Activation of the insular cortex during dynamic exercise in humans

DEFF Research Database (Denmark)

Williamson, James; Nobrega, A C; McColl, R

1997-01-01

role as a site for regulation of autonomic activity. 2. Eight subjects were studied during voluntary active cycling and passively induced cycling. Additionally, four of the subjects underwent passive movement combined with electrical stimulation of the legs. 3. Increases in regional cerebral blood flow...... during active, but not passive cycling. There were no significant changes in rCBF for the right insula. Also, the magnitude of rCBF increase for leg primary motor areas was significantly greater for both active cycling and passive cycling combined with electrical stimulation compared with passive cycling...... alone. 5. These findings provide the first evidence of insular activation during dynamic exercise in humans, suggesting that the left insular cortex may serve as a site for cortical regulation of cardiac autonomic (parasympathetic) activity. Additionally, findings during passive cycling with electrical...

The role of identified neurotransmitter systems in the response of insular cortex to unfamiliar taste: activation of ERK1-2 and formation of a memory trace.

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Berman, D E; Hazvi, S; Neduva, V; Dudai, Y

2000-09-15

In the behaving rat, the consumption of an unfamiliar taste activates the extracellular signal-regulated kinase 1-2 (ERK1-2) in the insular cortex, which contains the taste cortex. In contrast, consumption of a familiar taste has no effect. Furthermore, activation of ERK1-2, culminating in modulation of gene expression, is obligatory for the encoding of long-term, but not short-term, memory of the new taste (Berman et al., 1998). Which neurotransmitter and neuromodulatory systems are involved in the activation of ERK1-2 by the unfamiliar taste and in the long-term encoding of the new taste information? Here we show, by the use of local microinjections of pharmacological agents to the insular cortex in the behaving rat, that multiple neurotransmitters and neuromodulators are required for encoding of taste memory in cortex. However, these systems vary in the specificity of their role in memory acquisition and in their contribution to the activation of ERK1-2. NMDA receptors, metabotropic glutamate receptors, muscarinic, and beta-adrenergic and dopaminergic receptors, all contribute to the acquisition of the new taste memory but not to its retrieval. Among these, only NMDA and muscarinic receptors specifically mediate taste-dependent activation of ERK1-2, whereas the beta-adrenergic function is independent of ERK1-2, and dopaminergic receptors regulate also the basal level of ERK1-2 activation. The data are discussed in the context of postulated novelty detection circuits in the central taste system.

Probabilistic tractography recovers a rostrocaudal trajectory of connectivity variability in the human insular cortex

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Cerliani, Leonardo; Thomas, Rajat M.; Jbabdi, Saad; Siero, Jeroen C. W.; Nanetti, Luca; Crippa, Alessandro; Gazzola, Valeria; D'Arceuil, Helen; Keysers, Christian

The insular cortex of macaques has a wide spectrum of anatomical connections whose distribution is related to its heterogeneous cytoarchitecture. Although there is evidence of a similar cytoarchitectural arrangement in humans, the anatomical connectivity of the insula in the human brain has not yet

Learning Touch Preferences with a Tactile Robot Using Dopamine Modulated STDP in a Model of Insular Cortex

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Ting-Shuo eChou

2015-07-01

Full Text Available Neurorobots enable researchers to study how behaviors are produced by neural mechanisms in an uncertain, noisy, real-world environment. To investigate how the somatosensory system processes noisy, real-world touch inputs, we introduce a neurorobot called CARL-SJR, which has a full-body tactile sensory area. The design of CARL-SJR is such that it encourages people to communicate with it through gentle touch. CARL-SJR provides feedback to users by displaying bright colors on its surface. In the present study, we show that CARL-SJR is capable of learning associations between conditioned stimuli (CS; a color pattern on its surface and unconditioned stimuli (US; a preferred touch pattern by applying a spiking neural network (SNN with neurobiologically inspired plasticity. Specifically, we modeled the primary somatosensory cortex, prefrontal cortex, striatum, and the insular cortex, which is important for hedonic touch, to process noisy data generated directly from CARL-SJR’s tactile sensory area. To facilitate learning, we applied dopamine-modulated Spike Timing Dependent Plasticity (STDP to our simulated prefrontal cortex, striatum and insular cortex. To cope with noisy, varying inputs, the SNN was tuned to produce traveling waves of activity that carried spatiotemporal information. Despite the noisy tactile sensors, spike trains, and variations in subject hand swipes, the learning was quite robust. Further, the plasticity (i.e., STDP in primary somatosensory cortex and insular cortex in the incremental pathway of dopaminergic reward system allowed us to control CARL-SJR’s preference for touch direction without heavily pre-processed inputs. The emerged behaviors we found in this model match animal’s behaviors wherein they prefer touch in particular areas and directions. Thus, the results in this paper could serve as an explanation on the underlying neural mechanisms for developing tactile preferences and hedonic touch.

Sex Differences in Insular Cortex Gyri Responses to the Valsalva Maneuver

OpenAIRE

Macey, Paul M.; Rieken, Nicholas S.; Kumar, Rajesh; Ogren, Jennifer A.; Middlekauff, Holly R.; Wu, Paula; Woo, Mary A.; Harper, Ronald M.

2016-01-01

Sex differences in autonomic regulation may underlie cardiovascular disease variations between females and males. One key autonomic brain region is the insular cortex, which typically consists of five main gyri in each hemisphere, and shows a topographical organization of autonomic function across those gyri. The present study aims to identify possible sex differences in organization of autonomic function in the insula. We studied brain functional magnetic resonance imaging (fMRI) responses t...

Antinociceptive tolerance to NSAIDs in the agranular insular cortex is mediated by opioid mechanism

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Pirkulashvili N

2017-07-01

Full Text Available Natia Pirkulashvili,1 Nana Tsiklauri,1 Marina Nebieridze,2 Merab G Tsagareli1 1Laboratory of Pain and Analgesia, 2Laboratory of Brain Metabolism, Beritashvili Center for Experimental Biomedicine, Tbilisi, Georgia Abstract: Several lines of investigations have shown that in some brain areas, in particular, in the midbrain periaqueductal gray matter, rostral ventromedial medulla, central nucleus of amygdala, nucleus raphe magnus, and dorsal hippocampus, microinjections of nonsteroidal anti-inflammatory drugs (NSAIDs induce antinociception with distinct development of tolerance. The agranular insular cortex (AIC is a small region of the cerebral cortex located on the lateral area of the rat’s cerebral hemisphere that is involved in the perception and response to pain. In the present study, we investigated the development of tolerance to the analgesic effects of NSAIDs diclofenac, ketorolac, and xefocam microinjected into the AIC in rats. Male Wistar rats receiving NSAIDs into the AIC were tested for antinociception by tail-flick and hot plate tests. Treatment with each NSAID significantly enhanced the tail-flick and hot plate latencies on the first day, followed by a progressive decrease in the analgesic effect over a 4-day period, ie, they developed tolerance. Pretreatment with an opioid antagonist naloxone completely prevented, and posttreatment naloxone abolished, the analgesic effects of the three NSAIDs in both behavioral assays. These findings support the notion that the development of tolerance to the antinociceptive effects of NSAIDs is mediated via an endogenous opioid system possibly involving descending pain modulatory systems. Keywords: antinociception, endogenous opioids, descending modulation, nociception, non­opioid tolerance

Loss of long-term depression in the insular cortex after tail amputation in adult mice.

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Liu, Ming-Gang; Zhuo, Min

2014-01-08

The insular cortex (IC) is an important forebrain structure involved in pain perception and taste memory formation. Using a 64-channel multi-electrode array system, we recently identified and characterized two major forms of synaptic plasticity in the adult mouse IC: long-term potentiation (LTP) and long-term depression (LTD). In this study, we investigate injury-related metaplastic changes in insular synaptic plasticity after distal tail amputation. We found that tail amputation in adult mice produced a selective loss of low frequency stimulation-induced LTD in the IC, without affecting (RS)-3,5-dihydroxyphenylglycine (DHPG)-evoked LTD. The impaired insular LTD could be pharmacologically rescued by priming the IC slices with a lower dose of DHPG application, a form of metaplasticity which involves activation of protein kinase C but not protein kinase A or calcium/calmodulin-dependent protein kinase II. These findings provide important insights into the synaptic mechanisms of cortical changes after peripheral amputation and suggest that restoration of insular LTD may represent a novel therapeutic strategy against the synaptic dysfunctions underlying the pathophysiology of phantom pain.

Involvement of the insular cortex in regulating glucocorticoid effects on memory consolidation of inhibitory avoidance training

NARCIS (Netherlands)

Fornari, Raquel V.; Wichmann, Romy; Atucha, Erika; Desprez, Tifany; Eggens-Meijer, Ellie; Roozendaal, Benno

2012-01-01

Glucocorticoids are known to enhance the consolidation of memory of emotionally arousing experiences by acting upon a network of interconnected brain regions. Although animal studies typically do not consider the insular cortex (IC) to be part of this network, the present findings indicate that the

Modulation of the storage of social recognition memory by neurotransmitter systems in the insular cortex.

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Cavalcante, Lorena E S; Zinn, Carolina G; Schmidt, Scheila D; Saenger, Bruna F; Ferreira, Flávia F; Furini, Cristiane R G; Myskiw, Jociane C; Izquierdo, Ivan

2017-09-15

The insular cortex (IC) receives projections from prefrontal, entorhinal and cingulate cortex, olfactory bulb and basal nuclei and has reciprocal connections with the amygdala and entorhinal cortex. These connections suggest a possible involvement in memory processes; this has been borne out by data on several behaviors. Social recognition memory (SRM) is essential to form social groups and to establish hierarchies and social and affective ties. Despite its importance, knowledge about the brain structures and the neurotransmitter mechanisms involved in its processing is still scarce. Here we study the participation of NMDA-glutamatergic, D1/D5-dopaminergic, H2-histaminergic, β-adrenergic and 5-HT 1A -serotoninergic receptors of the IC in the consolidation of SRM. Male Wistar rats received intra-IC infusions of substances acting on these receptors immediately after the sample phase of a social discrimination task and 24h later were exposed to a 5-min retention test. The intra-IC infusion of antagonists of D1/D5, β-adrenergic or 5-HT 1A receptors immediately after the sample phase impaired the consolidation of SRM. These effects were blocked by the concomitant intra-IC infusion of agonists of these receptors. Antagonists and agonists of NMDA and H2 receptors had no effect on SRM. The results suggest that the dopaminergic D1/D5, β-adrenergic and serotonergic 5-HT 1A receptors in the IC, but not glutamatergic NMDA and the histaminergic H2 receptors, participate in the consolidation of SRM in the IC. Copyright © 2017 Elsevier B.V. All rights reserved.

Acute infusion of brain-derived neurotrophic factor in the insular cortex promotes conditioned taste aversion extinction.

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Rodríguez-Serrano, Luis M; Ramírez-León, Betsabee; Rodríguez-Durán, Luis F; Escobar, Martha L

2014-12-01

Brain-derived neurotrophic factor (BDNF) has emerged as one of the most potent molecular mediators not only for synaptic plasticity, but also for the behavioral organism-environment interactions. Our previous studies in the insular cortex (IC), a neocortical region that has been related with acquisition and retention of conditioned taste aversion (CTA), have demonstrated that intracortical microinfusion of BDNF induces a lasting potentiation of synaptic efficacy in the basolateral amygdaloid nucleus (Bla)-IC projection and enhances the retention of CTA memory of adult rats in vivo. The aim of the present study was to analyze whether acute BDNF-infusion in the IC modifies the extinction of CTA. Accordingly, animals were trained in the CTA task and received bilateral IC microinfusions of BDNF before extinction training. Our results showed that taste aversion was significantly reduced in BDNF rats from the first extinction trial. Additionally, we found that the effect of BDNF on taste aversion did not require extinction training. Finally we showed that the BDNF effect does not degrade the original taste aversion memory trace. These results emphasize that BDNF activity underlies memory extinction in neocortical areas and support the idea that BDNF is a key regulator and mediator of long-term synaptic modifications. Copyright © 2014 Elsevier Inc. All rights reserved.

Probabilistic Tractography Recovers a Rostrocaudal Trajectory of Connectivity Variability in the Human Insular Cortex

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Cerliani, Leonardo; Thomas, Rajat M; Jbabdi, Saad; Siero, Jeroen CW; Nanetti, Luca; Crippa, Alessandro; Gazzola, Valeria; D'Arceuil, Helen; Keysers, Christian

2012-01-01

The insular cortex of macaques has a wide spectrum of anatomical connections whose distribution is related to its heterogeneous cytoarchitecture. Although there is evidence of a similar cytoarchitectural arrangement in humans, the anatomical connectivity of the insula in the human brain has not yet been investigated in vivo. In the present work, we used in vivo probabilistic white-matter tractography and Laplacian eigenmaps (LE) to study the variation of connectivity patterns across insular territories in humans. In each subject and hemisphere, we recovered a rostrocaudal trajectory of connectivity variation ranging from the anterior dorsal and ventral insula to the dorsal caudal part of the long insular gyri. LE suggested that regional transitions among tractography patterns in the insula occur more gradually than in other brain regions. In particular, the change in tractography patterns was more gradual in the insula than in the medial premotor region, where a sharp transition between different tractography patterns was found. The recovered trajectory of connectivity variation in the insula suggests a relation between connectivity and cytoarchitecture in humans resembling that previously found in macaques: tractography seeds from the anterior insula were mainly found in limbic and paralimbic regions and in anterior parts of the inferior frontal gyrus, while seeds from caudal insular territories mostly reached parietal and posterior temporal cortices. Regions in the putative dysgranular insula displayed more heterogeneous connectivity patterns, with regional differences related to the proximity with either putative granular or agranular regions. Hum Brain Mapp 33:2005–2034, 2012. © 2011 Wiley Periodicals, Inc. PMID:21761507

Modulation of functionally localized right insular cortex activity using real-time fMRI-based neurofeedback

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Brian D Berman

2013-10-01

Full Text Available The capacity for subjects to learn to volitionally control localized brain activity using neurofeedback is actively being investigated. We aimed to investigate the ability of healthy volunteers to quickly learn to use visual feedback during real-time functional MRI (rtfMRI to modulate brain activity within their anterior right insular cortex (RIC localized during a blink suppression task, an approach of possible interest in the use of rtfMRI to reduce urges. The RIC region of interest (RIC-ROI was functionally localized using a blink suppression task, and BOLD signal changes within RIC-ROI used to create a constantly updating display fed back to the subject in the scanner. Subjects were instructed to use emotional imagery to try and increase activity within RIC-ROI during four feedback training runs (FB1–FB4. A ‘control’ run (CNTRL before training and a ‘transfer’ run (XSFR after training were performed without feedback to assess for baseline abilities and learning effects. Fourteen participants completed all neurofeedback training runs. At the group level, increased BOLD activity was seen in the anterior RIC during all the FB runs, but a significant increase in the functionally defined RIC-ROI was only attained during FB2. In atlas-defined insular cortex ROIs, significant increases were seen bilaterally during the CNTRL, FB1, FB2, and FB4 runs. Increased activity within the insular cortices did not show lateralization. Training did, however, result in a significant increase in functional connectivity between the RIC-ROI and the medial frontal gyrus when comparing FB4 to FB1. Since neurofeedback training did not lead to an increase in BOLD signal across all feedback runs, we suggest that learning to control one’s brain activity in this fashion may require longer or repeated rtfMRI training sessions.

Bidirectional modulation of taste aversion extinction by insular cortex LTP and LTD.

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Rodríguez-Durán, Luis F; Martínez-Moreno, Araceli; Escobar, Martha L

2017-07-01

The history of activity of a given neuron has been proposed to bidirectionally influence its future response to synaptic inputs. In particular, induction of synaptic plasticity expressions such as long-term potentiation (LTP) and long-term depression (LTD) modifies the performance of several behavioral tasks. Our previous studies in the insular cortex (IC), a neocortical region that has been related to acquisition and retention of conditioned taste aversion (CTA), have demonstrated that induction of LTP in the basolateral amygdaloid nucleus (Bla)-IC pathway before CTA training enhances the retention of this task. In addition, we reported that CTA training triggers a persistent impairment in the ability to induce in vivo LTP in the IC. The aim of the present study was to investigate whether LTD can be induced in the Bla-IC projection in vivo, as well as, whether the extinction of CTA is bidirectionally modified by previous synaptic plasticity induction in this pathway. Thus, rats received 900 train pulses (five 250μs pulses at 250Hz) delivered at 1Hz in the Bla-IC projection in order to induce LTD or 10 trains of 100Hz/1s with an intertrain interval of 20s in order to induce LTP. Seven days after surgery, rats were trained in the CTA task including the extinction trials. Our results show that the Bla-IC pathway is able to express in vivo LTD in an N-Methyl-D-aspartate (NMDA) receptor-dependent manner. Induction of LTD in the Bla-IC projection previous to CTA training facilitates the extinction of this task. Conversely, LTP induction enhances CTA retention. The present results show the bidirectional modulation of CTA extinction in response to IC-LTP and LTD, providing evidence of the homeostatic adaptation of taste learning. Copyright © 2016 Elsevier Inc. All rights reserved.

Delay discounting mediates the association between posterior insular cortex volume and social media addiction symptoms.

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Turel, Ofir; He, Qinghua; Brevers, Damien; Bechara, Antoine

2018-04-25

Addiction-like symptoms in relation to excessive and compulsive social media use are common in the general population. Because they can lead to various adverse effects, there is a growing need to understand the brain systems and processes that are involved in potential social media addiction. We focus on the morphology of the posterior subdivision of the insular cortex (i.e., the insula), because it has been shown to be instrumental to supporting the maintenance of substance addictions and problematic behaviors. Assuming that social media addiction shares neural similarities with more established ones and consistent with evidence from the neuroeconomics domain, we further examine one possible reason for this association-namely that insular morphology influences one's delay discounting and that this delay discounting contributes to exaggerated preference for immediate social media rewards and consequent addiction-like symptoms. Based on voxel-based morphometry techniques applied to MRI scans of 32 social media users, we show that the gray matter volumes of the bilateral posterior insula are negatively associated with social media addiction symptoms. We further show that this association is mediated by delay discounting. This provides initial evidence that insular morphology can be associated with potential social media addiction, in part, through its contribution to poor foresight and impulsivity as captured by delay discounting.

The Anterior Insular Cortex→Central Amygdala Glutamatergic Pathway Is Critical to Relapse after Contingency Management.

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Venniro, Marco; Caprioli, Daniele; Zhang, Michelle; Whitaker, Leslie R; Zhang, Shiliang; Warren, Brandon L; Cifani, Carlo; Marchant, Nathan J; Yizhar, Ofer; Bossert, Jennifer M; Chiamulera, Cristiano; Morales, Marisela; Shaham, Yavin

2017-10-11

Despite decades of research on neurobiological mechanisms of psychostimulant addiction, the only effective treatment for many addicts is contingency management, a behavioral treatment that uses alternative non-drug reward to maintain abstinence. However, when contingency management is discontinued, most addicts relapse to drug use. The brain mechanisms underlying relapse after cessation of contingency management are largely unknown, and, until recently, an animal model of this human condition did not exist. Here we used a novel rat model, in which the availability of a mutually exclusive palatable food maintains prolonged voluntary abstinence from intravenous methamphetamine self-administration, to demonstrate that the activation of monosynaptic glutamatergic projections from anterior insular cortex to central amygdala is critical to relapse after the cessation of contingency management. We identified the anterior insular cortex-to-central amygdala projection as a new addiction- and motivation-related projection and a potential target for relapse prevention. Published by Elsevier Inc.

Attenuated sensitivity to the emotions of others by insular lesion

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Yuri eTerasawa

2015-09-01

Full Text Available The insular cortex has been considered to be the neural base of visceral sensation for many years. Previous studies in psychology and cognitive neuroscience have accumulated evidence indicating that interoception is an essential factor in the subjective feeling of emotion. Recent neuroimaging studies have demonstrated that anterior insular cortex activation is associated with accessing interoceptive information and underpinning the subjective experience of emotional state.Only a small number of studies have focused on the influence of insular damage on emotion processing and interoceptive awareness. Moreover, disparate hypotheses have been proposed for the alteration of emotion processing by insular lesions. Some studies show that insular lesions yield an inability for understanding and representing disgust exclusively, but other studies suggest that such lesions modulate arousal and valence judgments for both positive and negative emotions.In this study, we examined the alteration in emotion recognition in three right insular and adjacent area damaged cases with well-preserved higher cognitive function. Participants performed an experimental task using morphed photos that ranged between neutral and emotional facial expressions (i.e., anger, sadness, disgust, and happiness. Recognition rates of particular emotions were calculated to measure emotional sensitivity. In addition, they performed heartbeat perception task for measuring interoceptive accuracy. The cases identified emotions that have high arousal level (e.g., anger as less aroused emotions (e.g., sadness and a case showed remarkably low interoceptive accuracy. The current results show that insular lesions lead to attenuated emotional sensitivity across emotions, rather than category-specific impairments such as to disgust. Despite the small number of cases, our findings suggest that the insular cortex modulates recognition of emotional saliency and mediates interoceptive and emotional

Posterior insular cortex - a site of vestibular-somatosensory interaction?

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Baier, Bernhard; Zu Eulenburg, Peter; Best, Christoph; Geber, Christian; Müller-Forell, Wibke; Birklein, Frank; Dieterich, Marianne

2013-09-01

Background In previous imaging studies the insular cortex (IC) has been identified as an essential part of the processing of a wide spectrum of perception and sensorimotor integration. Yet, there are no systematic lesion studies in a sufficient number of patients examining whether processing of vestibular and the interaction of somatosensory and vestibular signals take place in the IC. Methods We investigated acute stroke patients with lesions affecting the IC in order to fill this gap. In detail, we explored signs of a vestibular tone imbalance such as the deviation of the subjective visual vertical (SVV). We applied voxel-lesion behaviour mapping analysis in 27 patients with acute unilateral stroke. Results Our data demonstrate that patients with lesions of the posterior IC have an abnormal tilt of SVV. Furthermore, re-analysing data of 20 patients from a previous study, we found a positive correlation between thermal perception contralateral to the stroke and the severity of the SVV tilt. Conclusions We conclude that the IC is a sensory brain region where different modalities might interact.

Disconnection of basolateral amygdala and insular cortex disrupts conditioned approach in Pavlovian lever autoshaping.

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Nasser, Helen M; Lafferty, Danielle S; Lesser, Ellen N; Bacharach, Sam Z; Calu, Donna J

2018-01-01

Previously established individual differences in appetitive approach and devaluation sensitivity observed in goal- and sign-trackers may be attributed to differences in the acquisition, modification, or use of associative information in basolateral amygdala (BLA) pathways. Here, we sought to determine the extent to which communication of associative information between BLA and anterior portions of insular cortex (IC) supports ongoing Pavlovian conditioned approach behaviors in sign- and goal-tracking rats, in the absence of manipulations to outcome value. We hypothesized that the BLA mediates goal-, but not sign- tracking approach through interactions with the IC, a brain region involved in supporting flexible behavior. We first trained rats in Pavlovian lever autoshaping to determine their sign- or goal-tracking tendency. During alternating test sessions, we gave unilateral intracranial injections of vehicle or a cocktail of gamma-aminobutyric acid (GABA) receptor agonists, baclofen and muscimol, unilaterally into the BLA and contralaterally or ipsilaterally into the IC prior to reinforced lever autoshaping sessions. Consistent with our hypothesis we found that contralateral inactivation of BLA and IC increased the latency to approach the food cup and decreased the number of food cup contacts in goal-trackers. While contralateral inactivation of BLA and IC did not affect the total number of lever contacts in sign-trackers, this manipulation increased the latency to approach the lever. Ipsilateral inactivation of BLA and IC did not impact approach behaviors in Pavlovian lever autoshaping. These findings, contrary to our hypothesis, suggest that communication between BLA and IC maintains a representation of initially learned appetitive associations that commonly support the initiation of Pavlovian conditioned approach behavior regardless of whether it is directed at the cue or the location of reward delivery. Copyright © 2017 Elsevier Inc. All rights reserved.

Sodium butyrate into the insular cortex during conditioned taste-aversion acquisition delays aversive taste memory extinction.

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Núñez-Jaramillo, Luis; Reyes-López, Julian; Miranda, María Isabel

2014-04-16

Histone acetylation is one mechanism that promotes gene expression, and it increases during learning of various tasks. Specifically, novel taste consumption produces an increased acetylation of histone lysine residues in the insular cortex (IC), where protein synthesis is crucial during memory consolidation of conditioned taste aversion (CTA). However, the role of this elevated histone acetylation during CTA learning has not been examined directly. Thus, the present study investigated the effects of sodium butyrate (NaBu), a histone deacetylase inhibitor, injected into the IC during CTA acquisition. Male Wistar rats, IC bilaterally implanted, were injected 60 min before saccharine presentation, with a total volume of 0.5 µl of NaBu solution (100, 500, and 10 µg/0.5 µl) or saline; 30 min later animals were injected intraperitoneally with lithium chloride, a malaise-inducing drug. The next day, CTA retrieval was tested. No effects of NaBu were observed during acquisition or retrieval, but during extinction trials, a significant delay in aversive memory extinction was observed in the group injected with the lowest NaBu dose. This result indicates that NaBu in the IC strengthens CTA and delays aversive memory extinction, and suggests that histone acetylation could increase long-term taste-aversive memory strength.

Memory Trace Reactivation and Behavioral Response during Retrieval Are Differentially Modulated by Amygdalar Glutamate Receptors Activity: Interaction between Amygdala and Insular Cortex

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Osorio-Gómez, Daniel; Guzmán-Ramos, Kioko; Bermúdez-Rattoni, Federico

2017-01-01

The insular cortex (IC) is required for conditioned taste aversion (CTA) retrieval. However, it remains unknown which cortical neurotransmitters levels are modified upon CTA retrieval. Using in vivo microdialysis, we observed that there were clear elevations in extracellular glutamate, norepinephrine, and dopamine in and around the center of the…

Posterior insular cortex – a site of vestibular–somatosensory interaction?

Science.gov (United States)

Baier, Bernhard; zu Eulenburg, Peter; Best, Christoph; Geber, Christian; Müller-Forell, Wibke; Birklein, Frank; Dieterich, Marianne

2013-01-01

Background In previous imaging studies the insular cortex (IC) has been identified as an essential part of the processing of a wide spectrum of perception and sensorimotor integration. Yet, there are no systematic lesion studies in a sufficient number of patients examining whether processing of vestibular and the interaction of somatosensory and vestibular signals take place in the IC. Methods We investigated acute stroke patients with lesions affecting the IC in order to fill this gap. In detail, we explored signs of a vestibular tone imbalance such as the deviation of the subjective visual vertical (SVV). We applied voxel-lesion behaviour mapping analysis in 27 patients with acute unilateral stroke. Results Our data demonstrate that patients with lesions of the posterior IC have an abnormal tilt of SVV. Furthermore, re-analysing data of 20 patients from a previous study, we found a positive correlation between thermal perception contralateral to the stroke and the severity of the SVV tilt. Conclusions We conclude that the IC is a sensory brain region where different modalities might interact. PMID:24392273

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

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Hassiba eBeldjoud

2015-04-01

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

Suppressive responses by visual food cues in postprandial activities of insular cortex as revealed by magnetoencephalography.

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Yoshikawa, Takahiro; Tanaka, Masaaki; Ishii, Akira; Watanabe, Yasuyoshi

2014-06-03

'Hara-Hachibu' in Japanese means a subjective sense by which we stop eating just before the motivation to eat is completely lost, a similar concept to caloric restriction (CR). Insular cortex is a critical platform which integrates sensory information into decision-making processes in eating behavior. We compared the responses of insular cortex, as assessed by magnetoencephalography (MEG), immediately after presentation of food images in the Fasting condition with those in the 'Hara-Hachibu' condition. Eleven healthy, right-handed males [age, 27.2±9.6 years; body mass index, 22.6±2.1kg/m(2) (mean±SD)] were enrolled in a randomized, two-crossover experiment (Fasting and 'Hara-Hachibu' conditions). Before the MEG recordings in the 'Hara-Hachibu' condition, the participants consumed rice balls as much as they judged themselves to have consumed shortly before reaching satiety. During the MEG recordings, they viewed food pictures projected on a screen. The intensities of MEG responses to viewing food pictures were significantly lower in the 'Hara-Hachibu' condition than those in the Fasting condition (Pvisual food stimuli in the 'Hara-Hachibu' condition was positively associated with the factor-3 (food tasted) (r=0.693, P=0.018) and aggregated scores (r=0.659, P=0.027) of the Power of Food Scale, a self-report measure of hedonic hunger. These findings may help to elucidate the neural basis of variability of appetite phenotypes under the condition of CR among individuals, and to develop possible strategies for the maintenance of adequate CR in daily life. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

CaMKII Requirement for in Vivo Insular Cortex LTP Maintenance and CTA Memory Persistence

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Yectivani Juárez-Muñoz

2017-11-01

Full Text Available Calcium-calmodulin/dependent protein kinase II (CaMKII plays an essential role in LTP induction, but since it has the capacity to remain persistently activated even after the decay of external stimuli it has been proposed that it can also be necessary for LTP maintenance and therefore for memory persistence. It has been shown that basolateral amygdaloid nucleus (Bla stimulation induces long-term potentiation (LTP in the insular cortex (IC, a neocortical region implicated in the acquisition and retention of conditioned taste aversion (CTA. Our previous studies have demonstrated that induction of LTP in the Bla-IC pathway before CTA training increased the retention of this task. Although it is known that IC-LTP induction and CTA consolidation share similar molecular mechanisms, little is known about the molecular actors that underlie their maintenance. The purpose of the present study was to evaluate the role of CaMKII in the maintenance of in vivo Bla-IC LTP as well as in the persistence of CTA long-term memory (LTM. Our results show that acute microinfusion of myr-CaMKIINtide, a selective inhibitor of CaMKII, in the IC of adult rats during the late-phase of in vivo Bla-IC LTP blocked its maintenance. Moreover, the intracortical inhibition of CaMKII 24 h after CTA acquisition impairs CTA-LTM persistence. Together these results indicate that CaMKII is a central key component for the maintenance of neocortical synaptic plasticity as well as for persistence of CTA-LTM.

Intracellular calcium chelation and pharmacological SERCA inhibition of Ca2+ pump in the insular cortex differentially affect taste aversive memory formation and retrieval.

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Miranda, María Isabel; González-Cedillo, Francisco J; Díaz-Muñoz, Mauricio

2011-09-01

Variation in intracellular calcium concentration regulates the induction of long-term synaptic plasticity and is associated with a variety of memory/retrieval and learning paradigms. Accordingly, impaired calcium mobilization from internal deposits affects synaptic plasticity and cognition in the aged brain. During taste memory formation several proteins are modulated directly or indirectly by calcium, and recent evidence suggests the importance of calcium buffering and the role of intracellular calcium deposits during cognitive processes. Thus, the main goal of this research was to study the consequence of hampering changes in cytoplasmic calcium and inhibiting SERCA activity by BAPTA-AM and thapsigargin treatments, respectively, in the insular cortex during different stages of taste memory formation. Using conditioned taste aversion (CTA), we found differential effects of BAPTA-AM and thapsigargin infusions before and after gustatory stimulation, as well as during taste aversive memory consolidation; BAPTA-AM, but not thapsigargin, attenuates acquisition and/or consolidation of CTA, but neither compound affects taste aversive memory retrieval. These results point to the importance of intracellular calcium dynamics in the insular cortex during different stages of taste aversive memory formation. Copyright © 2011 Elsevier Inc. All rights reserved.

Anti-correlated cortical networks of intrinsic connectivity in the rat brain.

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Schwarz, Adam J; Gass, Natalia; Sartorius, Alexander; Risterucci, Celine; Spedding, Michael; Schenker, Esther; Meyer-Lindenberg, Andreas; Weber-Fahr, Wolfgang

2013-01-01

In humans, resting-state blood oxygen level-dependent (BOLD) signals in the default mode network (DMN) are temporally anti-correlated with those from a lateral cortical network involving the frontal eye fields, secondary somatosensory and posterior insular cortices. Here, we demonstrate the existence of an analogous lateral cortical network in the rat brain, extending laterally from anterior secondary sensorimotor regions to the insular cortex and exhibiting low-frequency BOLD fluctuations that are temporally anti-correlated with a midline "DMN-like" network comprising posterior/anterior cingulate and prefrontal cortices. The primary nexus for this anti-correlation relationship was the anterior secondary motor cortex, close to regions that have been identified with frontal eye fields in the rat brain. The anti-correlation relationship was corroborated after global signal removal, underscoring this finding as a robust property of the functional connectivity signature in the rat brain. These anti-correlated networks demonstrate strong anatomical homology to networks identified in human and monkey connectivity studies, extend the known preserved functional connectivity relationships between rodent and primates, and support the use of resting-state functional magnetic resonance imaging as a translational imaging method between rat models and humans.

Engagement of the Rat Hindlimb Motor Cortex across Natural Locomotor Behaviors.

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DiGiovanna, Jack; Dominici, Nadia; Friedli, Lucia; Rigosa, Jacopo; Duis, Simone; Kreider, Julie; Beauparlant, Janine; van den Brand, Rubia; Schieppati, Marco; Micera, Silvestro; Courtine, Grégoire

2016-10-05

Contrary to cats and primates, cortical contribution to hindlimb locomotor movements is not critical in rats. However, the importance of the motor cortex to regain locomotion after neurological disorders in rats suggests that cortical engagement in hindlimb motor control may depend on the behavioral context. To investigate this possibility, we recorded whole-body kinematics, muscle synergies, and hindlimb motor cortex modulation in freely moving rats performing a range of natural locomotor procedures. We found that the activation of hindlimb motor cortex preceded gait initiation. During overground locomotion, the motor cortex exhibited consistent neuronal population responses that were synchronized with the spatiotemporal activation of hindlimb motoneurons. Behaviors requiring enhanced muscle activity or skilled paw placement correlated with substantial adjustment in neuronal population responses. In contrast, all rats exhibited a reduction of cortical activity during more automated behavior, such as stepping on a treadmill. Despite the facultative role of the motor cortex in the production of locomotion in rats, these results show that the encoding of hindlimb features in motor cortex dynamics is comparable in rats and cats. However, the extent of motor cortex modulations appears linked to the degree of volitional engagement and complexity of the task, reemphasizing the importance of goal-directed behaviors for motor control studies, rehabilitation, and neuroprosthetics. We mapped the neuronal population responses in the hindlimb motor cortex to hindlimb kinematics and hindlimb muscle synergies across a spectrum of natural locomotion behaviors. Robust task-specific neuronal population responses revealed that the rat motor cortex displays similar modulation as other mammals during locomotion. However, the reduced motor cortex activity during more automated behaviors suggests a relationship between the degree of engagement and task complexity. This relationship

Gray matter volume of the anterior insular cortex and social networking.

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Spagna, Alfredo; Dufford, Alexander J; Wu, Qiong; Wu, Tingting; Zheng, Weihao; Coons, Edgar E; Hof, Patrick R; Hu, Bin; Wu, Yanhong; Fan, Jin

2018-05-01

In human life, social context requires the engagement in complex interactions among individuals as the dynamics of social networks. The evolution of the brain as the neurological basis of the mind must be crucial in supporting social networking. Although the relationship between social networking and the amygdala, a small but core region for emotion processing, has been reported, other structures supporting sophisticated social interactions must be involved and need to be identified. In this study, we examined the relationship between morphology of the anterior insular cortex (AIC), a structure involved in basic and high-level cognition, and social networking. Two independent cohorts of individuals (New York group n = 50, Beijing group n = 100) were recruited. Structural magnetic resonance images were acquired and the social network index (SNI), a composite measure summarizing an individual's network diversity, size, and complexity, was measured. The association between morphological features of the AIC, in addition to amygdala, and the SNI was examined. Positive correlations between the measures of the volume as well as sulcal depth of the AIC and the SNI were found in both groups, while a significant positive correlation between the volume of the amygdala and the SNI was only found in the New York group. The converging results from the two groups suggest that the AIC supports network-level social interactions. © 2018 Wiley Periodicals, Inc.

Parental Praise Correlates with Posterior Insular Cortex Gray Matter Volume in Children and Adolescents.

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Izumi Matsudaira

Full Text Available A positive parenting style affects psychological and cognitive development in children. Neuroimaging studies revealed that a positive parenting style influenced brain structure in children. Parental praise is a concrete behavior observed in positive parenting. Although previous psychological studies revealed a positive effect of parental praise on children, little is known about the relationship between parental praise and brain structure in children. Thus, the purpose of the present study was to determine whether there was a correlation between the parental attitude towards praising their child and gray matter volume in the children (116 boys and 109 girls; mean age, 10.6 years old. We examined the correlation between regional gray matter volume and parental praise using voxel-based morphometry (VBM following magnetic resonance imaging (MRI. In addition, to confirm the positive effects of parental praise, we analyzed the correlation between the frequency of parental praise and personality traits in children. We showed that the parental attitude towards praising their child was significantly and positively correlated with the gray matter volume of the left posterior insular cortex in children. Moreover, we found a significant positive correlation between parental attitude towards praising their child and the personality traits of conscientiousness and openness to experience in the children. Prior studies said that gray matter volume in the posterior insula was correlated with empathy, and the functional connectivity between this area and the amygdala was associated with emotional regulation. Furthermore, the posterior insula relates to auditory function, and therefore, was likely involved in the processing of parental praise. Considering the possibility of experience-dependent plasticity, frequent parental praise would lead to increased posterior insular gray matter volume in children. Our study is the first to elucidate the relationship between

PKMζ inhibition prevents the metaplastic change induced by conditioned taste aversion on insular cortex long-term potentiation in vivo.

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Ángeles-Durán, Sandybel; Ramos-Languren, Laura E; Escobar, Martha L

2012-01-01

The activity history of a given neuron or pathway has been suggested to influence its future responses to synaptic inputs. In particular, training in several learning tasks produces a metaplastic change, that is, a change in the ability to induce subsequent synaptic plasticity. Experimental evidence shows that the maintenance of long term memory and long-term potentiation (LTP) requires the persistent action of the atypical protein kinase Cisoform, protein kinase M ζ (PKM ζ ). Recent work has demonstrated that the inactivation of PKM ζ in the insular cortex (IC) abolishes conditioned taste aversion (CTA) long term memory. Our previous studies in the IC have demonstrated that the induction of LTP in the basolateral amygdaloid nucleus (Bla)-IC projection previous to CTA training enhances the retention of this task. Moreover, recently, we have observed that CTA training blocks the subsequent induction of LTP in the Bla-IC projection. The aim of the present study was to investigate the participation of PKM ζon the CTA-dependent modification of the ability to induce subsequent LTP in the Bla-IC projection in vivo . Thus, we have delivered high-frequency stimulation in the Bla-IC projection in order to induce in vivo IC-LTP in the rats that underwent or did not have an impairment of CTA retention due to the intracortical administration of the selective PKM ζ pseudosubstrate inhibitory peptide, ZIP. Our results show that the microinfusion of ZIP into the IC of the behaving rats impairs long-term memory of CTA and prevents its effects on IC-LTP. These results indicate that PKM ζ is a key component of the cellular mechanisms necessary for the persistence of lasting memory traces as well as for those underlying metaplastic changes in neocortex, contributing to the persistence of aversive memories.

Insular subdivisions functional connectivity dysfunction within major depressive disorder.

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Peng, Xiaolong; Lin, Pan; Wu, Xiaoping; Gong, Ruxue; Yang, Rui; Wang, Jue

2018-02-01

Major depressive disorder (MDD) is a mental disorder characterized by cognitive and affective deficits. Previous studies suggested that insula is a crucial node of the salience network for initiating network switching, and dysfunctional connection to this region may be related to the mechanism of MDD. In this study, we systematically investigated and quantified the altered functional connectivity (FC) of the specific insular subdivisions and its relationship to psychopathology of MDD. Resting-state FC of insular subdivisions, including bilateral ventral/dorsal anterior insula and posterior insula, were estimated in 19 MDD patients and 19 healthy controls. Abnormal FC was quantified between groups. Additionally, we investigated the relationships between insular connectivity and depressive symptom severity. MDD patients demonstrated aberrant FC for insular subdivisions to superior temporal sulcus, inferior prefrontal gyrus, amygdala and posterior parietal cortex. Moreover, depression symptoms (Hamilton Depression Rating Scale and Hamilton Anxiety Rating Scale scorers) were associated with the FC values of insular subdivisions. First, the sample size of our current study is relatively small, which may affect the statistic power. Second, using standardized insular subdivision seeds for FC analyses may neglect subtle natural differences in size and location of functional area across individuals and may thus affect connectivity maps. Abnormal FC of insular subdivisions to default network and central executive network may represent impaired intrinsic networks switching which may affect the underlying emotional and sensory disturbances in MDD. And our findings can help to understand the pathophysiology and underlying neural mechanisms of MDD. Copyright © 2017 Elsevier B.V. All rights reserved.

Conditioned taste aversion prevents the long-lasting BDNF-induced enhancement of synaptic transmission in the insular cortex: A metaplastic effect.

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Rivera-Olvera, Alejandro; Rodríguez-Durán, Luis F; Escobar, Martha L

2016-04-01

Homeostatic plasticity mechanisms dynamically adjust synaptic strengths to promote stability that is crucial for memory storage. Metaplasticity is an example of these forms of plasticity that modify the capacity of synapses to experience subsequent Hebbian modifications. In particular, training in several behavioral tasks modifies the ability to induce long-term potentiation (LTP). Recently, we have reported that prior training in conditioned taste aversion (CTA) prevents the subsequent induction of LTP generated by high frequency stimulation in the projection from the basolateral nucleus of the amygdala (Bla) to the insular cortex (IC). One of the key molecular players that underlie long-term synaptic plasticity is brain-derived neurotrophic factor (BDNF). Previous studies from our group reported that acute microinfusion of BDNF in the IC induces a lasting potentiation of synaptic efficacy at the Bla-IC projection. Thus, the aim of the present study was to analyze whether CTA training modifies the ability to induce subsequent BDNF-induced potentiation of synaptic transmission in the Bla-IC projection in vivo. Accordingly, CTA trained rats received intracortical microinfusion of BDNF in order to induce lasting potentiation 48h after the aversion test. Our results show that CTA training prevents the induction of in vivo BDNF-LTP in the Bla-IC projection. The present results provide evidence that CTA modulates BDNF-dependent changes in IC synaptic strength. Copyright © 2016 Elsevier Inc. All rights reserved.

Mutism and auditory agnosia due to bilateral insular damage--role of the insula in human communication.

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Habib, M; Daquin, G; Milandre, L; Royere, M L; Rey, M; Lanteri, A; Salamon, G; Khalil, R

1995-03-01

We report a case of transient mutism and persistent auditory agnosia due to two successive ischemic infarcts mainly involving the insular cortex on both hemispheres. During the 'mutic' period, which lasted about 1 month, the patient did not respond to any auditory stimuli and made no effort to communicate. On follow-up examinations, language competences had re-appeared almost intact, but a massive auditory agnosia for non-verbal sounds was observed. From close inspection of lesion site, as determined with brain resonance imaging, and from a study of auditory evoked potentials, it is concluded that bilateral insular damage was crucial to both expressive and receptive components of the syndrome. The role of the insula in verbal and non-verbal communication is discussed in the light of anatomical descriptions of the pattern of connectivity of the insular cortex.

Androgen receptor immunoreactivity in rat occipital cortex after callosotomy

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G Lepore

2009-08-01

Full Text Available Gonadal steroidogenesis can be influenced by direct neural links between the central nervous system and the gonads. It is known that androgen receptor (AR is expressed in many areas of the rat brain involved in neuroendocrine control of reproduction, such as the cerebral cortex. It has been recently shown that the occipital cortex exerts an inhibitory effect on testicular stereoidogenesis by a pituitary-independent neural mechanism. Moreover, the complete transection of the corpus callosum leads to an increase in testosterone (T secretion of hemigonadectomized rats. The present study was undertaken to analyze the possible corticocortical influences regulating male reproductive activities. Adult male Wistar rats were divided into 4 groups: 1 intact animals as control; 2 rats undergoing sham callosotomy; 3 posterior callosotomy; 4 gonadectomy and posterior callosotomy. Western blot analysis showed no remarkable variations in cortical AR expression in any of the groups except in group I where a significant decrease in AR levels was found. Similarly, both immunocytochemical study and cell count estimation showed a lower AR immunoreactivity in occipital cortex of callosotomized rats than in other groups. In addition, there was no difference in serum T and LH concentration between sham-callosotomized and callosotomized rats. In conclusion, our results show that posterior callosotomy led to a reduction in AR in the right occipital cortex suggesting a putative inhibiting effect of the contralateral cortical area.

Individual variations in maternal care early in life correlate with later life decision-making and c-fos expression in prefrontal subregions of rats.

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Felisa N van Hasselt

Full Text Available Early life adversity affects hypothalamus-pituitary-adrenal axis activity, alters cognitive functioning and in humans is thought to increase the vulnerability to psychopathology--e.g. depression, anxiety and schizophrenia--later in life. Here we investigated whether subtle natural variations among individual rat pups in the amount of maternal care received, i.e. differences in the amount of licking and grooming (LG, correlate with anxiety and prefrontal cortex-dependent behavior in young adulthood. Therefore, we examined the correlation between LG received during the first postnatal week and later behavior in the elevated plus maze and in decision-making processes using a rodent version of the Iowa Gambling Task (rIGT. In our cohort of male and female animals a high degree of LG correlated with less anxiety in the elevated plus maze and more advantageous choices during the last 10 trials of the rIGT. In tissue collected 2 hrs after completion of the task, the correlation between LG and c-fos expression (a marker of neuronal activity was established in structures important for IGT performance. Negative correlations existed between rIGT performance and c-fos expression in the lateral orbitofrontal cortex, prelimbic cortex, infralimbic cortex and insular cortex. The insular cortex correlations between c-fos expression and decision-making performance depended on LG background; this was also true for the lateral orbitofrontal cortex in female rats. Dendritic complexity of insular or infralimbic pyramidal neurons did not or weakly correlate with LG background. We conclude that natural variations in maternal care received by pups may significantly contribute to later-life decision-making and activity of underlying brain structures.

Decoding bipedal locomotion from the rat sensorimotor cortex

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Rigosa, J.; Panarese, A.; Dominici, N.; Friedli, L.; van den Brand, R.; Carpaneto, J.; DiGiovanna, J.; Courtine, G.; Micera, S.

