensory stimulation-evoked neuronal activity of various spinal dorsal horn neurons, monitoring these activities from large ensembles of neurons is needed to obtain a comprehensive view of the spinal dorsal horn circuitry. In the present study, we established in vivo calcium imaging of multiple spinal dorsal horn neurons by using a two-photon microscope and extracted three-dimensional neuronal activity maps of these neurons in response to cutaneous sensory stimulation. For calcium imaging, a fluorescence resonance energy transfer (FRET-based calcium indicator protein, Yellow Cameleon, which is insensitive to motion artifacts of living animals was introduced into spinal dorsal horn neurons by in utero electroporation. In vivo calcium imaging following pinch, brush, and heat stimulation suggests that laminar distribution of sensory stimulation-evoked neuronal activity in the spinal dorsal horn largely corresponds to that of primary afferent inputs. In addition, cutaneous pinch stimulation elicited activities of neurons in the spinal cord at least until 2 spinal segments away from the central projection field of primary sensory neurons responsible for the stimulated skin point. These results provide a clue to understand neuronal processing of sensory information in the spinal dorsal horn.

  13. Neurons and tumor suppressors.

    Science.gov (United States)

    Zochodne, Douglas W

    2014-08-20

    Neurons choose growth pathways with half hearted reluctance, behavior that may be appropriate to maintain fixed long lasting connections but not to regenerate them. We now recognize that intrinsic brakes on regrowth are widely expressed in these hesitant neurons and include classical tumor suppressor molecules. Here, we review how two brakes, PTEN (phosphatase and tensin homolog deleted on chromosome 10) and retinoblastoma emerge as new and exciting knockdown targets to enhance neuron plasticity and improve outcome from damage or disease.

  14. Prefrontal parvalbumin interneurons shape neuronal activity to drive fear expression.

    Science.gov (United States)

    Courtin, Julien; Chaudun, Fabrice; Rozeske, Robert R; Karalis, Nikolaos; Gonzalez-Campo, Cecilia; Wurtz, Hélène; Abdi, Azzedine; Baufreton, Jerome; Bienvenu, Thomas C M; Herry, Cyril

    2014-01-02

    Synchronization of spiking activity in neuronal networks is a fundamental process that enables the precise transmission of information to drive behavioural responses. In cortical areas, synchronization of principal-neuron spiking activity is an effective mechanism for information coding that is regulated by GABA (γ-aminobutyric acid)-ergic interneurons through the generation of neuronal oscillations. Although neuronal synchrony has been demonstrated to be crucial for sensory, motor and cognitive processing, it has not been investigated at the level of defined circuits involved in the control of emotional behaviour. Converging evidence indicates that fear behaviour is regulated by the dorsomedial prefrontal cortex (dmPFC). This control over fear behaviour relies on the activation of specific prefrontal projections to the basolateral complex of the amygdala (BLA), a structure that encodes associative fear memories. However, it remains to be established how the precise temporal control of fear behaviour is achieved at the level of prefrontal circuits. Here we use single-unit recordings and optogenetic manipulations in behaving mice to show that fear expression is causally related to the phasic inhibition of prefrontal parvalbumin interneurons (PVINs). Inhibition of PVIN activity disinhibits prefrontal projection neurons and synchronizes their firing by resetting local theta oscillations, leading to fear expression. Our results identify two complementary neuronal mechanisms mediated by PVINs that precisely coordinate and enhance the neuronal activity of prefrontal projection neurons to drive fear expression.

  15. Giant neurons in the macaque pulvinar: a distinct relay subpopulation

    Directory of Open Access Journals (Sweden)

    Kosuke Imura

    2007-07-01

    Full Text Available Calbindin positive (CB+ giant neurons are known to occur within the pulvinar nucleus in subhuman primates. Here, we demonstrate by combined retrograde tracing and immunocytochemistry that at least some of these are pulvinocortical relay neurons, and further report several distinctive features. First, in contrast with non-giant relay neurons, the giant neurons are often solitary and isolated from a main projection focus. The question thus arises of whether their cortical projections may be non-reciprocal or otherwise distinctive. Second, these neurons are positive for GluR4; but third, they are otherwise neurochemically heterogeneous, in that about one-third are positive for both parvalbumin (PV and CB. Presumably, these subpopulations are also functionally heterogeneous. These results provide further evidence for the idea of multiple, interleaved organizations within the pulvinar; and they imply that thalamocortical projections are more disparate than has yet been appreciated. Finally, we found that giant CB+ neurons have a distinctive meshwork of large, PV+ terminations, prominent at the first dendritic branch point. In size and location, these resemble inhibitory terminations from the zona incerta or anterior pretectal nucleus (APT, as recently described in higher order thalamic nuclei in rats. One can speculate that giant neurons in the macaque pulvinar participate in a layer 5-APT-thalamus (giant neuron extrareticular pathway, functionally distinct from the layer 6-reticular nucleus-thalamus network.

  16. 用细胞内注射法观察雏鸡投射向圆核的视顶盖 SGC 神经元形态%Morphology of chick SGC neurons projecting to nucleus rotundus observing by intracellular filling method

    Institute of Scientific and Technical Information of China (English)

    卫雪娇; 孙利净; 韩秋月; 胡满; 崔亚利

    2015-01-01

    为了进一步了解鸟类投射向圆核的视顶盖中央灰质层(SGC )神经元的形态特征,向雏鸡圆核内注射快蓝(Fast blue ,FB)逆向荧光标记视顶盖SGC神经元,84 h后灌流固定,制作300μm厚的中脑振动切片,荧光显微镜下,通过显微操作系统向FB标记的SGC神经元内微电泳法注入荧光染料荧光黄(Lucifer yellow ,LY)。结果显示,此法可观察到完整的投射向圆核的SGC神经元胞体和突起。与其它标记法相比,LY细胞内注射法可以标记单一神经元,不会被周围细胞的纤维干扰,是一种研究中枢神经系统神经元间投射关系及其起源细胞的好方法。%To study the morphological characteristics of tectal cells in stratum griseum centrale (SGC) which project to nucleus rotundus (Rt) in chick ,SGC neurons were retrogradely la‐beled by injecting a small amount of Fast blue (FB) into Rt .After 84 hours ,the chicks were perfused with fixative and the midbrains were sectioned with vibratome into 300 μm slices . Lucifer yellow (LY) was injected into FB labeled SGC neurons by micro electrophoresis under fluorescence microscopy .The result showed that this method can labele integrative SGC soma and neurites that project to Rt .Contrasting to other labeling methods ,the LY intracellular filling method has the advantages of being able to label a single neuron ,avoiding the interferer by the fibers of other neurons .It is a good method to study the projection between neurons and the morphology of the original cells .

  17. Oscillatorylike behavior in feedforward neuronal networks

    Science.gov (United States)

    Payeur, Alexandre; Maler, Leonard; Longtin, André

    2015-07-01

    We demonstrate how rhythmic activity can arise in neural networks from feedforward rather than recurrent circuitry and, in so doing, we provide a mechanism capable of explaining the temporal decorrelation of γ -band oscillations. We compare the spiking activity of a delayed recurrent network of inhibitory neurons with that of a feedforward network with the same neural properties and axonal delays. Paradoxically, these very different connectivities can yield very similar spike-train statistics in response to correlated input. This happens when neurons are noisy and axonal delays are short. A Taylor expansion of the feedback network's susceptibility—or frequency-dependent gain function—can then be stopped at first order to a good approximation, thus matching the feedforward net's susceptibility. The feedback network is known to display oscillations; these oscillations imply that the spiking activity of the population is felt by all neurons within the network, leading to direct spike correlations in a given neuron. On the other hand, in the output layer of the feedforward net, the interaction between the external drive and the delayed feedforward projection of this drive by the input layer causes indirect spike correlations: spikes fired by a given output layer neuron are correlated only through the activity of the input layer neurons. High noise and short delays partially bridge the gap between these two types of correlation, yielding similar spike-train statistics for both networks. This similarity is even stronger when the delay is distributed, as confirmed by linear response theory.

  18. Targeting neuronal populations of the striatum

    Directory of Open Access Journals (Sweden)

    Pierre F Durieux

    2011-07-01

    Full Text Available The striatum is critically involved in motor and motivational functions. The dorsal striatum, caudate-putamen, is primarily implicated in motor control and the learning of habits and skills, whereas the ventral striatum, the nucleus accumbens (NAc, is essential for motivation and drug reinforcement. The GABA medium-sized spiny neurons (MSNs, about 95% of striatal neurons, which are targets of the cerebral cortex and the midbrain dopaminergic neurons, form two pathways. The dopamine D1 receptor–positive (D1R striatonigral MSNs project to the medial globus pallidus and substantia nigra pars reticulata (direct pathway and co-express D1R and substance P, whereas dopamine D2 receptor–positive (D2R striatopallidal MSNs project to the lateral globus pallidus (indirect pathway and co-express D2R, adenosine A2A receptor (A2AR and enkephalin (Enk. The specific role of the two efferent pathways in motor and motivational control remained poorly understood until recently. Indeed, D1R striatonigral and D2R striatopallidal neurons, are intermingled and morphologically indistinguishable, and, hence, cannot be functionally dissociated with techniques such as chemical lesions or surgery.In view of the still debated respective functions of projection D2R-striatopallidal and D1R-striatonigral neurons and striatal interneurons, both in motor control and learning but also in more cognitive processes such as motivation, the present review sum up the development of new models and techniques (BAC transgenesis, optogenetic, viral transgenesis allowing the selective targeting of these striatal neuronal populations in adult animal brain to understand their specific roles.