2015-10-01

Objective. Decoding forelimb movements from the firing activity of cortical neurons has been interfaced with robotic and prosthetic systems to replace lost upper limb functions in humans. Despite the potential of this approach to improve locomotion and facilitate gait rehabilitation, decoding lower limb movement from the motor cortex has received comparatively little attention. Here, we performed experiments to identify the type and amount of information that can be decoded from neuronal ensemble activity in the hindlimb area of the rat motor cortex during bipedal locomotor tasks. Approach. Rats were trained to stand, step on a treadmill, walk overground and climb staircases in a bipedal posture. To impose this gait, the rats were secured in a robotic interface that provided support against the direction of gravity and in the mediolateral direction, but behaved transparently in the forward direction. After completion of training, rats were chronically implanted with a micro-wire array spanning the left hindlimb motor cortex to record single and multi-unit activity, and bipolar electrodes into 10 muscles of the right hindlimb to monitor electromyographic signals. Whole-body kinematics, muscle activity, and neural signals were simultaneously recorded during execution of the trained tasks over multiple days of testing. Hindlimb kinematics, muscle activity, gait phases, and locomotor tasks were decoded using offline classification algorithms. Main results. We found that the stance and swing phases of gait and the locomotor tasks were detected with accuracies as robust as 90% in all rats. Decoded hindlimb kinematics and muscle activity exhibited a larger variability across rats and tasks. Significance. Our study shows that the rodent motor cortex contains useful information for lower limb neuroprosthetic development. However, brain-machine interfaces estimating gait phases or locomotor behaviors, instead of continuous variables such as limb joint positions or speeds

Fetal frontal cortex transplant (14C) 2-deoxyglucose uptake and histology: survival in cavities of host rat brain motor cortex

International Nuclear Information System (INIS)

Sharp, F.R.; Gonzalez, M.F.

1984-01-01

Fetal frontal neocortex from 18-day-old rat embryonic brain was transplanted into cavities in 30-day-old host motor cortex. Sixty days after transplantation, 5 of 15 transplanted rats had surviving fetal transplants. The fetal cortex transplants were physically attached to the host brain, completely filled the original cavity, and had numerous surviving cells including pyramidal neurons. Cell lamination within the fetal transplant was abnormal. The ( 14 C) 2-deoxyglucose uptake of all five of the fetal neocortex transplants was less than adjacent cortex and contralateral host motor-sensory cortex, but more than adjacent corpus callosum white matter. The results indicate that fetal frontal neocortex can be transplanted into damaged rat motor cortex. The metabolic rate of the transplants suggests they could be partially functional

Long-term aversive taste memory requires insular and amygdala protein degradation.

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Rodriguez-Ortiz, Carlos J; Balderas, Israela; Saucedo-Alquicira, Fernando; Cruz-Castañeda, Paulina; Bermudez-Rattoni, Federico

2011-03-01

Some reports have shown that the ubiquitin-proteasome system (UPS) is necessary to degrade repressor factors to produce new proteins essential to memory consolidation. Furthermore, recent evidence suggests that memory updating also relies on protein degradation through the UPS. To evaluate whether degradation of proteins is part of the cellular events needed for long-term storage of taste aversion, we injected lactacystin--an UPS inhibitor--into the amygdala and/or insular cortex 30 min before the first or second training trials. The results revealed that degradation of proteins in either the amygdala or insular cortex suffices for long-term stabilization of first-time encounter taste aversion. On the other hand, lactacystin applied in the insula, but not in the amygdala, before the second training prevented long-term storage of updated information. Our results support that degradation of proteins by means of the UPS is required every time taste aversion is to be stored in long-term memory. Copyright © 2010 Elsevier Inc. All rights reserved.

Engagement of the Rat Hindlimb Motor Cortex across Natural Locomotor Behaviors

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DiGiovanna, J.; Dominici, N.; Friedli, L.; Rigosa, J.; Duis, S.; Kreider, J.; Beauparlant, J.; van den Brand, R.; Schieppati, M.; Micera, S.; Courtine, G.

2016-01-01

Contrary to cats and primates, cortical contribution to hindlimb locomotor movements is not critical in rats. However, the importance of the motor cortex to regain locomotion after neurological disorders in rats suggests that cortical engagement in hindlimb motor control may depend on the behavioral context. To investigate this possibility, we recorded whole-body kinematics, muscle synergies, and hindlimb motor cortex modulation in freely moving rats performing a range of natural locomotor pr...

Development of rat female genital cortex and control of female puberty by sexual touch.

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Constanze Lenschow

2017-09-01

Full Text Available Rat somatosensory cortex contains a large sexually monomorphic genital representation. Genital cortex undergoes an unusual 2-fold expansion during puberty. Here, we investigate genital cortex development and female rat sexual maturation. Ovariectomies and estradiol injections suggested sex hormones cause the pubertal genital cortex expansion but not its maintenance at adult size. Genital cortex expanded by thalamic afferents invading surrounding dysgranular cortex. Genital touch was a dominant factor driving female sexual maturation. Raising female rats in contact with adult males promoted genital cortex expansion, whereas contact to adult females or nontactile (audio-visual-olfactory male cues did not. Genital touch imposed by human experimenters powerfully advanced female genital cortex development and sexual maturation. Long-term blocking of genital cortex by tetrodotoxin in pubescent females housed with males prevented genital cortex expansion and decelerated vaginal opening. Sex hormones, sexual experience, and neural activity shape genital cortex, which contributes to the puberty promoting effects of sexual touch.

Development of rat female genital cortex and control of female puberty by sexual touch.

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Lenschow, Constanze; Sigl-Glöckner, Johanna; Brecht, Michael

2017-09-01

Rat somatosensory cortex contains a large sexually monomorphic genital representation. Genital cortex undergoes an unusual 2-fold expansion during puberty. Here, we investigate genital cortex development and female rat sexual maturation. Ovariectomies and estradiol injections suggested sex hormones cause the pubertal genital cortex expansion but not its maintenance at adult size. Genital cortex expanded by thalamic afferents invading surrounding dysgranular cortex. Genital touch was a dominant factor driving female sexual maturation. Raising female rats in contact with adult males promoted genital cortex expansion, whereas contact to adult females or nontactile (audio-visual-olfactory) male cues did not. Genital touch imposed by human experimenters powerfully advanced female genital cortex development and sexual maturation. Long-term blocking of genital cortex by tetrodotoxin in pubescent females housed with males prevented genital cortex expansion and decelerated vaginal opening. Sex hormones, sexual experience, and neural activity shape genital cortex, which contributes to the puberty promoting effects of sexual touch.

Encoding changes in orbitofrontal cortex in reversal-impaired aged rats.

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Schoenbaum, Geoffrey; Setlow, Barry; Saddoris, Michael P; Gallagher, Michela

2006-03-01

Previous work in rats and primates has shown that normal aging can be associated with a decline in cognitive flexibility mediated by prefrontal circuits. For example, aged rats are impaired in rapid reversal learning, which in young rats depends critically on the orbitofrontal cortex. To assess whether aging-related reversal impairments reflect orbitofrontal dysfunction, we identified aged rats with reversal learning deficits and then recorded single units as these rats, along with unimpaired aged cohorts and young control rats, learned and reversed a series of odor discrimination problems. We found that the flexibility of neural correlates in orbitofrontal cortex was markedly diminished in aged rats characterized as reversal-impaired in initial training. In particular, although many cue-selective neurons in young and aged-unimpaired rats reversed odor preference when the odor-outcome associations were reversed, cue-selective neurons in reversal-impaired aged rats did not. In addition, outcome-expectant neurons in aged-impaired rats failed to become active during cue sampling after learning. These altered features of neural encoding could provide a basis for cognitive inflexibility associated with normal aging.

Functional role for suppression of the insular-striatal circuit in modulating interoceptive effects of alcohol.

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Jaramillo, Anel A; Agan, Verda E; Makhijani, Viren H; Pedroza, Stephen; McElligott, Zoe A; Besheer, Joyce

2017-09-27

The insular cortex (IC) is a region proposed to modulate, in part, interoceptive states and motivated behavior. Interestingly, IC dysfunction and deficits in interoceptive processing are often found among individuals with substance-use disorders. Furthermore, the IC projects to the nucleus accumbens core (AcbC), a region known to modulate the discriminative stimulus/interoceptive effects of alcohol and other drug-related behaviors. Therefore, the goal of the present work was to investigate the possible role of the IC ➔ AcbC circuit in modulating the interoceptive effects of alcohol. Thus, we utilized a chemogenetic technique (hM4D i designer receptor activation by designer drugs) to silence neuronal activity in the IC of rats trained to discriminate alcohol (1 g/kg, IG) versus water using an operant or Pavlovian alcohol discrimination procedure. Chemogenetic silencing of the IC or IC ➔ AcbC neuronal projections resulted in potentiated sensitivity to the interoceptive effects of alcohol in both the operant and Pavlovian tasks. Together, these data provide critical evidence for the nature of the complex IC circuitry and, specifically, suppression of the insular-striatal circuit in modulating behavior under a drug stimulus control. © 2017 Society for the Study of Addiction.

Peripheral nerve injury in developing rats reorganizes representation pattern in motor cortex.

OpenAIRE

Donoghue, J P; Sanes, J N

1987-01-01

We investigated the effect of neonatal nerve lesions on cerebral motor cortex organization by comparing the cortical motor representation of normal adult rats with adult rats that had one forelimb removed on the day of birth. Mapping of cerebral neocortex with electrical stimulation revealed an altered relationship between the motor cortex and the remaining muscles. Whereas distal forelimb movements are normally elicited at the lowest threshold in the motor cortex forelimb area, the same stim...

Gender differences in functional connectivities between insular subdivisions and selective pain-related brain structures.

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Dai, Yu-Jie; Zhang, Xin; Yang, Yang; Nan, Hai-Yan; Yu, Ying; Sun, Qian; Yan, Lin-Feng; Hu, Bo; Zhang, Jin; Qiu, Zi-Yu; Gao, Yi; Cui, Guang-Bin; Chen, Bi-Liang; Wang, Wen

2018-03-14

The incidence of pain disorders in women is higher than in men, making gender differences in pain a research focus. The human insular cortex is an important brain hub structure for pain processing and is divided into several subdivisions, serving different functions in pain perception. Here we aimed to examine the gender differences of the functional connectivities (FCs) between the twelve insular subdivisions and selected pain-related brain structures in healthy adults. Twenty-six healthy males and 11 age-matched healthy females were recruited in this cross-sectional study. FCs between the 12 insular subdivisions (as 12 regions of interest (ROIs)) and the whole brain (ROI-whole brain level) or 64 selected pain-related brain regions (64 ROIs, ROI-ROI level) were measured between the males and females. Significant gender differences in the FCs of the insular subdivisions were revealed: (1) The FCs between the dorsal dysgranular insula (dId) and other brain regions were significantly increased in males using two different techniques (ROI-whole brain and ROI-ROI analyses); (2) Based on the ROI-whole brain analysis, the FC increases in 4 FC-pairs were observed in males, including the left dId - the right median cingulate and paracingulate/ right posterior cingulate gyrus/ right precuneus, the left dId - the right median cingulate and paracingulate, the left dId - the left angular as well as the left dId - the left middle frontal gyrus; (3) According to the ROI-ROI analysis, increased FC between the left dId and the right rostral anterior cingulate cortex was investigated in males. In summary, the gender differences in the FCs of the insular subdivisions with pain-related brain regions were revealed in the current study, offering neuroimaging evidence for gender differences in pain processing. ClinicalTrials.gov, NCT02820974 . Registered 28 June 2016.

Peripheral Nerve Injury in Developing Rats Reorganizes Representation Pattern in Motor Cortex

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Donoghue, John P.; Sanes, Jerome N.

1987-02-01

We investigated the effect of neonatal nerve lesions on cerebral motor cortex organization by comparing the cortical motor representation of normal adult rats with adult rats that had one forelimb removed on the day of birth. Mapping of cerebral neocortex with electrical stimulation revealed an altered relationship between the motor cortex and the remaining muscles. Whereas distal forelimb movements are normally elicited at the lowest threshold in the motor cortex forelimb area, the same stimuli activated shoulder and trunk muscles in experimental animals. In addition, an expanded cortical representation of intact body parts was present and there was an absence of a distinct portion of motor cortex. These data demonstrate that representation patterns in motor cortex can be altered by peripheral nerve injury during development.

Comparison of anterior cingulate versus insular cortex as targets for real-time fMRI regulation during pain stimulation

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Kirsten eEmmert

2014-10-01

Full Text Available Real-time functional magnetic resonance imaging (rt-fMRI neurofeedback allows learning voluntary control over specific brain areas by means of operant conditioning and has been shown to decrease pain perception. To further increase the effect of rt-fMRI neurofeedback on pain, we directly compared two different target regions of the pain network i.e. the anterior insular cortex (AIC and the anterior cingulate cortex (ACC.Participants for this prospective study were randomly assigned to two age-matched groups of 14 participants each (7 females per group for AIC and ACC feedback. First, a functional localizer using block-design heat pain stimulation was performed to define the pain-sensitive target region within the AIC or ACC. Second, subjects were asked to down-regulate the feedback signal in four neurofeedback runs during identical pain stimulation. Data analysis included task-related and functional connectivity analysis.At the behavioral level, pain ratings significantly decreased during feedback versus localizer runs, but there was no difference between AIC and ACC groups. Concerning neuroimaging, ACC and AIC showed consistent involvement of the caudate nucleus for subjects that learned down-regulation (17/28 in both task-related and functional connectivity analysis. The functional connectivity towards the caudate nucleus is stronger for the ACC while the AIC is more heavily connected to the ventrolateral prefrontal cortex.Consequently, the ACC and AIC are suitable targets for real-time fMRI neurofeedback during pain perception as they both affect the caudate nucleus, although functional connectivity indicates that the direct connection seems to be stronger with the ACC. Additionally, the caudate, an important area involved in pain perception and suppression, could be a rt-fMRI target itself. Future studies are needed to identify parameters characterizing successful regulators and to assess the effect of repeated rt-fMRI neurofeedback on pain

Effect of thuringiensin on adenylate cyclase in rat cerebral cortex

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Tsai, S.-F.; Yang Chi; Wang, S.-C.; Wang, J.-S.; Hwang, J.-S.; Ho, S.-P.

2004-01-01

The purpose of this work is to evaluate the effect of thuringiensin on the adenylate cyclase activity in rat cerebral cortex. The cyclic adenosine 3'5'-monophosphate (cAMP) levels were shown to be dose-dependently elevated 17-450% or 54-377% by thuringiensin at concentrations of 10 μM-100 mM or 0.5-4 mM, due to the activation of basal adenylate cyclase activity of rat cerebral cortical membrane preparation. Thuringiensin also activated basal activity of a commercial adenylate cyclase from Escherichia coli. However, the forskolin-stimulated adenylate cyclase activity in rat cerebral cortex was inhibited by thuringiensin at concentrations of 1-100 μM, thus cAMP production decreased. Furthermore, thuringiensin or adenylate cyclase inhibitor (MDL-12330A) reduced the forskolin (10 μM)-stimulated adenylate cyclase activity at concentrations of 10 μM, 49% or 43% inhibition, respectively. In conclusion, this study demonstrated that thuringiensin could activate basal adenylate cyclase activity and increase cAMP concentrations in rat cerebral cortex or in a commercial adenylate cyclase. Comparing the dose-dependent effects of thuringiensin on the basal and forskolin-stimulated adenylate cyclase activity, thuringiensin can be regarded as a weak activator of adenylate cyclase or an inhibitor of forskolin-stimulated adenylate cyclase

Altered insular activation and increased insular functional connectivity during sad and happy face processing in adolescent major depressive disorder.

Science.gov (United States)

Henje Blom, Eva; Connolly, Colm G; Ho, Tiffany C; LeWinn, Kaja Z; Mobayed, Nisreen; Han, Laura; Paulus, Martin P; Wu, Jing; Simmons, Alan N; Yang, Tony T

2015-06-01

Major depressive disorder (MDD) is a leading cause of disability worldwide and occurs commonly first during adolescence. The insular cortex (IC) plays an important role in integrating emotion processing with interoception and has been implicated recently in the pathophysiology of adult and adolescent MDD. However, no studies have yet specifically examined the IC in adolescent MDD during processing of faces in the sad-happy continuum. Thus, the aim of the present study is to investigate the IC during sad and happy face processing in adolescents with MDD compared to healthy controls (HCL). Thirty-one adolescents (22 female) with MDD and 36 (23 female) HCL underwent a well-validated emotional processing fMRI paradigm that included sad and happy face stimuli. The MDD group showed significantly less differential activation of the anterior/middle insular cortex (AMIC) in response to sad versus happy faces compared to the HCL group. AMIC also showed greater functional connectivity with right fusiform gyrus, left middle frontal gyrus, and right amygdala/parahippocampal gyrus in the MDD compared to HCL group. Moreover, differential activation to sad and happy faces in AMIC correlated negatively with depression severity within the MDD group. Small age-range and cross-sectional nature precluded assessment of development of the AMIC in adolescent depression. Given the role of the IC in integrating bodily stimuli with conscious cognitive and emotional processes, our findings of aberrant AMIC function in adolescent MDD provide a neuroscientific rationale for targeting the AMIC in the development of new treatment modalities. Copyright © 2015 Elsevier B.V. All rights reserved.

Corticosterone and decision-making in male Wistar rats: the effect of corticosterone application in the infralimbic and orbitofrontal cortex.

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Koot, Susanne; Koukou, Magdalini; Baars, Annemarie; Hesseling, Peter; van 't Klooster, José; Joëls, Marian; van den Bos, Ruud

2014-01-01

Corticosteroid hormones, released after stress, are known to influence neuronal activity and produce a wide range of effects upon the brain. They affect cognitive tasks including decision-making. Recently it was shown that systemic injections of corticosterone (CORT) disrupt reward-based decision-making in rats when tested in a rat model of the Iowa Gambling Task (rIGT), i.e., rats do not learn across trial blocks to avoid the long-term disadvantageous option. This effect was associated with a change in neuronal activity in prefrontal brain areas, i.e., the infralimbic (IL), lateral orbitofrontal (lOFC) and insular cortex, as assessed by changes in c-Fos expression. Here, we studied whether injections of CORT directly into the IL and lOFC lead to similar changes in decision-making. As in our earlier study, CORT was injected during the final 3 days of the behavioral paradigm, 25 min prior to behavioral testing. Infusions of vehicle into the IL led to a decreased number of visits to the disadvantageous arm across trial blocks, while infusion with CORT did not. Infusions into the lOFC did not lead to differences in the number of visits to the disadvantageous arm between vehicle treated and CORT treated rats. However, compared to vehicle treated rats of the IL group, performance of vehicle treated rats of the lOFC group was impaired, possibly due to cannulation/infusion-related damage of the lOFC affecting decision-making. Overall, these results show that infusions with CORT into the IL are sufficient to disrupt decision-making performance, pointing to a critical role of the IL in corticosteroid effects on reward-based decision-making. The data do not directly support that the same holds true for infusions into the lOFC.

ASIC1a regulates insular long-term depression and is required for the extinction of conditioned taste aversion.

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Li, Wei-Guang; Liu, Ming-Gang; Deng, Shining; Liu, Yan-Mei; Shang, Lin; Ding, Jing; Hsu, Tsan-Ting; Jiang, Qin; Li, Ying; Li, Fei; Zhu, Michael Xi; Xu, Tian-Le

2016-12-07

Acid-sensing ion channel 1a (ASIC1a) has been shown to play important roles in synaptic plasticity, learning and memory. Here we identify a crucial role for ASIC1a in long-term depression (LTD) at mouse insular synapses. Genetic ablation and pharmacological inhibition of ASIC1a reduced the induction probability of LTD without affecting that of long-term potentiation in the insular cortex. The disruption of ASIC1a also attenuated the extinction of established taste aversion memory without altering the initial associative taste learning or its long-term retention. Extinction of taste aversive memory led to the reduced insular synaptic efficacy, which precluded further LTD induction. The impaired LTD and extinction learning in ASIC1a null mice were restored by virus-mediated expression of wild-type ASIC1a, but not its ion-impermeable mutant, in the insular cortices. Our data demonstrate the involvement of an ASIC1a-mediated insular synaptic depression mechanism in extinction learning, which raises the possibility of targeting ASIC1a to manage adaptive behaviours.

ASIC1a regulates insular long-term depression and is required for the extinction of conditioned taste aversion

OpenAIRE

Li, Wei-Guang; Liu, Ming-Gang; Deng, Shining; Liu, Yan-Mei; Shang, Lin; Ding, Jing; Hsu, Tsan-Ting; Jiang, Qin; Li, Ying; Li, Fei; Zhu, Michael Xi; Xu, Tian-Le

2016-01-01

Acid-sensing ion channel 1a (ASIC1a) has been shown to play important roles in synaptic plasticity, learning and memory. Here we identify a crucial role for ASIC1a in long-term depression (LTD) at mouse insular synapses. Genetic ablation and pharmacological inhibition of ASIC1a reduced the induction probability of LTD without affecting that of long-term potentiation in the insular cortex. The disruption of ASIC1a also attenuated the extinction of established taste aversion memory without alte...

Diazepam reduces excitability of amygdala and further influences auditory cortex following sodium salicylate treatment in rats.

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Song, Yu; Liu, Junxiu; Ma, Furong; Mao, Lanqun

2016-12-01

Diazepam can reduce the excitability of lateral amygdala and eventually suppress the excitability of the auditory cortex in rats following salicylate treatment, indicating the regulating effect of lateral amygdala to the auditory cortex in the tinnitus procedure. To study the spontaneous firing rates (SFR) of the auditory cortex and lateral amygdala regulated by diazepam in the tinnitus rat model induced by sodium salicylate. This study first created a tinnitus rat modal induced by sodium salicylate, and recorded SFR of both auditory cortex and lateral amygdala. Then diazepam was intraperitoneally injected and the SFR changes of lateral amygdala recorded. Finally, diazepam was microinjected on lateral amygdala and the SFR changes of the auditory cortex recorded. Both SFRs of the auditory cortex and lateral amygdala increased after salicylate treatment. SFR of lateral amygdala decreased after intraperitoneal injection of diazepam. Microinjecting diazepam to lateral amygdala decreased SFR of the auditory cortex ipsilaterally and contralaterally.

Analysis on bilateral hindlimb mapping in motor cortex of the rat by an intracortical microstimulation method.

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Seong, Han Yu; Cho, Ji Young; Choi, Byeong Sam; Min, Joong Kee; Kim, Yong Hwan; Roh, Sung Woo; Kim, Jeong Hoon; Jeon, Sang Ryong

2014-04-01

Intracortical microstimulation (ICMS) is a technique that was developed to derive movement representation of the motor cortex. Although rats are now commonly used in motor mapping studies, the precise characteristics of rat motor map, including symmetry and consistency across animals, and the possibility of repeated stimulation have not yet been established. We performed bilateral hindlimb mapping of motor cortex in six Sprague-Dawley rats using ICMS. ICMS was applied to the left and the right cerebral hemisphere at 0.3 mm intervals vertically and horizontally from the bregma, and any movement of the hindlimbs was noted. The majority (80%± 11%) of responses were not restricted to a single joint, which occurred simultaneously at two or three hindlimb joints. The size and shape of hindlimb motor cortex was variable among rats, but existed on the convex side of the cerebral hemisphere in all rats. The results did not show symmetry according to specific joints in each rats. Conclusively, the hindlimb representation in the rat motor cortex was conveniently mapped using ICMS, but the characteristics and inter-individual variability suggest that precise individual mapping is needed to clarify motor distribution in rats.

Engagement of the Rat Hindlimb Motor Cortex across Natural Locomotor Behaviors

NARCIS (Netherlands)

DiGiovanna, J.; Dominici, N.; Friedli, L.; Rigosa, J.; Duis, S.; Kreider, J.; Beauparlant, J.; van den Brand, R.; Schieppati, M.; Micera, S.; Courtine, G.

2016-01-01

Contrary to cats and primates, cortical contribution to hindlimb locomotor movements is not critical in rats. However, the importance of the motor cortex to regain locomotion after neurological disorders in rats suggests that cortical engagement in hindlimb motor control may depend on the behavioral

Hippocampus, Perirhinal Cortex, and Complex Visual Discriminations in Rats and Humans

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Hales, Jena B.; Broadbent, Nicola J.; Velu, Priya D.; Squire, Larry R.; Clark, Robert E.

2015-01-01

Structures in the medial temporal lobe, including the hippocampus and perirhinal cortex, are known to be essential for the formation of long-term memory. Recent animal and human studies have investigated whether perirhinal cortex might also be important for visual perception. In our study, using a simultaneous oddity discrimination task, rats with…

High-order motor cortex in rats receives somatosensory inputs from the primary motor cortex via cortico-cortical pathways.

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Kunori, Nobuo; Takashima, Ichiro

2016-12-01

The motor cortex of rats contains two forelimb motor areas; the caudal forelimb area (CFA) and the rostral forelimb area (RFA). Although the RFA is thought to correspond to the premotor and/or supplementary motor cortices of primates, which are higher-order motor areas that receive somatosensory inputs, it is unknown whether the RFA of rats receives somatosensory inputs in the same manner. To investigate this issue, voltage-sensitive dye (VSD) imaging was used to assess the motor cortex in rats following a brief electrical stimulation of the forelimb. This procedure was followed by intracortical microstimulation (ICMS) mapping to identify the motor representations in the imaged cortex. The combined use of VSD imaging and ICMS revealed that both the CFA and RFA received excitatory synaptic inputs after forelimb stimulation. Further evaluation of the sensory input pathway to the RFA revealed that the forelimb-evoked RFA response was abolished either by the pharmacological inactivation of the CFA or a cortical transection between the CFA and RFA. These results suggest that forelimb-related sensory inputs would be transmitted to the RFA from the CFA via the cortico-cortical pathway. Thus, the present findings imply that sensory information processed in the RFA may be used for the generation of coordinated forelimb movements, which would be similar to the function of the higher-order motor cortex in primates. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Distribution of catecholamines and serotonin in the rat cerebral cortex:

International Nuclear Information System (INIS)

Reader, T.A.

1981-01-01

The rat cerebral cortex was dissected in five regions and analyzed for the catecholamines noradrenaline, adrenaline and dopamine, and for the indoleamine seroton in using sensitive radioenzymatic assay methods with thin-layer-chromatography. The noradrenaline concentration was highest in the ventral cortex, lateral to the hypothalamus, had intermediate values for the prefrontal, frontal and parietal cortical areas and was lowest in the occipital cortex. Dopamine levels were also highest in the cortex lateral to the hypothalamus, and moderate in the prefrontal and frontal cortical areas, with the lowest values measured for the occipital cortex. The ratios dopamine/noradrenaline further support the hypothesis that they are independent transmitters. Traces of adrenaline were measured in all regions examined. The serotonin distribution was found to be non-homogeneous, with the highest values for the prefrontal cortex and ventral cortex lateral to the hypothalamus. The functional significance of these amines and their ratios are discussed in relation to their role as putative modulators of cortical neuronal excitability. (author)

Hindlimb spasticity after unilateral motor cortex lesion in rats is reduced by contralateral nerve root transfer.

Science.gov (United States)

Zong, Haiyang; Ma, Fenfen; Zhang, Laiyin; Lu, Huiping; Gong, Jingru; Cai, Min; Lin, Haodong; Zhu, Yizhun; Hou, Chunlin

2016-12-01

Lower extremity spasticity is a common sequela among patients with acquired brain injury. The optimum treatment remains controversial. The aim of our study was to test the feasibility and effectiveness of contralateral nerve root transfer in reducing post stroke spasticity of the affected hindlimb muscles in rats. In our study, we for the first time created a novel animal hindlimb spastic hemiplegia model in rats with photothrombotic lesion of unilateral motor cortex and we established a novel surgical procedure in reducing motor cortex lesion-induced hindlimb spastic hemiplegia in rats. Thirty six rats were randomized into three groups. In group A, rats received sham operation. In group B, rats underwent unilateral hindlimb motor cortex lesion. In group C, rats underwent unilateral hindlimb cortex lesion followed by contralateral L4 ventral root transfer to L5 ventral root of the affected side. Footprint analysis, Hoffmann reflex (H-reflex), cholera toxin subunit B (CTB) retrograde tracing of gastrocnemius muscle (GM) motoneurons and immunofluorescent staining of vesicle glutamate transporter 1 (VGLUT1) on CTB-labelled motoneurons were used to assess spasticity of the affected hindlimb. Sixteen weeks postoperatively, toe spread and stride length recovered significantly in group C compared with group B (Pmotor cortex lesion-induced hindlimb spasticity in rats. Our data indicated that this could be an alternative treatment for unilateral lower extremity spasticity after brain injury. Therefore, contralateral neurotization may exert a potential therapeutic candidate to improve the function of lower extremity in patients with spastic hemiplegia. © 2016 The Author(s).

Minocycline restores cognitive-relative altered proteins in young bile duct-ligated rat prefrontal cortex.

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Li, Shih-Wen; Chen, Yu-Chieh; Sheen, Jiunn-Ming; Hsu, Mei-Hsin; Tain, You-Lin; Chang, Kow-Aung; Huang, Li-Tung

2017-07-01

Bile duct ligation (BDL) model is used to study hepatic encephalopathy accompanied by cognitive impairment. We employed the proteomic analysis approach to evaluate cognition-related proteins in the prefrontal cortex of young BDL rats and analyzed the effect of minocycline on these proteins and spatial memory. BDL was induced in young rats at postnatal day 17. Minocycline as a slow-release pellet was implanted into the peritoneum. Morris water maze test and two-dimensional liquid chromatography-tandem mass spectrometry were used to evaluate spatial memory and prefrontal cortex protein expression, respectively. We used 2D/LC-MS/MS to analyze for affected proteins in the prefrontal cortex of young BDL rats. Results were verified with Western blotting, immunohistochemistry, and quantitative real-time PCR. The effect of minocycline in BDL rats was assessed. BDL induced spatial deficits, while minocycline rescued it. Collapsin response mediator protein 2 (CRMP2) and manganese-dependent superoxide dismutase (MnSOD) were upregulated and nucleoside diphosphate kinase B (NME2) was downregulated in young BDL rats. BDL rats exhibited decreased levels of brain-derived neurotrophic factor (BDNF) mRNA as compared with those by the control. However, minocycline treatment restored CRMP2 and NME2 protein expression, BDNF mRNA level, and MnSOD activity to control levels. We demonstrated that BDL altered the expression of CRMP2, NME2, MnSOD, and BDNF in the prefrontal cortex of young BDL rats. However, minocycline treatment restored the expression of the affected mediators that are implicated in cognition. Copyright © 2017 Elsevier Inc. All rights reserved.

Complete reorganization of the motor cortex of adult rats following long-term spinal cord injuries.

Science.gov (United States)

Tandon, Shashank; Kambi, Niranjan; Mohammed, Hisham; Jain, Neeraj

2013-07-01

Understanding brain reorganization following long-term spinal cord injuries is important for optimizing recoveries based on residual function as well as developing brain-controlled assistive devices. Although it has been shown that the motor cortex undergoes partial reorganization within a few weeks after peripheral and spinal cord injuries, it is not known if the motor cortex of rats is capable of large-scale reorganization after longer recovery periods. Here we determined the organization of the rat (Rattus norvegicus) motor cortex at 5 or more months after chronic lesions of the spinal cord at cervical levels using intracortical microstimulation. The results show that, in the rats with the lesions, stimulation of neurons in the de-efferented forelimb motor cortex no longer evokes movements of the forelimb. Instead, movements of the body parts in the adjacent representations, namely the whiskers and neck were evoked. In addition, at many sites, movements of the ipsilateral forelimb were observed at threshold currents. The extent of representations of the eye, jaw and tongue movements was unaltered by the lesion. Thus, large-scale reorganization of the motor cortex leads to complete filling-in of the de-efferented cortex by neighboring representations following long-term partial spinal cord injuries at cervical levels in adult rats. © 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

[Effects of intermittent hypoxia on the responses of genioglossus motor cortex to transcranial magnetic stimulation in rats].

Science.gov (United States)

Li, Ting; Wang, Wei; Kong, De-lei; Su, Jiao; Kang, Jian

2012-04-01

To explore the influence of intermittent hypoxia on the responses of genioglossus motor cortex to transcranial magnetic stimulation. Male Sprague-Dawley rats were randomly divided into a control group and a chronic intermittent hypoxia group. Transcranial magnetic stimulation was applied in genioglossus motor cortex of the 2 groups. The responses of transcranial magnetic stimulation were recorded and analyzed by single factor analysis of variance. The anterolateral area provided an optimal motor evoked potential response to transcranial magnetic stimulation in the genioglossus motor cortex of the rats. Genioglossus motor evoked potential latency and amplitude were significantly modified by intermittent hypoxic exposure, with a significant decrease in latency (F = 3.294, P motor cortex in rats.

Is the ipsilateral cortex surrounding the lesion or the non-injured contralateral cortex important for motor recovery in rats with photochemically induced cortical lesions?

Science.gov (United States)

Takata, Kotaro; Yamauchi, Hideki; Tatsuno, Hisashi; Hashimoto, Keiji; Abo, Masahiro

2006-01-01

To determine whether the ipsilateral cortex surrounding the lesion or the non-injured contralateral cortex is important for motor recovery after brain damage in the photochemically initiated thrombosis (PIT) model. We induced PIT in the sensorimotor cortex in rats and examined the recovery of motor function using the beam-walking test. In 24 rats, the right sensorimotor cortex was lesioned after 2 days of training for the beam-walking test (group 1). After 10 days, PIT was induced in the left sensorimotor cortex. Eight additional rats (group 2) received 2 days training in beam walking, then underwent the beam-walking test to evaluate function. After 10 days of testing, the left sensorimotor cortex was lesioned and recovery was monitored by the beam-walking test for 8 days. In group 1 animals, left hindlimb function caused by a right sensorimotor cortex lesion recovered within 10 days after the operation. Right hindlimb function caused by the left-side lesion recovered within 6 days. In group 2, right hindlimb function caused by induction of the left-side lesion after a total of 12 days of beam-walking training and testing recovered within 6 days as with the double PIT model. The training effect may be relevant to reorganization and neuromodulation. Motor recovery patterns did not indicate whether motor recovery was dependent on the ipsilateral cortex surrounding the lesion or the cortex of the contralateral side. The results emphasize the need for selection of appropriate programs tailored to the area of cortical damage in order to enhance motor functional recovery in this model. Copyright 2006 S. Karger AG, Basel.

Analysis on Bilateral Hindlimb Mapping in Motor Cortex of the Rat by an Intracortical Microstimulation Method

OpenAIRE

Seong, Han Yu; Cho, Ji Young; Choi, Byeong Sam; Min, Joong Kee; Kim, Yong Hwan; Roh, Sung Woo; Kim, Jeong Hoon; Jeon, Sang Ryong

2014-01-01

Intracortical microstimulation (ICMS) is a technique that was developed to derive movement representation of the motor cortex. Although rats are now commonly used in motor mapping studies, the precise characteristics of rat motor map, including symmetry and consistency across animals, and the possibility of repeated stimulation have not yet been established. We performed bilateral hindlimb mapping of motor cortex in six Sprague-Dawley rats using ICMS. ICMS was applied to the left and the righ...

Investigation of Implantable Multi-Channel Electrode Array in Rat Cerebral Cortex Used for Recording

Science.gov (United States)

Taniguchi, Noriyuki; Fukayama, Osamu; Suzuki, Takafumi; Mabuchi, Kunihiko

There have recently been many studies concerning the control of robot movements using neural signals recorded from the brain (usually called the Brain-Machine interface (BMI)). We fabricated implantable multi-electrode arrays to obtain neural signals from the rat cerebral cortex. As any multi-electrode array should have electrode alignment that minimizes invasion, it is necessary to customize the recording site. We designed three types of 22-channel multi-electrode arrays, i.e., 1) wide, 2) three-layered, and 3) separate. The first extensively covers the cerebral cortex. The second has a length of 2 mm, which can cover the area of the primary motor cortex. The third array has a separate structure, which corresponds to the position of the forelimb and hindlimb areas of the primary motor cortex. These arrays were implanted into the cerebral cortex of a rat. We estimated the walking speed from neural signals using our fabricated three-layered array to investigate its feasibility for BMI research. The neural signal of the rat and its walking speed were simultaneously recorded. The results revealed that evaluation using either the anterior electrode group or posterior group provided accurate estimates. However, two electrode groups around the center yielded poor estimates although it was possible to record neural signals.

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.

Plasticity in the Prefrontal Cortex of Adult Rats

Directory of Open Access Journals (Sweden)

Bryan eKolb

2015-02-01

Full Text Available We review the plastic changes of the prefrontal cortex of the rat in response to a wide range of experiences including sensory and motor experience, gonadal hormones, psychoactive drugs, learning tasks, stress, social experience, metaplastic experiences, and brain injury. Our focus is on synaptic changes (dendritic morphology and spine density in pyramidal neurons and the relationship to behavioral changes. The most general conclusion we can reach is that the prefrontal cortex is extremely plastic and that the medial and orbital prefrontal regions frequently respond very differently to the same experience in the same brain and the rules that govern prefrontal plasticity appear to differ for those of other cortical regions.

Cerebral cortex modulation of pain

Institute of Scientific and Technical Information of China (English)

Yu-feng XIE; Fu-quan HUO; Jing-shi TANG

2009-01-01

Pain is a complex experience encompassing sensory-discriminative, affective-motivational and cognitiv e-emotional com-ponents mediated by different mechanisms. Contrary to the traditional view that the cerebral cortex is not involved in pain perception, an extensive cortical network associated with pain processing has been revealed using multiple methods over the past decades. This network consistently includes, at least, the anterior cingulate cortex, the agranular insular cortex, the primary (SⅠ) and secondary somatosensory (SⅡ) cortices, the ventrolateral orbital cortex and the motor cortex. These corti-cal structures constitute the medial and lateral pain systems, the nucleus submedius-ventrolateral orbital cortex-periaque-ductal gray system and motor cortex system, respectively. Multiple neurotransmitters, including opioid, glutamate, GABA and dopamine, are involved in the modulation of pain by these cortical structures. In addition, glial cells may also be in-volved in cortical modulation of pain and serve as one target for pain management research. This review discusses recent studies of pain modulation by these cerebral cortical structures in animals and human.

Effect of hindlimb unloading on stereological parameters of the motor cortex and hippocampus in male rats.

Science.gov (United States)

Salehi, Mohammad Saied; Mirzaii-Dizgah, Iraj; Vasaghi-Gharamaleki, Behnoosh; Zamiri, Mohammad Javad

2016-11-09

Hindlimb unloading (HU) can cause motion and cognition dysfunction, although its cellular and molecular mechanisms are not well understood. The aim of the present study was to determine the stereological parameters of the brain areas involved in motion (motor cortex) and spatial learning - memory (hippocampus) under an HU condition. Sixteen adult male rats, kept under a 12 : 12 h light-dark cycle, were divided into two groups of freely moving (n=8) and HU (n=8) rats. The volume of motor cortex and hippocampus, the numerical cell density of neurons in layers I, II-III, V, and VI of the motor cortex, the entire motor cortex as well as the primary motor cortex, and the numerical density of the CA1, CA3, and dentate gyrus subregions of the hippocampus were estimated. No significant differences were observed in the evaluated parameters. Our results thus indicated that motor cortical and hippocampal atrophy and cell loss may not necessarily be involved in the motion and spatial learning memory impairment in the rat.

Acoustic Trauma Changes the Parvalbumin-Positive Neurons in Rat Auditory Cortex

Directory of Open Access Journals (Sweden)

Congli Liu

2018-01-01

Full Text Available Acoustic trauma is being reported to damage the auditory periphery and central system, and the compromised cortical inhibition is involved in auditory disorders, such as hyperacusis and tinnitus. Parvalbumin-containing neurons (PV neurons, a subset of GABAergic neurons, greatly shape and synchronize neural network activities. However, the change of PV neurons following acoustic trauma remains to be elucidated. The present study investigated how auditory cortical PV neurons change following unilateral 1 hour noise exposure (left ear, one octave band noise centered at 16 kHz, 116 dB SPL. Noise exposure elevated the auditory brainstem response threshold of the exposed ear when examined 7 days later. More detectable PV neurons were observed in both sides of the auditory cortex of noise-exposed rats when compared to control. The detectable PV neurons of the left auditory cortex (ipsilateral to the exposed ear to noise exposure outnumbered those of the right auditory cortex (contralateral to the exposed ear. Quantification of Western blotted bands revealed higher expression level of PV protein in the left cortex. These findings of more active PV neurons in noise-exposed rats suggested that a compensatory mechanism might be initiated to maintain a stable state of the brain.

Dissociating movement from movement timing in the rat primary motor cortex.

Science.gov (United States)

Knudsen, Eric B; Powers, Marissa E; Moxon, Karen A

2014-11-19

Neural encoding of the passage of time to produce temporally precise movements remains an open question. Neurons in several brain regions across different experimental contexts encode estimates of temporal intervals by scaling their activity in proportion to the interval duration. In motor cortex the degree to which this scaled activity relies upon afferent feedback and is guided by motor output remains unclear. Using a neural reward paradigm to dissociate neural activity from motor output before and after complete spinal transection, we show that temporally scaled activity occurs in the rat hindlimb motor cortex in the absence of motor output and after transection. Context-dependent changes in the encoding are plastic, reversible, and re-established following injury. Therefore, in the absence of motor output and despite a loss of afferent feedback, thought necessary for timed movements, the rat motor cortex displays scaled activity during a broad range of temporally demanding tasks similar to that identified in other brain regions. Copyright © 2014 the authors 0270-6474/14/3415576-11$15.00/0.

Effects of Mercury Chloride on the Cerebral Cortex of Adult Wistar Rats

African Journals Online (AJOL)

Mercury is among the heavy metals that have been reported to cause devastating health problem worldwide. The primary site of action of mercury chloride is the central nervous system. This study investigated the effect of mercury chloride on the cerebral cortex of adult wistar rats. Twenty-four (24) adult wistar rats were used ...

Inactivation of the prelimbic or infralimbic cortex impairs decision-making in the rat gambling task.

Science.gov (United States)

Zeeb, Fiona D; Baarendse, P J J; Vanderschuren, L J M J; Winstanley, Catharine A

2015-12-01

Studies employing the Iowa Gambling Task (IGT) demonstrated that areas of the frontal cortex, including the ventromedial prefrontal cortex, orbitofrontal cortex (OFC), dorsolateral prefrontal cortex, and anterior cingulate cortex (ACC), are involved in the decision-making process. However, the precise role of these regions in maintaining optimal choice is not clear. We used the rat gambling task (rGT), a rodent analogue of the IGT, to determine whether inactivation of or altered dopamine signalling within discrete cortical sub-regions disrupts decision-making. Following training on the rGT, animals were implanted with guide cannulae aimed at the prelimbic (PrL) or infralimbic (IL) cortices, the OFC, or the ACC. Prior to testing, rats received an infusion of saline or a combination of baclofen and muscimol (0.125 μg of each/side) to inactivate the region and an infusion of a dopamine D2 receptor antagonist (0, 0.1, 0.3, and 1.0 μg/side). Rats tended to increase their choice of a disadvantageous option and decrease their choice of the optimal option following inactivation of either the IL or PrL cortex. In contrast, OFC or ACC inactivation did not affect decision-making. Infusion of a dopamine D2 receptor antagonist into any sub-region did not alter choice preference. Online activity of the IL or PrL cortex is important for maintaining an optimal decision-making strategy, but optimal performance on the rGT does not require frontal cortex dopamine D2 receptor activation. Additionally, these results demonstrate that the roles of different cortical regions in cost-benefit decision-making may be dissociated using the rGT.

Radial oxygen gradients over rat cortex arterioles

OpenAIRE

Galler, Michael

2011-01-01

Purpose: We present the results of the visualisation of radial oxygen gradients in rats’ cortices and their use in neurocritical management. Methods: PO2 maps of the cortex of 10 wistar rats were obtained with a camera (SensiMOD, PCO, Kehlheim, Germany). Those pictures were analyzed and edited by a custom-made software. We chose a vessel for examination. A matrix, designed to evaluate the cortical O2 partial pressure, was placed vertically to the artery and afterwards multiple regio...

Late emergence of the vibrissa direction selectivity map in the rat barrel cortex.

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Kremer, Yves; Léger, Jean-François; Goodman, Dan; Brette, Romain; Bourdieu, Laurent

2011-07-20

In the neocortex, neuronal selectivities for multiple sensorimotor modalities are often distributed in topographical maps thought to emerge during a restricted period in early postnatal development. Rodent barrel cortex contains a somatotopic map for vibrissa identity, but the existence of maps representing other tactile features has not been clearly demonstrated. We addressed the issue of the existence in the rat cortex of an intrabarrel map for vibrissa movement direction using in vivo two-photon imaging. We discovered that the emergence of a direction map in rat barrel cortex occurs long after all known critical periods in the somatosensory system. This map is remarkably specific, taking a pinwheel-like form centered near the barrel center and aligned to the barrel cortex somatotopy. We suggest that this map may arise from intracortical mechanisms and demonstrate by simulation that the combination of spike-timing-dependent plasticity at synapses between layer 4 and layer 2/3 and realistic pad stimulation is sufficient to produce such a map. Its late emergence long after other classical maps suggests that experience-dependent map formation and refinement continue throughout adult life.

Restoring susceptibility induced MRI signal loss in rat brain at 9.4 T: A step towards whole brain functional connectivity imaging.

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Rupeng Li

Full Text Available The aural cavity magnetic susceptibility artifact leads to significant echo planar imaging (EPI signal dropout in rat deep brain that limits acquisition of functional connectivity fcMRI data. In this study, we provide a method that recovers much of the EPI signal in deep brain. Needle puncture introduction of a liquid-phase fluorocarbon into the middle ear allows acquisition of rat fcMRI data without signal dropout. We demonstrate that with seeds chosen from previously unavailable areas, including the amygdala and the insular cortex, we are able to acquire large scale networks, including the limbic system. This tool allows EPI-based neuroscience and pharmaceutical research in rat brain using fcMRI that was previously not feasible.

Time and decision making: differential contribution of the posterior insular cortex and the striatum during a delay discounting task.