  19. Whole-brain mapping of direct inputs to midbrain dopamine neurons.

    Science.gov (United States)

    Watabe-Uchida, Mitsuko; Zhu, Lisa; Ogawa, Sachie K; Vamanrao, Archana; Uchida, Naoshige

    2012-06-07

    Recent studies indicate that dopamine neurons in the ventral tegmental area (VTA) and substantia nigra pars compacta (SNc) convey distinct signals. To explore this difference, we comprehensively identified each area's monosynaptic inputs using the rabies virus. We show that dopamine neurons in both areas integrate inputs from a more diverse collection of areas than previously thought, including autonomic, motor, and somatosensory areas. SNc and VTA dopamine neurons receive contrasting excitatory inputs: the former from the somatosensory/motor cortex and subthalamic nucleus, which may explain their short-latency responses to salient events; and the latter from the lateral hypothalamus, which may explain their involvement in value coding. We demonstrate that neurons in the striatum that project directly to dopamine neurons form patches in both the dorsal and ventral striatum, whereas those projecting to GABAergic neurons are distributed in the matrix compartment. Neuron-type-specific connectivity lays a foundation for studying how dopamine neurons compute outputs.

  20. Medial prefrontal D1 dopamine neurons control food intake.

    Science.gov (United States)

    Land, Benjamin B; Narayanan, Nandakumar S; Liu, Rong-Jian; Gianessi, Carol A; Brayton, Catherine E; Grimaldi, David M; Sarhan, Maysa; Guarnieri, Douglas J; Deisseroth, Karl; Aghajanian, George K; DiLeone, Ralph J

    2014-02-01

    Although the prefrontal cortex influences motivated behavior, its role in food intake remains unclear. Here, we demonstrate a role for D1-type dopamine receptor-expressing neurons in the medial prefrontal cortex (mPFC) in the regulation of feeding. Food intake increases activity in D1 neurons of the mPFC in mice, and optogenetic photostimulation of D1 neurons increases feeding. Conversely, inhibition of D1 neurons decreases intake. Stimulation-based mapping of prefrontal D1 neuron projections implicates the medial basolateral amygdala (mBLA) as a downstream target of these afferents. mBLA neurons activated by prefrontal D1 stimulation are CaMKII positive and closely juxtaposed to prefrontal D1 axon terminals. Finally, photostimulating these axons in the mBLA is sufficient to increase feeding, recapitulating the effects of mPFC D1 stimulation. These data describe a new circuit for top-down control of food intake.

  1. C1 neurons: the body's EMTs

    Science.gov (United States)

    Stornetta, Ruth L.; Bochorishvili, Genrieta; DePuy, Seth D.; Burke, Peter G. R.; Abbott, Stephen B. G.

    2013-01-01

    The C1 neurons reside in the rostral and intermediate portions of the ventrolateral medulla (RVLM, IVLM). They use glutamate as a fast transmitter and synthesize catecholamines plus various neuropeptides. These neurons regulate the hypothalamic pituitary axis via direct projections to the paraventricular nucleus and regulate the autonomic nervous system via projections to sympathetic and parasympathetic preganglionic neurons. The presympathetic C1 cells, located in the RVLM, are probably organized in a roughly viscerotopic manner and most of them regulate the circulation. C1 cells are variously activated by hypoglycemia, infection or inflammation, hypoxia, nociception, and hypotension and contribute to most glucoprivic responses. C1 cells also stimulate breathing and activate brain stem noradrenergic neurons including the locus coeruleus. Based on the various effects attributed to the C1 cells, their axonal projections and what is currently known of their synaptic inputs, subsets of C1 cells appear to be differentially recruited by pain, hypoxia, infection/inflammation, hemorrhage, and hypoglycemia to produce a repertoire of stereotyped autonomic, metabolic, and neuroendocrine responses that help the organism survive physical injury and its associated cohort of acute infection, hypoxia, hypotension, and blood loss. C1 cells may also contribute to glucose and cardiovascular homeostasis in the absence of such physical stresses, and C1 cell hyperactivity may contribute to the increase in sympathetic nerve activity associated with diseases such as hypertension. PMID:23697799

  2. Pacemaking Kisspeptin Neurons

    Science.gov (United States)

    Kelly, Martin J.; Zhang, Chunguang; Qiu, Jian; Rønnekleiv, Oline K.

    2013-01-01

    Kisspeptin (Kiss1) neurons are vital for reproduction. GnRH neurons express the kisspeptin receptor, GPR 54, and kisspeptins potently stimulate the release of GnRH by depolarising and inducing sustained action potential firing in GnRH neurons. As such Kiss1 neurons may be the pre-synaptic pacemaker neurons in the hypothalamic circuitry that controls reproduction. There are at least two different populations of Kiss1 neurons: one in the rostral periventricular area (RP3V) that is stimulated by oestrogens and the other in the arcuate nucleus that is inhibited by oestrogens. How each of these Kiss1 neuronal populations participate in the regulation of the reproductive cycle is currently under intense investigation. Based on electrophysiological studies in the guinea pig and mouse, Kiss1 neurons in general are capable of generating burst firing behavior. Essentially all Kiss1 neurons, which have been studied thus far in the arcuate nucleus, express the ion channels necessary for burst firing, which include hyperpolarization-activated, cyclic nucleotide gated cation (HCN) channels and the T-type calcium (Cav3.1) channels. Under voltage clamp conditions, these channels produce distinct currents that under current clamp conditions can generate burst firing behavior. The future challenge is to identify other key channels and synaptic inputs involved in the regulation of the firing properties of Kiss1 neurons and the physiological regulation of the expression of these channels and receptors by oestrogens and other hormones. The ultimate goal is to understand how Kiss1 neurons control the different phases of GnRH neurosecretion and hence reproduction. PMID:23884368

  3. Huntingtin-Mediated Multipolar-Bipolar Transition of Newborn Cortical Neurons Is Critical for Their Postnatal Neuronal Morphology.

    Science.gov (United States)

    Barnat, Monia; Le Friec, Julien; Benstaali, Caroline; Humbert, Sandrine

    2017-01-04

    In the developing cortex, projection neurons undergo multipolar-bipolar transition, radial-directed migration, and maturation. The contribution of these developmental steps to the structure of the adult cortex is not completely understood. Here, we report that huntingtin (HTT), the protein mutated in Huntington's disease, is enriched in polarizing projection neurons. The depletion of HTT in postmitotic projection neurons leads to the mislocalization of layer-specific neuronal populations in the mouse neocortex. HTT is required for the multipolar-bipolar transition of projection neurons and for the maintenance of their bipolar shape during their radial migration. HTT mediates these effects in vivo through the regulation of RAB11-dependent N-Cadherin trafficking. Importantly, HD pathological HTT alters RAB11-dependent neuronal migration. Finally, we show that the cortical defects resulting from the postmitotic loss of HTT specifically during embryonic development affect neuronal morphology at adulthood. Our data reveal a new HTT-RAB11-N-Cadherin pathway regulating multipolar-bipolar transition with direct implications for mature brain. VIDEO ABSTRACT.

  4. Stereological estimates of dopaminergic, GABAergic and glutamatergic neurons in the ventral tegmental area, substantia nigra and retrorubral field in the rat

    OpenAIRE

    Nair-Roberts, R.G.; Chatelain-Badie, S.D.; Benson, E.; White-Cooper, H; BOLAM, J. P.; Ungless, M.A.

    2008-01-01

    Midbrain dopamine neurons in the ventral tegmental area, substantia nigra and retrorubral field play key roles in reward processing, learning and memory, and movement. Within these midbrain regions and admixed with the dopamine neurons, are also substantial populations of GABAergic neurons that regulate dopamine neuron activity and have projection targets similar to those of dopamine neurons. Additionally, there is a small group of putative glutamatergic neurons within the ventral tegmental a...

  5. Separate groups of dopamine neurons innervate caudate head and tail encoding flexible and stable value memories.

    Science.gov (United States)

    Kim, Hyoung F; Ghazizadeh, Ali; Hikosaka, Okihide

    2014-01-01

    Dopamine (DA) neurons are thought to be critical for reward value-based learning by modifying synaptic transmissions in the striatum. Yet, different regions of the striatum seem to guide different kinds of learning. Do DA neurons contribute to the regional differences of the striatum in learning? As a first step to answer this question, we examined whether the head and tail of the caudate nucleus of the monkey (Macaca mulatta) receive inputs from the same or different DA neurons. We chose these caudate regions because we previously showed that caudate head neurons learn values of visual objects quickly and flexibly, whereas caudate tail neurons learn object values slowly but retain them stably. Here we confirmed the functional difference by recording single neuronal activity while the monkey performed the flexible and stable value tasks, and then injected retrograde tracers in the functional domains of caudate head and tail. The projecting dopaminergic neurons were identified using tyrosine hydroxylase immunohistochemistry. We found that two groups of DA neurons in the substantia nigra pars compacta project largely separately to the caudate head and tail. These groups of DA neurons were mostly separated topographically: head-projecting neurons were located in the rostral-ventral-medial region, while tail-projecting neurons were located in the caudal-dorsal-lateral regions of the substantia nigra. Furthermore, they showed different morphological features: tail-projecting neurons were larger and less circular than head-projecting neurons. Our data raise the possibility that different groups of DA neurons selectively guide learning of flexible (short-term) and stable (long-term) memories of object values.

  6. Separate groups of dopamine neurons innervate caudate head and tail encoding flexible and stable value memories

    Directory of Open Access Journals (Sweden)

    Hyoung F Kim

    2014-10-01

    Full Text Available Dopamine neurons are thought to be critical for reward value-based learning by modifying synaptic transmissions in the striatum. Yet, different regions of the striatum seem to guide different kinds of learning. Do dopamine neurons contribute to the regional differences of the striatum in learning? As a first step to answer this question, we examined whether the head and tail of the caudate nucleus of the monkey (Macaca mulatta receive inputs from the same or different dopamine neurons. We chose these caudate regions because we previously showed that caudate head neurons learn values of visual objects quickly and flexibly, whereas caudate tail neurons learn object values slowly but retain them stably. Here we confirmed the functional difference by recording single neuronal activity while the monkey performed the flexible and stable value tasks, and then injected retrograde tracers in the functional domains of caudate head and tail. The projecting dopaminergic neurons were identified using tyrosine hydroxylase immunohistochemistry. We found that two groups of dopamine neurons in the substantia nigra pars compacta project largely separately to the caudate head and tail. These groups of dopamine neurons were mostly separated topographically: head-projecting neurons were located in the rostral-ventral-medial region, while tail-projecting neurons were located in the caudal-dorsal-lateral regions of the substantia nigra. Furthermore, they showed different morphological features: tail-projecting neurons were larger and less circular than head-projecting neurons. Our data raise the possibility that different groups of dopamine neurons selectively guide learning of flexible (short-term and stable (long-term memories of object values.

  7. Androgen receptors and estrogen receptors are colocalized in male rat hypothalamic and limbic neurons that express Fos immunoreactivity induced by mating.

    Science.gov (United States)

    Gréco, B; Edwards, D A; Michael, R P; Clancy, A N

    1998-01-01

    Conversion of testosterone into estradiol is important for male rat sexual behavior, and both steroids probably contribute to mating. The distributions of neurons containing androgen receptors (AR) and estrogen receptors (ER) overlap, and many AR-immunoreactive (AR-ir) neurons express Fos immunoreactivity (Fos-ir) induced by mating. Because mating-induced Fos-ir in the male rat occurs mainly in AR-ir neurons, and because both steroids are important for mating, we hypothesized that (i) AR-ir and ER-ir are colocalized and that (ii) some of these neurons are activated during mating. We examined, in adjacent sections from the medial preoptic area (MPN) through the central tegmental field (CTF), the expression of ER-ir in: (i) AR-ir-containing neurons, and (ii) Fos-ir-expressive neurons. PG21 anti-AR, OA-11-824 anti-c-fos, H222 or 1D5 anti-ER primary antibodies were visualized, respectively, with cyanine-conjugated, fluorescein- or cyanine-conjugated, and fluorescein-conjugated secondary antibodies in male rats which were killed 1 h after ejaculating with a receptive female. In MPN, bed nucleus of the stria terminalis (BNST), and medial amygdala (MEA), 80-90% of ER-ir labeling occurred in AR-ir-positive neurons but only about 30% of AR-ir neurons were ER-ir-positive. No ER-ir was found in the CTF. This suggests the presence of three types of brain neurons sensitive to gonadal steroid hormones: neurons sensitive to androgens only, neurons sensitive to both androgens and estrogens, and neurons sensitive to estrogens only. About 50% of ER-ir labeling occurred in cells expressing mating-induced Fos-ir but only about 30% of Fos-ir neurons were ER-ir-positive. These findings suggest that, in the MPN, at least two different neuronal populations are activated during mating: the first contains AR-ir only and the second contains AR-ir and ER-ir. In the BNST and MEA, at least three hormonally sensitive populations are activated during mating: the two described above plus a third

  8. Culturing rat hippocampal neurons.

    Science.gov (United States)

    Audesirk, G; Audesirk, T; Ferguson, C

    2001-01-01

    Cultured neurons are widely used to investigate the mechanisms of neurotoxicity. Embryonic rat hippocampal neurons may be grown as described under a wide variety of conditions to suit differing experimental procedures, including electrophysiology, morphological analysis of neurite development, and various biochemical and molecular analyses.

  9. Imaging calcium in neurons.

    Science.gov (United States)

    Grienberger, Christine; Konnerth, Arthur

    2012-03-08

    Calcium ions generate versatile intracellular signals that control key functions in all types of neurons. Imaging calcium in neurons is particularly important because calcium signals exert their highly specific functions in well-defined cellular subcompartments. In this Primer, we briefly review the general mechanisms of neuronal calcium signaling. We then introduce the calcium imaging devices, including confocal and two-photon microscopy as well as miniaturized devices that are used in freely moving animals. We provide an overview of the classical chemical fluorescent calcium indicators and of the protein-based genetically encoded calcium indicators. Using application examples, we introduce new developments in the field, such as calcium imaging in awake, behaving animals and the use of calcium imaging for mapping single spine sensory inputs in cortical neurons in vivo. We conclude by providing an outlook on the prospects of calcium imaging for the analysis of neuronal signaling and plasticity in various animal models.

  10. NEURON and Python

    Directory of Open Access Journals (Sweden)

    Michael Hines

    2009-01-01

    Full Text Available The NEURON simulation program now allows Python to be used, alone or in combination with NEURON's traditional Hoc interpreter. Adding Python to NEURON has the immediate benefit of making available a very extensive suite of analysis tools written for engineering and science. It also catalyzes NEURON software development by offering users a modern programming tool that is recognized for its flexibility and power to create and maintain complex programs. At the same time, nothing is lost because all existing models written in Hoc, including GUI tools, continue to work without change and are also available within the Python context. An example of the benefits of Python availability is the use of the XML module in implementing NEURON's Import3D and CellBuild tools to read MorphML and NeuroML model specifications.

  11. NEURON and Python.

    Science.gov (United States)

    Hines, Michael L; Davison, Andrew P; Muller, Eilif

    2009-01-01

    The NEURON simulation program now allows Python to be used, alone or in combination with NEURON's traditional Hoc interpreter. Adding Python to NEURON has the immediate benefit of making available a very extensive suite of analysis tools written for engineering and science. It also catalyzes NEURON software development by offering users a modern programming tool that is recognized for its flexibility and power to create and maintain complex programs. At the same time, nothing is lost because all existing models written in Hoc, including graphical user interface tools, continue to work without change and are also available within the Python context. An example of the benefits of Python availability is the use of the xml module in implementing NEURON's Import3D and CellBuild tools to read MorphML and NeuroML model specifications.

  12. Identification of neurons that express ghrelin receptors in autonomic pathways originating from the spinal cord.

    Science.gov (United States)

    Furness, John B; Cho, Hyun-Jung; Hunne, Billie; Hirayama, Haruko; Callaghan, Brid P; Lomax, Alan E; Brock, James A

    2012-06-01

    Functional studies have shown that subsets of autonomic preganglionic neurons respond to ghrelin and ghrelin mimetics and in situ hybridisation has revealed receptor gene expression in the cell bodies of some preganglionic neurons. Our present goal has been to determine which preganglionic neurons express ghrelin receptors by using mice expressing enhanced green fluorescent protein (EGFP) under the control of the promoter for the ghrelin receptor (also called growth hormone secretagogue receptor). The retrograde tracer Fast Blue was injected into target organs of reporter mice under anaesthesia to identify specific functional subsets of postganglionic sympathetic neurons. Cryo-sections were immunohistochemically stained by using anti-EGFP and antibodies to neuronal markers. EGFP was detected in nerve terminal varicosities in all sympathetic chain, prevertebral and pelvic ganglia and in the adrenal medulla. Non-varicose fibres associated with the ganglia were also immunoreactive. No postganglionic cell bodies contained EGFP. In sympathetic chain ganglia, most neurons were surrounded by EGFP-positive terminals. In the stellate ganglion, neurons with choline acetyltransferase immunoreactivity, some being sudomotor neurons, lacked surrounding ghrelin-receptor-expressing terminals, although these terminals were found around other neurons. In the superior cervical ganglion, the ghrelin receptor terminals innervated subgroups of neurons including neuropeptide Y (NPY)-immunoreactive neurons that projected to the anterior chamber of the eye. However, large NPY-negative neurons projecting to the acini of the submaxillary gland were not innervated by EGFP-positive varicosities. In the celiaco-superior mesenteric ganglion, almost all neurons were surrounded by positive terminals but the VIP-immunoreactive terminals of intestinofugal neurons were EGFP-negative. The pelvic ganglia contained groups of neurons without ghrelin receptor terminal innervation and other groups with

  13. Single neuron computation

    CERN Document Server

    McKenna, Thomas M; Zornetzer, Steven F

    1992-01-01

    This book contains twenty-two original contributions that provide a comprehensive overview of computational approaches to understanding a single neuron structure. The focus on cellular-level processes is twofold. From a computational neuroscience perspective, a thorough understanding of the information processing performed by single neurons leads to an understanding of circuit- and systems-level activity. From the standpoint of artificial neural networks (ANNs), a single real neuron is as complex an operational unit as an entire ANN, and formalizing the complex computations performed by real n

  14. Mesmerising mirror neurons.

    Science.gov (United States)

    Heyes, Cecilia

    2010-06-01

    Mirror neurons have been hailed as the key to understanding social cognition. I argue that three currents of thought-relating to evolution, atomism and telepathy-have magnified the perceived importance of mirror neurons. When they are understood to be a product of associative learning, rather than an adaptation for social cognition, mirror neurons are no longer mesmerising, but they continue to raise important questions about both the psychology of science and the neural bases of social cognition. Copyright 2010 Elsevier Inc. All rights reserved.