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Wittmann, Marc; Leland, David S; Paulus, Martin P

2007-06-01

Delay discounting refers to the fact that an immediate reward is valued more than the same reward if it occurs some time in the future. To examine the neural substrates underlying this process, we studied 13 healthy volunteers who repeatedly had to decide between an immediate and parametrically varied delayed hypothetical reward using a delay discounting task during event-related functional magnetic resonance imaging. Subject's preference judgments resulted in different discounting slopes for shorter ( or =1 year) delays. Neural activation associated with the shorter delays relative to the longer delays was associated with increased activation in the head of the left caudate nucleus and putamen. When individuals selected the delayed relative to the immediate reward, a strong activation was found in bilateral posterior insular cortex. Several brain areas including the left caudate nucleus showed a correlation between the behaviorally determined discounting and brain activation for the contrast of intervals with delays or =1 year. These results suggest that (1) the posterior insula, which is a critical component of the decision-making neural network, is involved in delaying gratification and (2) the degree of neural activation in the striatum, which plays a fundamental role in reward prediction and in time estimation, may code for the time delay.

Characterization of beta-adrenergic receptors in synaptic membranes from rat cerebral cortex and cerebellum

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Lautens, L.

1986-01-01

Beta-adrenergic receptor ligand binding sites have been characterized in synaptic membranes from rat cerebral cortex and cerebellum using radioligand binding techniques. The equilibrium and kinetic properties of binding were assessed. The binding sites were non-interacting and exhibited two states of agonist binding which were sensitive to guanyl nucleotide. Synaptic membranes from cerebral cortex contained an equal number of beta 1 - and beta 2 -receptors; membranes from cerebellum possessed more beta 2 -than beta 1 -receptors. Photoaffinity labeling experiments revealed two different beta-adrenergic receptor polypeptides, R 1 and R 2 (and possibly a third, R 3 ) in synaptic membranes. The ratios of incorporation of photoaffinity label into R 1 : 2 were approximately 1:1 (cerebral cortex) and 5:1 (cerebellum). Photoaffinity labeling of R 1 and R 2 was inhibited equally well by both agonist and antagonist in synaptic membranes from cerebellum; whereas agonist was a less potent inhibitor in membranes from cerebral cortex. Both subtypes of beta-adrenergic receptors exhibited the same apparent molecular weight in synaptic membranes from cerebral cortex. The beta-adrenergic receptors in synaptic membranes from cerebral cortex and cerebellum were glycoproteins which exhibited the same apparent molecular weight after exposure to endoglycosidase F. The partial proteolytic digest maps of photoaffinity labeled beta-adrenergic receptors from rat cerebral cortex, cerebellum, lung and heart were compared

Neural Representations of Natural and Scrambled Movies Progressively Change from Rat Striate to Temporal Cortex

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Vinken, Kasper; Van den Bergh, Gert; Vermaercke, Ben; Op de Beeck, Hans P.

2016-01-01

In recent years, the rodent has come forward as a candidate model for investigating higher level visual abilities such as object vision. This view has been backed up substantially by evidence from behavioral studies that show rats can be trained to express visual object recognition and categorization capabilities. However, almost no studies have investigated the functional properties of rodent extrastriate visual cortex using stimuli that target object vision, leaving a gap compared with the primate literature. Therefore, we recorded single-neuron responses along a proposed ventral pathway in rat visual cortex to investigate hallmarks of primate neural object representations such as preference for intact versus scrambled stimuli and category-selectivity. We presented natural movies containing a rat or no rat as well as their phase-scrambled versions. Population analyses showed increased dissociation in representations of natural versus scrambled stimuli along the targeted stream, but without a clear preference for natural stimuli. Along the measured cortical hierarchy the neural response seemed to be driven increasingly by features that are not V1-like and destroyed by phase-scrambling. However, there was no evidence for category selectivity for the rat versus nonrat distinction. Together, these findings provide insights about differences and commonalities between rodent and primate visual cortex. PMID:27146315

Brain-wide map of efferent projections from rat barrel cortex

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Izabela M. Zakiewicz

2014-02-01

Full Text Available The somatotopically organized whisker barrel field of the rat primary somatosensory (S1 cortex is a commonly used model system for anatomical and physiological investigations of sensory processing. The neural connections of the barrel cortex have been extensively mapped. But most investigations have focused on connections to limited regions of the brain, and overviews in the literature of the connections across the brain thus build on a range of material from different laboratories, presented in numerous publications. Furthermore, given the limitations of the conventional journal article format, analyses and interpretations are hampered by lack of access to the underlying experimental data. New opportunities for analyses have emerged with the recent release of an online resource of experimental data consisting of collections of high-resolution images from 6 experiments in which anterograde tracers were injected in S1 whisker or forelimb representations. Building on this material, we have conducted a detailed analysis of the brain wide distribution of the efferent projections of the rat barrel cortex. We compare our findings with the available literature and reports accumulated in the Brain Architecture Management System (BAMS2 database. We report well-known and less known intracortical and subcortical projections of the barrel cortex, as well as distinct differences between S1 whisker and forelimb related projections. Our results correspond well with recently published overviews, but provide additional information about relative differences among S1 projection targets. Our approach demonstrates how collections of shared experimental image data are suitable for brain-wide analysis and interpretation of connectivity mapping data.

FGF-2 induces behavioral recovery after early adolescent injury to the motor cortex of rats.

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Nemati, Farshad; Kolb, Bryan

2011-11-20

Motor cortex injuries in adulthood lead to poor performance in behavioral tasks sensitive to limb movements in the rat. We have shown previously that motor cortex injury on day 10 or day 55 allow significant spontaneous recovery but not injury in early adolescence (postnatal day 35 "P35"). Previous studies have indicated that injection of basic fibroblast growth factor (FGF-2) enhances behavioral recovery after neonatal cortical injury but such effect has not been studied following motor cortex lesions in early adolescence. The present study undertook to investigate the possibility of such behavioral recovery. Rats with unilateral motor cortex lesions were assigned to two groups in which they received FGF-2 or bovine serum albumin (BSA) and were tested in a number of behavioral tests (postural asymmetry, skilled reaching, sunflower seed manipulation, forepaw inhibition in swimming). Golgi-Cox analysis was used to examine the dendritic structure of pyramidal cells in the animals' parietal (layer III) and forelimb (layer V) area of the cortex. The results indicated that rats injected with FGF-2 (but not BSA) showed significant behavioral recovery that was associated with increased dendritic length and spine density. The present study suggests a role for FGF-2 in the recovery of function following injury during early adolescence. Copyright © 2011 Elsevier B.V. All rights reserved.

Attenuation of pCREB and Egr1 expression in the insular and anterior cingulate cortices associated with enhancement of CFA-evoked mechanical hypersensitivity after repeated forced swim stress.

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Imbe, Hiroki; Kimura, Akihisa

2017-09-01

The perception and response to pain are severely impacted by exposure to stressors. In some animal models, stress increases pain sensitivity, which is termed stress-induced hyperalgesia (SIH). The insular cortex (IC) and anterior cingulate cortex (ACC), which are typically activated by noxious stimuli, affect pain perception through the descending pain modulatory system. In the present study, we examined the expression of phospho-cAMP response element-binding protein (pCREB) and early growth response 1 (Egr1) in the IC and ACC at 3h (the acute phase of peripheral tissue inflammation) after complete Freund's adjuvant (CFA) injection in naïve rats and rats preconditioned with forced swim stress (FS) to clarify the effect of FS, a stressor, on cortical cell activities in the rats showing SIH induced by FS. The CFA injection into the hindpaw induced mechanical hypersensitivity and increased the expression of the pCREB and Egr1 in the IC and ACC at 3h after the injection. FS (day 1, 10min; days 2-3, 20min) prior to the CFA injection enhanced the CFA-induced mechanical hypersensitivity and attenuated the increase in the expression of pCREB and Egr1 in the IC and ACC. These findings suggested that FS modulates the CFA injection-induced neuroplasticity in the IC and ACC to enhance the mechanical hypersensitivity. These findings are thought to signify stressor-induced dysfunction of the descending pain modulatory system. Copyright © 2017 Elsevier Inc. All rights reserved.

3D Reconstruction and Standardization of the Rat Vibrissal Cortex for Precise Registration of Single Neuron Morphology

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Egger, Robert; Narayanan, Rajeevan T.; Helmstaedter, Moritz; de Kock, Christiaan P. J.; Oberlaender, Marcel

2012-01-01

The three-dimensional (3D) structure of neural circuits is commonly studied by reconstructing individual or small groups of neurons in separate preparations. Investigation of structural organization principles or quantification of dendritic and axonal innervation thus requires integration of many reconstructed morphologies into a common reference frame. Here we present a standardized 3D model of the rat vibrissal cortex and introduce an automated registration tool that allows for precise placement of single neuron reconstructions. We (1) developed an automated image processing pipeline to reconstruct 3D anatomical landmarks, i.e., the barrels in Layer 4, the pia and white matter surfaces and the blood vessel pattern from high-resolution images, (2) quantified these landmarks in 12 different rats, (3) generated an average 3D model of the vibrissal cortex and (4) used rigid transformations and stepwise linear scaling to register 94 neuron morphologies, reconstructed from in vivo stainings, to the standardized cortex model. We find that anatomical landmarks vary substantially across the vibrissal cortex within an individual rat. In contrast, the 3D layout of the entire vibrissal cortex remains remarkably preserved across animals. This allows for precise registration of individual neuron reconstructions with approximately 30 µm accuracy. Our approach could be used to reconstruct and standardize other anatomically defined brain areas and may ultimately lead to a precise digital reference atlas of the rat brain. PMID:23284282

Cortex-dependent recovery of unassisted hindlimb locomotion after complete spinal cord injury in adult rats

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Manohar, Anitha; Foffani, Guglielmo; Ganzer, Patrick D; Bethea, John R; Moxon, Karen A

2017-01-01

After paralyzing spinal cord injury the adult nervous system has little ability to ‘heal’ spinal connections, and it is assumed to be unable to develop extra-spinal recovery strategies to bypass the lesion. We challenge this assumption, showing that completely spinalized adult rats can recover unassisted hindlimb weight support and locomotion without explicit spinal transmission of motor commands through the lesion. This is achieved with combinations of pharmacological and physical therapies that maximize cortical reorganization, inducing an expansion of trunk motor cortex and forepaw sensory cortex into the deafferented hindlimb cortex, associated with sprouting of corticospinal axons. Lesioning the reorganized cortex reverses the recovery. Adult rats can thus develop a novel cortical sensorimotor circuit that bypasses the lesion, probably through biomechanical coupling, to partly recover unassisted hindlimb locomotion after complete spinal cord injury. DOI: http://dx.doi.org/10.7554/eLife.23532.001 PMID:28661400

The rat frontal cortex serotonin receptors. Influence of supraletal irradiation

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Chanez, P.O.; Timmermans, R.; Gerber, G.B.

1984-01-01

The density of the frontal cortex serotonin-2 receptors was determined after a supralethal irradiation (20 Gy) in Wistar rat. Using spiperone as ligand, we observed an important decrease in the density of serotonin-2 receptor and an increase in the dissociation constant receptor-ligand, 3 days after exposure [fr

Right vs. left sensorimotor cortex suction-ablation in the rat: no difference in beam-walking recovery.

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Goldstein, L B

1995-03-13

The ability of rats to traverse a narrow elevated beam has been used to quantitate recovery of hindlimb motor function after unilateral injury to the sensorimotor cortex. We tested the hypothesis that the rate of spontaneous beam-walking recovery varies with the side of the cortex lesion. Groups of rats that were trained at the beam-walking task underwent suction-ablation of either the right or left hindlimb sensorimotor cortex. There was no difference in hindlimb motor function between the groups on the first post-operative beam-waking trial carried out the day after cortex ablation and no difference between the groups in overall recovery rates over the next two weeks. Subsequent analyses of lesion surface parameters showed no differences in lesion size or extent. Regardless of the side of the lesion, there were also no differences between the right and left hemispheres in norepinephrine content of the lesioned or contralateral cortex. We conclude that the side of sensorimotor cortex ablation injury does not differentially affect the rate of spontaneous motor recovery as measured with the beam-walking task.

Neuropathological changes in brain cortex and hippocampus in a rat model of Alzheimer's disease.

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Nobakht, Maliheh; Hoseini, Seyed Mohammad; Mortazavi, Pejman; Sohrabi, Iraj; Esmailzade, Banafshe; Rahbar Rooshandel, Nahid; Omidzahir, Shila

2011-01-01

Alzheimer's disease (AD) is a neurodegenerative disorder with progressive loss of cognitive abilities and memory loss. The aim of this study was to compare neuropathological changes in hippocampus and brain cortex in a rat model of AD. Adult male Albino Wistar rats (weighing 250-300 g) were used for behavioral and histopathological studies. The rats were randomly assigned to three groups: control, sham and Beta amyloid (ABeta) injection. For behavioral analysis, Y-maze and shuttle box were used, respectively at 14 and 16 days post-lesion. For histological studies, Nissl, modified Bielschowsky and modified Congo red staining were performed. The lesion was induced by injection of 4 muL of ABeta (1-40) into the hippocampal fissure. In the present study, ABeta (1-40) injection into hippocampus could decrease the behavioral indexes and the number of CA1 neurons in hippocampus. ABeta injection CA1 caused ABeta deposition in the hippocampus and less than in cortex. We observed the loss of neurons in the hippocampus and cerebral cortex and certain subcortical regions. Y-maze test and single-trial passive avoidance test showed reduced memory retention in AD group. We found a significant decreased acquisition of passive avoidance and alternation behavior responses in AD group compared to control and sham group (P<0.0001). Compacted amyloid cores were present in the cerebral cortex, hippocampus and white matter, whereas, scattered amyloid cores were seen in cortex and hippocampus of AD group. Also, reduced neuronal density was indicated in AD group.

The Consolidation of Object and Context Recognition Memory Involve Different Regions of the Temporal Lobe

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Balderas, Israela; Rodriguez-Ortiz, Carlos J.; Salgado-Tonda, Paloma; Chavez-Hurtado, Julio; McGaugh, James L.; Bermudez-Rattoni, Federico

2008-01-01

These experiments investigated the involvement of several temporal lobe regions in consolidation of recognition memory. Anisomycin, a protein synthesis inhibitor, was infused into the hippocampus, perirhinal cortex, insular cortex, or basolateral amygdala of rats immediately after the sample phase of object or object-in-context recognition memory…

Agmatine protection against chlorpromazine-induced forebrain cortex injury in rats.

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Dejanovic, Bratislav; Stevanovic, Ivana; Ninkovic, Milica; Stojanovic, Ivana; Lavrnja, Irena; Radicevic, Tatjana; Pavlovic, Milos

2016-03-01

This study was conducted to investigate whether agmatine (AGM) provides protection against oxidative stress induced by treatment with chlorpromazine (CPZ) in Wistar rats. In addition, the role of reactive oxygen species and efficiency of antioxidant protection in the brain homogenates of forebrain cortexes prepared 48 h after treatment were investigated. Chlorpromazine was applied intraperitoneally (i.p.) in single dose of 38.7 mg/kg body weight (BW) The second group was treated with both CPZ and AGM (75 mg/kg BW). The control group was treated with 0.9% saline solution in the same manner. All tested compounds were administered i.p. in a single dose. Rats were sacrificed by decapitation 48 h after treatment Treatment with AGM significantly attenuated the oxidative stress parameters and restored antioxidant capacity in the forebrain cortex. The data indicated that i.p. administered AGM exerted antioxidant action in CPZ-treated animals. Moreover, reactive astrocytes and microglia may contribute to secondary nerve-cell damage and participate in the balance of destructive vs. protective actions involved in the pathogenesis after poisoning.

Reduced spontaneous neuronal activity in the insular cortex and thalamus in healthy adults with insomnia symptoms.

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Liu, Chun-Hong; Liu, Cun-Zhi; Zhang, Jihui; Yuan, Zhen; Tang, Li-Rong; Tie, Chang-Le; Fan, Jin; Liu, Qing-Quan

2016-10-01

Poor sleep and insomnia have been recognized to be strongly correlated with the development of depression. The exploration of the basic mechanism of sleep disturbance could provide the basis for improved understanding and treatment of insomnia and prevention of depression. In this study, 31 subjects with insomnia symptoms as measured by the Hamilton Rating Scale for Depression (HAMD-17) and 71 age- and gender-matched subjects without insomnia symptoms were recruited to participate in a clinical trial. Using resting-state functional magnetic resonance imaging (rs-fMRI), we examined the alterations in spontaneous brain activity between the two groups. Correlations between the fractional amplitude of low frequency fluctuations (fALFF) and clinical measurements (e.g., insomnia severity and Hamilton Depression Rating Scale [HAMD] scores) were also tested in all subjects. Compared to healthy participants without insomnia symptoms, participants with insomnia symptoms showed a decreased fALFF in the left ventral anterior insula, bilateral posterior insula, left thalamus, and pons but an increased fALFF in the bilateral middle occipital gyrus and right precentral gyrus. More specifically, a significant, negative correlation of fALFF in the left thalamus with early morning awakening scores and HAMD scores in the overall sample was identified. These results suggest that insomnia symptoms are associated with altered spontaneous activity in the brain regions of several important functional networks, including the insular cortex of the salience and the thalamus of the hyperarousal network. The altered fALFF in the left thalamus supports the "hyperarousal theory" of insomnia symptoms, which could serve as a biomarker for insomnia. Copyright © 2016 Elsevier B.V. All rights reserved.

Production rates and turnover of triiodothyronine in rat-developing cerebral cortex and cerebellum. Responses to hypothyroidism

International Nuclear Information System (INIS)

Silva, J.E.; Matthews, P.S.

1984-01-01

Local 5'-deiodination of serum thyroxine (T4) is the main source of triiodothyronine (T3) for the brain. Since we noted in previous studies that the cerebral cortex of neonatal rats tolerated marked reductions in serum T4 without biochemical hypothyroidism, we examined the in vivo T4 and T3 metabolism in that tissue and in the cerebellum of euthyroid and hypothyroid 2-wk-old rats. We also assessed the contribution of enhanced tissue T4 to T3 conversion and decreased T3 removal from the tissues to the T3 homeostasis in hypothyroid brain. Congenital and neonatal hypothyroidism was induced by adding methimazole to the drinking water. Serum, cerebral cortex (Cx), cerebellum (Cm), liver (L) and kidney (R) concentrations of 125I-T4, 125I-T3(T4), and 131I-T3 were measured at various times after injecting 125I-T4 and 131I-T3. The rate of T3 removal from the tissues was measured after injecting an excess of anti-T3-antibody to rats previously injected with tracer T3. In hypothyroidism, the fractional removal rates and clearances were reduced in all tissues, in cortex and cerebellum by 70%, and in liver and kidney ranging from 30 to 50%. While greater than 80% of the 125I-T3(T4) in the brain tissues of euthyroid rats was locally produced, in hypothyroid cerebral cortex and cerebellum the integrated concentrations of 125I-T3(T4) were 2.7- and 1.5-fold greater than in euthyroid rats

Anticipatory activity in rat medial prefrontal cortex during a working memory task

Institute of Scientific and Technical Information of China (English)

Wenwen Bai; Tiaotiao Liu; Hu Yi; Shuangyan Li; Xin Tian

2012-01-01

Objective Working memory is a key cognitive function in which the prefrontal cortex plays a crucial role.This study aimed to show the firing patterns of a neuronal population in the prefrontal cortex of the rat in a working memory task and to explore how a neuronal ensemble encodes a working memory event.Methods Sprague-Dawley rats were trained in a Y-maze until they reached an 80％ correct rate in a working memory task.Then a 16-channel microelectrode array was implanted in the prefrontal cortex.After recovery,neuronal population activity was recorded during the task,using the Cerebus data-acquisition system.Spatio-temporal trains of action potentials were obtained from the original neuronal population signals.Results During the Y-maze working memory task,some neurons showed significantly increased firing rates and evident neuronal ensemble activity.Moreover,the anticipatory activity was associated with the delayed alternate choice of the upcoming movement.In correct trials,the averaged pre-event firing rate (10.86 ± 1.82 spikes/bin) was higher than the post-event rate (8.17 ± 1.15 spikes/bin) (P ＜0.05).However,in incorrect trials,the rates did not differ.Conclusion The results indicate that the anticipatory activity of a neuronal ensemble in the prefrontal cortex may play a role in encoding working memory events.

Neuroprotective Effect of Melatonin Against PCBs Induced Behavioural, Molecular and Histological Changes in Cerebral Cortex of Adult Male Wistar Rats.

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Bavithra, S; Selvakumar, K; Sundareswaran, L; Arunakaran, J

2017-02-01

There is ample evidence stating Polychlorinated biphenyls (PCBs) as neurotoxins. In the current study, we have analyzed the behavioural impact of PCBs exposure in adult rats and assessed the simultaneous effect of antioxidant melatonin against the PCBs action. The rats were grouped into four and treated intraperitoneally with vehicle, PCBs, PCBs + melatonin and melatonin alone for 30 days, respectively. After the treatment period the rats were tested for locomotor activity and anxiety behaviour analysis. We confirmed the neuronal damage in the cerebral cortex by molecular and histological analysis. Our data indicates that there is impairment in locomotor activity and behaviour of PCBs treated rats compared to control. The simultaneous melatonin treated rat shows increased motor coordination and less anxiety like behaviour compared to PCBs treated rats. Molecular and histological analysis supports that, the impaired motor coordination in PCBs treated rats is due to neurodegeneration in motor cortex region. The results proved that melatonin treatment improved the motor co-ordination and reduced anxiety behaviour, prevented neurodegeneration in the cerebral cortex of PCBs-exposed adult male rats.

Higher density of serotonin-1A receptors in the hippocampus and cerebral cortex of alcohol-preferring P rats

International Nuclear Information System (INIS)

Wong, D.T.; Threlkeld, P.G.; Lumeng, L.; Li, Ting-Kai

1990-01-01

Saturable [ 3 H]-80HDPAT binding to 5HT-1A receptors in membranes prepared from hippocampus and frontal cerebral cortex of alcohol-preferring (P) rats and of alcohol-nonpreferring (NP) rats has been compared. The B max values or densities of recognition sites for 5HT-1A receptors in both brain areas of the P rats are 38 and 44 percent lower in the P rats than in the NP rats. The corresponding K D values are 38 and 44 percent lower in the P rats than in the NP rats, indicating higher affinities of the recognition sites for the 5HT-1A receptors in hippocampus and cerebral cortex of the P rats. These findings indicate either an enrichment of 5HT-1A receptor density during selective breeding for alcohol preference or an upregulation of 5HT-1A receptors of 5HT found in these brain areas of P rats as compared with the NP rats

Extinction of aversive taste memory homeostatically prevents the maintenance of in vivo insular cortex LTP: Calcineurin participation.

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Rivera-Olvera, Alejandro; Nelson-Mora, Janikua; Gonsebatt, María E; Escobar, Martha L

2018-04-06

Accumulating evidence indicates that homeostatic plasticity mechanisms dynamically adjust synaptic strength to promote stability that is crucial for memory storage. Our previous studies have shown that prior training in conditioned taste aversion (CTA) prevents the subsequent induction of long-term potentiation (LTP) in the projection from the basolateral nucleus of the amygdala (Bla) to the insular cortex (IC) in vivo. We have also reported that induction of LTP in the Bla-IC pathway modifies the CTA extinction. Memoryextinction involves the formation of a new associativememorythat inhibits a previously conditioned association. The aim of the present study was to analyze the effect of CTA extinction on the ability to induce subsequent LTP in the Bla-IC projection in vivo. Thus, 48 h after CTA extinction animals received high frequency stimulation in order to induce IC-LTP. Our results show that extinction training allows the induction but not the maintenance of IC-LTP. In addition, with the purpose of exploring part of the mechanisms involved in this process and since a body of evidence suggests that protein phosphatase calcineurin (CaN) is involved in the extinction of some behavioral tasks, we analyzed the participation of this phosphatase. The present results show that extinction training increases the CaN expression in the IC, as well as that the inhibition of this phosphatase reverts the effects of the CTA-extinction on the IC-LTP. These findings reveal that CTA extinction promotes a homeostatic regulation of subsequent IC synaptic plasticity maintenance through increases in CaN levels. Copyright © 2018 Elsevier Inc. All rights reserved.

Rapid reorganization of adult rat motor cortex somatic representation patterns after motor nerve injury.

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Sanes, J N; Suner, S; Lando, J F; Donoghue, J P

1988-01-01

The potential for peripheral nerve injury to reorganize motor cortical representations was investigated in adult rats. Maps reflecting functional connections between the motor cortex and somatic musculature were generated with intracortical electrical stimulation techniques. Comparison of cortical somatotopic maps obtained in normal rats with maps generated from rats with a facial nerve lesion indicated that the forelimb and eye/eyelid representations expanded into the normal vibrissa area. R...

Characterizing synaptic protein development in human visual cortex enables alignment of synaptic age with rat visual cortex

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Joshua G.A Pinto

2015-02-01

Full Text Available Although many potential neuroplasticity based therapies have been developed in the lab, few have translated into established clinical treatments for human neurologic or neuropsychiatric diseases. Animal models, especially of the visual system, have shaped our understanding of neuroplasticity by characterizing the mechanisms that promote neural changes and defining timing of the sensitive period. The lack of knowledge about development of synaptic plasticity mechanisms in human cortex, and about alignment of synaptic age between animals and humans, has limited translation of neuroplasticity therapies. In this study, we quantified expression of a set of highly conserved pre- and post-synaptic proteins (Synapsin, Synaptophysin, PSD-95, Gephyrin and found that synaptic development in human primary visual cortex continues into late childhood. Indeed, this is many years longer than suggested by neuroanatomical studies and points to a prolonged sensitive period for plasticity in human sensory cortex. In addition, during childhood we found waves of inter-individual variability that are different for the 4 proteins and include a stage during early development (<1 year when only Gephyrin has high inter-individual variability. We also found that pre- and post-synaptic protein balances develop quickly, suggesting that maturation of certain synaptic functions happens within the first year or two of life. A multidimensional analysis (principle component analysis showed that most of the variance was captured by the sum of the 4 synaptic proteins. We used that sum to compare development of human and rat visual cortex and identified a simple linear equation that provides robust alignment of synaptic age between humans and rats. Alignment of synaptic ages is important for age-appropriate targeting and effective translation of neuroplasticity therapies from the lab to the clinic.

Increasing CNS norepinephrine levels by the precursor L-DOPS facilitates beam-walking recovery after sensorimotor cortex ablation in rats.

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Kikuchi, K; Nishino, K; Ohyu, H

2000-03-31

The present investigation was conducted to document a role of L-threo-3,4-dihydroxyphenylserine (L-DOPS), precursor of L-norepinephrine (NE), in the functional recovery from beam-walking performance deficits in rats after unilateral sensorimotor cortex ablation. L-DOPS was administered simultaneously with benserazide (BSZ; a peripheral aromatic amino acid decarboxylase inhibitor), and the regional contents of NE in the cerebral cortex, hippocampus, and cerebellum were assayed. Behavioral recovery was demonstrated by the rats treated with L-DOPS and BSZ, and the rate of recovery was significantly different from that of either BSZ-treated or vehicle-treated control rats. The NE tissue levels in the three discrete regions of the rat brain were significantly elevated in the experimental rats receiving both L-DOPS and BSZ. The present studies indicate that increasing NE levels by the precursor L-DOPS may be responsible for facilitating behavioral recovery from beam-walking performance deficits in rats, and further suggest that L-DOPS may become one of the candidate compounds for further clinical human trials promoting functional recovery after injuries to the cerebral cortex.

The effect of electroacupuncture on proteomic changes in the motor cortex of 6-OHDA Parkinsonian rats.

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Li, Min; Li, Lijuan; Wang, Ke; Su, Wenting; Jia, Jun; Wang, Xiaomin

2017-10-15

Electroacupuncture (EA) has been reported to alleviate motor deficits in Parkinson's disease (PD) patients, and PD animal models. However, the mechanisms by which EA improves motor function have not been investigated. We have employed a 6-hydroxydopamine (6-OHDA) unilateral injection induced PD model to investigate whether EA alters protein expression in the motor cortex. We found that 4weeks of EA treatment significantly improved spontaneous floor plane locomotion and rotarod performance. High-throughput proteomic analysis in the motor cortex was employed. The expression of 54 proteins were altered in the unlesioned motor cortex, and 102 protein expressions were altered in the lesioned motor cortex of 6-OHDA rats compared to sham rats. Compared to non-treatment PD control, EA treatment reversed 6 proteins in unlesioned and 19 proteins in lesioned motor cortex. The present study demonstrated that PD induces proteomic changes in the motor cortex, some of which are rescued by EA treatment. These targeted proteins were mainly involved in increasing autophagy, mRNA processing and ATP binding and maintaining the balance of neurotransmitters. Copyright © 2017 Elsevier B.V. All rights reserved.

Neonatal Stress Has a Long-Lasting Sex-Dependent Effect on Anxiety-Like Behavior and Neuronal Morphology in the Prefrontal Cortex and Hippocampus.

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de Melo, Silvana Regina; de David Antoniazzi, Caren Tatiane; Hossain, Shakhawat; Kolb, Bryan

2018-01-01

The long-lasting effects of early stress on brain development have been well studied. Recent evidence indicates that males and females respond differently to the same stressor. We examined the chronic effects of daily maternal separation (MS) on behavior and cerebral morphology in both male and female rats. Cognitive and anxiety-like behaviors were evaluated, and neuroplastic changes in 2 subregions of the prefrontal cortex (dorsal agranular insular cortex [AID] and cingulate cortex [Cg3]) and hippocampus (CA1 and dentate gyrus) were measured in adult male and female rats. The animals were subjected to MS on postnatal day (P) 3-14 for 3 h per day. Cognitive and emotional behaviors were assessed in the object/context mismatch task, elevated plus maze, and locomotor activity test in early adulthood (P87-P95). Anatomical assessments were performed in the prefrontal cortex (i.e., cortical thickness and spine density) and hippocampus (i.e., spine density). Sex-dependent effects were observed. MS increased anxiety-related behavior only in males, whereas locomotor activity was higher in females, with no effects on cognition. MS decreased spine density in the AID and increased spine density in the CA1 area in males. Females exhibited an increase in spine density in the Cg3. Our findings confirm previous work that found that MS causes long-term behavioral and anatomical effects, and these effects were dependent on sex and the duration of MS stress. © 2018 S. Karger AG, Basel.

Neuron activity in rat hippocampus and motor cortex during discrimination reversal.

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Disterhoft, J F; Segal, M

1978-01-01

Chronic unit activity and gross movement were recorded from rats during two discrimination reversals in a classical appetitive conditioning situation. The anticipatory movement decreased in response to the former CS+ tone and increased to the previous CS- tone after each reversal. Hippocampus and motor cortex were differently related to these two kinds of behavioral change. Response rates of hippocampal neurons were more closely related to the increased movement response to the former CS- which now signaled food. Motor cortex neuron responses were more closely correlated with the decrease in movement responses to the former CS+ which became neutral after the reversal. It appeared that hippocampal neurons could have been involved in one cognitive aspect of the situation, motor cortex neurons in another. The data were related to current functional concepts of these brain regions.

Effects of electroacupuncture on metabolic changes in motor cortex and striatum of 6-hydroxydopamine-induced Parkinsonian rats.

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Li, Min; Wang, Ke; Su, Wen-Ting; Jia, Jun; Wang, Xiao-Min

2017-10-06

To explore the possible underlying mechanism by investigating the effect of electroacupuncture (EA) treatment on the primary motor cortex and striatum in a unilateral 6-hydroxydopamine (6-OHDA) induced rat Parkinson's disease (PD) model. Male Sprague-Dawley rats were randomly divided into sham group (n=16), model group (n=14), and EA group (n=14). EA stimulation at Dazhui (GV 14) and Baihui (GV20) was applied to PD rats in the EA group for 4 weeks. Behavioral tests were conducted to evaluate the effectiveness of EA treatment. Metabolites were detected by 7.0 T proton nuclear magnetic resonance. Following 4 weeks of EA treatment in PD model rats, the abnormal behavioral impairment induced by 6-OHDA was alleviated. In monitoring changes in metabolic activity, ratios of myoinositol/creatine (Cr) and N-acetyl aspartate (NAA)/Cr in the primary motor cortex were significantly lower at the injected side than the non-injected side in PD rats (P=0.024 and 0.020). The ratios of glutamate + glutamine (Glx)/Cr and NAA/Cr in the striatum were higher and lower, respectively, at the injected side than the non-injected side (P=0.046 and 0.008). EA treatment restored the balance of metabolic activity in the primary motor cortex and striatum. In addition, the taurine/Cr ratio and Glx/Cr ratio were elevated in the striatum of PD model rats compared to sham-lesioned rats (P=0.026 and 0.000). EA treatment alleviated the excessive glutamatergic transmission by down-regulating the striatal Glx/Cr ratio (P=0.001). The Glx/Cr ratio was negatively correlated with floor plane spontaneous locomotion in PD rats (P=0.027 and P=0.0007). EA treatment is able to normalize the metabolic balance in the primary motor cortex and striatum of PD rats, which may contribute to its therapeutic effect on motor deficits. The striatal Glx/Cr ratio may serve as a potential indicator of PD and a therapeutic target of EA treatment.

CRYOPRESERVATION OF FRESHLY ISOLATED SYNAPTOSOMES PREPARED FROM THE CEREBRAL-CORTEX OF RATS

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GLEITZ, J; BEILE, A; WILFFERT, B; TEGTMEIER, F

In the present study, we established a cryopreservation method for freshly isolated synaptosomes prepared from the cerebral cortex of rats. Freshly prepared synaptosomes were either shock-frozen or frozen under temperature-controlled conditions using a programmable temperature controller. Each group

Laminar-specific distribution of zinc: evidence for presence of layer IV in forelimb motor cortex in the rat.

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Alaverdashvili, Mariam; Hackett, Mark J; Pickering, Ingrid J; Paterson, Phyllis G

2014-12-01

The rat is the most widely studied pre-clinical model system of various neurological and neurodegenerative disorders affecting hand function. Although brain injury to the forelimb region of the motor cortex in rats mostly induces behavioral abnormalities in motor control of hand movements, behavioral deficits in the sensory-motor domain are also observed. This questions the prevailing view that cortical layer IV, a recipient of sensory information from the thalamus, is absent in rat motor cortex. Because zinc-containing neurons are generally not found in pathways that run from the thalamus, an absence of zinc (Zn) in a cortical layer would be suggestive of sensory input from the thalamus. To test this hypothesis, we used synchrotron micro X-ray fluorescence imaging to measure Zn distribution across cortical layers. Zn maps revealed a heterogeneous layered Zn distribution in primary and secondary motor cortices of the forelimb region in the adult rat. Two wider bands with elevated Zn content were separated by a narrow band having reduced Zn content, and this was evident in two rat strains. The Zn distribution pattern was comparable to that in sensorimotor cortex, which is known to contain a well demarcated layer IV. Juxtaposition of Zn maps and the images of brain stained for Nissl bodies revealed a "Zn valley" in primary motor cortex, apparently starting at the ventral border of pyramidal layer III and ending at the close vicinity of layer V. This finding indicates the presence of a conspicuous cortical layer between layers III and V, i.e. layer IV, the presence of which previously has been disputed. The results have implications for the use of rat models to investigate human brain function and neuropathology, such as after stroke. The presence of layer IV in the forelimb region of the motor cortex suggests that therapeutic interventions used in rat models of motor cortex injury should target functional abnormalities in both motor and sensory domains. The finding

Neuropathological Changes in Brain Cortex and Hippocampus in a Rat Model of Alzheimer’s Disease

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Nobakht, Maliheh; Hoseini, Seyed Mohammad; Mortazavi, Pejman; Sohrabi, Iraj; Esmailzade, Banafshe; Roosh, Nahid Rahbar; Omidzahir, Shila

2011-01-01

Background: Alzheimer’s disease (AD) is a neurodegenerative disorder with progressive loss of cognitive abilities and memory loss. The aim of this study was to compare neuropathological changes in hippocampus and brain cortex in a rat model of AD. Methods: Adult male Albino Wistar rats (weighing 250-300 g) were used for behavioral and histopathological studies. The rats were randomly assigned to three groups: control, sham and β-amyloid (Aβ) injection. For behavioral analysis, Y-maze and shuttle box were used, respectively at 14 and 16 days post-lesion. For histological studies, Nissl, modified Bielschowsky and modified Congo red staining were performed. The lesion was induced by injection of 4 µL of Aβ (1-40) into the hippocampal fissure. Results: In the present study, Aβ (1-40) injection into hippocampus could decrease the behavioral indexes and the number of CA1 neurons in hippocampus. Aβ injection CA1 caused Aβ deposition in the hippocampus and less than in cortex. We observed the loss of neurons in the hippocampus and cerebral cortex and certain subcortical regions. Y-maze test and single-trial passive avoidance test showed reduced memory retention in AD group. Conclusion: We found a significant decreased acquisition of passive avoidance and alternation behavior responses in AD group compared to control and sham group (P<0.0001). Compacted amyloid cores were present in the cerebral cortex, hippocampus and white matter, whereas, scattered amyloid cores were seen in cortex and hippocampus of AD group. Also, reduced neuronal density was indicated in AD group. PMID:21725500

Tramadol Pretreatment Enhances Ketamine-Induced Antidepressant Effects and Increases Mammalian Target of Rapamycin in Rat Hippocampus and Prefrontal Cortex

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Chun Yang

2012-01-01

Full Text Available Several lines of evidence have demonstrated that acute administration of ketamine elicits fast-acting antidepressant effects. Moreover, tramadol also has potential antidepressant effects. The aim of this study was to investigate the effects of pretreatment with tramadol on ketamine-induced antidepressant activity and was to determine the expression of mammalian target of rapamycin (mTOR in rat hippocampus and prefrontal cortex. Rats were intraperitoneally administrated with ketamine at the dose of 10 mg/kg or saline 1 h before the second episode of the forced swimming test (FST. Tramadol or saline was intraperitoneally pretreated 30 min before the former administration of ketamine or saline. The locomotor activity and the immobility time of FST were both measured. After that, rats were sacrificed to determine the expression of mTOR in hippocampus and prefrontal cortex. Tramadol at the dose of 5 mg/kg administrated alone did not elicit the antidepressant effects. More importantly, pretreatment with tramadol enhanced the ketamine-induced antidepressant effects and upregulated the expression of mTOR in rat hippocampus and prefrontal cortex. Pretreatment with tramadol enhances the ketamine-induced antidepressant effects, which is associated with the increased expression of mTOR in rat hippocampus and prefrontal cortex.

Distortion of time interval reproduction in an epileptic patient with a focal lesion in the right anterior insular/inferior frontal cortices.

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Monfort, Vincent; Pfeuty, Micha; Klein, Madelyne; Collé, Steffie; Brissart, Hélène; Jonas, Jacques; Maillard, Louis

2014-11-01

This case report on an epileptic patient suffering from a focal lesion at the junction of the right anterior insular cortex (AIC) and the adjacent inferior frontal cortex (IFC) provides the first evidence that damage to this brain region impairs temporal performance in a visual time reproduction task in which participants had to reproduce the presentation duration (3, 5 and 7s) of emotionally-neutral and -negative pictures. Strikingly, as compared to a group of healthy subjects, the AIC/IFC case considerably overestimated reproduction times despite normal variability. The effect was obtained in all duration and emotion conditions. Such a distortion in time reproduction was not observed in four other epileptic patients without insular or inferior frontal damage. Importantly, the absolute extent of temporal over-reproduction increased in proportion to the magnitude of the target durations, which concurs with the scalar property of interval timing, and points to an impairment of time-specific rather than of non temporal (such as motor) mechanisms. Our data suggest that the disability in temporal reproduction of the AIC/IFC case would result from a distorted memory representation of the encoded duration, occurring during the process of storage and/or of recovery from memory and leading to a deviation of the temporal judgment during the reproduction task. These findings support the recent proposal that the anterior insular/inferior frontal cortices would be involved in time interval representation. Copyright © 2014 Elsevier Ltd. All rights reserved.

ITI-signals and prelimbic cortex facilitate avoidance acquisition and reduce avoidance latencies, respectively, in male WKY rats

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Kevin D Beck

2014-11-01

Full Text Available As a model of anxiety disorder vulnerability, male Wistar-Kyoto (WKY rats acquire lever-press avoidance behavior more readily than outbred Sprague Dawley rats, and their acquisition is enhanced by the presence of a discrete signal presented during the inter-trial intervals (ITIs, suggesting it is perceived as a safety signal. A series of experiments were conducted to determine if this is the case. Additional experiments investigated if the avoidance facilitation relies upon processing through medial prefrontal cortex (mPFC. The results suggest that the ITI-signal facilitates acquisition during the early stages of the avoidance acquisition process, when the rats are initially acquiring escape behavior and then transitioning to avoidance behavior. Post-avoidance introduction of the visual ITI-signal into other associative learning tasks failed to confirm that the visual stimulus had acquired the properties of a conditioned inhibitor. Shortening the signal from the entirety of the 3 min ITI to only the first 5 s of the 3 min ITI slowed acquisition during the first 4 sessions, suggesting the flashing light is not functioning as a feedback signal. The prelimbic (PL cortex showed greater activation during the period of training when the transition from escape responding to avoidance responding occurs. Only combined PL+infralimbic cortex lesions modestly slowed avoidance acquisition, but PL cortex lesions slowed avoidance response latencies. Thus, the flashing light ITI-signal is not likely perceived as a safety signal nor is it serving as a feedback signal. The functional role of the PL cortex appears to be to increase the drive towards responding to the threat of the warning signal. Hence, avoidance susceptibility displayed by male WKY rats may be driven, in part, both by external stimuli (ITI signal as well as by enhanced threat recognition to the warning signal via the PL cortex.

Effects of chronic stress in adolescence on learned fear, anxiety, and synaptic transmission in the rat prelimbic cortex.

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Negrón-Oyarzo, Ignacio; Pérez, Miguel Ángel; Terreros, Gonzalo; Muñoz, Pablo; Dagnino-Subiabre, Alexies

2014-02-01

The prelimbic cortex and amygdala regulate the extinction of conditioned fear and anxiety, respectively. In adult rats, chronic stress affects the dendritic morphology of these brain areas, slowing extinction of learned fear and enhancing anxiety. The aim of this study was to determine whether rats subjected to chronic stress in adolescence show changes in learned fear, anxiety, and synaptic transmission in the prelimbic cortex during adulthood. Male Sprague Dawley rats were subjected to seven days of restraint stress on postnatal day forty-two (PND 42, adolescence). Afterward, the fear-conditioning paradigm was used to study conditioned fear extinction. Anxiety-like behavior was measured one day (PND 50) and twenty-one days (PND 70, adulthood) after stress using the elevated-plus maze and dark-light box tests, respectively. With another set of rats, excitatory synaptic transmission was analyzed with slices of the prelimbic cortex. Rats that had been stressed during adolescence and adulthood had higher anxiety-like behavior levels than did controls, while stress-induced slowing of learned fear extinction in adolescence was reversed during adulthood. As well, the field excitatory postsynaptic potentials of stressed adolescent rats had significantly lower amplitudes than those of controls, although the amplitudes were higher in adulthood. Our results demonstrate that short-term stress in adolescence induces strong effects on excitatory synaptic transmission in the prelimbic cortex and extinction of learned fear, where the effect of stress on anxiety is more persistent than on the extinction of learned fear. These data contribute to the understanding of stress neurobiology. Copyright © 2013 Elsevier B.V. All rights reserved.

A radial map of multi-whisker correlation selectivity in the rat barrel cortex.

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Estebanez, Luc; Bertherat, Julien; Shulz, Daniel E; Bourdieu, Laurent; Léger, Jean-François

2016-11-21

In the barrel cortex, several features of single-whisker stimuli are organized in functional maps. The barrel cortex also encodes spatio-temporal correlation patterns of multi-whisker inputs, but so far the cortical mapping of neurons tuned to such input statistics is unknown. Here we report that layer 2/3 of the rat barrel cortex contains an additional functional map based on neuronal tuning to correlated versus uncorrelated multi-whisker stimuli: neuron responses to uncorrelated multi-whisker stimulation are strongest above barrel centres, whereas neuron responses to correlated and anti-correlated multi-whisker stimulation peak above the barrel-septal borders, forming rings of multi-whisker synchrony-preferring cells.

Differential requirement of de novo Arc protein synthesis in the insular cortex and the amygdala for safe and aversive taste long-term memory formation.

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Guzmán-Ramos, Kioko; Venkataraman, Archana; Morin, Jean-Pascal; Osorio-Gómez, Daniel; Bermúdez-Rattoni, Federico

2018-04-16

Several immediate early genes products are known to be involved in the facilitation of structural and functional modifications at distinct synapses activated through experience. The IEG-encoded protein Arc (activity regulated cytoskeletal-associated protein) has been widely implicated in long-term memory formation and stabilization. In this study, we sought to evaluate a possible role for de novo Arc protein synthesis in the insular cortex (IC) and in the amygdala (AMY) during long-term taste memory formation. We found that acute inhibition of Arc protein synthesis through the infusion of antisense oligonucleotides administered in the IC before a novel taste presentation, affected consolidation of a safe taste memory trace (ST) but spared consolidation of conditioned taste aversion (CTA). Conversely, blocking Arc synthesis within the AMY impaired CTA consolidation but had no effect on ST long-term memory formation. Our results suggest that Arc-dependent plasticity during taste learning is required within distinct structures of the medial temporal lobe, depending on the emotional valence of the memory trace. Copyright © 2018 Elsevier B.V. All rights reserved.

Prenatal Mercuric Chloride Exposure Causes Developmental Deficits in Rat Cortex

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Tayebeh Rastegar

2011-09-01

Full Text Available Introduction: Environmental pollution with heavy metals such as mercury is a major health problem. Growing studies on the field have shown the deleterious effects of mercury on human and nonhuman nervous system, especially in infants, however the effects of prenatal exposure to mercuricchloride on cortical development are not yet well understood. The aim of this study was to investigate the effect of prenatal exposure to mercuric chloride on morphological characteristics of brain cortex. Methods: Mercuric chloride (2 mg/kg or normal saline were injected (I.P. to 36 Sprague – dawley rats in the 8th, 9th or 10th day of gestation. The embryos were surgically removed in the 15th day of gestation, and brain cortices were studied by histological techniques. Results: Histological studies showed that embryos of mercuric chloride treated rats hadcortical neuronal disarrangement withdifferent orientations of nuclei, increased diameter of cortex, increased mitosis of cells, increased cell death, decreased cellular density and increased intracellular space. Conclusion: These findings suggest some micro structural abnormalities in cortical regions after prenatal exposure to mercuric chloride. These structural abnormalities may underliesome neurologic disturbances following mercury intoxication.

Hyperthyroidism modifies ecto-nucleotidase activities in synaptosomes from hippocampus and cerebral cortex of rats in different phases of development.

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Bruno, Alessandra Nejar; Da Silva, Rosane Souza; Bonan, Carla Denise; Battastini, Ana Maria Oliveira; Barreto-chaves, Maria Luiza M; Sarkis, João José Freitas

2003-11-01

Here we investigate the possible effects of the hyperthyroidism on the hydrolysis of the ATP to adenosine in the synaptosomes of hippocampus, cerebral cortex and blood serum of rats in different developmental phases. Manifestations of hyperthyroidism include anxiety, nervousness, tachycardia, physical hyperactivity and weight loss amongst others. The thyroid hormones modulate a number of physiological functions in central nervous system, including development, function, expression of adenosine A(1) receptors and transport of neuromodulator adenosine. Thus, hyperthyroidism was induced in male Wistar rats (5-, 60-, 150- and 330-day old) by daily injections of L-thyroxine (T4) for 14 days. Nucleotide hydrolysis was decreased by about 14-52% in both hippocampus and cerebral cortex in 5 to 60-day-old rats. These changes were also observed in rat blood serum. In addition, in 11-month-old rats, inhibition of ADP and AMP hydrolysis persisted in the hippocampus, whereas, in cerebral cortex, an increase in AMP hydrolysis was detected. Thus, hyperthyroidism affects the extracellular nucleotides balance and adenosine production, interfering in neurotransmitter release, development and others physiological processes in different systems.

Exposure to Music and Noise During Pregnancy Influences Neurogenesis and Thickness in Motor and Somatosensory Cortex of Rat Pups

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Chang-Hee Kim

2013-09-01

Full Text Available Purpose Prenatal environmental conditions affect the development of the fetus. In the present study, we investigated the effects of exposure to music and noise during pregnancy on neurogenesis and thickness in the motor and somatosensory cortex of rat pups. Methods The pregnant rats in the music-applied group were exposed to 65 dB of comfortable music for 1 hour, once per day, from the 15th day of pregnancy until delivery. The pregnant rats in the noise-applied group were exposed to 95 dB of sound from a supersonic sound machine for 1 hour, once per day, from the 15th day of pregnancy until delivery. After birth, the offspring were left undisturbed together with their mother. The rat pups were sacrificed at 21 days after birth. Results Exposure to music during pregnancy increased neurogenesis in the motor and somatosensory cortex of rat pups. In contrast, rat pups exposed to noise during pregnancy showed decreased neurogenesis and thickness in the motor and somatosensory cortex. Conclusions Our study suggests that music and noise during the developmental period are important factors influencing brain development and urogenital disorders.

Choice Behavior Guided by Learned, But Not Innate, Taste Aversion Recruits the Orbitofrontal Cortex.

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Ramírez-Lugo, Leticia; Peñas-Rincón, Ana; Ángeles-Durán, Sandybel; Sotres-Bayon, Francisco

2016-10-12

The ability to select an appropriate behavioral response guided by previous emotional experiences is critical for survival. Although much is known about brain mechanisms underlying emotional associations, little is known about how these associations guide behavior when several choices are available. To address this, we performed local pharmacological inactivations of several cortical regions before retrieval of an aversive memory in choice-based versus no-choice-based conditioned taste aversion (CTA) tasks in rats. Interestingly, we found that inactivation of the orbitofrontal cortex (OFC), but not the dorsal or ventral medial prefrontal cortices, blocked retrieval of choice CTA. However, OFC inactivation left retrieval of no-choice CTA intact, suggesting its role in guiding choice, but not in retrieval of CTA memory. Consistently, OFC activity increased in the choice condition compared with no-choice, as measured with c-Fos immunolabeling. Notably, OFC inactivation did not affect choice behavior when it was guided by innate taste aversion. Consistent with an anterior insular cortex (AIC) involvement in storing taste memories, we found that AIC inactivation impaired retrieval of both choice and no-choice CTA. Therefore, this study provides evidence for OFC's role in guiding choice behavior and shows that this is dissociable from AIC-dependent taste aversion memory. Together, our results suggest that OFC is required and recruited to guide choice selection between options of taste associations relayed from AIC. Survival and mental health depend on being able to choose stimuli not associated with danger. This is particularly important when danger is associated with stimuli that we ingest. Although much is known about the brain mechanisms that underlie associations with dangerous taste stimuli, very little is known about how these stored emotional associations guide behavior when it involves choice. By combining pharmacological and immunohistochemistry tools with taste

Memory of conditioned taste aversion is erased by inhibition of PI3K in the insular cortex.

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Slouzkey, Ilana; Rosenblum, Kobi; Maroun, Mouna

2013-06-01

The conditioned taste aversion (CTA) paradigm, in which association between a novel taste and visceral malaise is formed, gives a unique experimental setting to examine the mechanisms underlying memory acquisition and extinction processes. AKT is a main kinase of the phosphoinositide 3-kinase cascade (PI3K) and has been implicated in long-term memory. We have recently reported that blockade of PI3K in the basolateral amygdala (BLA) before retrieval of fear memory was associated with long-term reduction in fear responses, suggesting a possible role of PI3K inhibition in fear erasure. In this study, we aimed to elucidate whether PI3K has a similar role in the insular cortex (IC), which has a crucial role in CTA acquisition, consolidation, maintenance, and extinction. To that end, we (1) monitored AKT phosphorylation in the IC following CTA acquisition and extinction and (2) inhibited PI3K by local microinjection of the PI3K inhibitor LY294002 at different stages of CTA acquisition and extinction. Our results show that while AKT phosphorylation is increased following CTA learning, it is decreased following CTA extinction. Inhibition of AKT phosphorylation in the IC before or after the first CTA retrieval test resulted in reduction in the aversion index. This reduction in aversion is due to the erasure of the original CTA trace memory, as re-application of the unconditioned stimulus (lithium chloride) did not induce the recovery of aversion in LY294002-treated animals. Our present data add new evidence to suggest that PI3K is engaged in consolidation of aversive memories, as its inhibition is associated with erasure of CTA memory.

Characterizing synaptic protein development in human visual cortex enables alignment of synaptic age with rat visual cortex

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Pinto, Joshua G. A.; Jones, David G.; Williams, C. Kate; Murphy, Kathryn M.

2015-01-01

Although many potential neuroplasticity based therapies have been developed in the lab, few have translated into established clinical treatments for human neurologic or neuropsychiatric diseases. Animal models, especially of the visual system, have shaped our understanding of neuroplasticity by characterizing the mechanisms that promote neural changes and defining timing of the sensitive period. The lack of knowledge about development of synaptic plasticity mechanisms in human cortex, and about alignment of synaptic age between animals and humans, has limited translation of neuroplasticity therapies. In this study, we quantified expression of a set of highly conserved pre- and post-synaptic proteins (Synapsin, Synaptophysin, PSD-95, Gephyrin) and found that synaptic development in human primary visual cortex (V1) continues into late childhood. Indeed, this is many years longer than suggested by neuroanatomical studies and points to a prolonged sensitive period for plasticity in human sensory cortex. In addition, during childhood we found waves of inter-individual variability that are different for the four proteins and include a stage during early development (visual cortex and identified a simple linear equation that provides robust alignment of synaptic age between humans and rats. Alignment of synaptic ages is important for age-appropriate targeting and effective translation of neuroplasticity therapies from the lab to the clinic. PMID:25729353

Encoding of temporal intervals in the rat hindlimb sensorimotor cortex

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Eric Bean Knudsen

2012-09-01

Full Text Available The gradual buildup of neural activity over experimentally imposed delay periods, termed climbing activity, is well documented and is a potential mechanism by which interval time is encoded by distributed cortico-thalamico-striatal networks in the brain. Additionally, when multiple delay periods are incorporated, this activity has been shown to scale its rate of climbing proportional to the delay period. However, it remains unclear whether these patterns of activity occur within areas of motor cortex dedicated to hindlimb movement. Moreover, the effects of behavioral training (e.g. motor tasks under different reward conditions but with similar behavioral output are not well addressed. To address this, we recorded activity from the hindlimb sensorimotor cortex (HLSMC of two groups of rats performing a skilled hindlimb press task. In one group, rats were trained only to a make a valid press within a finite window after cue presentation for reward (non-interval trained, nIT; n=5, while rats in the second group were given duration-specific cues in which they had to make presses of either short or long duration to receive reward (interval trained, IT; n=6. Using PETH analyses, we show that cells recorded from both groups showed climbing activity during the task in similar proportions (35% IT and 47% nIT, however only climbing activity from IT rats was temporally scaled to press duration. Furthermore, using single trial decoding techniques (Wiener filter, we show that press duration can be inferred using climbing activity from IT animals (R=0.61 significantly better than nIT animals (R=0.507, p<0.01, suggesting IT animals encode press duration through temporally scaled climbing activity. Thus, if temporal intervals are behaviorally relevant then the activity of climbing neurons is temporally scaled to encode the passage of time.

Mitochondrial dysfunction in brain cortex mitochondria of STZ-diabetic rats: effect of l-Arginine.

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Ortiz, M Del Carmen; Lores-Arnaiz, Silvia; Albertoni Borghese, M Florencia; Balonga, Sabrina; Lavagna, Agustina; Filipuzzi, Ana Laura; Cicerchia, Daniela; Majowicz, Monica; Bustamante, Juanita

2013-12-01

Mitochondrial dysfunction has been implicated in many diseases, including diabetes. It is well known that oxygen free radical species are produced endogenously by mitochondria, and also nitric oxide (NO) by nitric oxide synthases (NOS) associated to mitochondrial membranes, in consequence these organelles constitute main targets for oxidative damage. The aim of this study was to analyze mitochondrial physiology and NO production in brain cortex mitochondria of streptozotocin (STZ) diabetic rats in an early stage of diabetes and the potential effect of L-arginine administration. The diabetic condition was characterized by a clear hyperglycaemic state with loose of body weight after 4 days of STZ injection. This hyperglycaemic state was associated with mitochondrial dysfunction that was evident by an impairment of the respiratory activity, increased production of superoxide anion and a clear mitochondrial depolarization. In addition, the alteration in mitochondrial physiology was associated with a significant decrease in both NO production and nitric oxide synthase type I (NOS I) expression associated to the mitochondrial membranes. An increased level of thiobarbituric acid-reactive substances (TBARS) in brain cortex homogenates from STZ-diabetic rats indicated the presence of lipid peroxidation. L-arginine treatment to diabetic rats did not change blood glucose levels but significantly ameliorated the oxidative stress evidenced by lower TBARS and a lower level of superoxide anion. This effect was paralleled by improvement of mitochondrial respiratory function and a partial mitochondrial repolarization.In addition, the administration of L-arginine to diabetic rats prevented the decrease in NO production and NOSI expression. These results could indicate that exogenously administered L-arginine may have beneficial effects on mitochondrial function, oxidative stress and NO production in brain cortex mitochondria of STZ-diabetic rats.

Malformation of the cerebral cortex of rats caused by embryonal exposure to x-ray

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Inoue, M [Nagoya Univ. (Japan). Research Inst. of Environmental Medicine

1978-03-01

200 R x-ray was irradiated to rat embryos, 17 days of age, and changes of the brain were observed histologically from one hour after the irradiation until they grew up. At start, there was not a great damage in the formation of bundles of major and minor hemisphere commissure passing through the terminal plate, although many cells died or fell off in the new brain mantle. After that, callosal fibers did not reach the midline because of the tissue destruction around the midline, and growth of the stem of the corpus callosum was pressed down. Defect of the stem of the corpus callosum was recognized in adult rats. Surviving mother cells gathered irregularly on the wall of the ventricle at the time of the repair of destructed tissues, and they remained as they stood around the midline of the brain mantle without rearrangement. In adult rats, there was abnormal formation of the cerebral cortex within medullary substances. Marked hypoplasia was recognized in the II-IV layer of the new cortex, bundle branches of dendritic processes of pyramidal cells in the V layer were small in number, and the directions of dendritic processes were abnormal. Pyramidal cell layer of the hippocampus fell into disorder and the directions of dendritic processes were irregular. It was demonstrated by the measurement of cubic volume of each part of the brain using reconstruction method that not only marked hypoplasia of the new cortex and the hippocampus but also hypoplasia of the old cortex, the basal ganglion, and the thalamus in which it was thought to be little disorder in the past were clear.

Malformation of the cerebral cortex of rats caused by embryonal exposure to x-ray

International Nuclear Information System (INIS)

Inoue, Minoru

1978-01-01

200 R x-ray was irradiated to rat embryos, 17 days of age, and changes of the brain were observed histologically from one hour after the irradiation until they grew up. At start, there was not a great damage in the formation of bundles of major and minor hemisphere commissure passing through the terminal plate, although many cells died or fell off in the new brain mantle. After that, callosal fibers did not reach the midline because of the tissue destruction around the midline, and growth of the stem of the corpus callosum was pressed down. Defect of the stem of the corpus callosum was recognized in adult rats. Surviving mother cells gathered irregularly on the wall of the ventricle at the time of the repair of destructed tissues, and they remained as they stood around the midline of the brain mantle without rearrangement. In adult rats, there was abnormal formation of the cerebral cortex within medullary substances. Marked hypoplasia was recognized in the II-IV layer of the new cortex, bundle branches of dendritic processes of pyramidal cells in the V layer were small in number, and the directions of dendritic processes were abnormal. Pyramidal cell layer of the hippocampus fell into disorder and the directions of dendritic processes were irregular. It was demonstrated by the measurement of cubic volume of each part of the brain using reconstruction method that not only marked hypoplasia of the new cortex and the hippocampus but also hypoplasia of the old cortex, the basal ganglion, and the thalamus in which it was thought to be little disorder in the past were clear. (Iwagami, H.)

Recruitment of the prefrontal cortex and cerebellum in Parkinsonian rats following skilled aerobic exercise.

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Wang, Zhuo; Guo, Yumei; Myers, Kalisa G; Heintz, Ryan; Holschneider, Daniel P

2015-05-01

Exercise modality and complexity play a key role in determining neurorehabilitative outcome in Parkinson's disease (PD). Exercise training (ET) that incorporates both motor skill training and aerobic exercise has been proposed to synergistically improve cognitive and automatic components of motor control in PD patients. Here we introduced such a skilled aerobic ET paradigm in a rat model of dopaminergic deafferentation. Rats with bilateral, intra-striatal 6-hydroxydopamine lesions were exposed to forced ET for 4weeks, either on a simple running wheel (non-skilled aerobic exercise, NSAE) or on a complex wheel with irregularly spaced rungs (skilled aerobic exercise, SAE). Cerebral perfusion was mapped during horizontal treadmill walking or at rest using [(14)C]-iodoantipyrine 1week after the completion of ET. Regional cerebral blood flow (rCBF) was quantified by autoradiography and analyzed in 3-dimensionally reconstructed brains by statistical parametric mapping. SAE compared to NSAE resulted in equal or greater recovery in motor deficits, as well as greater increases in rCBF during walking in the prelimbic area of the prefrontal cortex, broad areas of the somatosensory cortex, and the cerebellum. NSAE compared to SAE animals showed greater activation in the dorsal caudate-putamen and dorsal hippocampus. Seed correlation analysis revealed enhanced functional connectivity in SAE compared to NSAE animals between the prelimbic cortex and motor areas, as well as altered functional connectivity between midline cerebellum and sensorimotor regions. Our study provides the first evidence for functional brain reorganization following skilled aerobic exercise in Parkinsonian rats, and suggests that SAE compared to NSAE results in enhancement of prefrontal cortex- and cerebellum-mediated control of motor function. Copyright © 2015 Elsevier Inc. All rights reserved.

Region and task-specific activation of Arc in primary motor cortex of rats following motor skill learning.

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Hosp, J A; Mann, S; Wegenast-Braun, B M; Calhoun, M E; Luft, A R

2013-10-10

Motor learning requires protein synthesis within the primary motor cortex (M1). Here, we show that the immediate early gene Arc/Arg3.1 is specifically induced in M1 by learning a motor skill. Arc mRNA was quantified using a fluorescent in situ hybridization assay in adult Long-Evans rats learning a skilled reaching task (SRT), in rats performing reaching-like forelimb movement without learning (ACT) and in rats that were trained in the operant but not the motor elements of the task (controls). Apart from M1, Arc expression was assessed within the rostral motor area (RMA), primary somatosensory cortex (S1), striatum (ST) and cerebellum. In SRT animals, Arc mRNA levels in M1 contralateral to the trained limb were 31% higher than ipsilateral (pmotor skill learning in rats. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

Curcumin modulates dopaminergic receptor, CREB and phospholipase c gene expression in the cerebral cortex and cerebellum of streptozotocin induced diabetic rats

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George Naijil

2010-05-01

Full Text Available Abstract Curcumin, an active principle component in rhizome of Curcuma longa, has proved its merit for diabetes through its anti-oxidative and anti-inflammatory properties. This study aims at evaluating the effect of curcumin in modulating the altered dopaminergic receptors, CREB and phospholipase C in the cerebral cortex and cerebellum of STZ induced diabetic rats. Radioreceptor binding assays and gene expression was done in the cerebral cortex and cerebellum of male Wistar rats using specific ligands and probes. Total dopaminergic receptor binding parameter, Bmax showed an increase in cerebral cortex and decrease in the cerebellum of diabetic rats. Gene expression studies using real time PCR showed an increased expression of dopamine D1 and D2 receptor in the cerebral cortex of diabetic rats. In cerebellum dopamine D1 receptor was down regulated and D2 receptor showed an up regulation. Transcription factor CREB and phospholipase C showed a significant down regulation in cerebral cortex and cerebellum of diabetic rats. We report that curcumin supplementation reduces diabetes induced alteration of dopamine D1, D2 receptors, transcription factor CREB and phospholipase C to near control. Our results indicate that curcumin has a potential to regulate diabetes induced malfunctions of dopaminergic signalling, CREB and Phospholipase C expression in cerebral cortex and cerebellum and thereby improving the cognitive and emotional functions associated with these regions. Furthermore, in line with these studies an interaction between curcumin and dopaminergic receptors, CREB and phospholipase C is suggested, which attenuates the cortical and cerebellar dysfunction in diabetes. These results suggest that curcumin holds promise as an agent to prevent or treat CNS complications in diabetes.

Curcumin modulates dopaminergic receptor, CREB and phospholipase C gene expression in the cerebral cortex and cerebellum of streptozotocin induced diabetic rats.

Science.gov (United States)

Kumar, T Peeyush; Antony, Sherin; Gireesh, G; George, Naijil; Paulose, C S

2010-05-31

Curcumin, an active principle component in rhizome of Curcuma longa, has proved its merit for diabetes through its anti-oxidative and anti-inflammatory properties. This study aims at evaluating the effect of curcumin in modulating the altered dopaminergic receptors, CREB and phospholipase C in the cerebral cortex and cerebellum of STZ induced diabetic rats. Radioreceptor binding assays and gene expression was done in the cerebral cortex and cerebellum of male Wistar rats using specific ligands and probes. Total dopaminergic receptor binding parameter, B(max) showed an increase in cerebral cortex and decrease in the cerebellum of diabetic rats. Gene expression studies using real time PCR showed an increased expression of dopamine D1 and D2 receptor in the cerebral cortex of diabetic rats. In cerebellum dopamine D1 receptor was down regulated and D2 receptor showed an up regulation. Transcription factor CREB and phospholipase C showed a significant down regulation in cerebral cortex and cerebellum of diabetic rats. We report that curcumin supplementation reduces diabetes induced alteration of dopamine D1, D2 receptors, transcription factor CREB and phospholipase C to near control. Our results indicate that curcumin has a potential to regulate diabetes induced malfunctions of dopaminergic signalling, CREB and Phospholipase C expression in cerebral cortex and cerebellum and thereby improving the cognitive and emotional functions associated with these regions. Furthermore, in line with these studies an interaction between curcumin and dopaminergic receptors, CREB and phospholipase C is suggested, which attenuates the cortical and cerebellar dysfunction in diabetes. These results suggest that curcumin holds promise as an agent to prevent or treat CNS complications in diabetes.

Glucose phosphorylation rate in rat parietal cortex during normoglycemia, hypoglycemia, acute hyperglycemia, and in diabetes-prone rats

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Broendsted, H.E.; Gjedde, A. (Department of General Physiology and Biophysics, Panum Institute, University of Copenhagen (Denmark))

1990-01-01

Cerebral metabolic rate for glucose (CMRglc) was studied in rats using (6-{sup 14}C)glucose. After intravenous injection the radioactivity of the parietal cortex was corrected for loss of labeled CO{sub 2} and divided by the integral of the arterial plasma glucose concentration, determined during tracer circulation. Treatment with insulin, resulting in plasma glucose concentrations less than 2.6 mmol/l, reduced CMRglc to 64% of the values found in control animals. CMRglc did not change in animals with acute hyper-glycemia produced by intraperiotoneal injection of a glucose solution or in diabetes-prone rats with or withour insulin treatment. (author).

Glucose phosphorylation rate in rat rarietal cortex during normoglycemia, hypoglycemia, acute hyperglycemia, and in diabetes-prone rats

International Nuclear Information System (INIS)

Broendsted, H.E.; Gjedde, A.

1990-01-01

Cerebral metabolic rate for glucose (CMRglc) was studied in rats using [6- 14 C]glucose. After intravenous injection the radioactivity of the parietal cortex was corrected for loss of labeled CO 2 and divided by the integral of the arterial plasma glucose concentration, determined during tracer circulation. Treatment with insulin, resulting in plasma glucose concentrations less than 2.6 mmol/l, reduced CMRglc to 64% of the values found in control animals. CMRglc did not change in animals with acute hyper-glycemia produced by intraperiotoneal injection of a glucose solution or in diabetes-prone rats with or withour insulin treatment. (author)

Long-term neuroplasticity of the face primary motor cortex and adjacent somatosensory cortex induced by tooth loss can be reversed following dental implant replacement in rats.

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Avivi-Arber, Limor; Lee, Jye-Chang; Sood, Mandeep; Lakschevitz, Flavia; Fung, Michelle; Barashi-Gozal, Maayan; Glogauer, Michael; Sessle, Barry J

2015-11-01

Tooth loss is common, and exploring the neuroplastic capacity of the face primary motor cortex (face-M1) and adjacent primary somatosensory cortex (face-S1) is crucial for understanding how subjects adapt to tooth loss and their prosthetic replacement. The aim was to test if functional reorganization of jaw and tongue motor representations in the rat face-M1 and face-S1 occurs following tooth extraction, and if subsequent dental implant placement can reverse this neuroplasticity. Rats (n = 22) had the right maxillary molar teeth extracted under local and general anesthesia. One month later, seven rats had dental implant placement into healed extraction sites. Naive rats (n = 8) received no surgical treatment. Intracortical microstimulation (ICMS) and recording of evoked jaw and tongue electromyographic responses were used to define jaw and tongue motor representations at 1 month (n = 8) or 2 months (n = 7) postextraction, 1 month postimplant placement, and at 1-2 months in naive rats. There were no significant differences across study groups in the onset latencies of the ICMS-evoked responses (P > 0.05), but in comparison with naive rats, tooth extraction caused a significant (P rats. These novel findings suggest that face-M1 and adjacent face-S1 may play a role in adaptive mechanisms related to tooth loss and their replacement with dental implants. © 2015 Wiley Periodicals, Inc.

Age-related changes of monoaminooxidases in rat cerebellar cortex

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FM Tranquilli Leali

2009-06-01

Full Text Available Age-related changes of the monoaminoxidases, evaluated by enzymatic staining, quantitative analysis of images, biochemical assay and statistical analysis of data were studied in cerebellar cortex of young (3-month-old and aged (26- month-old male Sprague-Dawley rats. The enzymatic staining shows the presence of monoamino-oxidases within the molecular and granular layers as well as within the Purkinje neurons of the cerebellum of young and aged animals. In molecular layer, and in Purkinje neurons the levels of monoaminooxidases were strongly increased in old rats. The granular layer showed, on the contrary, an age-dependent loss of enzymatic staining. These morphological findings were confirmed by biochemical results. The possibility that age-related changes in monoaminooxidase levels may be due to impaired energy production mechanisms and/or represent the consequence of reduced energetic needs is discussed.

Effects of fluoxetine on the rat brain in the forced swimming test: a [F-18]FDG micro-PET imaging study.

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Jang, Dong-Pyo; Lee, So-Hee; Park, Chan-Woong; Lee, Sang-Yoon; Kim, Young-Bo; Cho, Zang-Hee

2009-02-13

We used the [F-18]FDG micro-PET neuroimaging to examine the effects of fluoxetine on brain activity in rats and on their behavioral response in the forced swimming test (FST). In the first experiment, the rats were administered doses of fluoxetine (10 or 20mg/kg) 24, 19 and 1h before the rat brains were scanned. Fluoxetine induced strong activation of the dorsal hippocampus and the deactivation of the inferior colliculus, medulla oblongata, and prelimbic cortex in a dose-dependent manner. These results seemed to be related with the changes in 5-HT (5-hydroxytryptamine, serotonin) levels after selective serotonin reuptake-inhibitor treatments. In the second experiment, the changes in glucose metabolism in the test session were measured after fluoxetine was given between pre-test and test sessions of the FST. Fluoxetine administration significantly decreased immobility behavior compared with saline administration. At the same time, the activity of the insular/piriform cortex decreased significantly. In contrast, the extent of cerebellar activation increased. The glucose metabolism of the dorsal hippocampus also increased, which suggests that post-stress changes in the facilitation of hippocampal serotonergic neurotransmission lead to decreased immobilization in the FST.

Differential involvement of cortical muscarinic and NMDA receptors in short- and long-term taste aversion memory.

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Ferreira, G; Gutiérrez, R; De La Cruz, V; Bermúdez-Rattoni, F

2002-09-01

In conditioned taste aversion, an animal avoids a taste previously associated with toxic effects, and this aversive memory formation requires an intact insular cortex. In this paper, we investigated the possible differential involvement of cholinergic and glutamatergic receptors in the insular cortex in short-term memory (STM) and long-term memory (LTM) of taste aversion in rats. Taste aversion was induced by intraperitoneal administration of lithium chloride (a malaise-inducing drug) 15 min after experience with an unfamiliar taste. In order to test STM and LTM of taste aversion, taste stimulus was again presented 4 h and 72 h after lithium injection, respectively. During the acquisition, microinjection of the muscarinic antagonist, scopolamine, in the insular cortex before, but not after, the presentation of the new taste, abolished STM as well as LTM. Blockade of the NMDA receptor, in the insular cortex, by AP5 before, but not after, the presentation of the taste stimulus, impaired LTM but left STM intact. Moreover, when injected 1 h after malaise induction (i.e., during taste-illness association), AP5 disrupted both STM and LTM. These results suggest that activation of muscarinic receptors in the insular cortex is involved in the acquisition of taste memory, whereas NMDA receptors participate in taste memory consolidation. These data demonstrate that different neurochemical mechanisms subserve different memory phases. NMDA receptors are also probably involved in processing the visceral input, thus allowing subsequent taste-illness association. This indicates that in the same cortical area the same neurotransmitter system can be involved in distinct processes: taste memory consolidation vs. taste-illness association.

Behavioral tolerance to lysergic acid diethylamide is associated with reduced serotonin-2A receptor signaling in rat cortex.

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Gresch, Paul J; Smith, Randy L; Barrett, Robert J; Sanders-Bush, Elaine

2005-09-01

Tolerance is defined as a decrease in responsiveness to a drug after repeated administration. Tolerance to the behavioral effects of hallucinogens occurs in humans and animals. In this study, we used drug discrimination to establish a behavioral model of lysergic acid diethylamide (LSD) tolerance and examined whether tolerance to the stimulus properties of LSD is related to altered serotonin receptor signaling. Rats were trained to discriminate 60 microg/kg LSD from saline in a two-lever drug discrimination paradigm. Two groups of animals were assigned to either chronic saline treatment or chronic LSD treatment. For chronic treatment, rats from each group were injected once per day with either 130 microg/kg LSD or saline for 5 days. Rats were tested for their ability to discriminate either saline or 60 microg/kg LSD, 24 h after the last chronic injection. Rats receiving chronic LSD showed a 44% reduction in LSD lever selection, while rats receiving chronic vehicle showed no change in percent choice on the LSD lever. In another group of rats receiving the identical chronic LSD treatment, LSD-stimulated [35S]GTPgammaS binding, an index of G-protein coupling, was measured in the rat brain by autoradiography. After chronic LSD, a significant reduction in LSD-stimulated [35S]GTPgammaS binding was observed in the medial prefrontal cortex and anterior cingulate cortex. Furthermore, chronic LSD produced a significant reduction in 2,5-dimethoxy-4-iodoamphetamine-stimulated [35S]GTPgammaS binding in medial prefrontal cortex and anterior cingulate cortex, which was blocked by MDL 100907, a selective 5-HT2A receptor antagonist, but not SB206553, a 5-HT2C receptor antagonist, indicating a reduction in 5-HT2A receptor signaling. 125I-LSD binding to 5-HT2A receptors was reduced in cortical regions, demonstrating a reduction in 5-HT2A receptor density. Taken together, these results indicate that adaptive changes in LSD-stimulated serotonin receptor signaling may mediate tolerance

Progressive motor cortex functional reorganization following 6-hydroxydopamine lesioning in rats.

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Viaro, Riccardo; Morari, Michele; Franchi, Gianfranco

2011-03-23

Many studies have attempted to correlate changes of motor cortex activity with progression of Parkinson's disease, although results have been controversial. In the present study we used intracortical microstimulation (ICMS) combined with behavioral testing in 6-hydroxydopamine hemilesioned rats to evaluate the impact of dopamine depletion on movement representations in primary motor cortex (M1) and motor behavior. ICMS allows for motor-effective stimulation of corticofugal neurons in motor areas so as to obtain topographic movements representations based on movement type, area size, and threshold currents. Rats received unilateral 6-hydroxydopamine in the nigrostriatal bundle, causing motor impairment. Changes in M1 were time dependent and bilateral, although stronger in the lesioned than the intact hemisphere. Representation size and threshold current were maximally impaired at 15 d, although inhibition was still detectable at 60-120 d after lesion. Proximal forelimb movements emerged at the expense of the distal ones. Movement lateralization was lost mainly at 30 d after lesion. Systemic L-3,4-dihydroxyphenylalanine partially attenuated motor impairment and cortical changes, particularly in the caudal forelimb area, and completely rescued distal forelimb movements. Local application of the GABA(A) antagonist bicuculline partially restored cortical changes, particularly in the rostral forelimb area. The local anesthetic lidocaine injected into the M1 of the intact hemisphere restored movement lateralization in the lesioned hemisphere. This study provides evidence for motor cortex remodeling after unilateral dopamine denervation, suggesting that cortical changes were associated with dopamine denervation, pathogenic intracortical GABA inhibition, and altered interhemispheric activity.

The toxic influence of dibromoacetic acid on the hippocampus and pre-frontal cortex of rat: involvement of neuroinflammation response and oxidative stress.

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Jiang, Wenbo; Li, Bai; Chen, Yingying; Gao, Shuying

2017-12-01

Dibromoacetic acid (DBA) exsits in drinking water as a by-product of disinfection as a result of chlorination or ozonation processes. Hippocampus and pre-frontal cortex are the key structures in memory formation and weanling babies are more sensitive to environmental toxicant than adults, so this study was conducted to evaluate the potential neurotoxicity effects of DBA exposure when administered intragastrically for 4 weeks to weanling Sprague-Dawley rats, at concentration of 0, 20, 50, 125 mg/kg via the neurobehavioral and neurochemical effects. Results indicated that animals weight gain and food consumption were not significantly affected by DBA. However, morris water maze test showed varying degrees of changes between control and high-dose group. Additionally, the level of malondialdehyde (MDA) and generation of reactive oxygen species (ROS) in the hippocampus and pre-frontal cortex of rats increased significantly. The activities of total superoxide dismutase (SOD) and the glutathione (GSH) content in the hippocampus and pre-frontal cortex of rats decreased significantly after treatment with DBA. Treatment with DBA increased the protein and mRNA expression of Iba-1, NF-κB, TNF-α, IL-6, IL-1β and HO-1 in the hippocampus and pre-frontal cortex of rats. These data suggested that DBA had a toxic influence on the hippocampus and pre-frontal cortex of rats, and that the mechanism of toxicity might be associated with the neuroinflammation response and oxidative stress.

Spiking in primary somatosensory cortex during natural whisking in awake head-restrained rats is cell-type specific

NARCIS (Netherlands)

de Kock, C.P.J.; Sakmann, B.

2009-01-01

Sensation involves active movement of sensory organs, but it remains unknown how position or movement of sensory organs is encoded in cortex. In the rat whisker system, each whisker is represented by an individual cortical (barrel) column. Here, we quantified in awake, head-fixed rats the impact of

Dopamine depletion increases the power and coherence of high-voltage spindles in the globus pallidus and motor cortex of freely moving rats.

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Ge, Shunnan; Yang, Chen; Li, Min; Li, Jiang; Chang, Xiaozan; Fu, Jian; Chen, Lei; Chang, Chongwang; Wang, Xuelian; Zhu, Junling; Gao, Guodong

2012-07-17

Studies on patients with Parkinson's disease and in animal models have observed enhanced synchronization of oscillations in several frequency bands within and between the cortical-basal ganglia (BG) structures. Recent research has also shown that synchronization of high-voltage spindles (HVSs) in the cortex, striatum and substantia nigra pars reticulate is increased by dopamine depletion. However, more evidence is needed to determine whether HVS activity in the whole cortex-BG network represents homologous alteration following dopamine depletion. As the globus pallidus (GP) is in a central position to propagate and synchronize oscillations in the cortical-BG circuits, we employed local-field potentials and electrocorticogram to simultaneously record oscillations in the GP and primary (M1) and secondary (M2) motor cortices on freely moving 6-hydroxydopamine (6-OHDA) lesioned and control rats. Results showed that HVS episodes recorded from GP, and M2 and M1 cortex areas were more numerous and longer in 6-OHDA lesioned rats compared to controls. Relative power associated with HVS activity in the GP, and M2 and M1 cortices of 6-OHDA lesioned rats was significantly greater than that for control rats. Coherence values for HVS activity between the GP, and M2 and M1 cortex areas were significantly increased by dopamine depletion. Time lag between the M1 cortex HVS and GP HVS was significantly shorter for dopamine depleted than normal rats. Findings indicate a crucial rule for dopamine in the regulation of HVS activity in the whole cortical-BG circuit, and suggest a close relationship between abnormally synchronized HVS oscillations in the cortex-BG network and Parkinson's disease. Copyright © 2012 Elsevier B.V. All rights reserved.

Motor cortex stimulation does not lead to functional recovery after experimental cortical injury in rats.

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Schönfeld, Lisa-Maria; Jahanshahi, Ali; Lemmens, Evi; Bauwens, Matthias; Hescham, Sarah-Anna; Schipper, Sandra; Lagiere, Melanie; Hendrix, Sven; Temel, Yasin

2017-01-01

Motor impairments are among the major complications that develop after cortical damage caused by either stroke or traumatic brain injury. Motor cortex stimulation (MCS) can improve motor functions in animal models of stroke by inducing neuroplasticity. In the current study, the therapeutic effect of chronic MCS was assessed in a rat model of severe cortical damage. A controlled cortical impact (CCI) was applied to the forelimb area of the motor cortex followed by implantation of a flat electrode covering the lesioned area. Forelimb function was assessed using the Montoya staircase test and the cylinder test before and after a period of chronic MCS. Furthermore, the effect of MCS on tissue metabolism and lesion size was measured using [18F]-fluorodesoxyglucose (FDG) μPET scanning. CCI caused a considerable lesion at the level of the motor cortex and dorsal striatum together with a long-lasting behavioral phenotype of forelimb impairment. However, MCS applied to the CCI lesion did not lead to any improvement in limb functioning when compared to non-stimulated control rats. Also, MCS neither changed lesion size nor distribution of FDG. The use of MCS as a standalone treatment did not improve motor impairments in a rat model of severe cortical damage using our specific treatment modalities.

Bilateral lesions of the medial frontal cortex disrupt recognition of social hierarchy during antiphonal communication in naked mole-rats (Heterocephalus glaber).

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Yosida, Shigeto; Okanoya, Kazuo

2012-02-01

Generation of the motor patterns of emotional sounds in mammals occurs in the periaqueductal gray matter of the midbrain and is not directly controlled by the cortex. The medial frontal cortex indirectly controls vocalizations, based on the recognition of social context. We examined whether the medial frontal cortex was responsible for antiphonal vocalization, or turn-taking, in naked mole-rats. In normal turn-taking, naked mole-rats vocalize more frequently to dominant individuals than to subordinate ones. Bilateral lesions of the medial frontal cortex disrupted differentiation of call rates to the stimulus animals, which had varied social relationships to the subject. However, medial frontal cortex lesions did not affect either the acoustic properties of the vocalizations or the timing of the vocal exchanges. This suggests that the medial frontal cortex may be involved in social cognition or decision making during turn-taking, while other regions of the brain regulate when animals vocalize and the vocalizations themselves.

Reduced Synapse and Axon Numbers in the Prefrontal Cortex of Rats Subjected to a Chronic Stress Model for Depression

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Csabai, Dávid; Wiborg, Ove; Czéh, Boldizsár

2018-01-01

Stressful experiences can induce structural changes in neurons of the limbic system. These cellular changes contribute to the development of stress-induced psychopathologies like depressive disorders. In the prefrontal cortex of chronically stressed animals, reduced dendritic length and spine loss have been reported. This loss of dendritic material should consequently result in synapse loss as well, because of the reduced dendritic surface. But so far, no one studied synapse numbers in the prefrontal cortex of chronically stressed animals. Here, we examined synaptic contacts in rats subjected to an animal model for depression, where animals are exposed to a chronic stress protocol. Our hypothesis was that long term stress should reduce the number of axo-spinous synapses in the medial prefrontal cortex. Adult male rats were exposed to daily stress for 9 weeks and afterward we did a post mortem quantitative electron microscopic analysis to quantify the number and morphology of synapses in the infralimbic cortex. We analyzed asymmetric (Type I) and symmetric (Type II) synapses in all cortical layers in control and stressed rats. We also quantified axon numbers and measured the volume of the infralimbic cortex. In our systematic unbiased analysis, we examined 21,000 axon terminals in total. We found the following numbers in the infralimbic cortex of control rats: 1.15 × 109 asymmetric synapses, 1.06 × 108 symmetric synapses and 1.00 × 108 myelinated axons. The density of asymmetric synapses was 5.5/μm3 and the density of symmetric synapses was 0.5/μm3. Average synapse membrane length was 207 nm and the average axon terminal membrane length was 489 nm. Stress reduced the number of synapses and myelinated axons in the deeper cortical layers, while synapse membrane lengths were increased. These stress-induced ultrastructural changes indicate that neurons of the infralimbic cortex have reduced cortical network connectivity. Such reduced network connectivity is likely

Reduced Synapse and Axon Numbers in the Prefrontal Cortex of Rats Subjected to a Chronic Stress Model for Depression

Directory of Open Access Journals (Sweden)

Dávid Csabai

2018-01-01

Full Text Available Stressful experiences can induce structural changes in neurons of the limbic system. These cellular changes contribute to the development of stress-induced psychopathologies like depressive disorders. In the prefrontal cortex of chronically stressed animals, reduced dendritic length and spine loss have been reported. This loss of dendritic material should consequently result in synapse loss as well, because of the reduced dendritic surface. But so far, no one studied synapse numbers in the prefrontal cortex of chronically stressed animals. Here, we examined synaptic contacts in rats subjected to an animal model for depression, where animals are exposed to a chronic stress protocol. Our hypothesis was that long term stress should reduce the number of axo-spinous synapses in the medial prefrontal cortex. Adult male rats were exposed to daily stress for 9 weeks and afterward we did a post mortem quantitative electron microscopic analysis to quantify the number and morphology of synapses in the infralimbic cortex. We analyzed asymmetric (Type I and symmetric (Type II synapses in all cortical layers in control and stressed rats. We also quantified axon numbers and measured the volume of the infralimbic cortex. In our systematic unbiased analysis, we examined 21,000 axon terminals in total. We found the following numbers in the infralimbic cortex of control rats: 1.15 × 109 asymmetric synapses, 1.06 × 108 symmetric synapses and 1.00 × 108 myelinated axons. The density of asymmetric synapses was 5.5/μm3 and the density of symmetric synapses was 0.5/μm3. Average synapse membrane length was 207 nm and the average axon terminal membrane length was 489 nm. Stress reduced the number of synapses and myelinated axons in the deeper cortical layers, while synapse membrane lengths were increased. These stress-induced ultrastructural changes indicate that neurons of the infralimbic cortex have reduced cortical network connectivity. Such reduced network

Encoding and retrieval of artificial visuoauditory memory traces in the auditory cortex requires the entorhinal cortex.

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Chen, Xi; Guo, Yiping; Feng, Jingyu; Liao, Zhengli; Li, Xinjian; Wang, Haitao; Li, Xiao; He, Jufang

2013-06-12

Damage to the medial temporal lobe impairs the encoding of new memories and the retrieval of memories acquired immediately before the damage in human. In this study, we demonstrated that artificial visuoauditory memory traces can be established in the rat auditory cortex and that their encoding and retrieval depend on the entorhinal cortex of the medial temporal lobe in the rat. We trained rats to associate a visual stimulus with electrical stimulation of the auditory cortex using a classical conditioning protocol. After conditioning, we examined the associative memory traces electrophysiologically (i.e., visual stimulus-evoked responses of auditory cortical neurons) and behaviorally (i.e., visual stimulus-induced freezing and visual stimulus-guided reward retrieval). The establishment of a visuoauditory memory trace in the auditory cortex, which was detectable by electrophysiological recordings, was achieved over 20-30 conditioning trials and was blocked by unilateral, temporary inactivation of the entorhinal cortex. Retrieval of a previously established visuoauditory memory was also affected by unilateral entorhinal cortex inactivation. These findings suggest that the entorhinal cortex is necessary for the encoding and involved in the retrieval of artificial visuoauditory memory in the auditory cortex, at least during the early stages of memory consolidation.

PET Mapping for Brain-Computer Interface Stimulation of the Ventroposterior Medial Nucleus of the Thalamus in Rats with Implanted Electrodes.

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Zhu, Yunqi; Xu, Kedi; Xu, Caiyun; Zhang, Jiacheng; Ji, Jianfeng; Zheng, Xiaoxiang; Zhang, Hong; Tian, Mei

2016-07-01

Brain-computer interface (BCI) technology has great potential for improving the quality of life for neurologic patients. This study aimed to use PET mapping for BCI-based stimulation in a rat model with electrodes implanted in the ventroposterior medial (VPM) nucleus of the thalamus. PET imaging studies were conducted before and after stimulation of the right VPM. Stimulation induced significant orienting performance. (18)F-FDG uptake increased significantly in the paraventricular thalamic nucleus, septohippocampal nucleus, olfactory bulb, left crus II of the ansiform lobule of the cerebellum, and bilaterally in the lateral septum, amygdala, piriform cortex, endopiriform nucleus, and insular cortex, but it decreased in the right secondary visual cortex, right simple lobule of the cerebellum, and bilaterally in the somatosensory cortex. This study demonstrated that PET mapping after VPM stimulation can identify specific brain regions associated with orienting performance. PET molecular imaging may be an important approach for BCI-based research and its clinical applications. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Protein Synthesis Inhibition in the Peri-Infarct Cortex Slows Motor Recovery in Rats.

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Schubring-Giese, Maximilian; Leemburg, Susan; Luft, Andreas Rüdiger; Hosp, Jonas Aurel

2016-01-01

Neuroplasticity and reorganization of brain motor networks are thought to enable recovery of motor function after ischemic stroke. Especially in the cortex surrounding the ischemic scar (i.e., peri-infarct cortex), evidence for lasting reorganization has been found at the level of neurons and networks. This reorganization depends on expression of specific genes and subsequent protein synthesis. To test the functional relevance of the peri-infarct cortex for recovery we assessed the effect of protein synthesis inhibition within this region after experimental stroke. Long-Evans rats were trained to perform a skilled-reaching task (SRT) until they reached plateau performance. A photothrombotic stroke was induced in the forelimb representation of the primary motor cortex (M1) contralateral to the trained paw. The SRT was re-trained after stroke while the protein synthesis inhibitor anisomycin (ANI) or saline were injected into the peri-infarct cortex through implanted cannulas. ANI injections reduced protein synthesis within the peri-infarct cortex by 69% and significantly impaired recovery of reaching performance through re-training. Improvement of motor performance within a single training session remained intact, while improvement between training sessions was impaired. ANI injections did not affect infarct size. Thus, protein synthesis inhibition within the peri-infarct cortex impairs recovery of motor deficits after ischemic stroke by interfering with consolidation of motor memory between training sessions but not short-term improvements within one session.

MUSCARINIC ACETYLCHOLINE RECEPTOR-EXPRESSION IN ASTROCYTES IN THE CORTEX OF YOUNG AND AGED RATS

NARCIS (Netherlands)

VANDERZEE, EA; DEJONG, GI; STROSBERG, AD; LUITEN, PGM

The present report describes the cellular and subcellular distribution pattern of immunoreactivity to M35, a monoclonal antibody raised against purified muscarinic acetylcholine receptor protein, in astrocytes in the cerebral cortex of young and aged rats. Most M35-positive astrocytes were localized

Secondary damage in the spinal cord after motor cortex injury in rats.