  15. A Thalamo-Hypothalamic Pathway That Activates Oxytocin Neurons in Social Contexts in Female Rats.

    Science.gov (United States)

    Cservenák, Melinda; Keller, Dávid; Kis, Viktor; Fazekas, Emese A; Öllös, Hanna; Lékó, András H; Szabó, Éva R; Renner, Éva; Usdin, Ted B; Palkovits, Miklós; Dobolyi, Árpád

    2017-02-01

    Oxytocin is released from neurons in the paraventricular hypothalamic nucleus (PVN) in mothers upon suckling and during adult social interactions. However, neuronal pathways that activate oxytocin neurons in social contexts are not yet established. Neurons in the posterior intralaminar complex of the thalamus (PIL), which contain tuberoinfundibular peptide 39 (TIP39) and are activated by pup exposure in lactating mothers, provide a candidate projection. Innervation of oxytocin neurons by TIP39 neurons was examined by double labeling in combination with electron microscopy and retrograde tract-tracing. Potential classic neurotransmitters in TIP39 neurons were investigated by in situ hybridization histochemistry. Neurons activated after encounter with a familiar conspecific female in a familiar environment were mapped with the c-Fos technique. PVN and the supraoptic nucleus oxytocin neurons were closely apposed by an average of 2.0 and 0.4 TIP39 terminals, respectively. Asymmetric (presumed excitatory) synapses were found between TIP39 terminals and cell bodies of oxytocin neurons. In lactating rats, PIL TIP39 neurons were retrogradely labeled from the PVN. TIP39 neurons expressed vesicular glutamate transporter 2 but not glutamic acid decarboxylase 67. PIL contained a markedly increased number of c-Fos-positive neurons in response to social encounter with a familiar conspecific female. Furthermore, the PIL received ascending input from the spinal cord and the inferior colliculus. Thus, TIP39 neurons in the PIL may receive sensory input in response to social interactions and project to the PVN to innervate and excite oxytocin neurons, suggesting that the PIL-PVN projection contributes to the activation of oxytocin neurons in social contexts. Copyright © 2017 by the Endocrine Society.

  16. Glutamate and GABA as rapid effectors of hypothalamic peptidergic neurons

    Directory of Open Access Journals (Sweden)

    Cornelia eSchöne

    2012-11-01

    Full Text Available Vital hypothalamic neurons regulating hunger, wakefulness, reward-seeking, and body weight are often defined by unique expression of hypothalamus-specific neuropeptides. Gene-ablation studies show that some of these peptides, notably orexin/hypocretin (hcrt/orx, are themselves critical for stable states of consciousness and metabolic health. However, neuron-ablation studies often reveal more severe phenotypes, suggesting key roles for co-expressed transmitters. Indeed, most hypothalamic neurons, including hcrt/orx cells, contain fast transmitters glutamate and GABA, as well as several neuropeptides. What are the roles and relations between different transmitters expressed by the same neuron? Here, we consider signaling codes for releasing different transmitters in relation to transmitter and receptor diversity in behaviorally-defined, widely-projecting peptidergic neurons, such as hcrt/orx cells. We then discuss latest optogenetic studies of endogenous transmitter release from defined sets of axons in situ, which suggest that recently-characterized vital peptidergic neurons (e.g. hcrt/orx, proopiomelanocortin , and agouti-related peptide cells, as well as classical modulatory neurons (e.g. dopamine and acetylcholine cells, all use fast transmitters to control their postsynaptic targets. These optogenetic insights are complemented by recent observations of behavioral deficiencies caused by genetic ablation of fast transmission from specific neuropeptidergic and aminergic neurons. Powerful and fast (millisecond-scale GABAergic and glutamatergic signaling from neurons previously considered to be primarily modulatory raises new questions about the roles of slower co-transmitters they co-express.

  17. Types of neurons in the enteric nervous system.

    Science.gov (United States)

    Furness, J B

    2000-07-01

    This paper, written for the symposium in honour of more than 40 years' contribution to autonomic research by Professor Geoffrey Burnstock, highlights the progress made in understanding the organisation of the enteric nervous system over this time. Forty years ago, the prevailing view was that the neurons within the gut wall were post-ganglionic neurons of parasympathetic pathways. This view was replaced as evidence accrued that the neurons are part of the enteric nervous system and are involved in reflex and integrative activities that can occur even in the absence of neuronal influence from extrinsic sources. Work in Burnstock's laboratory led to the discovery of intrinsic inhibitory neurons with then novel pharmacology of transmission, and precipitated investigation of neuron types in the enteric nervous system. All the types of neurons in the enteric nervous system of the small intestine of the guinea-pig have now been identified in terms of their morphologies, projections, primary neurotransmitters and physiological identification. In this region there are 14 functionally defined neuron types, each with a characteristic combination of morphological, neurochemical and biophysical properties. The nerve circuits underlying effects on motility, blood flow and secretion that are mediated through the enteric nervous system are constructed from these neurons. The circuits for simple motility reflexes are now known, and progress has been made in analysing those involved in local control of blood flow and transmucosal fluid movement in the small intestine.

  18. Characterization of pruriceptive trigeminothalamic tract neurons in rats.

    Science.gov (United States)

    Moser, Hannah R; Giesler, Glenn J

    2014-04-01

    Rodent models of facial itch and pain provide a valuable tool for distinguishing between behaviors related to each sensation. In rats, pruritogens applied to the face elicit scratching using the hindlimb while algogens elicit wiping using the forelimb. We wished to determine the role of trigeminothalamic tract (VTT) neurons in carrying information regarding facial itch and pain to the forebrain. We have characterized responses to facially applied pruritogens (serotonin, BAM8-22, chloroquine, histamine, capsaicin, and cowhage) and noxious stimuli in 104 VTT neurons recorded from anesthetized rats. Each VTT neuron had a mechanically sensitive cutaneous receptive field on the ipsilateral face. All pruriceptive VTT neurons also responded to noxious mechanical and/or thermal stimulation. Over half of VTT neurons responsive to noxious stimuli also responded to at least one pruritogen. Each tested pruritogen, with the exception of cowhage, produced an increase in discharge rate in a subset of VTT neurons. The response to each pruritogen was characterized, including maximum discharge rate, response duration, and spike timing dynamics. Pruriceptive VTT neurons were recorded from throughout superficial and deep layers of the spinal trigeminal nucleus and were shown to project via antidromic mapping to the ventroposterior medial nucleus or posterior thalamic nuclei. These results indicate that pruriceptive VTT neurons are a subset of polymodal nociceptive VTT neurons and characterize a system conducive to future experiments regarding the similarities and differences between facial itch and pain.

  19. AgRP Neurons Can Increase Food Intake during Conditions of Appetite Suppression and Inhibit Anorexigenic Parabrachial Neurons.

    Science.gov (United States)

    Essner, Rachel A; Smith, Alison G; Jamnik, Adam A; Ryba, Anna R; Trutner, Zoe D; Carter, Matthew E

    2017-09-06

    To maintain energy homeostasis, orexigenic (appetite-inducing) and anorexigenic (appetite suppressing) brain systems functionally interact to regulate food intake. Within the hypothalamus, neurons that express agouti-related protein (AgRP) sense orexigenic factors and orchestrate an increase in food-seeking behavior. In contrast, calcitonin gene-related peptide (CGRP)-expressing neurons in the parabrachial nucleus (PBN) suppress feeding. PBN CGRP neurons become active in response to anorexigenic hormones released following a meal, including amylin, secreted by the pancreas, and cholecystokinin (CCK), secreted by the small intestine. Additionally, exogenous compounds, such as lithium chloride (LiCl), a salt that creates gastric discomfort, and lipopolysaccharide (LPS), a bacterial cell wall component that induces inflammation, exert appetite-suppressing effects and activate PBN CGRP neurons. The effects of increasing the homeostatic drive to eat on feeding behavior during appetite suppressing conditions are unknown. Here, we show in mice that food deprivation or optogenetic activation of AgRP neurons induces feeding to overcome the appetite suppressing effects of amylin, CCK, and LiCl, but not LPS. AgRP neuron photostimulation can also increase feeding during chemogenetic-mediated stimulation of PBN CGRP neurons. AgRP neuron stimulation reduces Fos expression in PBN CGRP neurons across all conditions. Finally, stimulation of projections from AgRP neurons to the PBN increases feeding following administration of amylin, CCK, and LiCl, but not LPS. These results demonstrate that AgRP neurons are sufficient to increase feeding during noninflammatory-based appetite suppression and to decrease activity in anorexigenic PBN CGRP neurons, thereby increasing food intake during homeostatic need.SIGNIFICANCE STATEMENT The motivation to eat depends on the relative balance of activity in distinct brain regions that induce or suppress appetite. An abnormal amount of activity in

  20. Neuromorphic silicon neuron circuits

    Directory of Open Access Journals (Sweden)

    Giacomo eIndiveri

    2011-05-01

    Full Text Available Hardware implementations of spiking neurons can be extremely useful for a large variety of applications, ranging from high-speed modeling of large-scale neural systems to real-time behaving systems, to bidirectional brain-machine interfaces. The specific circuit solutions used to implement silicon neurons depend on the application requirements. In this paper we describe the most common building blocks and techniques used to implement these circuits, and present an overview of a wide range of neuromorphic silicon neurons, which implement different computational models, ranging from biophysically realistic and conductance based Hodgkin-Huxley models to bi-dimensional generalized adaptive Integrate and Fire models. We compare the different design methodologies used for each silicon neuron design described, and demonstrate their features with experimental results, measured from a wide range of fabricated VLSI chips.