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Weishaupt, Nina; Silasi, Gergely; Colbourne, Frederick; Fouad, Karim

2010-08-01

When neurons within the motor cortex are fatally injured, their axons, many of which project into the spinal cord, undergo wallerian degeneration. Pathological processes occurring downstream of the cortical damage have not been extensively studied. We created a focal forelimb motor cortex injury in rats and found that axons from cell bodies located in the hindlimb motor cortex (spared by the cortical injury) become secondarily damaged in the spinal cord. To assess axonal degeneration in the spinal cord, we quantified silver staining in the corticospinal tract (CST) at 1 week and 4 weeks after the injury. We found a significant increase in silver deposition at the thoracic spinal cord level at 4 weeks compared to 1 week post-injury. At both time points, no degenerating neurons could be found in the hindlimb motor cortex. In a separate experiment, we showed that direct injury of neurons within the hindlimb motor cortex caused marked silver deposition in the thoracic CST at 1 week post-injury, and declined thereafter. Therefore, delayed axonal degeneration in the thoracic spinal cord after a focal forelimb motor cortex injury is indicative of secondary damage at the spinal cord level. Furthermore, immunolabeling of spinal cord sections showed that a local inflammatory response dominated by partially activated Iba-1-positive microglia is mounted in the CST, a viable mechanism to cause the observed secondary degeneration of fibers. In conclusion, we demonstrate that following motor cortex injury, wallerian degeneration of axons in the spinal cord leads to secondary damage, which is likely mediated by inflammatory processes.

Antinociception induced by epidural motor cortex stimulation in naive conscious rats is mediated by the opioid system.

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Fonoff, Erich Talamoni; Dale, Camila Squarzoni; Pagano, Rosana Lima; Paccola, Carina Cicconi; Ballester, Gerson; Teixeira, Manoel Jacobsen; Giorgi, Renata

2009-01-03

Epidural motor cortex stimulation (MCS) has been used for treating patients with neuropathic pain resistant to other therapeutic approaches. Experimental evidence suggests that the motor cortex is also involved in the modulation of normal nociceptive response, but the underlying mechanisms of pain control have not been clarified yet. The aim of this study was to investigate the effects of epidural electrical MCS on the nociceptive threshold of naive rats. Electrodes were placed on epidural motor cortex, over the hind paw area, according to the functional mapping accomplished in this study. Nociceptive threshold and general activity were evaluated under 15-min electrical stimulating sessions. When rats were evaluated by the paw pressure test, MCS induced selective antinociception in the paw contralateral to the stimulated cortex, but no changes were noticed in the ipsilateral paw. When the nociceptive test was repeated 15 min after cessation of electrical stimulation, the nociceptive threshold returned to basal levels. On the other hand, no changes in the nociceptive threshold were observed in rats evaluated by the tail-flick test. Additionally, no behavioral or motor impairment were noticed in the course of stimulation session at the open-field test. Stimulation of posterior parietal or somatosensory cortices did not elicit any changes in the general activity or nociceptive response. Opioid receptors blockade by naloxone abolished the increase in nociceptive threshold induced by MCS. Data shown herein demonstrate that epidural electrical MCS elicits a substantial and selective antinociceptive effect, which is mediated by opioids.

Extreme insular dwarfism evolved in a mammoth.

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Herridge, Victoria L; Lister, Adrian M

2012-08-22

The insular dwarfism seen in Pleistocene elephants has come to epitomize the island rule; yet our understanding of this phenomenon is hampered by poor taxonomy. For Mediterranean dwarf elephants, where the most extreme cases of insular dwarfism are observed, a key systematic question remains unresolved: are all taxa phyletic dwarfs of a single mainland species Palaeoloxodon antiquus (straight-tusked elephant), or are some referable to Mammuthus (mammoths)? Ancient DNA and geochronological evidence have been used to support a Mammuthus origin for the Cretan 'Palaeoloxodon' creticus, but these studies have been shown to be flawed. On the basis of existing collections and recent field discoveries, we present new, morphological evidence for the taxonomic status of 'P'. creticus, and show that it is indeed a mammoth, most probably derived from Early Pleistocene Mammuthus meridionalis or possibly Late Pliocene Mammuthus rumanus. We also show that Mammuthus creticus is smaller than other known insular dwarf mammoths, and is similar in size to the smallest dwarf Palaeoloxodon species from Sicily and Malta, making it the smallest mammoth species known to have existed. These findings indicate that extreme insular dwarfism has evolved to a similar degree independently in two elephant lineages.

Second Surgery in Insular Low-Grade Gliomas

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Tamara Ius

2015-01-01

Full Text Available Background. Given the technical difficulties, a limited number of works have been published on insular gliomas surgery and risk factors for tumor recurrence (TR are poorly documented. Objective. The aim of the study was to determine TR in adult patients with initial diagnosis of insular Low-Grade Gliomas (LGGs that subsequently underwent second surgery. Methods. A consecutive series of 53 patients with insular LGGs was retrospectively reviewed; 23 patients had two operations for TR. Results. At the time of second surgery, almost half of the patients had experienced progression into high-grade gliomas (HGGs. Univariate analysis showed that TR is influenced by the following: extent of resection (EOR (P<0.002, ΔVT2T1 value (P<0.001, histological diagnosis of oligodendroglioma (P=0.017, and mutation of IDH1 (P=0.022. The multivariate analysis showed that EOR at first surgery was the independent predictor for TR (P<0.001. Conclusions. In patients with insular LGG the EOR at first surgery represents the major predictive factor for TR. At time of TR, more than 50% of cases had progressed in HGG, raising the question of the oncological management after the first surgery.

Chronic ethanol exposure during adolescence in rats induces motor impairments and cerebral cortex damage associated with oxidative stress.

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Teixeira, Francisco Bruno; Santana, Luana Nazaré da Silva; Bezerra, Fernando Romualdo; De Carvalho, Sabrina; Fontes-Júnior, Enéas Andrade; Prediger, Rui Daniel; Crespo-López, Maria Elena; Maia, Cristiane Socorro Ferraz; Lima, Rafael Rodrigues

2014-01-01

Binge drinking is common among adolescents, and this type of ethanol exposure may lead to long-term nervous system damage. In the current study, we evaluated motor performance and tissue alterations in the cerebral cortex of rats subjected to intermittent intoxication with ethanol from adolescence to adulthood. Adolescent male Wistar rats (35 days old) were treated with distilled water or ethanol (6.5 g/kg/day, 22.5% w/v) during 55 days by gavage to complete 90 days of age. The open field, inclined plane and the rotarod tests were used to assess the spontaneous locomotor activity and motor coordination performance in adult animals. Following completion of behavioral tests, half of animals were submitted to immunohistochemical evaluation of NeuN (marker of neuronal bodies), GFAP (a marker of astrocytes) and Iba1 (microglia marker) in the cerebral cortex while the other half of the animals were subjected to analysis of oxidative stress markers by biochemical assays. Chronic ethanol intoxication in rats from adolescence to adulthood induced significant motor deficits including impaired spontaneous locomotion, coordination and muscle strength. These behavioral impairments were accompanied by marked changes in all cellular populations evaluated as well as increased levels of nitrite and lipid peroxidation in the cerebral cortex. These findings indicate that continuous ethanol intoxication from adolescence to adulthood is able to provide neurobehavioral and neurodegenerative damage to cerebral cortex.

Trunk Robot Rehabilitation Training with Active Stepping Reorganizes and Enriches Trunk Motor Cortex Representations in Spinal Transected Rats

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Oza, Chintan S.

2015-01-01

Trunk motor control is crucial for postural stability and propulsion after low thoracic spinal cord injury (SCI) in animals and humans. Robotic rehabilitation aimed at trunk shows promise in SCI animal models and patients. However, little is known about the effect of SCI and robot rehabilitation of trunk on cortical motor representations. We previously showed reorganization of trunk motor cortex after adult SCI. Non-stepping training also exacerbated some SCI-driven plastic changes. Here we examine effects of robot rehabilitation that promotes recovery of hindlimb weight support functions on trunk motor cortex representations. Adult rats spinal transected as neonates (NTX rats) at the T9/10 level significantly improve function with our robot rehabilitation paradigm, whereas treadmill-only trained do not. We used intracortical microstimulation to map motor cortex in two NTX groups: (1) treadmill trained (control group); and (2) robot-assisted treadmill trained (improved function group). We found significant robot rehabilitation-driven changes in motor cortex: (1) caudal trunk motor areas expanded; (2) trunk coactivation at cortex sites increased; (3) richness of trunk cortex motor representations, as examined by cumulative entropy and mutual information for different trunk representations, increased; (4) trunk motor representations in the cortex moved toward more normal topography; and (5) trunk and forelimb motor representations that SCI-driven plasticity and compensations had caused to overlap were segregated. We conclude that effective robot rehabilitation training induces significant reorganization of trunk motor cortex and partially reverses some plastic changes that may be adaptive in non-stepping paraplegia after SCI. PMID:25948267

Pharmacokinetics of Maleic Acid as a Food Adulterant Determined by Microdialysis in Rat Blood and Kidney Cortex

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Mei-Ling Hou

2016-03-01

Full Text Available Maleic acid has been shown to be used as a food adulterant in the production of modified starch by the Taiwan Food and Drug Administration. Due to the potential toxicity of maleic acid to the kidneys, this study aimed to develop an analytical method to investigate the pharmacokinetics of maleic acid in rat blood and kidney cortex. Multiple microdialysis probes were simultaneously inserted into the jugular vein and the kidney cortex for sampling after maleic acid administration (10 or 30 mg/kg, i.v., respectively. The pharmacokinetic results demonstrated that maleic acid produced a linear pharmacokinetic phenomenon within the doses of 10 and 30 mg/kg. The area under concentration versus time curve (AUC of the maleic acid in kidney cortex was 5-fold higher than that in the blood after maleic acid administration (10 and 30 mg/kg, i.v., respectively, indicating that greater accumulation of maleic acid occurred in the rat kidney.

Daily consumption of white tea (Camellia sinensis (L.)) improves the cerebral cortex metabolic and oxidative profile in prediabetic Wistar rats.

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Nunes, Ana R; Alves, Marco G; Tomás, Gonçalo D; Conde, Vanessa R; Cristóvão, Ana C; Moreira, Paula I; Oliveira, Pedro F; Silva, Branca M

2015-03-14

Diabetes mellitus (DM) is a major public health problem and its incidence is rising dramatically. The brain, particularly the cerebral cortex, is very susceptible to glucose fluctuations and hyperglycaemia-induced oxidative stress. Tea (Camellia sinensis (L.)) is widely consumed; however, the antidiabetic properties of white tea remain largely unexplored. In the present study, we investigated the effects of daily consumption of white tea on the cerebral cortex of prediabetic rats. The cerebral cortex metabolic profile was evaluated, and the expression levels of GLUT, phosphofructokinase-1, lactate dehydrogenase (LDH) and monocarboxylate transporter 4 were assessed. LDH activity was also determined. The cerebral cortex oxidative profile was determined by evaluating its antioxidant power, lipid peroxidation and protein oxidation levels. Catalase, glutathione, glutamate, N-acetylaspartate, aspartate, choline, γ-aminobutyric acid, taurine and valine contents were determined. Daily consumption of white tea ameliorated glucose tolerance and insulin sensitivity. Moreover, white tea altered the cortex glycolytic profile, modulating GLUT expression and lactate and alanine contents. Finally, white tea consumption restored protein oxidation and lipid peroxidation levels and catalase expression, and improved antioxidant capacity. In conclusion, daily consumption of white tea improved the cerebral cortex metabolic and oxidative profile in prediabetic rats, suggesting it as a good, safe and inexpensive strategy to prevent DM-related effects in the cerebral cortex.

Insular epilepsy: similarities to temporal lobe epilepsy case report Epilepsia insular: similaridades à epilepsia do lobo temporal - relato de caso

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ARTHUR CUKIERT

1998-03-01

Full Text Available Insular epilepsy has been rarely reported and its clinical and electrographic features are poorly understood. The electrographic study of the insula is difficult since it is hidden from the brain surface by the frontal and temporal lobe. A 48 years-old woman started having simple partial autonomic and complex partial seizures with automatisms and ictal left arm paresis 8 years prior to admission. Seizure's frequency was 1 per week. Pre-operative EEG showed a right temporal lobe focus. Neuropsychological testing disclosed right fronto-temporal dysfunction. MRI showed a right anterior insular cavernous angioma. Intraoperative ECoG obtained after spliting of the sylvian fissure showed independent spiking from the insula and temporal lobe and insular spikes that spread to the temporal lobe. The cavernous angioma and the surrounding gliotic tissue were removed and the temporal lobe was left in place. Post-resection ECoG still disclosed independent temporal and insular spiking with a lower frequency. The patient has been seizure-free since surgery. Insular epilepsy may share many clinical and electroencephalographic features with temporal lobe epilepsy.A epilepsia insular tem sido raramente relatada e suas características clínicas e eletrencefalográficas são pobremente conhecidas. O estudo eletrográfico da ínsula é difícil já que ela se encontra recoberta pelos lobos frontal e temporal. Uma paciente, de 48 anos, começou a ter crises parciais simples autonômicas e crises parciais complexas com automatismos e paresia crítica de membro superior esquerdo 8 anos antes desta internação. A frequência de crises era de 1/semana . O EEG pré-operatório mostrou foco temporal direito. Testagem neuropsicológica demonstrou disfunção fronto-temporal direita. RMN demonstrou cavernoma insular anterior direito. A eletrocorticografia intraoperatória obtida após a abertura da fissura sylviana demonstrou a presença de espículas independentes na �

Brain regions associated with the acquisition of conditioned place preference for cocaine vs. social interaction.

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El Rawas, Rana; Klement, Sabine; Kummer, Kai K; Fritz, Michael; Dechant, Georg; Saria, Alois; Zernig, Gerald

2012-01-01

Positive social interaction could play an essential role in switching the preference of the substance dependent individual away from drug related activities. We have previously shown that conditioned place preference (CPP) for cocaine at the dose of 15 mg/kg and CPP for four 15-min episodes of social interaction were equally strong when rats were concurrently conditioned for place preference by pairing cocaine with one compartment and social interaction with the other. The aim of the present study was to investigate the differential activation of brain regions related to the reward circuitry after acquisition/expression of cocaine CPP or social interaction CPP. Our findings indicate that cocaine CPP and social interaction CPP activated almost the same brain regions. However, the granular insular cortex and the dorsal part of the agranular insular cortex were more activated after cocaine CPP, whereas the prelimbic cortex and the core subregion of the nucleus accumbens were more activated after social interaction CPP. These results suggest that the insular cortex appears to be potently activated after drug conditioning learning while activation of the prelimbic cortex-nucleus accumbens core projection seems to be preferentially involved in the conditioning to non-drug stimuli such as social interaction.

Depression of calcium pump activity in renal cortex of vitamin D-deficient rats with secondary hyperparathyroidism

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Tsukamoto, Yusuke; Saitoh, Michiyo; Takita, Yumiko; Nakano, Toshiaki; Tamura, Teiichi

1990-01-01

To examine the hormonal regulation of the ATP-dependent Ca 2+ pump in the kidneys, the ATP-dependent Ca 2+ uptake by the basolateral membrane vesicles in the renal cortex was measured using radioactive calcium ( 45 Ca 2+ ) in rats with vitamin D deficiency or rats undergoing thyroparathyroidectomy. The V max of the Ca 2+ pump activity was increased not only by administering calcitriol, but also by normalizing the serum calcium level in vitamin D-deficient rats. PTH suppressed the Ca 2+ pump activity in normocalcemic vitamin D-deficient rats. Thyroparathyroidectomy did not affect the Ca 2+ pump activity in the kidneys of normal rats. It was concluded that the ATP-dependent Ca 2+ pump activity was depressed by secondary hyperparathyroidism in vitamin D-deficient rats. (author)

Alternate cadmium exposure differentially affects the content of gamma-aminobutyric acid (GABA) and taurine within the hypothalamus, median eminence, striatum and prefrontal cortex of male rats

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Esquifino, A.I. [Dept. de Bioquimica y Biologia Molecular III, Universidad Complutense, Madrid (Spain); Seara, R.; Fernandez-Rey, E.; Lafuente, A. [Lab. de Toxicologia, Universidad de Vigo, Orense (Spain)

2001-05-01

This work examines changes of gamma aminobutyric acid (GABA) and taurine contents in the hypothalamus, striatum and prefrontal cortex of the rat after an alternate schedule of cadmium administration. Age-associated changes were also evaluated, of those before puberty and after adult age. In control rats GABA content decreased with age in the median eminence and in anterior, mediobasal and posterior hypothalamus, prefrontal cortex and the striatum. Taurine content showed similar results with the exception of mediobasal hypothalamus and striatum, where no changes were detected. In pubertal rats treated with cadmium from 30 to 60 days of life, GABA content significantly decreased in all brain regions except in the striatum. When cadmium was administered from day 60 to 90 of life, GABA content was significantly changed in prefrontal cortex only compared with the age matched controls. Taurine content showed similar results in pubertal rats, with the exception of the median eminence and the mediobasal hypothalamus, neither of which showed a change. However, when cadmium was administered to rats from day 60 to 90 of life, taurine content only changed in prefrontal cortex compared with the age matched controls. These results suggest that cadmium differentially affects GABA and taurine contents within the hypothalamus, median eminence, striatum and prefrontal cortex as a function of age. (orig.)

Alternate cadmium exposure differentially affects the content of gamma-aminobutyric acid (GABA) and taurine within the hypothalamus, median eminence, striatum and prefrontal cortex of male rats

International Nuclear Information System (INIS)

Esquifino, A.I.; Seara, R.; Fernandez-Rey, E.; Lafuente, A.

2001-01-01

This work examines changes of gamma aminobutyric acid (GABA) and taurine contents in the hypothalamus, striatum and prefrontal cortex of the rat after an alternate schedule of cadmium administration. Age-associated changes were also evaluated, of those before puberty and after adult age. In control rats GABA content decreased with age in the median eminence and in anterior, mediobasal and posterior hypothalamus, prefrontal cortex and the striatum. Taurine content showed similar results with the exception of mediobasal hypothalamus and striatum, where no changes were detected. In pubertal rats treated with cadmium from 30 to 60 days of life, GABA content significantly decreased in all brain regions except in the striatum. When cadmium was administered from day 60 to 90 of life, GABA content was significantly changed in prefrontal cortex only compared with the age matched controls. Taurine content showed similar results in pubertal rats, with the exception of the median eminence and the mediobasal hypothalamus, neither of which showed a change. However, when cadmium was administered to rats from day 60 to 90 of life, taurine content only changed in prefrontal cortex compared with the age matched controls. These results suggest that cadmium differentially affects GABA and taurine contents within the hypothalamus, median eminence, striatum and prefrontal cortex as a function of age. (orig.)

Changes in Male Rat Sexual Behavior and Brain Activity Revealed by Functional Magnetic Resonance Imaging in Response to Chronic Mild Stress.

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Chen, Guotao; Yang, Baibing; Chen, Jianhuai; Zhu, Leilei; Jiang, Hesong; Yu, Wen; Zang, Fengchao; Chen, Yun; Dai, Yutian

2018-02-01

Non-organic erectile dysfunction (noED) at functional imaging has been related to abnormal brain activity and requires animal models for further research on the associated molecular mechanisms. To develop a noED animal model based on chronic mild stress and investigate brain activity changes. We used 6 weeks of chronic mild stress to induce depression. The sucrose consumption test was used to assess the hedonic state. The apomorphine test and sexual behavior test were used to select male rats with ED. Rats with depression and ED were considered to have noED. Blood oxygen level-dependent-based resting-state functional magnetic resonance imaging (fMRI) studies were conducted on these rats, and the amplitude of low-frequency fluctuations and functional connectivity were analyzed to determine brain activity changes. The sexual behavior test and resting-state fMRI were used for outcome measures. The induction of depression was confirmed by the sucrose consumption test. A low intromission ratio and increased mount and intromission latencies were observed in male rats with depression. No erection was observed in male rats with depression during the apomorphine test. Male rats with depression and ED were considered to have noED. The possible central pathologic mechanism shown by fMRI involved the amygdaloid body, dorsal thalamus, hypothalamus, caudate-putamen, cingulate gyrus, insular cortex, visual cortex, sensory cortex, motor cortex, and cerebellum. Similar findings have been found in humans. The present study provided a novel noED rat model for further research on the central mechanism of noED. The present study developed a novel noED rat model and analyzed brain activity changes based at fMRI. The observed brain activity alterations might not extend to humans. The present study developed a novel noED rat model with brain activity alterations related to sexual arousal and erection, which will be helpful for further research involving the central mechanism of noED. Chen

Trunk robot rehabilitation training with active stepping reorganizes and enriches trunk motor cortex representations in spinal transected rats.

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Oza, Chintan S; Giszter, Simon F

2015-05-06

Trunk motor control is crucial for postural stability and propulsion after low thoracic spinal cord injury (SCI) in animals and humans. Robotic rehabilitation aimed at trunk shows promise in SCI animal models and patients. However, little is known about the effect of SCI and robot rehabilitation of trunk on cortical motor representations. We previously showed reorganization of trunk motor cortex after adult SCI. Non-stepping training also exacerbated some SCI-driven plastic changes. Here we examine effects of robot rehabilitation that promotes recovery of hindlimb weight support functions on trunk motor cortex representations. Adult rats spinal transected as neonates (NTX rats) at the T9/10 level significantly improve function with our robot rehabilitation paradigm, whereas treadmill-only trained do not. We used intracortical microstimulation to map motor cortex in two NTX groups: (1) treadmill trained (control group); and (2) robot-assisted treadmill trained (improved function group). We found significant robot rehabilitation-driven changes in motor cortex: (1) caudal trunk motor areas expanded; (2) trunk coactivation at cortex sites increased; (3) richness of trunk cortex motor representations, as examined by cumulative entropy and mutual information for different trunk representations, increased; (4) trunk motor representations in the cortex moved toward more normal topography; and (5) trunk and forelimb motor representations that SCI-driven plasticity and compensations had caused to overlap were segregated. We conclude that effective robot rehabilitation training induces significant reorganization of trunk motor cortex and partially reverses some plastic changes that may be adaptive in non-stepping paraplegia after SCI. Copyright © 2015 the authors 0270-6474/15/357174-16$15.00/0.

Antioxidant Activity of Grapevine Leaf Extracts against Oxidative Stress Induced by Carbon Tetrachloride in Cerebral Cortex, Hippocampus and Cerebellum of Rats

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Mariane Wohlenberg

2014-04-01

Full Text Available In recent years, it has become increasingly important to study the beneficial properties of derivatives of grapes and grapevine. The objective of this study was to determine the antioxidant activity of Vitis labrusca leaf extracts, comparing conventional and organic grapevines, in different brain areas of rats. We used male Wistar rats treated with grapevine leaf extracts for a period of 14 days, and on the 15th day, we administered in half of the rats, mineral oil and the other half, carbon tetrachloride (CCl4. The animals were euthanized by decapitation and the cerebral cortex, hippocampus and cerebellum were removed to assess oxidative stress parameters and the activity of antioxidant enzymes. Lipid peroxidation levels (TBARS were unchanged. However, CCl4 induced oxidative damage to proteins in all tissues studied, and this injury was prevented by both extracts. Superoxide dismutase (SOD activity was increased by CCl4 in the cerebral cortex and decreased in other tissues. However, CCl4 increased catalase (CAT activity in the cerebellum and decreased it in the cerebral cortex. The SOD/CAT ratio was restored in the cerebellum by both extracts and only in the cerebral cortex by the organic extract.

Visual deprivation alters dendritic bundle architecture in layer 4 of rat visual cortex.

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Gabbott, P L; Stewart, M G

2012-04-05

The effect of visual deprivation followed by light exposure on the tangential organisation of dendritic bundles passing through layer 4 of the rat visual cortex was studied quantitatively in the light microscope. Four groups of animals were investigated: (I) rats reared in an environment illuminated normally--group 52 dL; (II) rats reared in the dark until 21 days postnatum (DPN) and subsequently light exposed for 31 days-group 21/31; (III) rats dark reared until 52 DPN and then subsequently light exposed for 3 days--group 3 dL; and (IV) rats totally dark reared until 52 DPN--group 52 DPN. Each group contained five animals. Semithin 0.5-1-μm thick resin-embedded sections were collected from tangential sampling levels through the middle of layer 4 in area 17 and stained with Toluidine Blue. These sections were used to quantitatively analyse the composition and distribution of dendritic clusters in the tangential plane. The key result of this study indicates a significant reduction in the mean number of medium- and small-sized dendritic profiles (diameter less than 2 μm) contributing to clusters in layer 4 of groups 3 dL and 52 dD compared with group 21/31. No differences were detected in the mean number of large-sized dendritic profiles composing a bundle in these experimental groups. Moreover, the mean number of clusters and their tangential distribution in layer 4 did not vary significantly between all four groups. Finally, the clustering parameters were not significantly different between groups 21/31 and the normally reared group 52 dL. This study demonstrates, for the first time, that extended periods of dark rearing followed by light exposure can alter the morphological composition of dendritic bundles in thalamorecipient layer 4 of rat visual cortex. Because these changes occur in the primary region of thalamocortical input, they may underlie specific alterations in the processing of visual information both cortically and subcortically during periods of

After-effects of anodal transcranial direct current stimulation on the excitability of the motor cortex in rats.

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Koo, Ho; Kim, Min Sun; Han, Sang Who; Paulus, Walter; Nitche, Michael A; Kim, Yun-Hee; Kim, Hyoung-Ihl; Ko, Sung-Hwa; Shin, Yong-Il

2016-09-21

Transcranial direct current stimulation (tDCS) is increasingly seen as a useful tool for noninvasive cortical neuromodulation. A number of studies in humans have shown that when tDCS is applied to the motor cortex it can modulate cortical excitability. It is especially interesting to note that when applied with sufficient duration and intensity, tDCS can enable long-lasting neuroplastic effects. However, the mechanism by which tDCS exerts its effects on the cortex is not fully understood. We investigated the effects of anodal tDCS under urethane anesthesia on field potentials in in vivo rats. These were measured on the skull over the right motor cortex of rats immediately after stimulating the left corpus callosum. Evoked field potentials in the motor cortex were gradually increased for more than one hour after anodal tDCS. To induce these long-lasting effects, a sufficient duration of stimulation (20 minutes or more) was found to may be required rather than high stimulation intensity. We propose that anodal tDCS with a sufficient duration of stimulation may modulate transcallosal plasticity.

Centella asiatica increases B-cell lymphoma 2 expression in rat prefrontal cortex

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Kuswati

2015-04-01

Full Text Available Background Stress is one of the factors that cause apoptosis in neuronal cells. Centella asiatica has a neuroprotective effect that can inhibit apoptosis. This study aimed to examine the effect of Centella asiatica ethanol extract on B-cell lymphoma 2 (Bcl-2 protein expression in the prefrontal cortex of rats. Methods An experimental study was conducted on 34 brain tissue samples from male Sprague Dawley rats exposed to chronic restraint stress for 21 days. The samples were taken from following groups: non-stress group K, negative control group P1 (stress + arabic gum powder, P2 (stress + C.asiatica at 150 mg/kgBW, P3 (stress + C.asiatica at 300 mg/kg BW, P4 (stress + C.asiatica at 600 mg/kg body weight and positive control group P5 (stress + fluoxetine at 10 mg/kgBW. The samples were made into sections that were stained immunohistochemically using Bcl-2 antibody to determine the percentage of cells expressing Bcl-2. Data were analyzed using one way ANOVA test followed by a post - hoc test. Results There were significant differences in mean Bcl-2 expression between the groups receiving Centella asiatica compared with the non-stress group and stress-only group (negative control group (p<0.05. The results were comparable to those of the fluoxetine treatment group. Conclusion The Centella asiatica ethanol extract was able to increase Bcl-2 expression in the prefrontal cortex of Sprague Dawley rats exposed to restraint stress. This study suggests that Centella asiatica may be useful in the treatment of cerebral stress.

Dopamine D1 sensitivity in the prefrontal cortex predicts general cognitive abilities and is modulated by working memory training.

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Wass, Christopher; Pizzo, Alessandro; Sauce, Bruno; Kawasumi, Yushi; Sturzoiu, Tudor; Ree, Fred; Otto, Tim; Matzel, Louis D

2013-10-15

A common source of variance (i.e., "general intelligence") underlies an individual's performance across diverse tests of cognitive ability, and evidence indicates that the processing efficacy of working memory may serve as one such source of common variance. One component of working memory, selective attention, has been reported to co-vary with general intelligence, and dopamine D1 signaling in prefrontal cortex can modulate attentional abilities. Based on their aggregate performance across five diverse tests of learning, here we characterized the general cognitive ability (GCA) of CD-1 outbred mice. In response to a D1 agonist (SKF82958, 1 mg/kg), we then assessed the relationship between GCA and activation of D1 receptor (D1R)-containing neurons in the prelimbic region of the medial prefrontal cortex, the agranular insular cortex, and the dorsomedial striatum. Increased activation of D1R-containing neurons in the prelimbic cortex (but not the agranular insular cortex or dorsomedial striatum) was observed in animals of high GCA relative to those of low GCA (quantified by c-Fos activation in response to the D1 agonist). However, a Western blot analysis revealed no differences in the density of D1Rs in the prelimbic cortex between animals of high and low GCA. Last, it was observed that working memory training promoted an increase in animals' GCA and enhanced D1R-mediated neuronal activation in the prelimbic cortex. These results suggest that the sensitivity (but not density) of D1Rs in the prelimbic cortex may both regulate GCA and be a target for working memory training.

The role of the medial prefrontal cortex in the play fighting of rats.

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Bell, Heather C; McCaffrey, David R; Forgie, Margaret L; Kolb, Bryan; Pellis, Sergio M

2009-12-01

Although decorticated rats are able to engage in play, their play is abnormal in three ways. First, decorticates do not display the normal, age-related shifts in defensive strategies during development. Second, decorticates do not modify their defensive tactics in response to the social identity of their partners. Third, decorticates display a global shift in defensive tactics from more complex to less complex strategies. It has been shown that lesions of the motor cortex (MC) selectively produce the abnormal developmental effects on play, and that lesions of the orbitofrontal cortex (OFC) selectively produce the deficits in behavioral discrimination between social partners. In the current set of experiments, we demonstrate that lesions of the medial prefrontal cortex (mPFC) produce the shift from more complex to less complex defensive tactics, while leaving intact the age-related and partner-related modulation of defensive strategies. Thus, we have evidence for a triple dissociation of function between the MC, the OFC, and the mPFC with respect to social play behavior.

Chronological changes in astrocytes induced by chronic electrical sensorimotor cortex stimulation in rats.

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Morishita, Takashi; Yamashita, Akiko; Katayama, Yoichi; Oshima, Hideki; Nishizaki, Yuji; Shijo, Katsunori; Fukaya, Chikashi; Yamamoto, Takamitsu

2011-01-01

Motor cortex stimulation (MCS) is a treatment option for various disorders such as medically refractory pain, poststroke hemiplegia, and movement disorders. However, the exact mechanisms underlying its effects remain unknown. In this study, the effects of long-term chronic MCS were investigated by observing changes in astrocytes. A quadripolar stimulation electrode was implanted on the dura over the sensorimotor cortex of adult rats, and the cortex was continuously stimulated for 3 hours, 1 week, 4 weeks, and 8 weeks. Immunohistochemical staining of microglia (ionized calcium-binding adaptor molecule 1 [Iba1] staining) and astrocytes (glial fibrillary acidic protein [GFAP] staining), and neuronal degeneration histochemistry (Fluoro-Jade B staining) were carried out to investigate the morphological changes following long-term chronic MCS. Iba1 staining and Fluoro-Jade B staining showed no evidence of Iba1-positive microglial changes or neurodegeneration. Following continuous MCS, GFAP-positive astrocytes were enlarged and their number increased in the cortex and the thalamus of the stimulated hemisphere. These findings indicate that chronic electrical stimulation can continuously activate astrocytes and result in morphological and quantitative changes. These changes may be involved in the mechanisms underlying the neuroplasticity effect induced by MCS.

Impaired glutamatergic projection from the motor cortex to the subthalamic nucleus in 6-hydroxydopamine-lesioned hemi-parkinsonian rats.

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Wang, Yan-Yan; Wang, Yong; Jiang, Hai-Fei; Liu, Jun-Hua; Jia, Jun; Wang, Ke; Zhao, Fei; Luo, Min-Hua; Luo, Min-Min; Wang, Xiao-Min

2018-02-01

The glutamatergic projection from the motor cortex to the subthalamic nucleus (STN) constitutes the cortico-basal ganglia circuit and plays a critical role in the control of movement. Emerging evidence shows that the cortico-STN pathway is susceptible to dopamine depletion. Specifically in Parkinson's disease (PD), abnormal electrophysiological activities were observed in the motor cortex and STN, while the STN serves as a key target of deep brain stimulation for PD therapy. However, direct morphological changes in the cortico-STN connectivity in response to PD progress are poorly understood at present. In the present study, we used a trans-synaptic anterograde tracing method with herpes simplex virus-green fluorescent protein (HSV-GFP) to monitor the cortico-STN connectivity in a rat model of PD. We found that the connectivity from the primary motor cortex (M1) to the STN was impaired in parkinsonian rats as manifested by a marked decrease in trans-synaptic infection of HSV-GFP from M1 neurons to STN neurons in unilateral 6-hydroxydopamine (6-OHDA)-lesioned rats. Ultrastructural analysis with electron microscopy revealed that excitatory synapses in the STN were also impaired in parkinsonian rats. Glutamatergic terminals identified by a specific marker (vesicular glutamate transporter 1) were reduced in the STN, while glutamatergic neurons showed an insignificant change in their total number in both the M1 and STN regions. These results indicate that the M1-STN glutamatergic connectivity is downregulated in parkinsonian rats. This downregulation is mediated probably via a mechanism involving the impairments of excitatory terminals and synapses in the STN. Copyright © 2017. Published by Elsevier Inc.

Social defeat stress causes depression-like behavior with metabolite changes in the prefrontal cortex of rats.

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Yi-Yun Liu

Full Text Available Major depressive disorder is a serious mental disorder with high morbidity and mortality. The role of social stress in the development of depression remains unclear. Here, we used the social defeat stress paradigm to induce depression-like behavior in rats, then evaluated the behavior of the rats and measured metabolic changes in the prefrontal cortex using gas chromatography-mass spectrometry. Within the first week after the social defeat procedure, the sucrose preference test (SPT, open field test (OFT, elevated plus maze (EPM and forced swim test (FST were conducted to examine the depressive-like and anxiety-like behaviors. For our metabolite analysis, multivariate statistics were applied to observe the distribution of all samples and to differentiate the socially defeated group from the control group. Ingenuity pathway analysis was used to find the potential relationships among the differential metabolites. In the OFT and EPM, there were no significant differences between the two experimental groups. In the SPT and FST, socially defeated rats showed less sucrose intake and longer immobility time compared with control rats. Metabolic profiling identified 25 significant variables with good predictability. Ingenuity pathways analysis revealed that "Hereditary Disorder, Neurological Disease, Lipid Metabolism" was the most significantly altered network. Stress-induced alterations of low molecular weight metabolites were observed in the prefrontal cortex of rats. Particularly, lipid metabolism, amino acid metabolism, and energy metabolism were significantly perturbed. The results of this study suggest that repeated social defeat can lead to metabolic changes and depression-like behavior in rats.

Social defeat stress causes depression-like behavior with metabolite changes in the prefrontal cortex of rats.

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Liu, Yi-Yun; Zhou, Xin-Yu; Yang, Li-Ning; Wang, Hai-Yang; Zhang, Yu-Qing; Pu, Jun-Cai; Liu, Lan-Xiang; Gui, Si-Wen; Zeng, Li; Chen, Jian-Jun; Zhou, Chan-Juan; Xie, Peng

2017-01-01

Major depressive disorder is a serious mental disorder with high morbidity and mortality. The role of social stress in the development of depression remains unclear. Here, we used the social defeat stress paradigm to induce depression-like behavior in rats, then evaluated the behavior of the rats and measured metabolic changes in the prefrontal cortex using gas chromatography-mass spectrometry. Within the first week after the social defeat procedure, the sucrose preference test (SPT), open field test (OFT), elevated plus maze (EPM) and forced swim test (FST) were conducted to examine the depressive-like and anxiety-like behaviors. For our metabolite analysis, multivariate statistics were applied to observe the distribution of all samples and to differentiate the socially defeated group from the control group. Ingenuity pathway analysis was used to find the potential relationships among the differential metabolites. In the OFT and EPM, there were no significant differences between the two experimental groups. In the SPT and FST, socially defeated rats showed less sucrose intake and longer immobility time compared with control rats. Metabolic profiling identified 25 significant variables with good predictability. Ingenuity pathways analysis revealed that "Hereditary Disorder, Neurological Disease, Lipid Metabolism" was the most significantly altered network. Stress-induced alterations of low molecular weight metabolites were observed in the prefrontal cortex of rats. Particularly, lipid metabolism, amino acid metabolism, and energy metabolism were significantly perturbed. The results of this study suggest that repeated social defeat can lead to metabolic changes and depression-like behavior in rats.

The effects of abnormalities of glucose homeostasis on the expression and binding of muscarinic receptors in cerebral cortex of rats.

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Sherin, Antony; Peeyush, Kumar T; Naijil, George; Nandhu, Mohan Sobhana; Jayanarayanan, Sadanandan; Jes, Paul; Paulose, Cheramadathikudiyil Skaria

2011-01-25

Glucose homeostasis in humans is an important factor for the functioning of nervous system. Both hypo and hyperglycemia contributes to neuronal functional deficit. In the present study, effect of insulin induced hypoglycemia and streptozotocin induced diabetes on muscarinic receptor binding, cholinergic enzymes; AChE, ChAT expression and GLUT3 in the cerebral cortex of experimental rats were analysed. Total muscarinic, muscarinic M(1) receptor showed a significant decrease and muscarinic M(3) receptor subtype showed a significant increased binding in the cerebral cortex of hypoglycemic rats compared to diabetic and control. Real-Time PCR analysis of muscarinic M(1), M(3) receptor subtypes confirmed the receptor binding studies. Immunohistochemistry of muscarinic M(1), M(3) receptors using specific antibodies were also carried out. AChE and GLUT3 expression up regulated and ChAT expression down regulated in hypoglycemic rats compared to diabetic and control rats. Our results showed that hypo/hyperglycemia caused impaired glucose transport in neuronal cells as shown by altered expression of GLUT3. Increased AChE and decreased ChAT expression is suggested to alter cortical acetylcholine metabolism in experimental rats along with altered muscarinic receptor binding in hypo/hyperglycemic rats, impair cholinergic transmission, which subsequently lead to cholinergic dysfunction thereby causing learning and memory deficits. We observed a prominent cholinergic functional disturbance in hypoglycemic condition than in hyperglycemia. Hypoglycemia exacerbated the neurochemical changes in cerebral cortex induced by hyperglycemia. These findings have implications for both therapy and identification of causes contributing to neuronal dysfunction in diabetes. Copyright © 2010 Elsevier B.V. All rights reserved.

c-Fos expression is elevated in GABAergic interneurons of the gustatory cortex following novel taste learning.

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Doron, Guy; Rosenblum, Kobi

2010-07-01

Long-term sensory memories are considered to be stored in the relevant cortical region subserving the given modality. We and others have recently identified a series of molecular alterations in the gustatory cortex (GC) of the rat at different time intervals following novel taste learning. Some of these correlative modifications were also necessary for taste memory acquisition and/or consolidation. However, very little is known about the localization of these molecular modifications within the GC or about the functional activation of the GC hours after novel taste learning. Here, we hypothesize that inhibitory interneurons are activated in the GC on a scale of hours following learning and used c-Fos expression and confocal microscopy with different markers to test this hypothesis. We found that GABAergic interneurons are activated in the GC in correlation with novel taste learning. The activation was evident in the deep but not superficial layers of the dysgranular insular cortex. These results suggest that the GABAergic machinery in the deep layers of the GC participates in the processing of taste information hours after learning, and provide evidence for the involvement of a local cortical circuit not only during acquisition of new information but also during off-line processing and consolidation of taste information.

The effects of low dose ionizing radiation on the development of rat cerebral cortex, (2)

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Matsushita, Koji

1993-01-01

In order to study the molecular mechanisms of neuronal migration on developing rat cerebral cortex, we need a tissue culture system in which neuronal migration can be observed. We prepared a tissue culture system of embryonic rat cerebral cortex starting on embryonic day 16 and cultivating it for 48 hours. The autoradiographic study in this system revealed not only the migration of 3 H-thymidine labeled neurons but also neuronal migration delays from low doses of ionizing radiation of more than 10 cGy. In addition, on immunohistochemical study, cell-cell adhesion molecule N-CAM staining was remarkably decreased in the matrix cell layer. In the tissue culture system where monoclonal anti-N-CAM antibodies were added, neuronal migration delay comparable to that of 20 cGy radiation was found. In conclusion, it was speculated that neuronal migration delay might be caused by disturbed N-CAM synthesis in matrix cells after low dose ionizing radiation. (author)

Characterization of claustral neurons by comparative gene expression profiling and dye-injection analyses

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Akiya eWatakabe

2014-05-01

Full Text Available The identity of the claustrum as a part of cerebral cortex, and in particular of the adjacent insular cortex, has been investigated by connectivity features and patterns of gene expression. In the present paper, we mapped the cortical and claustral expression of several cortical genes in rodent and macaque monkey brains (nurr1, latexin, cux2, and netrinG2 to further assess shared features between cortex and claustrum. In mice, these genes were densely expressed in the claustrum, but very sparsely in the cortex and not present in the striatum. To test whether the cortical vs. claustral cell types can be distinguished by co-expression of these genes, we performed a panel of double ISH in mouse and macaque brain. NetrinG2 and nurr1 genes were co-expressed across entire cortex and claustrum, but cux2 and nurr1 were co-expressed only in the insular cortex and claustrum. Latexin was expressed, in the macaque, only in the claustrum. The nurr1+ claustral neurons expressed VGluT1, a marker for cortical glutamatergic cells and send cortical projections. Taken together, our data suggest a partial commonality between claustral neurons and a subtype of cortical neurons in the monkey brain. Moreover, in the embryonic (E110 macaque brain, many nurr1+ neurons were scattered in the white matter between the claustrum and the insular cortex, possibly representing their migratory history. In a second set of experiments, we injected Lucifer Yellow intracellularly in mouse and rat slices to investigate whether dendrites of insular and claustral neurons can cross the border of the two brain regions. Dendrites of claustral neurons did not invade the overlying insular territory. In summary, gene expression profile of the claustrum is similar to that of the neocortex, in both rodent and macaque brains, but with modifications in density of expression and cellular co-localization of specific genes.

Enoxacin elevates microRNA levels in rat frontal cortex and prevents learned helplessness

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Neil R Smalheiser

2014-02-01

Full Text Available Major depressive disorder (MDD is a major public health concern. Despite tremendous advancement, the pathogenic mechanisms associated with MDD are still unclear. Moreover, a significant number of MDD subjects do not respond to the currently available medication. MicroRNAs (miRNAs are a class of small non-coding RNAs that control gene expression by modulating translation, mRNA degradation or stability of mRNA targets. The role of miRNAs in disease pathophysiology is emerging rapidly. Recently, we reported that miRNA expression is down-regulated in frontal cortex of depressed suicide subjects, and that rats exposed to repeated inescapable shock show differential miRNA changes depending on whether they exhibited normal adaptive responses or learned helpless behavior. Enoxacin, a fluoroquinolone used clinically as an antibacterial compound, enhances the production of miRNAs in vitro and in peripheral tissues in vivo, but has not yet been tested as an experimental tool to study the relation of miRNA expression to neural functions or behavior. Treatment of rats with 10 or 25 mg/kg enoxacin for one week increased the expression of miRNAs in frontal cortex and decreased the proportion of rats exhibiting learned helpless behavior following inescapable shock. Further studies are warranted to learn whether enoxacin may ameliorate depressive behavior in other rodent paradigms and in human clinical situations, and if so whether its mechanism is due to upregulation of miRNAs.

Structural brain correlates of executive engagement in working memory: children's inter-individual differences are reflected in the anterior insular cortex.

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Rossi, Sandrine; Lubin, Amélie; Simon, Grégory; Lanoë, Céline; Poirel, Nicolas; Cachia, Arnaud; Pineau, Arlette; Houdé, Olivier

2013-06-01

Although the development of executive functions has been extensively investigated at a neurofunctional level, studies of the structural relationships between executive functions and brain anatomy are still scarce. Based on our previous meta-analysis of functional neuroimaging studies examining executive functions in children (Houdé, Rossi, Lubin, and Joliot, (2010). Developmental Science, 13, 876-885), we investigated six a priori regions of interest: the left anterior insular cortex (AIC), the left and the right supplementary motor areas, the right middle and superior frontal gyri, and the left precentral gyrus. Structural magnetic resonance imaging scans were acquired from 22 to 10-year-old children. Local gray matter volumes, assessed automatically using a standard voxel-based morphometry approach, were correlated with executive and storage working memory capacities evaluated using backward and forward digit span tasks, respectively. We found an association between smaller gray matter volume--i.e., an index of neural maturation--in the left AIC and high backward memory span while gray matter volumes in the a priori selected regions of interest were not linked with forward memory span. These results were corroborated by a whole-brain a priori free analysis that revealed a significant negative correlation in the frontal and prefrontal regions, including the left AIC, with the backward memory span, and in the right inferior parietal lobe, with the forward memory span. Taken together, these results suggest a distinct and specific association between regional gray matter volume and the executive component vs. the storage component of working memory. Moreover, they support a key role for the AIC in the executive network of children. Copyright © 2013 Elsevier Ltd. All rights reserved.

Possible involvements of glutamate and adrenergic receptors on acute toxicity of methylphenidate in isolated hippocampus and cerebral cortex of adult rats.

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Motaghinejad, Majid; Motevalian, Manijeh; Shabab, Behnaz

2017-04-01

Neurodegeneration induced by methylphenidate (MPH), as a central stimulant with unknown long-term consequences, in adult rats' brain and the possible mechanisms involved were studied. Rats were acutely treated with MPH in the presence and absence of some receptor antagonists such as ketamine, topiramate, yohimbine, and haloperidol. Motor activity and anxiety level in rats were monitored. Antioxidant and inflammatory parameters were also measured in isolated hippocampus and cerebral cortex. MPH-treated groups (10 and 20 mg/kg) demonstrated anxiety-like behavior and increased motor activity. MPH significantly increased lipid peroxidation, GSSG content, IL-1β and TNF-α levels in isolated tissues, and also significantly reduced GSH content, superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione reductase (GR) activities in hippocampus and cerebral cortex. Pretreatment of animals by receptor antagonists caused inhibition of MPH-induced motor activity disturbances and anxiety-like behavior. Pretreatment of animals by ketamine, topiramate, and yohimbine inhibited the MPH-induced oxidative stress and inflammation; it significantly decreased lipid peroxidation, GSSG level, IL-1β and TNF-α levels and increased GSH content, SOD, GPx, and GR activities in hippocampus and cerebral cortex of acutely MPH-treated rats. Pretreatment with haloperidol did not cause any change in MPH-induced oxidative stress and inflammation. In conclusion, acute administration of high doses of MPH can cause oxidative and inflammatory changes in brain cells and induce neurodegeneration in hippocampus and cerebral cortex of adult rats and these changes might probably be mediated by glutamate (NMDA or AMPA) and/or α 2 -adrenergic receptors. © 2016 Société Française de Pharmacologie et de Thérapeutique.