  1. Motor neurone disease.

    Science.gov (United States)

    2016-03-23

    Essential facts Motor neurone disease describes a group of related diseases, affecting the neurones in the brain and spinal cord. Progressive, incurable and life-limiting, MND is rare, with about 1,100 people developing it each year in the UK and up to 5,000 people affected at any one time. One third of people will die within a year of diagnosis and more than half within two years. About 5% to 10% are alive at ten years.

  2. Neurons and Tumor Suppressors

    OpenAIRE

    Douglas W Zochodne

    2014-01-01

    Neurons choose growth pathways with half hearted reluctance, behavior that may be appropriate to maintain fixed long lasting connections but not to regenerate them. We now recognize that intrinsic brakes on regrowth are widely expressed in these hesitant neurons and include classical tumor suppressor molecules. Here, we review how two brakes, PTEN (phosphatase and tensin homolog deleted on chromosome 10) and retinoblastoma emerge as new and exciting knockdown targets to e...

  3. THE PVN-HIPPOCAMPAL ghrelin NEURONS PROJECTION AND ITS EFFECTS ON ELECTRICAL ACTIVITY OF THE HIPPOCAMPUS%PVN-海马ghrelin神经元投射及对海马电活动影响

    Institute of Scientific and Technical Information of China (English)

    邱贝贝; 徐珞

    2013-01-01

    目的 了解电刺激大鼠下丘脑室旁核(PVN)对海马CA1区ghrelin调控胃扩张(GD)敏感神经元放电活动的影响,初步探讨ghrelin在PVN-海马通路中的调控作用.方法 选用成年Wistar大鼠84只,采用电刺激PVN、核团微量注射及细胞外记录神经元单位放电方法,记录电刺激PVN海马CA1区GD敏感神经元自发放电活动的改变;同时观察海马CA1区给予ghrelin受体阻断剂[D-Lys-3]-GHRP-6,海马CA1区GD敏感神经元放电活动的变化.结果 海马CA1区记录的255个神经元中有120个(47.1%)神经元对GD刺激有反应,其中84个(70.0%)为GD兴奋性(GD-E)神经元,36个(30.0%)为GD抑制性(GD-Ⅰ)神经元.在GD-E神经元中,微量注射ghrelin可兴奋其中53.1%的神经元,与核团注射生理盐水组相比,放电频率显著增加(t=2.686,P<0.05);而在GD-Ⅰ神经元中,微量注射ghrelin后58.3%神经元呈抑制效应,放电频率显著降低(t=3.591,P<0.05),且ghrelin的效应可被其受体阻断剂[D-Lys-3]-GHRP-6完全阻断.对ghrelin有兴奋反应的GD-E神经元,电刺激PVN,其中23.5% GD-E神经元的兴奋效应可被[D-Lys-3]-GHRP-6部分阻断.结论 PVN可调控海马CA1区GD敏感神经元放电活动,在PVN-海马直接或间接通路中ghrelin参与了兴奋传递的调控.%Objective To explore the effects of electrical stimulation of hypothalamic paraventricular nucles (PVN) in rats on the activity of ghrelin regulation of gastric distention (GD) sensitive neurons in the hippocampal CA1 region, and preliminarily study the regulation of ghrelin in the PVN-hippocampal pathway. Methods Eighty-four adult Wistar rats were selected in this experiment. The effects of electrical stimulation of PVN on the activity of GD sensitive neurons in the hippocampal CA1 region were observed by electrical stimulation of PVN, nuclei microinjecion and recording extracellular potentials of single neuron. The changes of the GD sensitive neurons discharge activities in

  4. Delayed death of identified reticulospinal neurons after spinal cord injury in lampreys.

    Science.gov (United States)

    Shifman, M I; Zhang, G; Selzer, M E

    2008-09-20

    There is controversy about whether axotomized neurons undergo death or only severe atrophy after spinal cord injury (SCI) in mammals. Lampreys recover from complete spinal transection, but only about half of the severed spinal-projecting axons regenerate through the site of injury. The fates of the unregenerated neurons remain unknown, and until now death of axotomized spinal-projecting neurons has not been described in the lamprey brain. We now report that in animals allowed to survive for 12 or more weeks after spinal cord transection, several identified reticulospinal (RS) neurons were missing in Nissl-stained or neurofilament-immunostained brain whole mounts. At earlier times, these neurons were swollen and pale in Nissl-stained preparations. Retrograde fluorescent labeling from the site of transection combined with TUNEL histochemistry suggested that neuronal death, including that of the identified RS neurons, began in animals 4 weeks posttransection, reaching a peak at 12-16 weeks. This was not seen in untransected animals. The TUNEL positivity suggests that some cells were dying by apoptosis. Of special interest, among the identified neurons, this delayed cell death was restricted to neurons that at earlier posttransection times have a low probability of regeneration. These data show that SCI induces delayed cell death in lamprey spinal-projecting neurons and suggest that the reason why some neurons are "bad regenerators" is that they are already undergoing apoptotic cell death. Thus protection from apoptosis may be necessary in order to enhance axonal regeneration after SCI. Copyright 2008 Wiley-Liss, Inc.

  5. Neuron division or enucleation.

    Science.gov (United States)

    Sotnikov, O S; Laktionova, A A; Solovieva, I A; Krasnova, T V

    2010-10-01

    The classical Bielschowsky-Gross neurohistological method was used to reproduce all the morphological phenomena interpreted by many authors as signs of neuron division, budding, and fission. It is suggested that these signs are associated with the effects of enucleation, which occurs in many cells of other tissue types in response to a variety of chemical and physical treatments. Studies were performed using neurons isolated from the mollusk Lymnaea stagnalis and exposed in tissue culture to the actin microfilament inhibitor cytochalasin B. Phase contrast time-lapse video recording over periods of 4-8 h demonstrated nuclear displacement, ectopization, and budding, to the level of almost complete fission of the neuron body. This repeats the pattern seen in static fixed preparations in "normal" conditions and after different experimental treatments. Budding of the cytoplasm was also sometimes seen at the early stages of the experiments. Control experiments in which cultured neurons were exposed to the solvent for cytochalasin B, i.e., dimethylsulfoxide (DMSO), did not reveal any changes in neurons over a period of 8 h. We take the view that the picture previously interpreted as neuron division and fission can be explained in terms of the inhibition of actin microfilaments, sometimes developing spontaneously in cells undergoing individual metabolic changes preventing the maintenance of cytoskeleton stability.

  6. Glycine activates myenteric neurones in adult guinea-pigs.

    Science.gov (United States)

    Neunlist, M; Michel, K; Reiche, D; Dobreva, G; Huber, K; Schemann, M

    2001-11-01

    1. We studied the effects of glycine on myenteric neurones and muscle activity in the colon and stomach of adult guinea-pigs. 2. Intracellular recordings revealed that myenteric neurones responded to local microejection of glycine (1 mM) with a fast, transient membrane potential depolarisation (57 % of 191 colonic neurones and 26 % of 50 gastric neurones). Most glycine-sensitive neurones had ascending projections and were choline acetyltransferase immunoreactive. Glycine preferentially activated neurones with a late afterhyperpolarisation (AH-neurones) and tonic spiking neurones with fast synaptic inputs (tonic S-neurones) but less frequently phasic S-neurones and inexcitable (non-spiking) neurones. The depolarisation had a reversal potential at -19 +/- 13 mV, which was increased by 18 +/- 10 % upon lowering extracellular chloride concentration and decreased by 38 +/- 14 % in furosemide (frusemide, 2 mM). 3. Strychnine (300 nM) reversibly abolished the glycine-induced depolarisation and the Cl(-) channel blocker picrotoxin (100 microM) reduced the amplitude of the depolarisation by 55 +/- 5 %. The glycine effect was a postsynaptic response because it was not changed after nerve blockade with tetrodotoxin (1 microM) or blockade of synaptic transmission in reduced extracellular [Ca(2+)]. The effect was specific since the response was not changed by the nicotinic antagonists hexamethonium (200 microM) and mecamylamine (100 microM), the GABA(A) receptor antagonist bicuculline (10 microM), the NMDA antagonist MK-801 (20 microM) or the 5-HT(3) antagonist ICS 205930 (1 microM). 4. Glycine (1 mM) induced a tetrodotoxin- and strychnine-sensitive contractile response in the colon; the contractile response in the stomach was tetrodotoxin insensitive. 5. Glycine activated myenteric neurones in the adult enteric nervous system through strychnine-sensitive mechanisms. The glycine-evoked depolarisation was caused by Cl(-) efflux and the maintenance of relatively high

  7. NeuronBank: A Tool for Cataloging Neuronal Circuitry.

    Science.gov (United States)

    Katz, Paul S; Calin-Jageman, Robert; Dhawan, Akshaye; Frederick, Chad; Guo, Shuman; Dissanayaka, Rasanjalee; Hiremath, Naveen; Ma, Wenjun; Shen, Xiuyn; Wang, Hsui C; Yang, Hong; Prasad, Sushil; Sunderraman, Rajshekhar; Zhu, Ying

    2010-01-01

    The basic unit of any nervous system is the neuron. Therefore, understanding the operation of nervous systems ultimately requires an inventory of their constituent neurons and synaptic connectivity, which form neural circuits. The presence of uniquely identifiable neurons or classes of neurons in many invertebrates has facilitated the construction of cellular-level connectivity diagrams that can be generalized across individuals within a species. Homologous neurons can also be recognized across species. Here we describe NeuronBank.org, a web-based tool that we are developing for cataloging, searching, and analyzing neuronal circuitry within and across species. Information from a single species is represented in an individual branch of NeuronBank. Users can search within a branch or perform queries across branches to look for similarities in neuronal circuits across species. The branches allow for an extensible ontology so that additional characteristics can be added as knowledge grows. Each entry in NeuronBank generates a unique accession ID, allowing it to be easily cited. There is also an automatic link to a Wiki page allowing an encyclopedic explanation of the entry. All of the 44 previously published neurons plus one previously unpublished neuron from the mollusc, Tritonia diomedea, have been entered into a branch of NeuronBank as have 4 previously published neurons from the mollusc, Melibe leonina. The ability to organize information about neuronal circuits will make this information more accessible, ultimately aiding research on these important models.

  8. NeuronBank: a tool for cataloging neuronal circuitry

    Directory of Open Access Journals (Sweden)

    Paul S Katz

    2010-04-01

    Full Text Available The basic unit of any nervous system is the neuron. Therefore, understanding the operation of nervous systems ultimately requires an inventory of their constituent neurons and synaptic connectivity, which form neural circuits. The presence of uniquely identifiable neurons or classes of neurons in many invertebrates has facilitated the construction of cellular-level connectivity diagrams that can be generalized across individuals within a species. Homologous neurons can also be recognized across species. Here we describe NeuronBank.org, a web-based tool that we are developing for cataloging, searching, and analyzing neuronal circuitry within and across species. Information from a single species is represented in an individual branch of NeuronBank. Users can search within a branch or perform queries across branches to look for similarities in neuronal circuits across species. The branches allow for an extensible ontology so that additional characteristics can be added as knowledge grows. Each entry in NeuronBank generates a unique accession ID, allowing it to be easily cited. There is also an automatic link to a Wiki page allowing an encyclopedic explanation of the entry. All of the 44 previously published neurons plus one previously unpublished neuron from the mollusc, Tritonia diomedea, have been entered into a branch of NeuronBank as have 4 previously published neurons from the mollusc, Melibe leonina. The ability to organize information about neuronal circuits will make this information more accessible, ultimately aiding research on these important models.

  9. NeuronBank: A Tool for Cataloging Neuronal Circuitry

    Science.gov (United States)

    Katz, Paul S.; Calin-Jageman, Robert; Dhawan, Akshaye; Frederick, Chad; Guo, Shuman; Dissanayaka, Rasanjalee; Hiremath, Naveen; Ma, Wenjun; Shen, Xiuyn; Wang, Hsui C.; Yang, Hong; Prasad, Sushil; Sunderraman, Rajshekhar; Zhu, Ying

    2010-01-01

    The basic unit of any nervous system is the neuron. Therefore, understanding the operation of nervous systems ultimately requires an inventory of their constituent neurons and synaptic connectivity, which form neural circuits. The presence of uniquely identifiable neurons or classes of neurons in many invertebrates has facilitated the construction of cellular-level connectivity diagrams that can be generalized across individuals within a species. Homologous neurons can also be recognized across species. Here we describe NeuronBank.org, a web-based tool that we are developing for cataloging, searching, and analyzing neuronal circuitry within and across species. Information from a single species is represented in an individual branch of NeuronBank. Users can search within a branch or perform queries across branches to look for similarities in neuronal circuits across species. The branches allow for an extensible ontology so that additional characteristics can be added as knowledge grows. Each entry in NeuronBank generates a unique accession ID, allowing it to be easily cited. There is also an automatic link to a Wiki page allowing an encyclopedic explanation of the entry. All of the 44 previously published neurons plus one previously unpublished neuron from the mollusc, Tritonia diomedea, have been entered into a branch of NeuronBank as have 4 previously published neurons from the mollusc, Melibe leonina. The ability to organize information about neuronal circuits will make this information more accessible, ultimately aiding research on these important models. PMID:20428500

  10. CALBINDIN CONTENT AND DIFFERENTIAL VULNERABILITY OF MIDBRAIN EFFERENT DOPAMINERGIC NEURONS IN MACAQUES

    Directory of Open Access Journals (Sweden)

    Iria G Dopeso-Reyes

    2014-12-01

    Full Text Available Calbindin (CB is a calcium binding protein reported to protect dopaminergic neurons from degeneration. Although a direct link between CB content and differential vulnerability of dopaminergic neurons has long been accepted, factors other than CB have also been suggested, particularly those related to the dopamine transporter. Indeed, several studies have reported that CB levels are not causally related to the differential vulnerability of dopaminergic neurons against neurotoxins. Here we have used dual stains for tyrosine hydroxylase (TH and CB in 3 control and 3 MPTP-treated monkeys to visualize dopaminergic neurons in the ventral tegmental area (VTA and in the dorsal and ventral tiers of the substantia nigra pars compacta (SNcd and SNcv co-expressing TH and CB. In control animals, the highest percentages of co-localization were found in VTA (58.2%, followed by neurons located in the SNcd (34.7%. As expected, SNcv neurons lacked CB expression. In MPTP-treated animals, the percentage of CB-ir/TH-ir neurons in the VTA was similar to control monkeys (62.1%, whereas most of the few surviving neurons in the SNcd were CB-ir/TH-ir (88.6%. Next, we have elucidated the presence of CB within identified nigrostriatal and nigroextrastriatal midbrain dopaminergic projection neurons. For this purpose, two control monkeys received one injection of Fluoro-Gold into the caudate nucleus and one injection of cholera toxin (CTB into the postcommissural putamen, whereas two more monkeys were injected with CTB into the internal division of the globus pallidus. As expected, all the nigrocaudate- and nigroputamen-projecting neurons were TH-ir, although surprisingly, all of these nigrostriatal-projecting neurons were negative for CB. Furthermore, all the nigropallidal-projecting neurons co-expressed both TH and CB. In summary, although CB-ir dopaminergic neurons seem to be less prone to MPTP-induced degeneration, our data clearly demonstrated that these neurons are not

  11. 大鼠三叉-小脑投射神经元表达磷酸激活的谷氨酰胺酶——双标法研究%Trigeminocerebellar projection neurons express phosphate activated glutaminase-like immunoreactivity: a double labeling study in the rat

    Institute of Scientific and Technical Information of China (English)

    张富兴; 董玉琳; 李金莲; 李继硕

    2002-01-01

    磷酸激活的谷氨酰胺酶(phosphate activated glutaminase,PAG)可作为谷氨酸能神经元的标志物.采用逆行束路追踪技术和PAG免疫荧光组织化学法,研究脑干三叉核团复合体中向小脑袢状小叶Crusl区投射神经元是否呈PAG样免疫反应阳性.结果表明:将荧光金(Fluoro-Gold,FG)注入小脑袢状小叶Crusl区后,在三叉神经感觉主核(Pr5)、三叉神经脊束核极间亚核(Sp5I)和吻侧亚核背内侧部(Sp5DM)、三叉间核(15)以及三叉神经运动核与上橄榄核之间的一个小区域(nucleus J)中均可见到FG逆行标记细胞.标记细胞出现在上述核团的双侧,但以同侧为主.PAG免疫荧光组织化学反应结果显示:许多FG标记神经元呈强PAG样免疫阳性,其中FG/PAG双标神经元占FG逆行标记神经元总数的73%~94%.结果提示:脑干三叉神经核团中的谷氨酸能神经元可能参与触觉信息从面口部向小脑的传递.%Phosphate activated glutaminase (PAG) has usually been considered as a marker for glutamatergic neurons. In the present study, combining immunofluorescence histochemistry for PAG with the retrograde tract-tracing technique, we examined if the neurons in the trigeminal brainstem complex which project to the crus 1 of the ansiform lobule (Cr l) of the cerebellum expressed PAG-like immunoreactivity (PAG-LI). The results showed that after injection of Fluoro-Gold (FG) into the Cr I of the cerebellum, many neurons in the trigeminal nuclei were retrogradely labeled with FG.Although observed bilaterally, the FG-labeled neurons were mainly distributed ipsilaterally in the principal sensory trigeminal nucleus ( Pr5 ), the dorsomedial part of the subnucleus oralis ( Sp5 DM) and the subnucleus interpolaris ( Sp5 I) of the spinal trigeminal nucleus, the intertrigeminal nucleus (I5) and a small region located between the motor trigeminal nucleus and the superior olivary nuclei (nucleus J). After the processing of immunofluorescence for PAG

  12. Morphology and distribution of neurons expressing serotonin 5-HT1A receptors in the rat hypothalamus and the surrounding diencephalic and telencephalic areas.