Differential structural and resting state connectivity between insular subdivisions and other pain-related brain regions.

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Wiech, K; Jbabdi, S; Lin, C S; Andersson, J; Tracey, I

2014-10-01

Functional neuroimaging studies suggest that the anterior, mid, and posterior division of the insula subserve different functions in the perception of pain. The anterior insula (AI) has predominantly been associated with cognitive-affective aspects of pain, while the mid and posterior divisions have been implicated in sensory-discriminative processing. We examined whether this functional segregation is paralleled by differences in (1) structural and (2) resting state connectivity and (3) in correlations with pain-relevant psychological traits. Analyses were restricted to the 3 insular subdivisions and other pain-related brain regions. Both type of analyses revealed largely overlapping results. The AI division was predominantly connected to the ventrolateral prefrontal cortex (structural and resting state connectivity) and orbitofrontal cortex (structural connectivity). In contrast, the posterior insula showed strong connections to the primary somatosensory cortex (SI; structural connectivity) and secondary somatosensory cortex (SII; structural and resting state connectivity). The mid insula displayed a hybrid connectivity pattern with strong connections with the ventrolateral prefrontal cortex, SII (structural and resting state connectivity) and SI (structural connectivity). Moreover, resting state connectivity revealed strong connectivity of all 3 subdivisions with the thalamus. On the behavioural level, AI structural connectivity was related to the individual degree of pain vigilance and awareness that showed a positive correlation with AI-amygdala connectivity and a negative correlation with AI-rostral anterior cingulate cortex connectivity. In sum, our findings show a differential structural and resting state connectivity for the anterior, mid, and posterior insula with other pain-relevant brain regions, which might at least partly explain their different functional profiles in pain processing. Copyright © 2014 The Authors. Published by Elsevier B.V. All

NMDA receptor activation and PKC but not PKA lead to the modification of the long-term potentiation in the insular cortex induced by conditioned taste aversion: differential role of kinases in metaplasticity.

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Rodríguez-Durán, Luis F; Escobar, Martha L

2014-06-01

It has been reported that training in behavioral tasks modifies the ability to induce long-term potentiation (LTP) in an N-methyl-D-aspartate receptor (NMDAR)-dependent manner. This receptor leads to calcium entry into neuronal cells, promoting the activation of protein kinases as protein kinase A (PKA) and protein kinase C (PKC), which contribute significantly to the formation of different types of memories and play a pivotal role in the expression of LTP. Our previous studies involving the insular cortex (IC) have demonstrated that induction of LTP in the basolateral amygdaloid nucleus (BLA)-IC projection prior to conditioned taste aversion (CTA) training enhances the retention of this task. Recently, we showed that CTA training triggers a persistent impairment in the ability to induce subsequent synaptic plasticity on the BLA-IC pathway in a protein synthesis-dependent manner, but the underlying molecular mechanisms remain unclear. In the present study we investigated whether the blockade of NMDAR, as well as the inhibition of PKC and PKA affects the CTA-dependent impairment of the IC-LTP. Thus, CTA-trained rats received high frequency stimulation in the Bla-IC projection in order to induce LTP 48 h after the aversion test. The NMDAR antagonist CPP and the specific inhibitors for PKC (chelerythrine) and PKA (KT-5720) were intracortically administered during the acquisition session. Our results show that the blockade of NMDAR and the inhibition of PKC activity prevent the CTA memory-formation as well as the IC-LTP impairment. Nevertheless, PKA inhibition prevents the memory formation of taste aversion but produces no interference with the CTA-dependent impairment of the IC-LTP. These findings reveal the differential roles of protein kinases on CTA-dependent modification of IC-LTP enhancing our understanding of the effects of memory-related changes on synaptic function. Copyright © 2014 Elsevier B.V. All rights reserved.

Morphological and electrophysiological changes in intratelencephalic-type pyramidal neurons in the motor cortex of a rat model of levodopa-induced dyskinesia.

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Ueno, Tatsuya; Yamada, Junko; Nishijima, Haruo; Arai, Akira; Migita, Keisuke; Baba, Masayuki; Ueno, Shinya; Tomiyama, Masahiko

2014-04-01

Levodopa-induced dyskinesia (LID) is a major complication of long-term dopamine replacement therapy for Parkinson's disease, and becomes increasingly problematic in the advanced stage of the disease. Although the cause of LID still remains unclear, there is accumulating evidence from animal experiments that it results from maladaptive plasticity, resulting in supersensitive excitatory transmission at corticostriatal synapses. Recent work using transcranial magnetic stimulation suggests that the motor cortex displays the same supersensitivity in Parkinson's disease patients with LID. To date, the cellular mechanisms underlying the abnormal cortical plasticity have not been examined. The morphology of the dendritic spines has a strong relationship to synaptic plasticity. Therefore, we explored the spine morphology of pyramidal neurons in the motor cortex in a rat model of LID. We used control rats, 6-hydroxydopamine-lesioned rats (a model of Parkinson's disease), 6-hydroxydopamine-lesioned rats chronically treated with levodopa (a model of LID), and control rats chronically treated with levodopa. Because the direct pathway of the basal ganglia plays a central role in the development of LID, we quantified the density and size of dendritic spines in intratelencephalic (IT)-type pyramidal neurons in M1 cortex that project to the striatal medium spiny neurons in the direct pathway. The spine density was not different among the four groups. In contrast, spine size became enlarged in the Parkinson's disease and LID rat models. The enlargement was significantly greater in the LID model than in the Parkinson's disease model. This enlargement of the spines suggests that IT-type pyramidal neurons acquire supersensitivity to excitatory stimuli. To confirm this possibility, we monitored miniature excitatory postsynaptic currents (mEPSCs) in the IT-type pyramidal neurons in M1 cortex using whole-cell patch clamp. The amplitude of the mEPSCs was significantly increased in the LID

Protein malnutrition during gestation and early life decreases neuronal size in the medial prefrontal cortex of post-pubertal rats

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Roelf J. Cruz-Rizzolo

2017-12-01

Full Text Available Retrospective studies in human populations indicate that protein deprivation during pregnancy and early life (early protein malnutrition, EPM is associated with cognitive impairments, learning disabilities and may represent a risk factor for the late onset of some psychiatric disorders, fundamentally schizophrenia, a condition where the prefrontal cortex plays an important role. The purpose of this study was to analyze whether EPM affects structural aspects of the rat medial prefrontal cortex (mPFC, such as cortical volume, neuronal density and neuronal soma size, which seem altered in patients with schizophrenia. For this, a rat model of EPM (5% casein from conception to postnatal day 60 was adopted and the rat mPFC volume, total number of neurons and average neuronal volume were evaluated on postnatal day 60 (post-pubertal animals by histo- and immunohistochemical techniques using unbiased stereological analysis. EPM did not alter the number of NeuN+ neurons in the rat mPFC. However, a very significant decrease in mPFC volume and average neuronal size was observed in malnourished rats. Although the present study does not establish causal relationships between malnutrition and schizophrenia, our results may indicate a similar structural phenomenon in these two situations.

Stereotactically-guided Ablation of the Rat Auditory Cortex, and Localization of the Lesion in the Brain.

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Lamas, Verónica; Estévez, Sheila; Pernía, Marianni; Plaza, Ignacio; Merchán, Miguel A

2017-10-11

The rat auditory cortex (AC) is becoming popular among auditory neuroscience investigators who are interested in experience-dependence plasticity, auditory perceptual processes, and cortical control of sound processing in the subcortical auditory nuclei. To address new challenges, a procedure to accurately locate and surgically expose the auditory cortex would expedite this research effort. Stereotactic neurosurgery is routinely used in pre-clinical research in animal models to engraft a needle or electrode at a pre-defined location within the auditory cortex. In the following protocol, we use stereotactic methods in a novel way. We identify four coordinate points over the surface of the temporal bone of the rat to define a window that, once opened, accurately exposes both the primary (A1) and secondary (Dorsal and Ventral) cortices of the AC. Using this method, we then perform a surgical ablation of the AC. After such a manipulation is performed, it is necessary to assess the localization, size, and extension of the lesions made in the cortex. Thus, we also describe a method to easily locate the AC ablation postmortem using a coordinate map constructed by transferring the cytoarchitectural limits of the AC to the surface of the brain.The combination of the stereotactically-guided location and ablation of the AC with the localization of the injured area in a coordinate map postmortem facilitates the validation of information obtained from the animal, and leads to a better analysis and comprehension of the data.

Therapeutic deep brain stimulation in Parkinsonian rats directly influences motor cortex.

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Li, Qian; Ke, Ya; Chan, Danny C W; Qian, Zhong-Ming; Yung, Ken K L; Ko, Ho; Arbuthnott, Gordon W; Yung, Wing-Ho

2012-12-06

Much recent discussion about the origin of Parkinsonian symptoms has centered around the idea that they arise with the increase of beta frequency waves in the EEG. This activity may be closely related to an oscillation between subthalamic nucleus (STN) and globus pallidus. Since STN is the target of deep brain stimulation, it had been assumed that its action is on the nucleus itself. By means of simultaneous recordings of the firing activities from populations of neurons and the local field potentials in the motor cortex of freely moving Parkinsonian rats, this study casts doubt on this assumption. Instead, we found evidence that the corrective action is upon the cortex, where stochastic antidromic spikes originating from the STN directly modify the firing probability of the corticofugal projection neurons, destroy the dominance of beta rhythm, and thus restore motor control to the subjects, be they patients or rodents. Copyright © 2012 Elsevier Inc. All rights reserved.

Contralateral Disconnection of the Rat Prelimbic Cortex and Dorsomedial Striatum Impairs Cue-Guided Behavioral Switching

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Baker, Phillip M.; Ragozzino, Michael E.

2014-01-01

Switches in reward outcomes or reward-predictive cues are two fundamental ways in which information is used to flexibly shift response patterns. The rat prelimbic cortex and dorsomedial striatum support behavioral flexibility based on a change in outcomes. The present experiments investigated whether these two brain regions are necessary for…

Unimodal primary sensory cortices are directly connected by long-range horizontal projections in the rat sensory cortex

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Jimmy eStehberg

2014-09-01

Full Text Available Research based on functional imaging and neuronal recordings in the barrel cortex subdivision of primary somatosensory cortex (SI of the adult rat has revealed novel aspects of structure-function relationships in this cortex. Specifically, it has demonstrated that single whisker stimulation evokes subthreshold neuronal activity that spreads symmetrically within gray matter from the appropriate barrel area, crosses cytoarchitectural borders of SI and reaches deeply into other unimodal primary cortices such as primary auditory (AI and primary visual (VI. It was further demonstrated that this spread is supported by a spatially matching underlying diffuse network of border-crossing, long-range projections that could also reach deeply into AI and VI. Here we seek to determine whether such a network of border-crossing, long-range projections is unique to barrel cortex or characterizes also other primary, unimodal sensory cortices and therefore could directly connect them. Using anterograde (BDA and retrograde (CTb tract-tracing techniques, we demonstrate that such diffuse horizontal networks directly and mutually connect VI, AI and SI. These findings suggest that diffuse, border-crossing axonal projections connecting directly primary cortices are an important organizational motif common to all major primary sensory cortices in the rat. Potential implications of these findings for topics including cortical structure-function relationships, multisensory integration, functional imaging and cortical parcellation are discussed.

Adolescent exposure to THC in female rats disrupts developmental changes in the prefrontal cortex.

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Rubino, Tiziana; Prini, Pamela; Piscitelli, Fabiana; Zamberletti, Erica; Trusel, Massimo; Melis, Miriam; Sagheddu, Claudia; Ligresti, Alessia; Tonini, Raffaella; Di Marzo, Vincenzo; Parolaro, Daniela

2015-01-01

Current concepts suggest that exposure to THC during adolescence may act as a risk factor for the development of psychiatric disorders later in life. However, the molecular underpinnings of this vulnerability are still poorly understood. To analyze this, we investigated whether and how THC exposure in female rats interferes with different maturational events occurring in the prefrontal cortex during adolescence through biochemical, pharmacological and electrophysiological means. We found that the endocannabinoid system undergoes maturational processes during adolescence and that THC exposure disrupts them, leading to impairment of both endocannabinoid signaling and endocannabinoid-mediated LTD in the adult prefrontal cortex. THC also altered the maturational fluctuations of NMDA subunits, leading to larger amounts of gluN2B at adulthood. Adult animals exposed to THC during adolescence also showed increased AMPA gluA1 with no changes in gluA2 subunits. Finally, adolescent THC exposure altered cognition at adulthood. All these effects seem to be triggered by the disruption of the physiological role played by the endocannabinoid system during adolescence. Indeed, blockade of CB1 receptors from early to late adolescence seems to prevent the occurrence of pruning at glutamatergic synapses. These results suggest that vulnerability of adolescent female rats to long-lasting THC adverse effects might partly reside in disruption of the pivotal role played by the endocannabinoid system in the prefrontal cortex maturation. Copyright © 2014 Elsevier Inc. All rights reserved.

Early growth hormone (GH) treatment promotes relevant motor functional improvement after severe frontal cortex lesion in adult rats.

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Heredia, Margarita; Fuente, A; Criado, J; Yajeya, J; Devesa, J; Riolobos, A S

2013-06-15

A number of studies, in animals and humans, describe the positive effects of the growth hormone (GH) treatment combined with rehabilitation on brain reparation after brain injury. We examined the effect of GH treatment and rehabilitation in adult rats with severe frontal motor cortex ablation. Thirty-five male rats were trained in the paw-reaching-for-food task and the preferred forelimb was recorded. Under anesthesia, the motor cortex contralateral to the preferred forelimb was aspirated or sham-operated. Animals were then treated with GH (0.15 mg/kg/day, s.c) or vehicle during 5 days, commencing immediately or 6 days post-lesion. Rehabilitation was applied at short- and long-term after GH treatment. Behavioral data were analized by ANOVA following Bonferroni post hoc test. After sacrifice, immunohistochemical detection of glial fibrillary acid protein (GFAP) and nestin were undertaken in the brain of all groups. Animal group treated with GH immediately after the lesion, but not any other group, showed a significant improvement of the motor impairment induced by the motor lesion, and their performances in the motor test were no different from sham-operated controls. GFAP immunolabeling and nestin immunoreactivity were observed in the perilesional area in all injured animals; nestin immunoreactivity was higher in GH-treated injured rats (mainly in animals GH-treated 6 days post-lesion). GFAP immunoreactivity was similar among injured rats. Interestingly, nestin re-expression was detected in the contralateral undamaged motor cortex only in GH-treated injured rats, being higher in animals GH-treated immediately after the lesion than in animals GH-treated 6 days post-lesion. Early GH treatment induces significant recovery of the motor impairment produced by frontal cortical ablation. GH effects include increased neurogenesis for reparation (perilesional area) and for increased brain plasticity (contralateral motor area). Copyright © 2013 Elsevier B.V. All rights

Sleep restriction in rats leads to changes in operant behaviour indicative of reduced prefrontal cortex function

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Kamphuis, Jeanine; Baichel, Swetlana; Lancel, Marike; De Boer, Sietse F.; Koolhaas, Jaap M.; Meerlo, Peter

Sleep deprivation has profound effects on cognitive performance, and some of these effects may be mediated by impaired prefrontal cortex function. In search of an animal model to investigate this relationship we studied the influence of restricted sleep on operant conditioning in rats, particularly

Juvenile social experience and differential age-related changes in the dendritic morphologies of subareas of the prefrontal cortex in rats.

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Himmler, Brett T; Mychasiuk, Richelle; Nakahashi, Ayuno; Himmler, Stephanie M; Pellis, Sergio M; Kolb, Bryan

2018-04-01

Juvenile social interactions have been shown to influence the dendritic complexity of neurons in the prefrontal cortex (PFC). In particular, social play induces pruning of the cells in the medial prefrontal cortex (mPFC), whereas interacting with multiple partners, whether those interactions involve play or not, increases the complexity of cells in the orbital frontal cortex (OFC). Previous studies suggest that these changes differ in their stability during adulthood. In the present study, rats were reared in groups of either four (quads) or two (pairs) and the brains of the rats from each rearing condition were then harvested at 60 days (i.e., shortly after sexual maturity) and 100 days (i.e., fully adult). The rats housed with multiple partners had more complex neurons of the OFC at 60 days and this complexity declined to a comparable level to that of pair housed rats by 100 days. In contrast, the play-induced changes of the mPFC remained similar at both ages. These findings suggest that the changes in the PFC induced by different social experiences in the juvenile period differ in how long they are maintained in adulthood. Differences in the functions regulated by the OFC and the mPFC are considered with regard to these differences in the stability of juvenile-induced neural changes. © 2017 Wiley Periodicals, Inc.

GluN2B-containing NMDA receptors and AMPA receptors in medial prefrontal cortex are necessary for odor span in rats

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Don A Davies

2013-12-01

Full Text Available Working memory is a type of short-term memory involved in the maintenance and manipulation of information essential for complex cognition. While memory span capacity has been extensively studied in humans as a measure of working memory, it has received considerably less attention in rodents. Our aim was to examine the role of the NMDA and AMPA glutamate receptors in odor span capacity using systemic injections or infusions of receptor antagonists into the medial prefrontal cortex. Long Evans rats were trained on a well-characterized odor span task. Initially, rats were trained to dig for a food reward in sand followed by training on a non-match to sample discrimination using sand scented with household spices. The rats were then required to perform a serial delayed non-match to sample procedure which was their odor span. Systemic injection of the broad spectrum NMDA receptor antagonist CPP (10 mg/kg or the GluN2B-selective antagonist Ro25-6981 (10 mg/kg but not 6 mg/kg significantly reduced odor span capacity. Infusions of the GluN2B- selective antagonist Ro25-6981 (2.5 µg/hemisphere into medial prefrontal cortex reduced span capacity, an effect that was nearly significant (p = 0.069. Infusions of the AMPA receptor antagonist CNQX (1.25 µg/hemisphere into medial prefrontal cortex reduced span capacity and latency for the rats to make a choice in the task. These results demonstrate span capacity in rats depends on ionotropic glutamate receptor activation in the medial prefrontal cortex. Further understanding of the circuitry underlying span capacity may aid in the novel therapeutic drug development for persons with working memory impairments as a result of disorders such as schizophrenia and Alzheimer’s disease.

Inactivation of the infralimbic prefrontal cortex in rats reduces the influence of inappropriate habitual responding in a response-conflict task.

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Haddon, J E; Killcross, S

2011-12-29

Previous research suggests the infralimbic cortex is important in situations when there is competition between goal-directed and habitual responding. Here we used a response conflict procedure to further explore the involvement of the infralimbic cortex in this relationship. Rats received training on two instrumental biconditional discriminations, one auditory and one visual, in two distinct contexts. One discrimination was "over-trained" relative to the other, "under-trained," discrimination in the ratio 3:1. At test, animals were presented with incongruent audiovisual stimulus compounds of the training stimuli in the under-trained context. The stimulus elements of these test compounds have previously dictated different lever press responses during training. Rats receiving control infusions into the infralimbic cortex showed a significant interference effect, producing more responses to the over-trained (habitual), but context-inappropriate, stimulus element of the incongruent compound. This interference effect was abolished by inactivation of the infralimbic cortex; animals showed a reduced tendency to produce the habitual but inappropriate response compared with animals receiving control infusions. This finding provides evidence that the infralimbic cortex is involved in attenuating the influence of goal-directed behavior, for example context-appropriate responding. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

Developmental Changes in Sensory-Evoked Optical Intrinsic Signals in the Rat Barrel Cortex

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Mikhail Sintsov

2017-12-01

Full Text Available Optical Intrinsic Signal imaging (OISi is a powerful technique for optical brain studies. OIS mainly reflects the hemodynamic response (HR and metabolism, but it may also involve changes in tissue light scattering (LS caused by transient cellular swelling in the active tissue. Here, we explored the developmental features of sensory-evoked OIS in the rat barrel cortex during the first 3 months after birth. Multispectral OISi revealed that two temporally distinct components contribute to the neonatal OIS: an early phase of LS followed by a late phase of HR. The contribution of LS to the early response was also evidenced by an increase in light transmission through the active barrel. The early OIS phase correlated in time and amplitude with the sensory-evoked electrophysiological response. Application of the Modified Beer-Lambert Law (MBLL to the OIS data revealed that HR during the early phase involved only a slight decrease in blood oxygenation without any change in blood volume. In contrast, HR during the late phase manifested an adult-like increase in blood volume and oxygenation. During development, the peak time of the delayed HR progressively shortened with age, nearly reaching the stimulus onset and overlapping with the early LS phase by the fourth postnatal week. Thus, LS contributes to the sensory-evoked OIS in the barrel cortex of rats at all ages, and it dominates the early OIS phase in neonatal rats due to delayed HR. Our results are also consistent with the delayed blood oxygen level dependent (BOLD signal in human preterm infants.

Motor Cortex Stimulation Regenerative Effects in Peripheral Nerve Injury: An Experimental Rat Model.

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Nicolas, Nicolas; Kobaiter-Maarrawi, Sandra; Georges, Samuel; Abadjian, Gerard; Maarrawi, Joseph

2018-06-01

Immediate microsurgical nerve suture remains the gold standard after peripheral nerve injuries. However, functional recovery is delayed, and it is satisfactory in only 2/3 of cases. Peripheral electrical nerve stimulation proximal to the lesion enhances nerve regeneration and muscle reinnervation. This study aims to evaluate the effects of the motor cortex electrical stimulation on peripheral nerve regeneration after injury. Eighty rats underwent right sciatic nerve section, followed by immediate microsurgical epineural sutures. Rats were divided into 4 groups: Group 1 (control, n = 20): no electrical stimulation; group 2 (n = 20): immediate stimulation of the sciatic nerve just proximal to the lesion; Group 3 (n = 20): motor cortex stimulation (MCS) for 15 minutes after nerve section and suture (MCSa); group 4 (n = 20): MCS performed over the course of two weeks after nerve suture (MCSc). Assessment included electrophysiology and motor functional score at day 0 (baseline value before nerve section), and at weeks 4, 8, and 12. Rats were euthanized for histological study at week 12. Our results showed that MCS enhances functional recovery, nerve regeneration, and muscle reinnervation starting week 4 compared with the control group (P < 0.05). The MCS induces higher reinnervation rates even compared with peripheral stimulation, with better results in the MCSa group (P < 0.05), especially in terms of functional recovery. MCS seems to have a beneficial effect after peripheral nerve injury and repair in terms of nerve regeneration and muscle reinnervation, especially when acute mode is used. Copyright © 2018 Elsevier Inc. All rights reserved.

Monosialotetrahexosylganglioside Inhibits the Expression of p-CREB and NR2B in the Auditory Cortex in Rats with Salicylate-Induced Tinnitus.

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Song, Rui-Biao; Lou, Wei-Hua

2015-01-01

This study investigated the effects of monosialotetrahexosylganglioside (GM1) on the expression of N-methyl-D-aspartate receptor subunit 2B (NR2B) and phosphorylated (p)-cyclic AMP response element-binding protein (CREB) in the auditory cortex of rats with tinnitus. Tinnitus-like behavior in rats was tested with the gap prepulse inhibition of acoustic startle paradigm. We then investigated the NR2B mRNA and protein and p-CREB protein levels in the auditory cortex of tinnitus rats compared with normal rats. Rats treated for 4 days with salicylate exhibited tinnitus. NR2B mRNA and protein and p-CREB protein levels were upregulated in these animals, with expression returning to normal levels 14 days after cessation of treatment; baseline levels of NR2B and p-CREB were also restored by GM1 administration. These data suggest that chronic salicylate administration induces tinnitus via upregulation of p-CREB and NR2B expression, and that GM1 can potentially be used to treat tinnitus.

Expression of Kv3.1b potassium channel is widespread in macaque motor cortex pyramidal cells: A histological comparison between rat and macaque.

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Soares, David; Goldrick, Isabelle; Lemon, Roger N; Kraskov, Alexander; Greensmith, Linda; Kalmar, Bernadett

2017-06-15

There are substantial differences across species in the organization and function of the motor pathways. These differences extend to basic electrophysiological properties. Thus, in rat motor cortex, pyramidal cells have long duration action potentials, while in the macaque, some pyramidal neurons exhibit short duration "thin" spikes. These differences may be related to the expression of the fast potassium channel Kv3.1b, which in rat interneurons is associated with generation of thin spikes. Rat pyramidal cells typically lack these channels, while there are reports that they are present in macaque pyramids. Here we made a systematic, quantitative comparison of the Kv3.1b expression in sections from macaque and rat motor cortex, using two different antibodies (NeuroMab, Millipore). As our standard reference, we examined, in the same sections, Kv3.1b staining in parvalbumin-positive interneurons, which show strong Kv3.1b immunoreactivity. In macaque motor cortex, a large sample of pyramidal neurons were nearly all found to express Kv3.1b in their soma membranes. These labeled neurons were identified as pyramidal based either by expression of SMI32 (a pyramidal marker), or by their shape and size, and lack of expression of parvalbumin (a marker for some classes of interneuron). Large (Betz cells), medium, and small pyramidal neurons all expressed Kv3.1b. In rat motor cortex, SMI32-postive pyramidal neurons expressing Kv3.1b were very rare and weakly stained. Thus, there is a marked species difference in the immunoreactivity of Kv3.1b in pyramidal neurons, and this may be one of the factors explaining the pronounced electrophysiological differences between rat and macaque pyramidal neurons. © 2017 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc.

The Role of the Rat Medial Prefrontal Cortex in Adapting to Changes in Instrumental Contingency

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Coutureau, Etienne; Esclassan, Frederic; Di Scala, Georges; Marchand, Alain R.

2012-01-01

In order to select actions appropriate to current needs, a subject must identify relationships between actions and events. Control over the environment is determined by the degree to which action consequences can be predicted, as described by action-outcome contingencies – i.e. performing an action should affect the probability of the outcome. We evaluated in a first experiment adaptation to contingency changes in rats with neurotoxic lesions of the medial prefrontal cortex. Results indicate that this brain region is not critical to adjust instrumental responding to a negative contingency where the rats must refrain from pressing a lever, as this action prevents reward delivery. By contrast, this brain region is required to reduce responding in a non-contingent situation where the same number of rewards is freely delivered and actions do not affect the outcome any more. In a second experiment, we determined that this effect does not result from a different perception of temporal relationships between actions and outcomes since lesioned rats adapted normally to gradually increasing delays in reward delivery. These data indicate that the medial prefrontal cortex is not directly involved in evaluating the correlation between action-and reward-rates or in the perception of reward delays. The deficit in lesioned rats appears to consist of an abnormal response to the balance between contingent and non-contingent rewards. By highlighting the role of prefrontal regions in adapting to the causal status of actions, these data contribute to our understanding of the neural basis of choice tasks. PMID:22496747

Infralimbic cortex Rho-kinase inhibition causes antidepressant-like activity in rats.

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Inan, Salim Yalcin; Soner, Burak Cem; Sahin, Ayse Saide

2015-03-03

Depression is one of the most common psychiatric disorders in the world; however, its mechanisms remain unclear. Recently, a new signal-transduction pathway, namely Rho/Rho-kinase signalling, has been suggested to be involved in diverse cellular events in the central nervous system; such as epilepsy, anxiety-related behaviors, regulation of dendritic and axonal morphology, antinociception, subarachnoid haemorrhage, spinal cord injury and amyotrophic lateral sclerosis. However there is no evidence showing the involvement of Rho-kinase pathway in depression. In addition, the infralimbic cortex, rodent equivalent to subgenual cingulate cortex has been shown to be responsible for emotional responses. Thus, in the present study, intracranial guide cannulae were stereotaxically implanted bilaterally into the infralimbic cortex, and the effects of repeated microinjections of a Rho-kinase (ROCK) inhibitor Y-27632 (10 nmol) were investigated in rats. Y-27632 significantly decreased immobility time and increased swimming and climbing behaviors when compared to fluoxetine (10 μg) and saline groups in the forced swim test. In addition, Y-27632 treatment did not affect spontaneous locomotor activity and forelimb use in the open-field and cylinder tests respectively; but it enhanced limb placing accuracy in the ladder rung walking test. Our results suggest that Y-27632 could be a potentially active antidepressant agent. Copyright © 2014 Elsevier Inc. All rights reserved.

Physiological slowing and upregulation of inhibition in cortex are correlated with behavioral deficits in protein malnourished rats.

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Rahul Chaudhary

Full Text Available Protein malnutrition during early development has been correlated with cognitive and learning disabilities in children, but the neuronal deficits caused by long-term protein deficiency are not well understood. We exposed rats from gestation up to adulthood to a protein-deficient (PD diet, to emulate chronic protein malnutrition in humans. The offspring exhibited significantly impaired performance on the 'Gap-crossing' (GC task after reaching maturity, a behavior that has been shown to depend on normal functioning of the somatosensory cortex. The physiological state of the somatosensory cortex was examined to determine neuronal correlates of the deficits in behavior. Extracellular multi-unit recording from layer 4 (L4 neurons that receive direct thalamocortical inputs and layers 2/3 (L2/3 neurons that are dominated by intracortical connections in the whisker-barrel cortex of PD rats exhibited significantly low spontaneous activity and depressed responses to whisker stimulation. L4 neurons were more severely affected than L2/3 neurons. The response onset was significantly delayed in L4 cells. The peak response latency of L4 and L2/3 neurons was delayed significantly. In L2/3 and L4 of the barrel cortex there was a substantial increase in GAD65 (112% over controls and much smaller increase in NMDAR1 (12-20%, suggesting enhanced inhibition in the PD cortex. These results show that chronic protein deficiency negatively affects both thalamo-cortical and cortico-cortical transmission during somatosensory information processing. The findings support the interpretation that sustained protein deficiency interferes with features of cortical sensory processing that are likely to underlie the cognitive impairments reported in humans who have suffered from prolonged protein deficiency.

[Effect of electro-acupuncture on metabolites in the cerebral cortex of ulcerative colitis rats based on Pi/Wei-brain related theory].

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Yang, Yang; Zhao, Ji-lan; Hou, Tian-shu; Han, Xiao-xia; Zhao, Zheng-yu; Peng, Xiao-hua; Wu, Qiao-Feng

2014-10-01

To study the effect of electro-acupuncture (EA) at points along Foot Yangming Channel on metabolite of ulcerative colitis (UC) rats' cerebral cortex and to identify key metabolites by referring to Pi/Wei-brain related theory in Chinese medicine (CM). The UC rat model was set up by dextran sulfate sodium (DSS) method. Male SD rats were randomly divided into the model group and the EA group, 13 in each group. Another 13 rats were recruited as the blank control group. Rats in the blank control group and the model group received no EA. EA was performed at Zusanli (ST36), Shangjuxu (ST37), and Tianshu (ST25) for 5 days by using disperse-dense wave. Then all rats were sacrificed. Their recto-colon and the ileocecal junction were pathomorphologically observed by light microscope and transmission electron microscope (TEM). Cerebral cortexes were extracted. Water-soluble and lipid-soluble brain tissue metabolites were respectively extracted for metabolic research using 1H nuclear magnetic resonance (1H-NMR). EA could obviously improve the general condition of UC model rats, decrease the value of DAI, reduce the infiltration of inflammatory cells in the intestinal tract, stabilize structures such as mitochondria, endoplasmic reticulum and so on (P theory.

Quantitative histological studies on aging changes in cerebral cortex of rhesus monkey and albino rat with notes on effects of prolonged low-dose ionizing irradiation in the rat

International Nuclear Information System (INIS)

Brizzee, K.R.

1973-01-01

Brains of a series of eight young adult control (150 days) and eight middle-aged control (550 days) rats were fixed by a two-stage perfusion procedure employing Heidenhain's 'susa' solution. An equal number of rats were exposed to γ-irradiation at 6.5 R/day beginning on the 50th postnatal day and were sacrificed in the same manner and at the same age levels as the previous group. Paraffin sections were cut at 20 and 6 μ from cerebral cortical area 3 in the rat brains. Sections used for cell counts were stained with Harris' hematoxylin and eosin or iron hematoxylin, gallocyanin, acid fuchsin and ponceau de xylidene. Counts of neurons and glia were carried out at 20 equally spaced submolecular depth levels, and cell frequency profiles were plotted for each of the two cell types. The mean neuron and glial packing density for the total depth of the submolecular cortex of area 3 was not significantly different in young adult and middle-aged controls or in young adult irradiated (total dose 650 R) and control animals. However, statistical evaluation of data for relative depth levels 7 through 20 indicated that the packing density in this zone was significantly less (P<0.02) in middle-aged controls than in young adult animals. In middle-aged irradiated rats (total dose about 3250 R) neuron and glial packing densities for total depth of submolecular cortex were not significantly different than in control animals at the same age level. However, the values obtained for neuron packing density at relative depth levels 1 through 8 were significantly lower in middle-aged irradiated than in middle-aged control rats. The neuron packing density in middle-aged irradiated rats was significantly lower than in the young adult irradiated males. In electron micrographs, an increase in the amount of glycogen granules in astrocyte cell processes in cerebral cortex of irradiated middle-aged rats was noted, but there was no evidence of any other ultrastructural alterations

Beta 2-adrenergic receptors are colocalized and coregulated with whisker barrels in rat somatosensory cortex

International Nuclear Information System (INIS)

Vos, P.; Kaufmann, D.; Hand, P.J.; Wolfe, B.B.

1990-01-01

Autoradiography has been used to visualize independently the subtypes of beta-adrenergic receptors in rat somatosensory cortex. Beta 2-adrenergic receptors, but not beta 1-adrenergic receptors colocalize with whisker barrels in this tissue. Thus, each whisker sends a specific multisynaptic pathway to the somatosensory cortex that can be histochemically visualized and only one subtype of beta-adrenergic receptor is specifically associated with this cortical representation. Additionally, neonatal lesion of any or all of the whisker follicles results in loss of the corresponding barrel(s) as shown by histochemical markers. This loss is paralleled by a similar loss in the organization of beta 2-adrenergic receptors in the somatosensory cortex. Other results indicate that these beta 2-adrenergic receptors are not involved in moment-to-moment signal transmission in this pathway and, additionally, are not involved in a gross way in the development of whisker-barrel array

Projections of the central medial nucleus of the thalamus in the rat: Node in cortical, striatal and limbic forebrain circuitry

Czech Academy of Sciences Publication Activity Database

Vertes, R. P.; Hoover, W. B.; Rodríguez Arellano, Jose Julio

2012-01-01

Roč. 219, 6 SEP (2012), s. 120-136 ISSN 0306-4522 R&D Projects: GA ČR GA309/09/1696 Institutional research plan: CEZ:AV0Z50390703 Keywords : medial prefrontal cortex * insular cortex * nucleus acc umbens Subject RIV: FH - Neurology Impact factor: 3.122, year: 2012

Hospital acquired pneumonia is linked to right hemispheric peri-insular stroke.

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André Kemmling

Full Text Available Hospital acquired pneumonia (HAP is a major complication of stroke. We sought to determine associations between infarction of specific brain regions and HAP.215 consecutive acute stroke patients with HAP (2003-2009 were carefully matched with 215 non-pneumonia controls by gender, then NIHSS, then age. Admission imaging and binary masks of infarction were registered to MNI-152 space. Regional atlas and voxel-based log-odds were calculated to assess the relationship between infarct location and the likelihood of HAP. An independently validated penalized conditional logistic regression model was used to identify HAP associated imaging regions.The HAP and control patients were well matched by gender (100%, age (95% within 5-years, NIHSS (98% within 1-point, infarct size, dysphagia, and six other clinical variables. Right hemispheric infarcts were more frequent in patients with HAP versus controls (43.3% vs. 34.0%, p = 0.054, whereas left hemispheric infarcts were more frequent in controls (56.7% vs. 44.7%, p = 0.012; there was no significant difference between groups in the rate of brainstem strokes (p = 1.0. Of the 10 most infarcted regions, only right insular cortex volume was different in HAP versus controls (20 vs. 12 ml, p = 0.02. In univariate analyses, the highest log-odds regions for pneumonia were right hemisphere, cerebellum, and brainstem. The best performing multivariate model selected 7 brain regions of infarction and 2 infarct volume-based variables independently associated with HAP.HAP is associated with right hemispheric peri-insular stroke. These associations may be related to autonomic modulation of immune mechanisms, supporting recent hypotheses of stroke mediated immune suppression.

[Effects of Betel shisanwei ingredients pill on AC-cAMP-PKA signal transduction pathways in hippocampus and prefrontal cortex of depressive rats].

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Tong, Hai-Ying; Wu, Jisiguleng; Bai, Liang-Feng; Bao, Wu-Ye; Hu, Rilebagen; Li, Jing; Zhang, Yue

2014-05-01

To observe the effects of Mongolian pharmaceutical Betel shisanwei ingredients pill on AC-cAMP-PKA signal transduction pathways in hippocampus and prefrontal cortex of depressive rats. Sixty male Wistar rats were randomly divided into six groups according to the sugar consumption test (10 rats in each group), normal control group,model group,fluoxetine group (3.3 mg x kg(-1)) and low dose, medium dose and high dose group (0.25, 0.5, 1 g x kg(-1)) of Betel shisanwei ingredients pill. Except the normal control,the other groups were treated with the chronic unpredictable mild stress stimulation combined with lonely raising for 28 days. 10 mL x kg(-1) of drugs were given to each rat once daily,continuously for 28 days. The AC activity of the hippocampus and prefrontal cortex were determined by radiation immunity analysis (RIA), while cAMP and PKA quantity were determinated by Enzyme-linked immunosorbent (ELISA). The AC activity, cAMP and PKA quantity of hippocampus and prefrontal of mouse model of Chronic stress depression decreased significantly than those of control group (P Betel shisanwei ingredients pill group indecreased significantly than those of model group (P Betel shisanwei ingredients pill. The AC-cAMP-PKA signal transduction pathways in hippocampus and prefrontal cortex of depression model of rats is down-regulated, whereas Mongolian pharmaceutical Betel shisanwei ingredients pill could up-regulated it to resist depression.

Stuttered swallowing: Electric stimulation of the right insula interferes with water swallowing. A case report

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Shoemaker J

2011-02-01

Full Text Available Abstract Background Various functional resonance imaging, magnetoencephalographic and lesion studies suggest the involvement of the insular cortex in the control of swallowing. However, the exact location of insular activation during swallowing and its functional significance remain unclear. Case presentation Invasive electroencephalographic monitoring was performed in a 24-year-old man with medically intractable stereotyped nocturnal hypermotor seizures due to a ganglioglioma. During stimulation of the right inferior posterior insular cortex with depth electrodes the patient spontaneously reported a perception of a "stutter in swallowing". Stimulation of the inferior posterior insular cortex at highest intensity (4 mA was also associated with irregular and delayed swallows. Swallowing was not impaired during stimulation of the superior posterior insular cortex, regardless of stimulation intensity. Conclusions These results indicate that the right inferior posterior insular cortex is involved in the neural circuitry underlying the control of swallowing.

Modulation of sibutramine-induced increases in extracellular noradrenaline concentration in rat frontal cortex and hypothalamus by α2-adrenoceptors

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Wortley, K E; Heal, D J; Stanford, S C

1999-01-01

The effects of sibutramine (0.25–10 mg kg−1 i.p.) on extracellular noradrenaline concentration in the frontal cortex and hypothalamus of freely-moving rats were investigated using microdialysis. The role of presynaptic α2-adrenoceptors in modulating the effects of sibutramine in these brain areas was also determined.Sibutramine induced an increase in extracellular noradrenaline concentration, the magnitude of which paralleled dose, in both brain areas. In the cortex, this increase was gradual and sustained, whereas in the hypothalamus it was more rapid and of shorter duration.In both the cortex and hypothalamus, pretreatment of rats with the α2-adrenoceptor antagonist RX821002 (3 mg kg−1 i.p.) potentiated increases in the accumulation of extracellular noradrenaline induced by sibutramine (10 mg kg−1 i.p.), by 7 and 10 fold respectively. RX821002 also reduced the latency of sibutramine to reach its maximum effect in the cortex, but not in the hypothalamus.Infusion of RX821002 (1 μM) via the probe increased the accumulation of extracellular noradrenaline induced by sibutramine (10 mg kg−1 i.p.) in both brain areas. In the hypothalamus, the effects of RX821002 on the accumulation of noradrenaline induced by sibutramine were 2 fold greater than those in the cortex.These findings support evidence that sibutramine inhibits the reuptake of noradrenaline in vivo, but that the accumulation of extracellular noradrenaline is limited by noradrenergic activation of presynaptic α2-adrenoceptors. Furthermore, the data suggest that terminal α2-adrenoceptors in the hypothalamus exert a greater inhibitory effect over the control of extracellular noradrenaline accumulation than do those in the cortex. PMID:10516646

Altered Insular and Occipital Responses to Simulated Vertical Self-Motion in Patients with Persistent Postural-Perceptual Dizziness

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Roberta Riccelli

2017-10-01

Full Text Available BackgroundPersistent postural-perceptual dizziness (PPPD is a common functional vestibular disorder characterized by persistent symptoms of non-vertiginous dizziness and unsteadiness that are exacerbated by upright posture, self-motion, and exposure to complex or moving visual stimuli. Recent physiologic and neuroimaging data suggest that greater reliance on visual cues for postural control (as opposed to vestibular cues—a phenomenon termed visual dependence and dysfunction in central visuo-vestibular networks may be important pathophysiologic mechanisms underlying PPPD. Dysfunctions are thought to involve insular regions that encode recognition of the visual effects of motion in the gravitational field.MethodsWe tested for altered activity in vestibular and visual cortices during self-motion simulation obtained via a visual virtual-reality rollercoaster stimulation using functional magnetic resonance imaging in 15 patients with PPPD and 15 healthy controls (HCs. We compared between groups differences in brain responses to simulated displacements in vertical vs horizontal directions and correlated the difference in directional responses with dizziness handicap in patients with PPPD.ResultsHCs showed increased activity in the anterior bank of the central insular sulcus during vertical relative to horizontal motion, which was not seen in patients with PPPD. However, for the same comparison, dizziness handicap correlated positively with activity in the visual cortex (V1, V2, and V3 in patients with PPPD.ConclusionWe provide novel insight into the pathophysiologic mechanisms underlying PPPD, including functional alterations in brain processes that affect balance control and reweighting of space-motion inputs to favor visual cues. For patients with PPPD, difficulties using visual data to discern the effects of gravity on self-motion may adversely affect balance control, particularly for individuals who simultaneously rely too heavily on visual

Insular networks for emotional processing and social cognition: comparison of two case reports with either cortical or subcortical involvement.

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Couto, Blas; Sedeño, Lucas; Sposato, Luciano A; Sigman, Mariano; Riccio, Patricia M; Salles, Alejo; Lopez, Vladimir; Schroeder, Johannes; Manes, Facundo; Ibanez, Agustin

2013-05-01

The processing of the emotion of disgust is attributed to the insular cortex (IC), which is also responsible for social emotions and higher-cognitive functions. We distinguish the role of the IC from its connections in regard to these functions through the assessment of emotions and social cognition in a double case report. These subjects were very rare cases that included a focal IC lesion and a subcortical focal stroke affecting the connections of the IC with frontotemporal areas. Both patients and a sample of 10 matched controls underwent neuropsychological and affective screening questionnaires, a battery of multimodal basic emotion recognition tests, an emotional inference disambiguation task using social contextual clues, an empathy task and a theory of mind task. The insular lesion (IL) patient showed no impairments in emotion recognition and social emotions and presented with a pattern of delayed reaction times (RTs) in a subset of both groups of tasks. The subcortical lesion (SL) patient was impaired in multimodal aversive emotion recognition, including disgust, and exhibited delayed RTs and a heterogeneous pattern of impairments in subtasks of empathy and in the contextual inference of emotions. Our results suggest that IC related networks, and not the IC itself, are related to negative emotional processing and social emotions. We discuss these results with respect to theoretical approaches of insular involvement in emotional and social processing and propose that IC connectivity with frontotemporal and subcortical regions might be relevant for contextual emotional processing and social cognition. Copyright © 2012 Elsevier Ltd. All rights reserved.

Individual differences in impulsive action and dopamine transporter function in rat orbitofrontal cortex.

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Yates, J R; Darna, M; Beckmann, J S; Dwoskin, L P; Bardo, M T

2016-01-28

Impulsivity, which can be subdivided into impulsive action and impulsive choice, is implicated as a factor underlying drug abuse vulnerability. Although previous research has shown that dopamine (DA) systems in prefrontal cortex are involved in impulsivity and substance abuse, it is not known if inherent variation in DA transporter (DAT) function contributes to impulsivity. The current study determined if individual differences in either impulsive action or impulsive choice are related to DAT function in orbitofrontal (OFC) and/or medial prefrontal cortex (mPFC). Rats were first tested both for impulsive action in a cued go/no-go task and for impulsive choice in a delay-discounting task. Following behavioral evaluation, in vitro [(3)H]DA uptake assays were performed in OFC and mPFC isolated from individual rats. Vmax in OFC, but not mPFC, was correlated with performance in the cued go/no-go task, with decreased OFC DAT function being associated with high impulsive action. In contrast, Vmax in OFC and mPFC was not correlated with performance in the delay-discounting task. The current results demonstrate that impulsive behavior in cued go/no-go performance is associated with decreased DAT function in OFC, suggesting that hyperdopaminergic tone in this prefrontal subregion mediates, at least in part, increased impulsive action. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

19 CFR 7.2 - Insular possessions of the United States other than Puerto Rico.

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2010-04-01

... than Puerto Rico. 7.2 Section 7.2 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF... NAVAL STATION § 7.2 Insular possessions of the United States other than Puerto Rico. (a) Insular possessions of the United States other than Puerto Rico are also American territory but, because those insular...

Energy metabolism of rat cerebral cortex, hypothalamus and hypophysis during ageing.

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Villa, R F; Ferrari, F; Gorini, A

2012-12-27

Ageing is one of the main risk factors for brain disorders. According to the neuroendocrine theory, ageing modifies the sensitivity of hypothalamus-pituitary-adrenal axis to homoeostatic signals coming from the cerebral cortex. The relationships between the energy metabolism of these areas have not been considered yet, in particular with respect to ageing. For these reasons, this study was undertaken to systematically investigate in female Sprague-Dawley rats aged 4, 6, 12, 18, 24, 28 months and in 4-month-old male ones, the catalytic properties of energy-linked enzymes of the Krebs' cycle, electron transport chain, glutamate and related amino acids on different mitochondrial subpopulations, i.e. non-synaptic perikaryal and intra-synaptic (two types) mitochondria. The biochemical enzymatic pattern of these mitochondria shows different expression of the above-mentioned enzymatic activities in the investigated brain areas, including frontal cerebral cortex, hippocampus, striatum, hypothalamus and hypophysis. The study shows that: (i) the energy metabolism of the frontal cerebral cortex is poorly affected by physiological ageing; (ii) the biochemical machinery of non-synaptic perikaryal mitochondria is differently expressed in the considered brain areas; (iii) at 4-6 months, hypothalamus and hypophysis possess lower oxidative metabolism with respect to the frontal cerebral cortex while (iv), during ageing, the opposite situation occurs. We hypothesised that these metabolic modifications likely try to grant HPA functionality in response to the incoming external stress stimuli increased during ageing. It is particularly notable that age-related changes in brain bioenergetics and in mitochondrial functionality may be considered as remarkable factors during physiological ageing and should play important roles in predisposing the brain to physiopathological events, tightly related to molecular mechanisms evoked for pharmacological treatments. Copyright © 2012 IBRO

Population structure and genetic variability of mainland and insular populations of the Neotropical water rat, Nectomys squamipes (Rodentia, Sigmodontinae

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Francisca C. Almeida

2005-12-01

Full Text Available Seven microsatellite loci were used to investigate the genetic variability and structure of six mainland and two island populations of the Neotropical water rat Nectomys squamipes, a South American semi-aquatic rodent species with a wide distribution. High levels of variability were found within mainland populations while island populations were less variable but the more differentiated in respect to allele number and frequency. The time of biological divergence between mainland and island populations coincided with geological data. A significant geographic structure was found in mainland populations (theta = 0.099; rho = 0.086 although the degree of differentiation was relatively low in respect to the distance between surveyed localities (24 to 740 km. Genetic and geographic distances were not positively correlated as previously found with random amplified polymorphic DNA (RAPD markers. Significant but low genetic differentiation in the mainland and lack of isolation by distance can be explained by large population size and/or recent population expansion. Additionally, the agreement between the age of geologic events (sea level fluctuations and divergence times for insular populations points to a good reference for molecular clock calibration to associate recent environmental changes and the distribution pattern of small mammals in the Brazilian Atlantic Forest.

Molecular Correlates of Cortical Network Modulation by Long-Term Sensory Experience in the Adult Rat Barrel Cortex

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Vallès, Astrid; Granic, Ivica; De Weerd, Peter; Martens, Gerard J. M.

2014-01-01

Modulation of cortical network connectivity is crucial for an adaptive response to experience. In the rat barrel cortex, long-term sensory stimulation induces cortical network modifications and neuronal response changes of which the molecular basis is unknown. Here, we show that long-term somatosensory stimulation by enriched environment…

RAT HIPPOCAMPAL LACTATE EFFLUX DURING ELECTROCONVULSIVE SHOCK OR STRESS IS DIFFERENTLY DEPENDENT ON ENTORHINAL CORTEX AND ADRENAL INTEGRITY

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KRUGERS, HJ; JAARSMA, D; KORF, J

The role of the entorhinal cortex and the adrenal gland in rat hippocampal lactate formation was assessed during and after a short-lasting immobilization stress and electroconvulsive shock (ECS). Extracellular lactate was measured on-line using microdialysis and enzyme reactions (a technique named

Changes in acetylcholinesterase, Na+,K+-ATPase, and Mg2+-ATPase activities in the frontal cortex and the hippocampus of hyper- and hypothyroid adult rats.

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Carageorgiou, Haris; Pantos, Constantinos; Zarros, Apostolos; Stolakis, Vasileios; Mourouzis, Iordanis; Cokkinos, Dennis; Tsakiris, Stylianos

2007-08-01

The thyroid hormones (THs) are crucial determinants of normal development and metabolism, especially in the central nervous system. The metabolic rate is known to increase in hyperthyroidism and decrease in hypothyroidism. The aim of this work was to investigate how changes in metabolism induced by THs could affect the activities of acetylcholinesterase (AChE), (Na+,K+)- and Mg2+-adenosinetriphosphatase (ATPase) in the frontal cortex and the hippocampus of adult rats. Hyperthyroidism was induced by subcutaneous administration of thyroxine (25 microg/100 g body weight) once daily for 14 days, and hypothyroidism was induced by oral administration of propylthiouracil (0.05%) for 21 days. All enzyme activities were evaluated spectrophotometrically in the homogenated brain regions of 10 three-animal pools. A region-specific behavior was observed concerning the examined enzyme activities in hyper- and hypothyroidism. In hyperthyroidism, AChE activity was significantly increased only in the hippocampus (+22%), whereas Na+,K+-ATPase activity was significantly decreased in the hyperthyroid rat hippocampus (-47%) and remained unchanged in the frontal cortex. In hypothyroidism, AChE activity was significantly decreased in the frontal cortex (-23%) and increased in the hippocampus (+21%). Na+,K+-ATPase activity was significantly decreased in both the frontal cortex (-35%) and the hippocampus (-43%) of hypothyroid rats. Mg2+-ATPase remained unchanged in the regions of both hyper- and hypothyroid rat brains. Our data revealed that THs affect the examined adult rat brain parameters in a region- and state-specific way. The TH-reduced Na+,K+-ATPase activity may increase the synaptic acetylcholine release and, thus, modulate AChE activity. Moreover, the above TH-induced changes may affect the monoamine neurotransmitter systems in the examined brain regions.

Effects of bilateral and unilateral locus coeruleus lesions on beam-walking recovery after subsequent unilateral sensorimotor cortex suction-ablation in the rat.

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Goldstein, L B

1997-01-01

The recovery of beam-walking ability following a unilateral sensorimotor cortex lesion in the rat is hypothesized to be noradrenergically-mediated. We carried out two experiments to further test this hypothesis. In the first experiment, bilateral 6-hydroxydopamine locus coeruleus (LC) lesions or sham LC lesions were made 2 weeks prior to a right sensorimotor cortex suction-ablation lesion or sham cortex lesion. In the second experiment, unilateral left or right LC lesions or sham LC lesions were made 2 weeks prior to a right sensorimotor cortex lesion or sham cortex lesion. Beam-walking recovery was measured over the 12 days following cortex lesioning in each experiment. Bilateral, unilateral left, and unilateral right LC lesions resulted in impaired recovery. These data provide additional support for the hypothesis that beam-walking recovery after sensorimotor cortex injury is, at least in part, noradrenergically mediated.

Characterization of hemodynamics and oxygenation in the renal cortex of rats

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Grosenick, Dirk; Wabnitz, Heidrun; Macdonald, Rainer; Niendorf, Thoralf; Cantow, Kathleen; Flemming, Bert; Arakelyan, Karen; Seeliger, Erdmann

2015-03-01

We have performed a pre-clinical study on 13 rats to investigate the potential of near-infrared spectroscopy for quantification of hemoglobin concentration and oxygen saturation of hemoglobin in the renal cortex of small animals. These measurements were combined with laser-Doppler fluxmetry and a fluorescence quenching technique for quantification of tissue oxygen tension. Hemoglobin concentration and oxygen saturation were determined from experimental data by a Monte Carlo model. The methods were applied to investigate and compare temporal changes during several types of interventions such as arterial and venous occlusions, as well as hyperoxia, hypoxia and hypercapnia induced by different mixtures of the inspired gas.

Sexually Monomorphic Maps and Dimorphic Responses in Rat Genital Cortex.

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Lenschow, Constanze; Copley, Sean; Gardiner, Jayne M; Talbot, Zoe N; Vitenzon, Ariel; Brecht, Michael

2016-01-11

Mammalian external genitals show sexual dimorphism [1, 2] and can change size and shape upon sexual arousal. Genitals feature prominently in the oldest pieces of figural art [3] and phallic depictions of penises informed psychoanalytic thought about sexuality [4, 5]. Despite this longstanding interest, the neural representations of genitals are still poorly understood [6]. In somatosensory cortex specifically, many studies did not detect any cortical representation of genitals [7-9]. Studies in humans debate whether genitals are represented displaced below the foot of the cortical body map [10-12] or whether they are represented somatotopically [13-15]. We wondered what a high-resolution mapping of genital representations might tell us about the sexual differentiation of the mammalian brain. We identified genital responses in rat somatosensory cortex in a region previously assigned as arm/leg cortex. Genital responses were more common in males than in females. Despite such response dimorphism, we observed a stunning anatomical monomorphism of cortical penis and clitoris input maps revealed by cytochrome-oxidase-staining of cortical layer 4. Genital representations were somatotopic and bilaterally symmetric, and their relative size increased markedly during puberty. Size, shape, and erect posture give the cortical penis representation a phallic appearance pointing to a role in sexually aroused states. Cortical genital neurons showed unusual multi-body-part responses and sexually dimorphic receptive fields. Specifically, genital neurons were co-activated by distant body regions, which are touched during mounting in the respective sex. Genital maps indicate a deep homology of penis and clitoris representations in line with a fundamentally bi-sexual layout [16] of the vertebrate brain. Copyright © 2016 Elsevier Ltd. All rights reserved.

Lycopene ameliorates atrazine-induced oxidative damage in adrenal cortex of male rats by activation of the Nrf2/HO-1 pathway.

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Abass, Marwa Ahmed; Elkhateeb, Shereen Ahmed; Abd El-Baset, Samia Adel; Kattaia, Asmaa Alhosiny; Mohamed, Eman Mosallam; Atteia, Hebatallah Husseini

2016-08-01

Atrazine (ATZ) is one of the most commonly used herbicides contaminating plants, soil and water resources. Several strategies have been used to counteract ATZ toxicity. Here, we tested the hypothesis that lycopene could ameliorate ATZ-induced toxicity in the adrenal cortex. For this purpose, 35 adult male albino rats were randomized into five equal groups: untreated control, vehicle control (received 0.5 mL corn oil/day), lycopene (treated with lycopene dissolved in 0.5 mL corn oil, 10 mg/kg b.w./day), ATZ (received ATZ dissolved in 0.5 mL corn oil 300 mg/kg b.w./day), and ATZ + lycopene (treated with ATZ and lycopene at the same previously mentioned doses). All treatments were given by oral gavage for 4 weeks. We found that ATZ exposure significantly increased relative adrenal weight, plasma ACTH levels, and adrenal oxidative stress as manifested by elevated malondialdehyde levels, decreased reduced glutathione content and depressed antioxidant enzyme activities in adrenal cortex tissues with respect to control groups. Furthermore, the transcription of adrenal cortex nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), nuclear factor kappa B, and caspase-3 genes was increased significantly compared with the control groups. This was accompanied with DNA fragmentation and structural and ultrastructural changes in zona glomerulosa and zona fasiculata of the adrenal cortex. Notably, all these changes were partially ameliorated in rats treated concomitantly with ATZ and lycopene. Our results showed that lycopene exerts protective effects against ATZ-induced toxicity in rat adrenal cortex. These effects may be attributed to the antioxidative property of lycopene and its ability to activate the Nrf2/HO-1 pathway.

Laminar pattern of cholinergic and adrenergic receptors in rat visual cortex using quantitative receptor autoradiography

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Schliebs, R.; Walch, C.

1989-01-01

The laminar distribution of muscarinic acetylcholine receptors, including the M1-receptor subtype, of beta-adrenergic receptors, and noradrenaline uptake sites, was studied in the adult rat visual, frontal, somatosensory and motor cortex, using quantitative receptor autoradiography. In the visual cortex, the highest density of muscarinic acetylcholine receptors was found in layer I. From layer II/III to layer V binding decreases continueously reaching a constant binding level in layers V and VI. This laminar pattern of muscarinic receptor density differs somewhat from that observed in the non-visual cortical regions examined: layer II/III contained the highest receptor density followed by layer I and IV: lowest density was found in layer V and VI. The binding profile of the muscarinic cholinergic M1-subtype through the visual cortex shows a peak in cortical layer II and in the upper part of layer VI, whereas in the non-visual cortical regions cited the binding level was high in layer II/III, moderate in layer I and IV, and low in layer VI. Layers I to IV of the visual cortex contained the highest beta-adrenergic receptor densities, whereas only low binding levels were observed in the deeper layers. A similar laminar distribution was found also in the frontal, somatosensory and motor cortex. The density of noradrenaline uptake sites was high in all layers of the cortical regions studied, but with noradrenaline uptake sites somewhat more concentrated in the superficial layers than in deeper ones. The distinct laminar pattern of cholinergic and noradrenergic receptor sites indicates a different role for acetylcholine and noradrenaline in the functional anatomy of the cerebral cortex, and in particular, the visual cortex. (author)

Laminar pattern of cholinergic and adrenergic receptors in rat visual cortex using quantitative receptor autoradiography

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Schliebs, R; Walch, C [Leipzig Univ. (German Democratic Republic). Bereich Medizin; Stewart, M G [Open Univ., Milton Keynes (UK)

1989-01-01

The laminar distribution of muscarinic acetylcholine receptors, including the M1-receptor subtype, of beta-adrenergic receptors, and noradrenaline uptake sites, was studied in the adult rat visual, frontal, somatosensory and motor cortex, using quantitative receptor autoradiography. In the visual cortex, the highest density of muscarinic acetylcholine receptors was found in layer I. From layer II/III to layer V binding decreases continueously reaching a constant binding level in layers V and VI. This laminar pattern of muscarinic receptor density differs somewhat from that observed in the non-visual cortical regions examined: layer II/III contained the highest receptor density followed by layer I and IV: lowest density was found in layer V and VI. The binding profile of the muscarinic cholinergic M1-subtype through the visual cortex shows a peak in cortical layer II and in the upper part of layer VI, whereas in the non-visual cortical regions cited the binding level was high in layer II/III, moderate in layer I and IV, and low in layer VI. Layers I to IV of the visual cortex contained the highest beta-adrenergic receptor densities, whereas only low binding levels were observed in the deeper layers. A similar laminar distribution was found also in the frontal, somatosensory and motor cortex. The density of noradrenaline uptake sites was high in all layers of the cortical regions studied, but with noradrenaline uptake sites somewhat more concentrated in the superficial layers than in deeper ones. The distinct laminar pattern of cholinergic and noradrenergic receptor sites indicates a different role for acetylcholine and noradrenaline in the functional anatomy of the cerebral cortex, and in particular, the visual cortex. (author).

Knockdown of the dyslexia-associated gene Kiaa0319 impairs temporal responses to speech stimuli in rat primary auditory cortex.

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Centanni, T M; Booker, A B; Sloan, A M; Chen, F; Maher, B J; Carraway, R S; Khodaparast, N; Rennaker, R; LoTurco, J J; Kilgard, M P

2014-07-01

One in 15 school age children have dyslexia, which is characterized by phoneme-processing problems and difficulty learning to read. Dyslexia is associated with mutations in the gene KIAA0319. It is not known whether reduced expression of KIAA0319 can degrade the brain's ability to process phonemes. In the current study, we used RNA interference (RNAi) to reduce expression of Kiaa0319 (the rat homolog of the human gene KIAA0319) and evaluate the effect in a rat model of phoneme discrimination. Speech discrimination thresholds in normal rats are nearly identical to human thresholds. We recorded multiunit neural responses to isolated speech sounds in primary auditory cortex (A1) of rats that received in utero RNAi of Kiaa0319. Reduced expression of Kiaa0319 increased the trial-by-trial variability of speech responses and reduced the neural discrimination ability of speech sounds. Intracellular recordings from affected neurons revealed that reduced expression of Kiaa0319 increased neural excitability and input resistance. These results provide the first evidence that decreased expression of the dyslexia-associated gene Kiaa0319 can alter cortical responses and impair phoneme processing in auditory cortex. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

A high-fat diet decreases GABA concentration in the frontal cortex and hippocampus of rats.

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Sandoval-Salazar, Cuauhtemoc; Ramírez-Emiliano, Joel; Trejo-Bahena, Aurora; Oviedo-Solís, Cecilia I; Solís-Ortiz, Martha Silvia

2016-02-29

It has been proposed that the γ-aminobutyric acid (GABA) plays a key role in the regulation of food intake and body weight by controlling the excitability, plasticity and the synchronization of neuronal activity in the frontal cortex (FC). It has been also proposed that the high-fat diet (HFD) could disturb the metabolism of glutamate and consequently the GABA levels, but the mechanism is not yet clearly understood. Therefore, the aim of this study was to investigate the effect of a HFD on the GABA levels in the FC and hippocampus of rats. The HFD significantly increased weight gain and blood glucose levels, whereas decreased the GABA levels in the FC and hippocampus compared with standard diet-fed rats. HFD decreases GABA levels in the FC and hippocampus of rat, which likely disrupts the GABAergic inhibitory processes, underlying feeding behavior.

Excessive endoplasmic reticulum stress and decreased neuroplasticity-associated proteins in prefrontal cortex of obese rats and the regulatory effects of aerobic exercise.

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Li, Feng; Liu, Bei Bei; Cai, Ming; Li, Jing Jing; Lou, Shu-Jie

2018-04-06

Studies have shown high fat diet induced obesity may cause cognition impairment and down-regulation of neuroplasticity-associated proteins, while aerobic exercise could improve that damage. Endoplasmic reticulum stress (ERS) has been reported to play a key role in regulating neuroplasticity-associated proteins expression, folding and post-translational modification in hippocampus of obese rodent models, however, the effects of ERS on neuroplasticity-associated proteins and possible underlying mechanisms in prefrontal cortex are not fully clear. In order to clarify changes of neuroplasticity-associated proteins and ERS in the prefrontal cortex of obese rats, male SD rats were fed on high fat diet for 8 weeks to establish the obese model. Then, 8 weeks of aerobic exercise treadmill intervention was arranged for the obese rats. Results showed that high fat diet induced obesity caused hyperlipidemia, and significantly promoted FATP1 expression in the prefrontal cortex, meanwhile, we found up-regulation of GRP78, p-PERK, p-eIF2α, caspase-12, CHOP, and Bax/Bcl-2, reflecting the activation of ERS and ERS-mediated apoptosis. Moreover, reduced BDNF and SYN was found in obese rats. However, FATP1, GRP78, p-PERK, p-eIF2α, caspase-12, CHOP, and Bax/Bcl-2 expressions were obviously reversed by aerobic exercise intervention. These results suggested that dietary obesity could induce Prefrontal ERS in SD rats and excessive ERS may play a critical role in decreasing the levels of neuroplasticity-associated proteins. Moreover, aerobic exercise could relieve ERS, thus promoted the expression of neuroplasticity-associated proteins. Copyright © 2018. Published by Elsevier Inc.

Du-Zhong (Eucommia ulmoides Oliv.) Cortex Extract Alleviates Lead Acetate-Induced Bone Loss in Rats.

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Qi, Shanshan; Zheng, Hongxing; Chen, Chen; Jiang, Hai

2018-05-09

The purpose of this study was to evaluate the protective effect of Du-Zhong cortex extract (DZCE) on lead acetate-induced bone loss in rats. Forty female Sprague-Dawley rats were randomly divided into four groups: group I (control) was provided with distilled water. Group II (PbAc) received 500 ppm lead acetate in drinking water for 60 days. Group III (PbAc+DZCE) received 500 ppm lead acetate in drinking water, and given intragastric DZCE (100 mg/kg body weight) for 60 days. Group IV (DZCE) was given intragastric DZCE (100 mg/kg body weight) for 60 days. The bone mineral density, serum biochemical markers, bone histomorphology, and bone marrow adipocyte parameters were analyzed using dual-energy X-ray absorptiometry, biochemistry, histomorphometry, and histopathology, respectively. The results showed that the lumbar spine and femur bone mineral density was significantly decreased in PbAc group compared with the control (P  0.05, vs. control and DZCE group). Serum calcium and serum phosphorus in the PbAc+DZCE group were greater than that in the PbAc group (P control group (P control, and DZCE groups (P > 0.05). Serum OPG and OPG/RANKL ration were significantly higher in the PbAc+DZCE group than that in the PbAc group (P control group, but those were restored in the PbAc+DZCE groups. The bone marrow adipocyte number, percent adipocyte volume per tissue volume (AV/TV), and mean adipocyte diameter were significantly increased in the PbAc group compared to the control (P control group were not significant. The results above indicate that the Du-Zhong cortex extract has protective effects on both stimulation of bone formation and suppression of bone resorption in lead-exposed rats, therefore, Du-Zhong cortex extract has the potential to prevent or treat osteoporosis resulting from lead expose.

Boundary Conditions for the Maintenance of Memory by PKM[zeta] in Neocortex

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Shema, Reul; Hazvi, Shoshi; Sacktor, Todd C.; Dudai, Yadin

2009-01-01

We report here that ZIP, a selective inhibitor of the atypical protein kinase C isoform PKM[zeta], abolishes very long-term conditioned taste aversion (CTA) associations in the insular cortex of the behaving rat, at least 3 mo after encoding. The effect of ZIP is not replicated by a general serine/threonine protein kinase inhibitor that is…

Dissociable effects of cingulate and medial frontal cortex lesions on stimulus-reward learning using a novel Pavlovian autoshaping procedure for the rat: implications for the neurobiology of emotion.

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Bussey, T J; Everitt, B J; Robbins, T W

1997-10-01

The effects of quinolinic acid-induced lesions of the anterior cingulate, posterior cingulate, and medial frontal cortices on stimulus-reward learning were investigated with a novel Pavlovian autoshaping procedure in an apparatus allowing the automated presentation of computer-graphic stimuli to rats (T. J. Bussey, J. L. Muir, & T. W. Robbins, 1994). White vertical rectangles were presented on the left or the right of a computer screen. One of these conditioned stimuli (the CS+) was always followed by the presentation of a sucrose pellet; the other, the CS-, was never followed by reward. With training, rats came to approach the CS+ more often than the CS-. Anterior cingulate cortex-lesioned rats failed to demonstrate normal discriminated approach, making significantly more approaches to the CS- than did sham-operated controls. Medial frontal cortex-lesioned rats acquired the task normally but had longer overall approach latencies. Posterior cingulate cortex lesions did not affect acquisition.

Two whisker motor areas in the rat cortex: evidence from thalamocortical connections.

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Mohammed, Hisham; Jain, Neeraj

2014-02-15

In primates, the motor cortex consists of at least seven different areas, which are involved in movement planning, coordination, initiation, and execution. However, for rats, only the primary motor cortex has been well described. A rostrally located second motor area has been proposed, but its extent, organization, and even definitive existence remain uncertain. Only a rostral forelimb area (RFA) has been definitively described, besides few reports of a rostral hindlimb area. We have previously proposed existence of a second whisker area, which we termed the rostral whisker area (RWA), based on its differential response to intracortical microstimulation compared with the caudal whisker area (CWA) in animals under deep anesthesia (Tandon et al. [2008] Eur J Neurosci 27:228). To establish that RWA is distinct from the caudally contiguous CWA, we determined sources of thalamic inputs to the two proposed whisker areas. Sources of inputs to RFA, caudal forelimb area (CFA), and caudal hindlimb region were determined for comparison. The results show that RWA and CWA can be distinguished based on differences in their thalamic inputs. RWA receives major projections from mediodorsal and ventromedial nuclei, whereas the major projections to CWA are from the ventral anterior, ventrolateral, and posterior nuclei. Moreover, the thalamic nuclei that provide major inputs to RWA are the same as for RFA, and the nuclei projecting to CWA are same as for CFA. The results suggest that rats have a second rostrally located motor area with RWA and RFA as its constituents. Copyright © 2013 Wiley Periodicals, Inc.

Electrocorticographic activity over sensorimotor cortex and motor function in awake behaving rats.

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Boulay, Chadwick B; Chen, Xiang Yang; Wolpaw, Jonathan R

2015-04-01

Sensorimotor cortex exerts both short-term and long-term control over the spinal reflex pathways that serve motor behaviors. Better understanding of this control could offer new possibilities for restoring function after central nervous system trauma or disease. We examined the impact of ongoing sensorimotor cortex (SMC) activity on the largely monosynaptic pathway of the H-reflex, the electrical analog of the spinal stretch reflex. In 41 awake adult rats, we measured soleus electromyographic (EMG) activity, the soleus H-reflex, and electrocorticographic activity over the contralateral SMC while rats were producing steady-state soleus EMG activity. Principal component analysis of electrocorticographic frequency spectra before H-reflex elicitation consistently revealed three frequency bands: μβ (5-30 Hz), low γ (γ1; 40-85 Hz), and high γ (γ2; 100-200 Hz). Ongoing (i.e., background) soleus EMG amplitude correlated negatively with μβ power and positively with γ1 power. In contrast, H-reflex size correlated positively with μβ power and negatively with γ1 power, but only when background soleus EMG amplitude was included in the linear model. These results support the hypothesis that increased SMC activation (indicated by decrease in μβ power and/or increase in γ1 power) simultaneously potentiates the H-reflex by exciting spinal motoneurons and suppresses it by decreasing the efficacy of the afferent input. They may help guide the development of new rehabilitation methods and of brain-computer interfaces that use SMC activity as a substitute for lost or impaired motor outputs. Copyright © 2015 the American Physiological Society.

Effect of Prenatal Protein Malnutrition on Long-Term Potentiation and BDNF Protein Expression in the Rat Entorhinal Cortex after Neocortical and Hippocampal Tetanization

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Alejandro Hernández

2008-01-01

Full Text Available Reduction of the protein content from 25 to 8% casein in the diet of pregnant rats results in impaired neocortical long-term potentiation (LTP of the offspring together with lower visuospatial memory performance. The present study was aimed to investigate whether this type of maternal malnutrition could result in modification of plastic capabilities of the entorhinal cortex (EC in the adult progeny. Unlike normal eutrophic controls, 55–60-day-old prenatally malnourished rats were unable to develop LTP in the medial EC to tetanizing stimulation delivered to either the ipsilateral occipital cortex or the CA1 hippocampal region. Tetanizing stimulation of CA1 also failed to increase the concentration of brain-derived neurotrophic factor (BDNF in the EC of malnourished rats. Impaired capacity of the EC of prenatally malnourished rats to develop LTP and to increase BDNF levels during adulthood may be an important factor contributing to deficits in learning performance having adult prenatally malnourished animals.

Effect of prenatal protein malnutrition on long-term potentiation and BDNF protein expression in the rat entorhinal cortex after neocortical and hippocampal tetanization.

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Hernández, Alejandro; Burgos, Héctor; Mondaca, Mauricio; Barra, Rafael; Núñez, Héctor; Pérez, Hernán; Soto-Moyano, Rubén; Sierralta, Walter; Fernández, Victor; Olivares, Ricardo; Valladares, Luis

2008-01-01

Reduction of the protein content from 25 to 8% casein in the diet of pregnant rats results in impaired neocortical long-term potentiation (LTP) of the offspring together with lower visuospatial memory performance. The present study was aimed to investigate whether this type of maternal malnutrition could result in modification of plastic capabilities of the entorhinal cortex (EC) in the adult progeny. Unlike normal eutrophic controls, 55-60-day-old prenatally malnourished rats were unable to develop LTP in the medial EC to tetanizing stimulation delivered to either the ipsilateral occipital cortex or the CA1 hippocampal region. Tetanizing stimulation of CA1 also failed to increase the concentration of brain-derived neurotrophic factor (BDNF) in the EC of malnourished rats. Impaired capacity of the EC of prenatally malnourished rats to develop LTP and to increase BDNF levels during adulthood may be an important factor contributing to deficits in learning performance having adult prenatally malnourished animals.

Effect of β-endorphin on catecholamine levels in rat hypothalamus and cerebral cortex

International Nuclear Information System (INIS)

Slavnov, V.N.; Valueva, G.V.; Markov, V.V.; Luchitskii, E.V.

1986-01-01

The authors studied the effect of beta-endorphin on catecholamine concentrations in the hypothalmus and cerebral cortex in rats, as a contribution to the explanation of the mechanism of action of this peptide on certain pituitary trophic functions. Concentrations of dopamine, noradrenalin, and adrenalin were determined by a radioenzymatic method. A Mark 3 scintillation system was used for radiometric investigation of the samples. The results of these experiments indicate that beta-endorphin has a marked effect on brain catecholamine levels mainly in the hypothalamus

Effect of. beta. -endorphin on catecholamine levels in rat hypothalamus and cerebral cortex

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Slavnov, V.N.; Valueva, G.V.; Markov, V.V.; Luchitskii, E.V.

1986-10-01

The authors studied the effect of beta-endorphin on catecholamine concentrations in the hypothalmus and cerebral cortex in rats, as a contribution to the explanation of the mechanism of action of this peptide on certain pituitary trophic functions. Concentrations of dopamine, noradrenalin, and adrenalin were determined by a radioenzymatic method. A Mark 3 scintillation system was used for radiometric investigation of the samples. The results of these experiments indicate that beta-endorphin has a marked effect on brain catecholamine levels mainly in the hypothalamus.

[Effect of Electroacupuncture on Cerebro-cortex Caspase-3 Expression and Blood Lipid Levels in Hyperlipemia Rats with Cerebral Ischemia].

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Wang, Zhuo-Yu; Ma, Jia-Jia; Guan, Han-Yu; Tian, Yao; Ren, Xiu-Jun; Ma, Hui-Fang

2017-04-25

To observe the effect of electroacupuncture (EA) stimulation of "Fenglong" (ST 40), "Sanyinjiao" (SP 6) plus manual acupuncture (MA) stimulation of "Shuigou" (GV 26) and "Baihui" (GV 20) on Caspase-3 protein expression in the cerebral cortex of rats with hyperlipemia and cerebral ischemia(HL-CI),so as to reveal its mechanisms underlying improvement of HL-CI. Forty-five rats were randomly divided into normal control,sham operation,model,EA group I(EA+MA was given for 14 days, i.e., 7 days before CI, and 7 days more after HL-CI)and EA group Ⅱ (EA+MA was given for only 7 days after HL-CI),with 9 rats being in each group. The HL-CI model was established by feeding the animals with high fat forage for 6 weeks and then making an occlusion of the unilateral middle cerebral artery by regional application of quantitative paper adsorbing 50% FeCl 3 solution (10 μL). Rats of the sham operation group were treated with the same procedures only without application of FeCl 3 solution. For rats of the EA group I,EA (1-3 mA, 2 Hz/100 Hz) was applied to bilateral acupoints SP 6 and ST 40 (for 20 min),and MA stimulation applied to GV 26 and GV 20. EA was conducted once daily for 7 days after 6 weeks' high fat fo-rage feeding, and EA+MA intervention was conducted once daily for 7 days after CI modeling. For rats in the EA group Ⅱ, EA+MA was applied to the same 4 acupoints once a day for 7 days only after CI modeling. The neurological impairment was assessed by Zea Longa's scoring. The blood sample was taken from the abdominal aorta for measuring the contents of serum cholesterol (CHO),triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C). Pathological changes of the cerebral cortex were observed after H.E. staining, and the expression of cerebro-cortex Caspase-3 was analyzed by immunohistochemistry. Following modeling,the neurological score,CHO, TG and LDL-C contents, and the number of Caspase-3 positive cells as well

Altered neuronal activities in the motor cortex with impaired motor performance in adult rats observed after infusion of cerebrospinal fluid from amyotrophic lateral sclerosis patients.

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Sankaranarayani, R; Nalini, A; Rao Laxmi, T; Raju, T R

2010-01-05

Although definite evidences are available to state that, neuronal activity is a prime determinant of animal behavior, the specific relationship between local field potentials of the motor cortex after intervention with CSF from human patients and animal behavior have remained opaque. The present study has investigated whether cerebrospinal fluid from sporadic amyotrophic lateral sclerosis (sALS) patients could disrupt neuronal activity of the motor cortex, which could be associated with disturbances in the motor performance of adult rats. CSF from ALS patients (ALS-CSF) was infused into the lateral ventricle of Wistar rats. After 24h, the impact of ALS-CSF on the local field potentials (LFPs) of the motor cortex and on the motor behavior of animals were examined. The results indicate that ALS-CSF produced a bivariate distribution on the relative power values of the LFPs of the motor cortex 24h following infusion. However, the behavioral results did not show bimodality, instead showed consistent decrease in motor performance: on rotarod and grip strength meter. The neuronal activity of the motor cortex negatively correlated with the duration of ALS symptoms at the time of lumbar puncture. Although the effect of ALS-CSF was more pronounced at 24h following infusion, the changes observed in LFPs and motor performance appeared to revert to baseline values at later time points of testing. In the current study, we have shown that, ALS-CSF has the potential to perturb neuronal activity of the rat motor cortex which was associated with poor performance on motor function tests.

Metabolic activity in striate and extrastriate cortex in the hooded rat: contralateral and ipsilateral eye input

International Nuclear Information System (INIS)

Thurlow, G.A.; Cooper, R.M.

1988-01-01

The extent of changes in glucose metabolism resulting from ipsilateral and contralateral eye activity in the posterior cortex of the hooded rat was demonstrated by means of the C-14 2-deoxyglucose autoradiographic technique. By stimulating one eye with square wave gratings and eliminating efferent activation from the other by means of enucleation or intraocular TTX injection, differences between ipsilaterally and contralaterally based visual activity in the two hemispheres were maximized. Carbon-14 levels in layer IV of autoradiographs of coronal sections were measured and combined across sections to form right and left matrices of posterior cortex metabolic activity. A difference matrix, formed by subtracting the metabolic activity matrix of cortex contralateral to the stimulated eye from the ipsilateral depressed matrix, emphasized those parts of the visual cortex that received monocular visual input. The demarcation of striate cortex by means of cholinesterase stain and the examination of autoradiographs from sections cut tangential to the cortical surface aided in the interpretation of the difference matrices. In striate cortex, differences were maximal in the medial monocular portion, and the lateral or binocular portion was shown to be divided metabolically into a far lateral contralaterally dominant strip along the cortical representation of the vertical meridian, and a more medial region of patches of more or less contralaterally dominant binocular input. Lateral peristriate differences were less than those of striate cortex, and regions of greater and lesser monocular input could be distinguished. We did not detect differences between the two hemispheres in either anterior or medial peristriate areas

Morphological and functional manifestations of rat adrenal-cortex response to sodium bromide administration under hypodynamic stress

Science.gov (United States)

Kirichek, L. T.; Zholudeva, V. I.

1979-01-01

Functional and morphological manifestations of adrenal cortex response to hypodynamia (2-hr immobilization on an operating table) under the influence of bromine preparations were studied. The sodium bromide was administered intraperitoneally in 100, 250, and 500 mg/kg doses once and repeatedly during ten days. The adrenal gland was evaluated functionally by ascorbic acid and cholesterol content and morphologically by coloring it with hematoxylin-eosin and Sudans for lipid revealing at freezing. Results are displayed in two tables and microphotographs. They are summarized as follows: the bromine weakens the functional state of the adrenal cortex in intact rats, causing changes similar to those under stress. During immobilization combined with preliminary bromine administration, a less pronounced stress reaction is noticeable.

Estimation of electrode location in a rat motor cortex by laminar analysis of electrophysiology and intracortical electrical stimulation

Science.gov (United States)

Yazdan-Shahmorad, A.; Lehmkuhle, M. J.; Gage, G. J.; Marzullo, T. C.; Parikh, H.; Miriani, R. M.; Kipke, D. R.

2011-08-01

While the development of microelectrode arrays has enabled access to disparate regions of a cortex for neurorehabilitation, neuroprosthetic and basic neuroscience research, accurate interpretation of the signals and manipulation of the cortical neurons depend upon the anatomical placement of the electrode arrays in a layered cortex. Toward this end, this report compares two in vivo methods for identifying the placement of electrodes in a linear array spaced 100 µm apart based on in situ laminar analysis of (1) ketamine-xylazine-induced field potential oscillations in a rat motor cortex and (2) an intracortical electrical stimulation-induced movement threshold. The first method is based on finding the polarity reversal in laminar oscillations which is reported to appear at the transition between layers IV and V in laminar 'high voltage spindles' of the rat cortical column. Analysis of histological images in our dataset indicates that polarity reversal is detected 150.1 ± 104.2 µm below the start of layer V. The second method compares the intracortical microstimulation currents that elicit a physical movement for anodic versus cathodic stimulation. It is based on the hypothesis that neural elements perpendicular to the electrode surface are preferentially excited by anodic stimulation while cathodic stimulation excites those with a direction component parallel to its surface. With this method, we expect to see a change in the stimulation currents that elicits a movement at the beginning of layer V when comparing anodic versus cathodic stimulation as the upper cortical layers contain neuronal structures that are primarily parallel to the cortical surface and lower layers contain structures that are primarily perpendicular. Using this method, there was a 78.7 ± 68 µm offset in the estimate of the depth of the start of layer V. The polarity reversal method estimates the beginning of layer V within ±90 µm with 95% confidence and the intracortical stimulation

A high-fat diet decreases GABA concentration in the frontal cortex and hippocampus of rats

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Cuauhtemoc Sandoval-Salazar

Full Text Available BACKGROUND: It has been proposed that the γ-aminobutyric acid (GABA plays a key role in the regulation of food intake and body weight by controlling the excitability, plasticity and the synchronization of neuronal activity in the frontal cortex (FC. It has been also proposed that the high-fat diet (HFD could disturb the metabolism of glutamate and consequently the GABA levels, but the mechanism is not yet clearly understood. Therefore, the aim of this study was to investigate the effect of a HFD on the GABA levels in the FC and hippocampus of rats RESULTS: The HFD significantly increased weight gain and blood glucose levels, whereas decreased the GABA levels in the FC and hippocampus compared with standard diet-fed rats CONCLUSIONS: HFD decreases GABA levels in the FC and hippocampus of rat, which likely disrupts the GABAergic inhibitory processes, underlying feeding behavior.

Neural coding of reward magnitude in the orbitofrontal cortex of the rat during a five-odor olfactory discrimination task.

NARCIS (Netherlands)

van Duuren, E.; Escamez, F.A.N.; Joosten, R.N.J.M.A.; Visser, R.; Mulder, A.B.; Pennartz, C.M.A.

2007-01-01

The orbitofrontal cortex (OBFc) has been suggested to code the motivational value of environmental stimuli and to use this information for the flexible guidance of goal-directed behavior. To examine whether information regarding reward prediction is quantitatively represented in the rat OBFc, neural

Cannabis agonist injection effect on the coupling architecture in cortex of WAG/Rij rats during absence seizures

Science.gov (United States)

Sysoeva, Marina V.; Kuznetsova, Galina D.; van Rijn, Clementina M.; Sysoev, Ilya V.

2016-04-01

WAG/Rij rats are well known genetic model of absence epilepsy, which is traditionally considered as a nonconvulsive generalised epilepsy of unknown aetiology. In current study the effect of (R)-(+)-WIN 55,212-2 (cannabis agonist) injection on the coupling between different parts of cortex was studied on 27 male 8 month old rats using local field potentials. Recently developed non-linear adapted Granger causality approach was used as a primary method. It was shown that first 2 hours after the injection the coupling between most channel pairs rises in comparison with the spontaneous activity, whilst long after the injection (2-6 hours) it drops down. The coupling increase corresponds to the mentioned before treatment effect, when the number and the longitude of seizures significantly decreases. However the subsequent decrease of the coupling in the cortex is accompanied by the dramatic increase of the longitude and the number of seizures. This assumes the hypothesis that a relatively higher coupling in the cortical network can prevent the seizure propagation and generalisation.

Effect of camphor essential oil on rat cerebral cortex activity as manifested by fractal dimension changes

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Grbić G.

2008-01-01

Full Text Available The aim of our study was to investigate the effect of camphor essential oil on rat cerebral cortex activity by fractal analysis. Fractal dimension (FD values of the parietal electrocortical activity were calculated before and after intra-peritoneal administration of camphor essential oil (450-675 μl/kg in anesthetized rats. Camphor oil induced seizure-like activity with single and multiple spiking of high amplitudes in the parietal electrocorticogram and occasional clonic limb convulsions. The FD values of cortical activity after camphor oil administration increased on the average. Only FD values of cortical ECoG sequences were lower than those before camphor oil administration.

Pattern of chondroitin sulfate proteoglycan expression after ablation of the sensorimotor cortex of the neonatal and adult rat brain

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Dacić Sanja

2008-01-01

Full Text Available The central nervous system has a limited capacity for self-repair after damage. However, the neonatal brain has agreater capacity for recovery than the adult brain. These differences in the regenerative capability depend on local environmental factors and the maturational stage of growing axons. Among molecules which have both growth-promoting and growth-inhibiting activities is the heterogeneous class of chondroitin sulfate proteoglycans (CSPGs. In this paper, we investigated the chondroitin-4 and chondroitin-6 sulfate proteoglycan expression profile after left sensorimotor cortex ablation of the neonatal and adult rat brain. Immunohistochemical analysis revealed that compared to the normal uninjured cortex, lesion provoked up regulation of CSPGs showing a different pattern of expression in the neonatal vs. the adult brain. Punctuate and membrane-bound labeling was predominate after neonatal lesion, where as heavy deposition of staining in the extracellular matrix was observed after adult lesion. Heavy deposition of CSPG immunoreactivity around the lesionsite in adult rats, in contrast to a less CSPG-rich environment in neonatal rats, indicated that enhancement of the recovery process after neonatal injury is due to amore permissive environment.

Prenatal Protein Malnutrition Decreases KCNJ3 and 2DG Activity in Rat Prefrontal Cortex

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Amaral, A.C.; Jakovcevski, M.; McGaughy, J.A.; Calderwood, S.K.; Mokler, D.J.; Rushmore, R.J.; Galler, J.R.; Akbarian, S.A.; Rosene, D.L.

2014-01-01

Prenatal protein malnutrition (PPM) in rats causes enduring changes in brain and behavior including increased cognitive rigidity and decreased inhibitory control. A preliminary gene microarray screen of PPM rat prefrontal cortex (PFC) identified alterations in KCNJ3 (GIRK1/Kir3.1), a gene important for regulating neuronal excitability. Follow-up with polymerase chain reaction and Western blot showed decreased KCNJ3 expression in PFC, but not hippocampus or brainstem. To verify localization of the effect to the PFC, baseline regional brain activity was assessed with 14C-2-deoxyglucose. Results showed decreased activation in PFC but not hippocampus. Together these findings point to the unique vulnerability of the PFC to the nutritional insult during early brain development, with enduring effects in adulthood on KCNJ3 expression and baseline metabolic activity. PMID:25446346

Systemic blockade of dopamine D2-like receptors increases high-voltage spindles in the globus pallidus and motor cortex of freely moving rats.

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Chen Yang

Full Text Available High-voltage spindles (HVSs have been reported to appear spontaneously and widely in the cortical-basal ganglia networks of rats. Our previous study showed that dopamine depletion can significantly increase the power and coherence of HVSs in the globus pallidus (GP and motor cortex of freely moving rats. However, it is unclear whether dopamine regulates HVS activity by acting on dopamine D₁-like receptors or D₂-like receptors. We employed local-field potential and electrocorticogram methods to simultaneously record the oscillatory activities in the GP and primary motor cortex (M1 in freely moving rats following systemic administration of dopamine receptor antagonists or saline. The results showed that the dopamine D₂-like receptor antagonists, raclopride and haloperidol, significantly increased the number and duration of HVSs, and the relative power associated with HVS activity in the GP and M1 cortex. Coherence values for HVS activity between the GP and M1 cortex area were also significantly increased by dopamine D₂-like receptor antagonists. On the contrary, the selective dopamine D₁-like receptor antagonist, SCH23390, had no significant effect on the number, duration, or relative power of HVSs, or HVS-related coherence between M1 and GP. In conclusion, dopamine D₂-like receptors, but not D₁-like receptors, were involved in HVS regulation. This supports the important role of dopamine D₂-like receptors in the regulation of HVSs. An siRNA knock-down experiment on the striatum confirmed our conclusion.

Systemic blockade of dopamine D2-like receptors increases high-voltage spindles in the globus pallidus and motor cortex of freely moving rats.

Science.gov (United States)

Yang, Chen; Ge, Shun-Nan; Zhang, Jia-Rui; Chen, Lei; Yan, Zhi-Qiang; Heng, Li-Jun; Zhao, Tian-Zhi; Li, Wei-Xin; Jia, Dong; Zhu, Jun-Ling; Gao, Guo-Dong

2013-01-01

High-voltage spindles (HVSs) have been reported to appear spontaneously and widely in the cortical-basal ganglia networks of rats. Our previous study showed that dopamine depletion can significantly increase the power and coherence of HVSs in the globus pallidus (GP) and motor cortex of freely moving rats. However, it is unclear whether dopamine regulates HVS activity by acting on dopamine D₁-like receptors or D₂-like receptors. We employed local-field potential and electrocorticogram methods to simultaneously record the oscillatory activities in the GP and primary motor cortex (M1) in freely moving rats following systemic administration of dopamine receptor antagonists or saline. The results showed that the dopamine D₂-like receptor antagonists, raclopride and haloperidol, significantly increased the number and duration of HVSs, and the relative power associated with HVS activity in the GP and M1 cortex. Coherence values for HVS activity between the GP and M1 cortex area were also significantly increased by dopamine D₂-like receptor antagonists. On the contrary, the selective dopamine D₁-like receptor antagonist, SCH23390, had no significant effect on the number, duration, or relative power of HVSs, or HVS-related coherence between M1 and GP. In conclusion, dopamine D₂-like receptors, but not D₁-like receptors, were involved in HVS regulation. This supports the important role of dopamine D₂-like receptors in the regulation of HVSs. An siRNA knock-down experiment on the striatum confirmed our conclusion.