    Science.gov (United States)

    Marvin, Eric; Scrogin, Karie; Dudás, Bertalan

    2010-07-01

    Disorders of serotonergic neurotransmission are involved in disturbances of numerous hypothalamic functions including circadian rhythm, mood, neuroendocrine functions, sleep and feeding. Among the serotonin receptors currently recognized, 5-HT(1A) receptors have received considerable attention due to their importance in the etiology of mood disorders. While previous studies have shown the presence of 5-HT(1A) receptors in several regions of the rat brain, there is no detailed map of the cellular distribution of 5-HT(1A) receptors in the rat diencephalon. In order to characterize the distribution and morphology of the neurons containing 5-HT(1A) receptors in the diencephalon and the adjacent telencephalic areas, single label immunohistochemistry was utilized. Large, multipolar, 5-HT(1A)-immunoreactive (IR) neurons were mainly detected in the magnocellular preoptic nucleus and in the nucleus of diagonal band of Broca, while the supraoptic nucleus contained mainly fusiform neurons. Medium-sized 5-HT(1A)-IR neurons with triangular or round-shaped somata were widely distributed in the diencephalon, populating the zona incerta, lateral hypothalamic area, anterior hypothalamic nucleus, substantia innominata, dorsomedial and premamillary nuclei, paraventricular nucleus and bed nucleus of stria terminalis. The present study provides schematic mapping of 5-HT(1A)-IR neurons in the rat diencephalon. In addition, the morphology of the detected 5-HT(1A)-IR neural elements is also described. Since rat is a widely used laboratory animal in pharmacological models of altered serotoninergic neurotransmission, detailed mapping of 5-HT(1A)-IR structures is pivotal for the neurochemical characterization of the neurons containing 5-HT(1A) receptors.

  13. Neurons of human nucleus accumbens

    Directory of Open Access Journals (Sweden)

    Sazdanović Maja

    2011-01-01

    Full Text Available Background/Aim. Nucleus accumbens is a part of the ventral striatum also known as a drug active brain region, especially related with drug addiction. The aim of the study was to investigate the Golgi morphology of the nucleus accumbens neurons. Methods. The study was performed on the frontal and sagittal sections of 15 human brains by the Golgi Kopsch method. We classified neurons in the human nucleus accumbens according to their morphology and size into four types: type I - fusiform neurons; type II - fusiform neurons with lateral dendrite, arising from a part of the cell body; type III - pyramidal-like neuron; type IV - multipolar neuron. The medium spiny neurons, which are mostly noted regarding to the drug addictive conditions of the brain, correspond to the type IV - multipolar neurons. Results. Two regions of human nucleus accumbens could be clearly recognized on Nissl and Golgi preparations each containing different predominant neuronal types. Central part of nucleus accumbens, core region, has a low density of impregnated neurons with predominant type III, pyramidal-like neurons, with spines on secondary branches and rare type IV, multipolar neurons. Contrary to the core, peripheral region, shell of nucleus, has a high density of impregnated neurons predominantly contained of type I and type IV - multipolar neurons, which all are rich in spines on secondary and tertiary dendritic branches. Conclusion. Our results indicate great morphological variability of human nucleus accumbens neurons. This requires further investigations and clarifying clinical significance of this important brain region.

  14. Neuronal avalanches and learning

    Energy Technology Data Exchange (ETDEWEB)

    Arcangelis, Lucilla de, E-mail: dearcangelis@na.infn.it [Department of Information Engineering and CNISM, Second University of Naples, 81031 Aversa (Italy)

    2011-05-01

    Networks of living neurons represent one of the most fascinating systems of biology. If the physical and chemical mechanisms at the basis of the functioning of a single neuron are quite well understood, the collective behaviour of a system of many neurons is an extremely intriguing subject. Crucial ingredient of this complex behaviour is the plasticity property of the network, namely the capacity to adapt and evolve depending on the level of activity. This plastic ability is believed, nowadays, to be at the basis of learning and memory in real brains. Spontaneous neuronal activity has recently shown features in common to other complex systems. Experimental data have, in fact, shown that electrical information propagates in a cortex slice via an avalanche mode. These avalanches are characterized by a power law distribution for the size and duration, features found in other problems in the context of the physics of complex systems and successful models have been developed to describe their behaviour. In this contribution we discuss a statistical mechanical model for the complex activity in a neuronal network. The model implements the main physiological properties of living neurons and is able to reproduce recent experimental results. Then, we discuss the learning abilities of this neuronal network. Learning occurs via plastic adaptation of synaptic strengths by a non-uniform negative feedback mechanism. The system is able to learn all the tested rules, in particular the exclusive OR (XOR) and a random rule with three inputs. The learning dynamics exhibits universal features as function of the strength of plastic adaptation. Any rule could be learned provided that the plastic adaptation is sufficiently slow.

  15. Basal Forebrain Cholinergic System and Orexin Neurons: Effects on Attention

    Science.gov (United States)

    Villano, Ines; Messina, Antonietta; Valenzano, Anna; Moscatelli, Fiorenzo; Esposito, Teresa; Monda, Vincenzo; Esposito, Maria; Precenzano, Francesco; Carotenuto, Marco; Viggiano, Andrea; Chieffi, Sergio; Cibelli, Giuseppe; Monda, Marcellino; Messina, Giovanni

    2017-01-01

    The basal forebrain (BF) cholinergic system has an important role in attentive functions. The cholinergic system can be activated by different inputs, and in particular, by orexin neurons, whose cell bodies are located within the postero-lateral hypothalamus. Recently the orexin-producing neurons have been proved to promote arousal and attention through their projections to the BF. The aim of this review article is to summarize the evidence showing that the orexin system contributes to attentional processing by an increase in cortical acetylcholine release and in cortical neurons activity. PMID:28197081

  16. Dynamic GABAergic afferent modulation of AgRP neurons

    Science.gov (United States)

    Garfield, Alastair S; Shah, Bhavik P; Burgess, Christian R; Li, Monica M; Li, Chia; Steger, Jennifer S; Madara, Joseph C; Campbell, John N; Kroeger, Daniel; Scammell, Thomas E; Tannous, Bakhos A; Myers, Martin G; Andermann, Mark L; Krashes, Michael J; Lowell, Bradford B

    2017-01-01

    Agouti-related peptide (AgRP) neurons of the arcuate nucleus of the hypothalamus (ARC) promote homeostatic feeding at times of caloric insufficiency, yet they are rapidly suppressed by food-related sensory cues prior to ingestion. Here we identify a highly selective inhibitory afferent to AgRP neurons that serves as a neural determinant of this rapid modulation. Specifically, GABAergic projections arising from the ventral compartment of the dorsomedial nucleus of the hypothalamus (vDMH) contribute to the pre-consummatory modulation of ARCAgRP neurons. In a manner reciprocal to ARCAgRP neurons, ARC-projecting leptin receptor (LepR)-expressing GABAergic DMH neurons exhibit rapid activation upon availability of food that additionally reflects the relative value of the food. Thus, DMHLepR neurons form part of the sensory network that relays real-time information about the nature and availability of food to dynamically modulate ARCAgRP neuron activity and feeding behavior. PMID:27643429

  17. Spinal cord projections to the cerebellum in the mouse.

    Science.gov (United States)

    Sengul, Gulgun; Fu, YuHong; Yu, You; Paxinos, George

    2015-09-01

    The projections from the spinal cord to the cerebellar cortex were studied using retrograde neuronal tracers. Thus far, no study has shown the detailed topographic mapping of the projections from the spinal neuron clusters to the cerebellar cortex regions for experimental animals, and there are no studies for the mouse. Tracers Fluoro-Gold and cholera toxin B were injected into circumscribed regions of the cerebellar cortex, and retrogradely labeled spinal cord neurons were mapped throughout the spinal cord. Spinal projections to the cerebellar cortex were mainly from five neuronal columns--central cervical nucleus, dorsal nucleus, lumbar and sacral precerebellar nuclei, and lumbar border precerebellar cells--and from scattered neurons located in the deep dorsal horn and laminae 6-8. The spinocerebellar projections to the cortex were mainly to the vermis. All five precerebellar cell columns projected to both anterior and posterior parts of the cerebellar cortex. Results of this study provide an amendment to the known rostral and caudal boundaries of the precerebellar cell columns in the mouse. Scattered precerebellar neurons in the most caudal deep dorsal horn and laminae 6-8 projected exclusively to the anterior part of the cerebellar cortex. In this study, no labeled spinal neurons were found to project to the lobules 6 and 7 of the cerebellar vermis, the flocculus, and the paraflocculus. Spinocerebellar neurons were located bilaterally, but the majority of the projections were contralateral for the central cervical nucleus, and ipsilateral for the remaining spinal precerebellar neuronal clusters.

  18. Identification and mechanosensitivity of viscerofugal neurons.

    Science.gov (United States)

    Hibberd, T J; Zagorodnyuk, V P; Spencer, N J; Brookes, S J H

    2012-12-06

    Enteric viscerofugal neurons are interneurons with cell bodies in the gut wall; they project to prevertebral ganglia where they provide excitatory synaptic drive to sympathetic neurons which control intestinal motility and secretion. Here, we studied the mechanosensitivity and firing of single, identified viscerofugal neurons in guinea-pig distal colon. Flat sheet preparations of gut were set up in vitro and conventional extracellular recordings made from colonic nerve trunks. The nicotinic agonist, 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP) (1mM), was locally pressure ejected onto individual myenteric ganglia. In a few ganglia, DMPP promptly evoked firing in colonic nerves. Biotinamide filling of colonic nerves revealed that DMPP-responsive sites corresponded to viscerofugal nerve cell bodies. This provides a robust means to positively identify viscerofugal neuron firing. Of 15 single units identified in this way, none responded to locally-applied capsaicin (1 μM). Probing with von Frey hairs at DMPP-responsive sites reliably evoked firing in all identified viscerofugal neurons (18/18 units tested; 0.8-5 mN). Circumferential stretch of the preparation increased firing in all 14/14 units (1-5 g, p<0.05). Both stretch and von Frey hair responses persisted in Ca(2+)-free solution (6 mM Mg(2+), 1mM EDTA), indicating that viscerofugal neurons are directly mechanosensitive. To investigate their adequate stimulus, circular muscle tension and length were independently modulated (BAY K8644, 1 μM and 10 μM, respectively). Increases in intramural tension without changes in length did not affect firing. However, contraction-evoked shortening, under constant load, significantly decreased firing (p<0.001). In conclusion, viscerofugal neuron action potentials contribute to recordings from colonic nerve trunks, in vitro. They provide a significant primary afferent output from the colon, encoding circumferential length, largely independent of muscle tension. All

  19. Control of REM sleep by ventral medulla GABAergic neurons.

    Science.gov (United States)

    Weber, Franz; Chung, Shinjae; Beier, Kevin T; Xu, Min; Luo, Liqun; Dan, Yang

    2015-10-15

    Rapid eye movement (REM) sleep is a distinct brain state characterized by activated electroencephalogram and complete skeletal muscle paralysis, and is associated with vivid dreams. Transection studies by Jouvet first demonstrated that the brainstem is both necessary and sufficient for REM sleep generation, and the neural circuits in the pons have since been studied extensively. The medulla also contains neurons that are active during REM sleep, but whether they play a causal role in REM sleep generation remains unclear. Here we show that a GABAergic (γ-aminobutyric-acid-releasing) pathway originating from the ventral medulla powerfully promotes REM sleep in mice. Optogenetic activation of ventral medulla GABAergic neurons rapidly and reliably initiated REM sleep episodes and prolonged their durations, whereas inactivating these neurons had the opposite effects. Optrode recordings from channelrhodopsin-2-tagged ventral medulla GABAergic neurons showed that they were most active during REM sleep (REMmax), and during wakefulness they were preferentially active during eating and grooming. Furthermore, dual retrograde tracing showed that the rostral projections to the pons and midbrain and caudal projections to the spinal cord originate from separate ventral medulla neuron populations. Activating the rostral GABAergic projections was sufficient for both the induction and maintenance of REM sleep, which are probably mediated in part by inhibition of REM-suppressing GABAergic neurons in the ventrolateral periaqueductal grey. These results identify a key component of the pontomedullary network controlling REM sleep. The capability to induce REM sleep on command may offer a powerful tool for investigating its functions.

  20. Project 2010 Project Management

    CERN Document Server

    Happy, Robert

    2010-01-01

    The ideal on-the-job reference guide for project managers who use Microsoft Project 2010. This must-have guide to using Microsoft Project 2010 is written from a real project manager's perspective and is packed with information you can use on the job. The book explores using Project 2010 during phases of project management, reveals best practices, and walks you through project flow from planning through tracking to closure. This valuable book follows the processes defined in the PMBOK Guide, Fourth Edition , and also provides exam prep for Microsoft's MCTS: Project 2010 certification.: Explains

  1. Immunohistochemical characterization of pelvic neurons projecting to the bladder in rats with the artificial somatic-autonomic reflex arc%人工体神经-内脏神经反射弧建立后大鼠盆神经节-膀胱神经通路和递质研究

    Institute of Scientific and Technical Information of China (English)

    李兵; 肖传国

    2010-01-01

    Objective Retrograde-tracing and immunohistochemical techniques were used in combination to investigate the types of putative transmitters in pelvic ganglia neurons projecting to the bladder of rats with the artificial somatic-autonomic reflex arc. Methods The artificial somatic-autonomic reflex arc was established in 8 rats by end-to-end microanastomosis of the proximal stump of the left L4 ventral root to the distal stump of L6 ventral root. The major pelvic ganglia (MPG) neurons innervating the urinary bladder were labeled by retrograde axonal tracing methods with the use of horseradish peroxidase (HRP) injected into the bladder wall and identified with TMB-HRP reaction. Then immunohistochemical (ChAT, TH, VIP, SP) and histochemical methods (NADPH-diaphorase activity and nitric oxide synthase immunoreac-tivity) were used to identify the neurotransmitters of HRP-labeled neurons projecting to the bladder. Results HRP-labeled neurons with spherical or oval shape mainly distributed in the MPG. The HRP-labeled neurons were positive for ChAT (112/279, 40. 1%), TH (50/245,20.4%), VIP(25/233, 10.7%), NOS ( 15/230, 6. 5% ) or SP (8/242, 3. 3% ) respectively. Conclusion These results suggest that ace-tylcholine and adrenaline are the predominant neurotransmitters of postganglionic neurons innervating bladder in rats with the artificial somatic-autonomic reflex arc. VIP, NO and SP may be as the neurotransmitters or neuromodulators to participate the procedure of urinary storage and voiding.%目的 观察人丁体神经-内脏神经反射弧建立后大鼠膀胱和盆神经节(MPG)之间的神经通路及神经递质性质.方法 8只成年wistar大鼠在体建立人工体神经-内脏神经反射弧.将辣根过氧化物酶(HRP)注射至实验大鼠的膀胱壁肌层,逆行神经追踪,通过免疫组织化学或组织化学方法显示HRP阳性标记细胞中的胆碱已酰转移酶(ChAT)、酪氨酸羟化酶(TH)、血管活性肠肽(VIP)、P物质(SP)和还原

  2. Neuronal survival in the brain: neuron type-specific mechanisms.

    Science.gov (United States)

    Pfisterer, Ulrich; Khodosevich, Konstantin

    2017-03-02

    Neurogenic regions of mammalian brain produce many more neurons that will eventually survive and reach a mature stage. Developmental cell death affects both embryonically produced immature neurons and those immature neurons that are generated in regions of adult neurogenesis. Removal of substantial numbers of neurons that are not yet completely integrated into the local circuits helps to ensure that maturation and homeostatic function of neuronal networks in the brain proceed correctly. External signals from brain microenvironment together with intrinsic signaling pathways determine whether a particular neuron will die. To accommodate this signaling, immature neurons in the brain express a number of transmembrane factors as well as intracellular signaling molecules that will regulate the cell survival/death decision, and many of these factors cease being expressed upon neuronal maturation. Furthermore, pro-survival factors and intracellular responses depend on the type of neuron and region of the brain. Thus, in addition to some common neuronal pro-survival signaling, different types of neurons possess a variety of 'neuron type-specific' pro-survival constituents that might help them to adapt for survival in a certain brain region. This review focuses on how immature neurons survive during normal and impaired brain development, both in the embryonic/neonatal brain and in brain regions associated with adult neurogenesis, and emphasizes neuron type-specific mechanisms that help to survive for various types of immature neurons. Importantly, we mainly focus on in vivo data to describe neuronal survival specifically in the brain, without extrapolating data obtained in the PNS or spinal cord, and thus emphasize the influence of the complex brain environment on neuronal survival during development.

  3. Stochastic neuron models

    CERN Document Server

    Greenwood, Priscilla E

    2016-01-01

    This book describes a large number of open problems in the theory of stochastic neural systems, with the aim of enticing probabilists to work on them. This includes problems arising from stochastic models of individual neurons as well as those arising from stochastic models of the activities of small and large networks of interconnected neurons. The necessary neuroscience background to these problems is outlined within the text, so readers can grasp the context in which they arise. This book will be useful for graduate students and instructors providing material and references for applying probability to stochastic neuron modeling. Methods and results are presented, but the emphasis is on questions where additional stochastic analysis may contribute neuroscience insight. An extensive bibliography is included. Dr. Priscilla E. Greenwood is a Professor Emerita in the Department of Mathematics at