Effects of Cortical Spreading Depression on Synaptic Activity, Blood Flow and Oxygen Consumption in Rat Cerebral Cortex

DEFF Research Database (Denmark)

Hansen, Henning Piilgaard

2010-01-01

As the title of this thesis indicates I have during my PhD studied the effects of cortical spreading depression (CSD) on synaptic activity, blood flow and oxygen consumption in rat cerebral cortex. This was performed in vivo using an open cranial window approach in anesthetized rats. I applied...... parameters of the whisker/infraorbital nerve etwork (IO) targeting the same cortical area. We tested the hypothesis that the relation between increases in CBF and CMRO2 evoked by stimulation and synaptic activity differed for the two activated networks and that activation of two distinct networks activate...

Proteomic analysis of rat cerebral cortex following subchronic acrolein toxicity

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Rashedinia, Marzieh; Lari, Parisa [Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad (Iran, Islamic Republic of); Abnous, Khalil, E-mail: Abnouskh@mums.ac.r [Pharmaceutical Research Center, Department of Medicinal Chemistry, Mashhad University of Medical Sciences, Mashhad (Iran, Islamic Republic of); Hosseinzadeh, Hossein, E-mail: Hosseinzadehh@mums.ac.ir [Pharmaceutical Research Center, Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad (Iran, Islamic Republic of)

2013-10-01

Acrolein, a member of reactive α,β-unsaturated aldehydes, is a major environmental pollutant. Acrolein is also produced endogenously as a toxic by-product of lipid peroxidation. Because of high reactivity, acrolein may mediate oxidative damages to cells and tissues. It has been shown to be involved in a wide variety of pathological states including pulmonary, atherosclerosis and neurodegenerative diseases. In this study we employed proteomics approach to investigate the effects of subchronic oral exposures to 3 mg/kg of acrolein on protein expression profile in the brain of rats. Moreover effects of acrolein on malondialdehyde (MDA) levels and reduced glutathione (GSH) content were investigated. Our results revealed that treatment with acrolein changed levels of several proteins in diverse physiological process including energy metabolism, cell communication and transport, response to stimulus and metabolic process. Interestingly, several differentially over-expressed proteins, including β-synuclein, enolase and calcineurin, are known to be associated with human neurodegenerative diseases. Changes in the levels of some proteins were confirmed by Western blot. Moreover, acrolein increases the level of MDA, as a lipid peroxidation biomarker and decreased GSH concentrations, as a non-enzyme antioxidant in the brain of acrolein treated rats. These findings suggested that acrolein induces the oxidative stress and lipid peroxidation in the brain, and so that may contribute to the pathophysiology of neurological disorders. - Highlights: • Acrolein intoxication increased lipid peroxidation and deplete GSH in rat brain. • Effect of acrolein on protein levels of cerebral cortex was analyzed by 2DE-PAGE. • Levels of a number of proteins with different biological functions were increased.

Proteomic analysis of rat cerebral cortex following subchronic acrolein toxicity

International Nuclear Information System (INIS)

Rashedinia, Marzieh; Lari, Parisa; Abnous, Khalil; Hosseinzadeh, Hossein

2013-01-01

Acrolein, a member of reactive α,β-unsaturated aldehydes, is a major environmental pollutant. Acrolein is also produced endogenously as a toxic by-product of lipid peroxidation. Because of high reactivity, acrolein may mediate oxidative damages to cells and tissues. It has been shown to be involved in a wide variety of pathological states including pulmonary, atherosclerosis and neurodegenerative diseases. In this study we employed proteomics approach to investigate the effects of subchronic oral exposures to 3 mg/kg of acrolein on protein expression profile in the brain of rats. Moreover effects of acrolein on malondialdehyde (MDA) levels and reduced glutathione (GSH) content were investigated. Our results revealed that treatment with acrolein changed levels of several proteins in diverse physiological process including energy metabolism, cell communication and transport, response to stimulus and metabolic process. Interestingly, several differentially over-expressed proteins, including β-synuclein, enolase and calcineurin, are known to be associated with human neurodegenerative diseases. Changes in the levels of some proteins were confirmed by Western blot. Moreover, acrolein increases the level of MDA, as a lipid peroxidation biomarker and decreased GSH concentrations, as a non-enzyme antioxidant in the brain of acrolein treated rats. These findings suggested that acrolein induces the oxidative stress and lipid peroxidation in the brain, and so that may contribute to the pathophysiology of neurological disorders. - Highlights: • Acrolein intoxication increased lipid peroxidation and deplete GSH in rat brain. • Effect of acrolein on protein levels of cerebral cortex was analyzed by 2DE-PAGE. • Levels of a number of proteins with different biological functions were increased

Hyperspectral optical tomography of intrinsic signals in the rat cortex

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Konecky, Soren D.; Wilson, Robert H.; Hagen, Nathan; Mazhar, Amaan; Tkaczyk, Tomasz S.; Frostig, Ron D.; Tromberg, Bruce J.

2015-01-01

Abstract. We introduce a tomographic approach for three-dimensional imaging of evoked hemodynamic activity, using broadband illumination and diffuse optical tomography (DOT) image reconstruction. Changes in diffuse reflectance in the rat somatosensory cortex due to stimulation of a single whisker were imaged at a frame rate of 5 Hz using a hyperspectral image mapping spectrometer. In each frame, images in 38 wavelength bands from 484 to 652 nm were acquired simultaneously. For data analysis, we developed a hyperspectral DOT algorithm that used the Rytov approximation to quantify changes in tissue concentration of oxyhemoglobin (ctHbO2) and deoxyhemoglobin (ctHb) in three dimensions. Using this algorithm, the maximum changes in ctHbO2 and ctHb were found to occur at 0.29±0.02 and 0.66±0.04  mm beneath the surface of the cortex, respectively. Rytov tomographic reconstructions revealed maximal spatially localized increases and decreases in ctHbO2 and ctHb of 321±53 and 555±96  nM, respectively, with these maximum changes occurring at 4±0.2  s poststimulus. The localized optical signals from the Rytov approximation were greater than those from modified Beer–Lambert, likely due in part to the inability of planar reflectance to account for partial volume effects. PMID:26835483

Structural and Ultrastructural Analysis of Cerebral Cortex, Cerebellum, and Hypothalamus from Diabetic Rats

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Juan P. Hernández-Fonseca

2009-01-01

Full Text Available Autonomic and peripheral neuropathies are well-described complications in diabetes. Diabetes mellitus is also associated to central nervous system damage. This little-known complication is characterized by impairment of brain functions and electrophysiological changes associated with neurochemical and structural abnormalities. The purpose of this study was to investigate brain structural and ultrastructural changes in rats with streptozotocin-induced diabetes. Cerebral cortex, hypothalamus, and cerebellum were obtained from controls and 8 weeks diabetic rats. Light and electron microscope studies showed degenerative changes of neurons and glia, perivascular and mitochondrial swelling, disarrangement of myelin sheath, increased area of myelinated axons, presynaptic vesicle dispersion in swollen axonal boutoms, fragmentation of neurofilaments, and oligodendrocyte abnormalities. In addition, depressive mood was observed in diabetic animals. The brain morphological alterations observed in diabetic animals could be related to brain pathologic process leading to abnormal function, cellular death, and depressive behavioral.

Effects of sleep deprivation on extracellular serotonin in hippocampus and frontal cortex of the rat

OpenAIRE

Bjorvatn, B; Grønli, J; Hamre, F; Sørensen, E; Fiske, E; Bjorkum, Alvhild Alette; Portas, CM; Ursin, R

2002-01-01

Sleep deprivation improves the mood of depressed patients, but the exact mechanism behind this effect is unclear. An enhancement of serotonergic neurotransmission has been suggested. In this study, we used in vivo microdialysis to monitor extracellular serotonin in the hippocampus and the frontal cortex of rats during an 8 h sleep deprivation period. These brain regions were selected since both have been implicated in depression. The behavioral state of the animal was continuously monitored b...

Bidirectional Modulation of Intrinsic Excitability in Rat Prelimbic Cortex Neuronal Ensembles and Non-Ensembles after Operant Learning.

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Whitaker, Leslie R; Warren, Brandon L; Venniro, Marco; Harte, Tyler C; McPherson, Kylie B; Beidel, Jennifer; Bossert, Jennifer M; Shaham, Yavin; Bonci, Antonello; Hope, Bruce T

2017-09-06

Learned associations between environmental stimuli and rewards drive goal-directed learning and motivated behavior. These memories are thought to be encoded by alterations within specific patterns of sparsely distributed neurons called neuronal ensembles that are activated selectively by reward-predictive stimuli. Here, we use the Fos promoter to identify strongly activated neuronal ensembles in rat prelimbic cortex (PLC) and assess altered intrinsic excitability after 10 d of operant food self-administration training (1 h/d). First, we used the Daun02 inactivation procedure in male FosLacZ-transgenic rats to ablate selectively Fos-expressing PLC neurons that were active during operant food self-administration. Selective ablation of these neurons decreased food seeking. We then used male FosGFP-transgenic rats to assess selective alterations of intrinsic excitability in Fos-expressing neuronal ensembles (FosGFP + ) that were activated during food self-administration and compared these with alterations in less activated non-ensemble neurons (FosGFP - ). Using whole-cell recordings of layer V pyramidal neurons in an ex vivo brain slice preparation, we found that operant self-administration increased excitability of FosGFP + neurons and decreased excitability of FosGFP - neurons. Increased excitability of FosGFP + neurons was driven by increased steady-state input resistance. Decreased excitability of FosGFP - neurons was driven by increased contribution of small-conductance calcium-activated potassium (SK) channels. Injections of the specific SK channel antagonist apamin into PLC increased Fos expression but had no effect on food seeking. Overall, operant learning increased intrinsic excitability of PLC Fos-expressing neuronal ensembles that play a role in food seeking but decreased intrinsic excitability of Fos - non-ensembles. SIGNIFICANCE STATEMENT Prefrontal cortex activity plays a critical role in operant learning, but the underlying cellular mechanisms are

Body size evolution in insular speckled rattlesnakes (Viperidae: Crotalus mitchellii.

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Jesse M Meik

2010-03-01

Full Text Available Speckled rattlesnakes (Crotalus mitchellii inhabit multiple islands off the coast of Baja California, Mexico. Two of the 14 known insular populations have been recognized as subspecies based primarily on body size divergence from putative mainland ancestral populations; however, a survey of body size variation from other islands occupied by these snakes has not been previously reported. We examined body size variation between island and mainland speckled rattlesnakes, and the relationship between body size and various island physical variables among 12 island populations. We also examined relative head size among giant, dwarfed, and mainland speckled rattlesnakes to determine whether allometric differences conformed to predictions of gape size (and indirectly body size evolving in response to shifts in prey size.Insular speckled rattlesnakes show considerable variation in body size when compared to mainland source subspecies. In addition to previously known instances of gigantism on Angel de la Guarda and dwarfism on El Muerto, various degrees of body size decrease have occurred frequently in this taxon, with dwarfed rattlesnakes occurring mostly on small, recently isolated, land-bridge islands. Regression models using the Akaike information criterion (AIC showed that mean SVL of insular populations was most strongly correlated with island area, suggesting the influence of selection for different body size optima for islands of different size. Allometric differences in head size of giant and dwarf rattlesnakes revealed patterns consistent with shifts to larger and smaller prey, respectively.Our data provide the first example of a clear relationship between body size and island area in a squamate reptile species; among vertebrates this pattern has been previously documented in few insular mammals. This finding suggests that selection for body size is influenced by changes in community dynamics that are related to graded differences in area over

Effects of L-arginine and Nω-nitro-L-arginine methylester on learning and memory and α7 nAChR expression in the prefrontal cortex and hippocampus of rats

Institute of Scientific and Technical Information of China (English)

Xiao-Ming Wei; Wei Yang; Li-Xia Liu; Wen-Xiu Qi

2013-01-01

Nitric oxide (NO) is a novel type of neurotransmitter that is closely associated with synaptic plasticity,learning and memory.In the present study,we assessed the effects of L-arginine and Nω-nitro-L-arginine methylester (L-NAME,a nitric oxide synthase inhibitor) on learning and memory.Rats were assigned to three groups receiving intracerebroventricular injections of L-Arg (the NO precursor),L-NAME,or 0.9％ NaCI (control),once daily for seven consecutive days.Twelve hours after the last injection,they underwent an electric shock-paired Y maze test.Twenty-four hours later,the rats' memory of the safe illuminated arm was tested.After that,the levels of NO and α7 nicotinic acetylcholine receptor (α7 nAChR) in the prefrontal cortex and hippocampus were assessed using an NO assay kit,and immunohistochemistry and Western blots,respectively.We found that,compared to controls,L-Arg-treated rats received fewer foot shocks and made fewer errors to reach the learning criterion,and made fewer errors during the memory-testing session.In contrast,L-NAME-treated rats received more foot shocks and made more errors than controls to reach the learning criterion,and made more errors during the memory-testing session.In parallel,NO content in the prefrontal cortex and hippocampus was higher in L-Arg-treated rats and lower in L-NAME rats,compared to controls.Similarly,α7 nAChR immunoreactivity and protein expression in the prefrontal cortex and hippocampus were higher in L-Arg-treated rats and lower in L-NAME rats,compared to controls.These results suggest that the modulation of NO content in the brain correlates with α7 nAChR distribution and expression in the prefrontal cortex and hippocampus,as well as with learning and memory performance in the Y-maze.

Pre-attentive, context-specific representation of fear memory in the auditory cortex of rat.

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Akihiro Funamizu

Full Text Available Neural representation in the auditory cortex is rapidly modulated by both top-down attention and bottom-up stimulus properties, in order to improve perception in a given context. Learning-induced, pre-attentive, map plasticity has been also studied in the anesthetized cortex; however, little attention has been paid to rapid, context-dependent modulation. We hypothesize that context-specific learning leads to pre-attentively modulated, multiplex representation in the auditory cortex. Here, we investigate map plasticity in the auditory cortices of anesthetized rats conditioned in a context-dependent manner, such that a conditioned stimulus (CS of a 20-kHz tone and an unconditioned stimulus (US of a mild electrical shock were associated only under a noisy auditory context, but not in silence. After the conditioning, although no distinct plasticity was found in the tonotopic map, tone-evoked responses were more noise-resistive than pre-conditioning. Yet, the conditioned group showed a reduced spread of activation to each tone with noise, but not with silence, associated with a sharpening of frequency tuning. The encoding accuracy index of neurons showed that conditioning deteriorated the accuracy of tone-frequency representations in noisy condition at off-CS regions, but not at CS regions, suggesting that arbitrary tones around the frequency of the CS were more likely perceived as the CS in a specific context, where CS was associated with US. These results together demonstrate that learning-induced plasticity in the auditory cortex occurs in a context-dependent manner.

Pre-attentive, context-specific representation of fear memory in the auditory cortex of rat.

Science.gov (United States)

Funamizu, Akihiro; Kanzaki, Ryohei; Takahashi, Hirokazu

2013-01-01

Neural representation in the auditory cortex is rapidly modulated by both top-down attention and bottom-up stimulus properties, in order to improve perception in a given context. Learning-induced, pre-attentive, map plasticity has been also studied in the anesthetized cortex; however, little attention has been paid to rapid, context-dependent modulation. We hypothesize that context-specific learning leads to pre-attentively modulated, multiplex representation in the auditory cortex. Here, we investigate map plasticity in the auditory cortices of anesthetized rats conditioned in a context-dependent manner, such that a conditioned stimulus (CS) of a 20-kHz tone and an unconditioned stimulus (US) of a mild electrical shock were associated only under a noisy auditory context, but not in silence. After the conditioning, although no distinct plasticity was found in the tonotopic map, tone-evoked responses were more noise-resistive than pre-conditioning. Yet, the conditioned group showed a reduced spread of activation to each tone with noise, but not with silence, associated with a sharpening of frequency tuning. The encoding accuracy index of neurons showed that conditioning deteriorated the accuracy of tone-frequency representations in noisy condition at off-CS regions, but not at CS regions, suggesting that arbitrary tones around the frequency of the CS were more likely perceived as the CS in a specific context, where CS was associated with US. These results together demonstrate that learning-induced plasticity in the auditory cortex occurs in a context-dependent manner.

Altered Functional Connectivity of Insular Subregions in Alzheimer’s Disease

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Xingyun Liu

2018-04-01

Full Text Available Recent researches have demonstrated that the insula is the crucial hub of the human brain networks and most vulnerable region of Alzheimer’s disease (AD. However, little is known about the changes of functional connectivity of insular subregions in the AD patients. In this study, we collected resting-state functional magnetic resonance imaging (fMRI data including 32 AD patients and 38 healthy controls (HCs. By defining three subregions of insula, we mapped whole-brain resting-state functional connectivity (RSFC and identified several distinct RSFC patterns of the insular subregions: For positive connectivity, three cognitive-related RSFC patterns were identified within insula that suggest anterior-to-posterior functional subdivisions: (1 an dorsal anterior zone of the insula that exhibits RSFC with executive control network (ECN; (2 a ventral anterior zone of insula, exhibits functional connectivity with the salience network (SN; (3 a posterior zone along the insula exhibits functional connectivity with the sensorimotor network (SMN. In addition, we found significant negative connectivities between the each insular subregion and several special default mode network (DMN regions. Compared with controls, the AD patients demonstrated distinct disruption of positive RSFCs in the different network (ECN and SMN, suggesting the impairment of the functional integrity. There were no differences of the positive RSFCs in the SN between the two groups. On the other hand, several DMN regions showed increased negative RSFCs to the sub-region of insula in the AD patients, indicating compensatory plasticity. Furthermore, these abnormal insular subregions RSFCs are closely correlated with cognitive performances in the AD patients. Our findings suggested that different insular subregions presented distinct RSFC patterns with various functional networks, which are differently affected in the AD patients.

Insular Area energy vulnerability, Puerto Rico, US Virgin Islands. Technical Appendix 1

International Nuclear Information System (INIS)

Stern, M.; Willard, E.E.; Efferding, S.

1994-05-01

This report was prepared in response to Section 1406 of the Energy Policy Act of 1992 (P.L. 192-486). The Act directed the Department of Energy (DOE) to ''conduct a study of the implications of the unique vulnerabilities of the insular areas to an oil supply disruption,'' and to ''outline how the insular areas shall gain access to vital oil supplies during times of national emergency.'' The Act defines the insular areas to be the US Virgin Islands and Puerto Rico in the Caribbean, and Guam, American Samoa, the Commonwealth of the Northern Mariana Islands (CNMI), and Palau in the Pacific. This report is the analysis of Puerto Rico and the US Virgin Islands. In the study, ''unique vulnerabilities'' were defined as susceptibility to: (1) more frequent or more likely interruptions of oil supplies compared to the mainland, and/or (2) disproportionately larger or more likely economic losses in the event of an oil supply disruption. In order to asses unique vulnerabilities, the study examined in the insular areas' experience during past global disruptions of oil supplies and during local emergencies caused by natural disasters. The effects of several possible future global disruptions and local emergencies were also analyzed. Analyses were based on historical data, simulations using energy and economic models, and interviews with officials in the insular governments and the energy industry

Insular Area energy vulnerability, Puerto Rico, US Virgin Islands. Technical Appendix 1

Energy Technology Data Exchange (ETDEWEB)

Stern, M.; Willard, E.E.; Efferding, S. [Ensys Energy & Systems, Inc., Flemington, NJ (United States)

1994-05-01

This report was prepared in response to Section 1406 of the Energy Policy Act of 1992 (P.L. 192-486). The Act directed the Department of Energy (DOE) to ``conduct a study of the implications of the unique vulnerabilities of the insular areas to an oil supply disruption,`` and to ``outline how the insular areas shall gain access to vital oil supplies during times of national emergency.`` The Act defines the insular areas to be the US Virgin Islands and Puerto Rico in the Caribbean, and Guam, American Samoa, the Commonwealth of the Northern Mariana Islands (CNMI), and Palau in the Pacific. This report is the analysis of Puerto Rico and the US Virgin Islands. In the study, ``unique vulnerabilities`` were defined as susceptibility to: (1) more frequent or more likely interruptions of oil supplies compared to the mainland, and/or (2) disproportionately larger or more likely economic losses in the event of an oil supply disruption. In order to asses unique vulnerabilities, the study examined in the insular areas` experience during past global disruptions of oil supplies and during local emergencies caused by natural disasters. The effects of several possible future global disruptions and local emergencies were also analyzed. Analyses were based on historical data, simulations using energy and economic models, and interviews with officials in the insular governments and the energy industry.

Structural and functional changes in the somatosensory cortex in euthymic females with bipolar disorder.

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Minuzzi, Luciano; Syan, Sabrina K; Smith, Mara; Hall, Alexander; Hall, Geoffrey Bc; Frey, Benicio N

2017-12-01

Current evidence from neuroimaging data suggests possible dysfunction of the fronto-striatal-limbic circuits in individuals with bipolar disorder. Somatosensory cortical function has been implicated in emotional recognition, risk-taking and affective responses through sensory modalities. This study investigates anatomy and function of the somatosensory cortex in euthymic bipolar women. In total, 68 right-handed euthymic women (bipolar disorder = 32 and healthy controls = 36) between 16 and 45 years of age underwent high-resolution anatomical and functional magnetic resonance imaging during the mid-follicular menstrual phase. The somatosensory cortex was used as a seed region for resting-state functional connectivity analysis. Voxel-based morphometry was used to evaluate somatosensory cortical gray matter volume between groups. We found increased resting-state functional connectivity between the somatosensory cortex and insular cortex, inferior prefrontal gyrus and frontal orbital cortex in euthymic bipolar disorder subjects compared to healthy controls. Voxel-based morphometry analysis showed decreased gray matter in the left somatosensory cortex in the bipolar disorder group. Whole-brain voxel-based morphometry analysis controlled by age did not reveal any additional significant difference between groups. This study is the first to date to evaluate anatomy and function of the somatosensory cortex in a well-characterized sample of euthymic bipolar disorder females. Anatomical and functional changes in the somatosensory cortex in this population might contribute to the pathophysiology of bipolar disorder.

State-dependent spike and local field synchronization between motor cortex and substantia nigra in hemiparkinsonian rats.

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Brazhnik, Elena; Cruz, Ana V; Avila, Irene; Wahba, Marian I; Novikov, Nikolay; Ilieva, Neda M; McCoy, Alex J; Gerber, Colin; Walters, Judith R

2012-06-06

Excessive beta frequency oscillatory and synchronized activity has been reported in the basal ganglia of parkinsonian patients and animal models of the disease. To gain insight into processes underlying this activity, this study explores relationships between oscillatory activity in motor cortex and basal ganglia output in behaving rats after dopamine cell lesion. During inattentive rest, 7 d after lesion, increases in motor cortex-substantia nigra pars reticulata (SNpr) coherence emerged in the 8-25 Hz range, with significant increases in local field potential (LFP) power in SNpr but not motor cortex. In contrast, during treadmill walking, marked increases in both motor cortex and SNpr LFP power, as well as coherence, emerged in the 25-40 Hz band with a peak frequency at 30-35 Hz. Spike-triggered waveform averages showed that 77% of SNpr neurons, 77% of putative cortical interneurons, and 44% of putative pyramidal neurons were significantly phase-locked to the increased cortical LFP activity in the 25-40 Hz range. Although the mean lag between cortical and SNpr LFPs fluctuated around zero, SNpr neurons phase-locked to cortical LFP oscillations fired, on average, 17 ms after synchronized spiking in motor cortex. High coherence between LFP oscillations in cortex and SNpr supports the view that cortical activity facilitates entrainment and synchronization of activity in basal ganglia after loss of dopamine. However, the dramatic increases in cortical power and relative timing of phase-locked spiking in these areas suggest that additional processes help shape the frequency-specific tuning of the basal ganglia-thalamocortical network during ongoing motor activity.

Insular activation during reward anticipation reflects duration of illness in abstinent pathological gamblers

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Kosuke eTsurumi

2014-09-01

Full Text Available Pathological gambling (PG is a chronic mental disorder characterized by a difficulty restraining gambling behavior despite negative consequences. Although brain abnormalities in patients with substance use disorders are caused by repetitive drug use and recover partly with drug abstinence, the relationship between brain activity and duration of illness or abstinence of gambling behavior in PG patients remains unclear. Here, using functional magnetic resonance imaging, we compared the brain activity of 23 PG patients recruited from a treatment facility with 27 demographically-matched healthy control subjects during reward anticipation, and examined the correlations between brain activity and duration of illness or abstinence in PG patients. During reward anticipation, PG patients showed decreased activity compared to healthy controls in a broad range of the reward system regions, including the insula cortex. In PG patients, activation in the left insula showed a significant negative correlation with illness duration. Our findings suggest that insular activation during reward anticipation may serve as a marker of progression of pathological gambling.

Unilateral nasal obstruction affects motor representation development within the face primary motor cortex in growing rats.

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Abe, Yasunori; Kato, Chiho; Uchima Koecklin, Karin Harumi; Okihara, Hidemasa; Ishida, Takayoshi; Fujita, Koichi; Yabushita, Tadachika; Kokai, Satoshi; Ono, Takashi

2017-06-01

Postnatal growth is influenced by genetic and environmental factors. Nasal obstruction during growth alters the electromyographic activity of orofacial muscles. The facial primary motor area represents muscles of the tongue and jaw, which are essential in regulating orofacial motor functions, including chewing and jaw opening. This study aimed to evaluate the effect of chronic unilateral nasal obstruction during growth on the motor representations within the face primary motor cortex (M1). Seventy-two 6-day-old male Wistar rats were randomly divided into control ( n = 36) and experimental ( n = 36) groups. Rats in the experimental group underwent unilateral nasal obstruction after cauterization of the external nostril at 8 days of age. Intracortical microstimulation (ICMS) mapping was performed when the rats were 5, 7, 9, and 11 wk old in control and experimental groups ( n = 9 per group per time point). Repeated-measures multivariate ANOVA was used for intergroup and intragroup statistical comparisons. In the control and experimental groups, the total number of positive ICMS sites for the genioglossus and anterior digastric muscles was significantly higher at 5, 7, and 9 wk, but there was no significant difference between 9 and 11 wk of age. Moreover, the total number of positive ICMS sites was significantly smaller in the experimental group than in the control at each age. It is possible that nasal obstruction induced the initial changes in orofacial motor behavior in response to the altered respiratory pattern, which eventually contributed to face-M1 neuroplasticity. NEW & NOTEWORTHY Unilateral nasal obstruction in rats during growth periods induced changes in arterial oxygen saturation (SpO 2 ) and altered development of the motor representation within the face primary cortex. Unilateral nasal obstruction occurring during growth periods may greatly affect not only respiratory function but also craniofacial function in rats. Nasal obstruction should be treated

Upregulation of the dorsal raphe nucleus-prefrontal cortex serotonin system by chronic treatment with escitalopram in hyposerotonergic Wistar-Kyoto rats

NARCIS (Netherlands)

Yamada, Makiko; Kawahara, Yukie; Kaneko, Fumi; Kishikawa, Yuki; Sotogaku, Naoki; Poppinga, Wilfred J.; Folgering, Joost H. A.; Dremencov, Eliyahu; Kawahara, Hiroshi; Nishi, Akinori

Wistar-Kyoto (WKY) rats are sensitive to chronic stressors and exhibit depression-like behavior. Dorsal raphe nucleus (DRN) serotonin (5-HT) neurons projecting to the prefrontal cortex (PFC) comprise the important neurocircuitry underlying the pathophysiology of depression. To evaluate the DRN-PFC

Acute stress increases depolarization-evoked glutamate release in the rat prefrontal/frontal cortex: the dampening action of antidepressants.

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Laura Musazzi

2010-01-01

Full Text Available Behavioral stress is recognized as a main risk factor for neuropsychiatric diseases. Converging evidence suggested that acute stress is associated with increase of excitatory transmission in certain forebrain areas. Aim of this work was to investigate the mechanism whereby acute stress increases glutamate release, and if therapeutic drugs prevent the effect of stress on glutamate release.Rats were chronically treated with vehicle or drugs employed for therapy of mood/anxiety disorders (fluoxetine, desipramine, venlafaxine, agomelatine and then subjected to unpredictable footshock stress. Acute stress induced marked increase in depolarization-evoked release of glutamate from synaptosomes of prefrontal/frontal cortex in superfusion, and the chronic drug treatments prevented the increase of glutamate release. Stress induced rapid increase in the circulating levels of corticosterone in all rats (both vehicle- and drug-treated, and glutamate release increase was blocked by previous administration of selective antagonist of glucocorticoid receptor (RU 486. On the molecular level, stress induced accumulation of presynaptic SNARE complexes in synaptic membranes (both in vehicle- and drug-treated rats. Patch-clamp recordings of pyramidal neurons in the prefrontal cortex revealed that stress increased glutamatergic transmission through both pre- and postsynaptic mechanisms, and that antidepressants may normalize it by reducing release probability.Acute footshock stress up-regulated depolarization-evoked release of glutamate from synaptosomes of prefrontal/frontal cortex. Stress-induced increase of glutamate release was dependent on stimulation of glucocorticoid receptor by corticosterone. Because all drugs employed did not block either elevation of corticosterone or accumulation of SNARE complexes, the dampening action of the drugs on glutamate release must be downstream of these processes. This novel effect of antidepressants on the response to stress

Characterization of α2-adrenergic receptors in rat cerebral cortex

International Nuclear Information System (INIS)

Nasseri, A.

1987-01-01

The properties of 3 H-RX 781094 binding sites and the receptors inhibiting norepinephrine (NE) release and cyclic AMP accumulation in rat cerebral cortex were compared. 3 H-RX 781094, a new α 2 -adrenergic receptor antagonist radioligand, labelled a homogeneous population of binding sites at 37 0 C with the pharmacological specificity expected of α 2 -adrenergic receptors. Gpp(NH)p and NaCl decreased the potencies of agonists at 3 H-RX 781094 binding sites 3-22 fold. Antagonists blocked the inhibition of potassium-evoked tritium release from cortical slices preloaded with 3 H-NE by exogenous NE with potencies similar to those observed in competition for specific 3 H-RX 781094 binding sites. EEDQ, an irreversible α 2 -adrenergic receptors and determine whether there was a receptor reserve for the inhibition of tritium release

["Entero-insular axis" and regulation of blood sugar and insulin levels following oral glucose loading].

Science.gov (United States)

Kuznetsov, B G

1978-11-01

The mineral water Essentuki 17 administered per so with glucose exerted a modifying effect on the regulation of glycaemia and insulinaemia in intact rats. This effect undergoes a few phases of changing and disappears by the 30th day. Under conditions of this adaptation, the glycaemia regulation is somewhat worsening. After i.v. administration of glucose during this period the regulation of glycaemia and insulinaemia remains unaltered. This suggests that the mineral water exerts its biological effect, mainly, on the entero-insular axis system (Unger and Eisentraut, 1969) and that the modifying effect is due not to a concrete complex of the mineral water electrolytes but rather to the unspecific factor of "perturbation" in the enteral medium.

Complex neural codes in rat prelimbic cortex are stable across days on a spatial decision task

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Nathaniel J. Powell

2014-04-01

Full Text Available The rodent prelimbic cortex has been shown to play an important role in cognitive processing, and has been implicated in encoding many different parameters relevant to solving decision-making tasks. However, it is not known how the prelimbic cortex represents all these disparate variables, and if they are simultaneously represented when the task requires it. In order to investigate this question, we trained rats to run the Multiple-T Left Right Alternate (MT-LRA task and recorded multi-unit ensembles from their prelimbic regions. Significant populations of cells in the prelimbic cortex represented the strategy controlling reward receipt on a given lap, whether the animal chose to go right or left on a given lap, and whether the animal made a correct decision or an error on a given lap. These populations overlapped in the cells recorded, with several cells demonstrating differential firing to all three variables. The spatial and strategic firing patterns of individual prelimbic cells were highly conserved across several days of running this task, indicating that each cell encoded the same information across days.

Cerebral Oxygenation of the Cortex and Striatum following Normobaric Hyperoxia and Mild Hypoxia in Rats by EPR Oximetry using Multi-Probe Implantable Resonators

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Hou, Huagang; Li, Hongbin; Dong, Ruhong; Mupparaju, Sriram; Khan, Nadeem; Swartz, Harold

2013-01-01

Multi-site electron paramagnetic resonance (EPR) oximetry, using multi-probe implantable resonators, was used to measure the partial pressure of oxygen (pO2) in the brains of rats following normobaric hyperoxia and mild hypoxia. The cerebral tissue pO2 was measured simultaneously in the cerebral cortex and striatum in the same rats before, during, and after normobaric hyperoxia and mild hypoxia challenges. The baseline mean tissue pO2 values (±SE) were not significantly different between the cortex and striatum. During 30 min of 100% O2 inhalation, a statistically significant increase in tissue pO2 of all four sites was observed, however, the tissue pO2 of the striatum area was significantly higher than in the forelimb area of the cortex. Brain pO2 significantly decreased from the baseline value during 15 min of 15% O2 challenge. No differences in the recovery of the cerebral cortex and striatum pO2 were observed when the rats were allowed to breathe 30% O2. It appears that EPR oximetry using implantable resonators can provide information on pO2 under the experimental conditions needed for such a study. The levels of pO2 that occurred in these experiments are readily resolvable by multi-site EPR oximetry with multi-probe resonators. In addition, the ability to simultaneously measure the pO2 in several areas of the brain provides important information that could potentially help differentiate the pO2 changes that can occur due to global or local mechanisms. PMID:21445770

[CHANGES IN THE NUMBER OF NEURONS IN THE MOTOR CORTEX OF RATS AND THEIR LOCOMOTOR ACTIVITY IN THE AGE ASPECT].

Science.gov (United States)

Piavchenko, G A; Shmarkova, L I; Nozdrin, V I

2015-01-01

Using Laboras hardware-software complex, which is a system of automatic registration of behavioral reactions, the locomotor activity 1-, 8- and 16-month-old male rats (12 animals in each group) was recorded followed by counting the number of neuron cell bodies of in the layer V of the motor cortex in Nissl stained slides. It was found that the number of neurons in the motor cortex varied in different age groups. Maximal number of neurons was observed in 8-month-old animals. Motor activity was found to correlate with the number of neurons.

Metabolomics identifies perturbations in amino acid metabolism in the prefrontal cortex of the learned helplessness rat model of depression.

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Zhou, Xinyu; Liu, Lanxiang; Zhang, Yuqing; Pu, Juncai; Yang, Lining; Zhou, Chanjuan; Yuan, Shuai; Zhang, Hanping; Xie, Peng

2017-02-20

Major depressive disorder is a serious psychiatric condition associated with high rates of suicide and is a leading cause of health burden worldwide. However, the underlying molecular mechanisms of major depression are still essentially unclear. In our study, a non-targeted gas chromatography-mass spectrometry-based metabolomics approach was used to investigate metabolic changes in the prefrontal cortex of the learned helplessness (LH) rat model of depression. Body-weight measurements and behavioral tests including the active escape test, sucrose preference test, forced swimming test, elevated plus-maze and open field test were used to assess changes in the behavioral spectrum after inescapable footshock stress. Rats in the stress group exhibited significant learned helpless and depression-like behaviors, while without any significant change in anxiety-like behaviors. Using multivariate and univariate statistical analysis, a total of 18 differential metabolites were identified after the footshock stress protocol. Ingenuity Pathways Analysis and MetaboAnalyst were applied for predicted pathways and biological functions analysis. "Amino Acid Metabolism, Molecule Transport, Small Molecule Biochemistry" was the most significantly altered network in the LH model. Amino acid metabolism, particularly glutamate metabolism, cysteine and methionine metabolism, arginine and proline metabolism, was significantly perturbed in the prefrontal cortex of LH rats. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Effect of superlarge dose of gamma radiation on the rat cerebral cortex (ultrastructural aspects)

International Nuclear Information System (INIS)

Abdrakhmanov, A.A.; AN Kazakhskoj SSR, Alma-Ata

1988-01-01

Puberal Wistar line mall rats (180-210 g) were subjected to single whole-body gamma irradiation with 150 Gy dose and 75 Gy/min dose rate. Electron-microscopic investigation into dynamics of sensory-motor cortex ultrastructural changes during 24 hours after irradiation is conducted. Along with destructive changes compensator-reduction processes are developed in brain tissue at this period. Already during the first hours after irradiation the neutron ultrastructure change dynamics has been determined, alongside with direct radiation effect, by indirect effects juries of neuroglia and microcirculatory channel

Effect of superlarge dose of gamma radiation on the rat cerebral cortex (ultrastructural aspects)

Energy Technology Data Exchange (ETDEWEB)

Abdrakhmanov, A A

1988-06-01

Puberal Wistar line mall rats (180-210 g) were subjected to single whole-body gamma irradiation with 150 Gy dose and 75 Gy/min dose rate. Electron-microscopic investigation into dynamics of sensory-motor cortex ultrastructural changes during 24 hours after irradiation is conducted. Along with destructive changes compensator-reduction processes are developed in brain tissue at this period. Already during the first hours after irradiation the neutron ultrastructure change dynamics has been determined, alongside with direct radiation effect, by indirect effects juries of neuroglia and microcirculatory channel.

Unusual patch-matrix organization in the retrosplenial cortex of the reeler mouse and Shaking rat Kawasaki.

Science.gov (United States)

Ichinohe, Noritaka; Knight, Adrian; Ogawa, Masaharu; Ohshima, Toshio; Mikoshiba, Katsuhiko; Yoshihara, Yoshihiro; Terashima, Toshio; Rockland, Kathleen S

2008-05-01

The rat granular retrosplenial cortex (GRS) is a simplified cortex, with distinct stratification and, in the uppermost layers, distinct modularity. Thalamic and cortical inputs are segregated by layers and in layer 1 colocalize, respectively, with apical dendritic bundles originating from neurons in layers 2 or 5. To further investigate this organization, we turned to reelin-deficient reeler mouse and Shaking rat Kawasaki. We found that the disrupted lamination, evident in Nissl stains in these rodents, is in fact a patch-matrix mosaic of segregated afferents and dendrites. Patches consist of thalamocortical connections, visualized by vesicular glutamate transporter 2 (VGluT2) or AChE. The surrounding matrix consists of corticocortical terminations, visualized by VGluT1 or zinc. Dendrites concentrate in the matrix or patches, depending on whether they are OCAM positive (matrix) or negative (patches). In wild-type rodents and, presumably, mutants, OCAM(+) structures originate from layer 5 neurons. By double labeling for dendrites (filled by Lucifer yellow in fixed slice) and OCAM immunofluorescence, we ascertained 2 populations in reeler: dendritic branches either preferred (putative layer 5 neurons) or avoided (putative supragranular neurons) the OCAM(+) matrix. We conclude that input-target relationships are largely preserved in the mutant GRS and that dendrite-dendrite interactions involving OCAM influence the formation of the mosaic configuration.

Continuous Force Decoding from Local Field Potentials of the Primary Motor Cortex in Freely Moving Rats.

Science.gov (United States)

Khorasani, Abed; Heydari Beni, Nargess; Shalchyan, Vahid; Daliri, Mohammad Reza

2016-10-21

Local field potential (LFP) signals recorded by intracortical microelectrodes implanted in primary motor cortex can be used as a high informative input for decoding of motor functions. Recent studies show that different kinematic parameters such as position and velocity can be inferred from multiple LFP signals as precisely as spiking activities, however, continuous decoding of the force magnitude from the LFP signals in freely moving animals has remained an open problem. Here, we trained three rats to press a force sensor for getting a drop of water as a reward. A 16-channel micro-wire array was implanted in the primary motor cortex of each trained rat, and obtained LFP signals were used for decoding of the continuous values recorded by the force sensor. Average coefficient of correlation and the coefficient of determination between decoded and actual force signals were r = 0.66 and R 2  = 0.42, respectively. We found that LFP signal on gamma frequency bands (30-120 Hz) had the most contribution in the trained decoding model. This study suggests the feasibility of using low number of LFP channels for the continuous force decoding in freely moving animals resembling BMI systems in real life applications.

Exchange transfusion with fluorocarbon for studying synaptically evoked optical signal in rat cortex.

Science.gov (United States)

Nomura, Y; Fujii, F; Sato, C; Nemoto, M; Tamura, M

2000-02-01

Optical imaging of intrinsic signal is a powerful technique for studying the functional organization of the brain [T. Bonhoeffer, D. S. Kim, D. Malonek, D. Shoham, A. Grinvald, Optical imaging of the layout of functional domains in area 17 and across the area 17/18 border in cat visual cortex, Eur. J. Neurosci. 7 (1995) 1973-1988; M. Hubener, D. Shoham, A. Grinvald, T. Bonhoeffer, Spatial relationships among three columnar systems in cat area 17, J. Neurosci. 17 (1997) 9270-9284; D. Malonek, A. Grinvald, Interactions between electrical activity and cortical microcirculation revealed by imaging spectroscopy: implications for functional brain mapping, Science 272 (1996) 551-554; A. Shmuel, A. Grinvald, Functional organization for direction of motion and its relationship to orientation maps in cat area 18, J. Neurosci. 16 (1996) 6945-6964] [1] [10] [14] [22]. Three components of intrinsic optical signal can be distinguished. Two of these components can be attributed either to changes in blood volume or to changes in oxygen consumption [R.D. Frostig, E.E. Lieke, D.Y. Ts'o, A. Grinvald, Cortical functional architecture and local coupling between neuronal activity and the microcirculation revealed by in vivo high resolution optical imaging of intrinsic signals, Proc. Natl. Acad. Sci. U. S. A. 87 (1990) 6082-6086] [7]. The origin of the third component is not yet clear but the component seems to be based on scattered light [H.U. Dodt, G. D'Arcangelo, E. Pestel, W. Zieglgansberger, The spread of excitation in neocortical columns visualized with infrared-dark field videomicroscopy, NeuroReport 7 (1996) 1553-1558; K. Holthoff, O.W. Witte, Intrinsic optical signals in rat neocortical slices measured with near-infrared dark-field microscopy reveal changes in extracellular space, J. Neurosci. 16 (1996) 2740-2749; B.A. MacVicar, D. Hochman, Imaging of synaptically evoked intrinsic optical signals in hippocampal slices, J. Neurosci. 11 (1991) 1458-1469; L. Trachsel, H.U. Dodt, W

Age-related decline of the cytochrome c oxidase subunit expression in the auditory cortex of the mimetic aging rat model associated with the common deletion.

Science.gov (United States)

Zhong, Yi; Hu, Yujuan; Peng, Wei; Sun, Yu; Yang, Yang; Zhao, Xueyan; Huang, Xiang; Zhang, Honglian; Kong, Weijia

2012-12-01

The age-related deterioration in the central auditory system is well known to impair the abilities of sound localization and speech perception. However, the mechanisms involved in the age-related central auditory deficiency remain unclear. Previous studies have demonstrated that mitochondrial DNA (mtDNA) deletions accumulated with age in the auditory system. Also, a cytochrome c oxidase (CcO) deficiency has been proposed to be a causal factor in the age-related decline in mitochondrial respiratory activity. This study was designed to explore the changes of CcO activity and to investigate the possible relationship between the mtDNA common deletion (CD) and CcO activity as well as the mRNA expression of CcO subunits in the auditory cortex of D-galactose (D-gal)-induced mimetic aging rats at different ages. Moreover, we explored whether peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α), nuclear respiratory factor 1 (NRF-1) and mitochondrial transcription factor A (TFAM) were involved in the changes of nuclear- and mitochondrial-encoded CcO subunits in the auditory cortex during aging. Our data demonstrated that d-gal-induced mimetic aging rats exhibited an accelerated accumulation of the CD and a gradual decline in the CcO activity in the auditory cortex during the aging process. The reduction in the CcO activity was correlated with the level of CD load in the auditory cortex. The mRNA expression of CcO subunit III was reduced significantly with age in the d-gal-induced mimetic aging rats. In contrast, the decline in the mRNA expression of subunits I and IV was relatively minor. Additionally, significant increases in the mRNA and protein levels of PGC-1α, NRF-1 and TFAM were observed in the auditory cortex of D-gal-induced mimetic aging rats with aging. These findings suggested that the accelerated accumulation of the CD in the auditory cortex may induce a substantial decline in CcO subunit III and lead to a significant decline in the Cc

Combinatorial Motor Training Results in Functional Reorganization of Remaining Motor Cortex after Controlled Cortical Impact in Rats.

Science.gov (United States)

Combs, Hannah L; Jones, Theresa A; Kozlowski, Dorothy A; Adkins, DeAnna L

2016-04-15

Cortical reorganization subsequent to post-stroke motor rehabilitative training (RT) has been extensively examined in animal models and humans. However, similar studies focused on the effects of motor training after traumatic brain injury (TBI) are lacking. We previously reported that after a moderate/severe TBI in adult male rats, functional improvements in forelimb use were accomplished only with a combination of skilled forelimb reach training and aerobic exercise, with or without nonimpaired forelimb constraint. Thus, the current study was designed to examine the relationship between functional motor cortical map reorganization after experimental TBI and the behavioral improvements resulting from this combinatorial rehabilitative regime. Adult male rats were trained to proficiency on a skilled reaching task, received a unilateral controlled cortical impact (CCI) over the forelimb area of the caudal motor cortex (CMC). Three days post-CCI, animals began RT (n = 13) or no rehabilitative training (NoRT) control procedures (n = 13). The RT group participated in daily skilled reach training, voluntary aerobic exercise, and nonimpaired forelimb constraint. This RT regimen significantly improved impaired forelimb reaching success and normalized reaching strategies, consistent with previous findings. RT also enlarged the area of motor cortical wrist representation, derived by intracortical microstimulation, compared to NoRT. These findings indicate that sufficient RT can greatly improve motor function and improve the functional integrity of remaining motor cortex after a moderate/severe CCI. When compared with findings from stroke models, these findings also suggest that more intense RT may be needed to improve motor function and remodel the injured cortex after TBI.

Mild Contralesional Hypothermia Reduces Use of the Unimpaired Forelimb in a Skilled Reaching Task After Motor Cortex Injury in Rats.

Science.gov (United States)

Klahr, Ana C; Fagan, Kelly; Aziz, Jasmine R; John, Roseleen; Colbourne, Frederick

2018-06-01

Therapeutic hypothermia (TH) mitigates neuronal injury in models of ischemic stroke. Although this therapy is meant for injured tissue, most protocols cool the whole body, including the contralesional hemisphere. Neuroplasticity responses within this hemisphere can affect functional outcome. Thus, cooling the contralesional hemisphere serves no clear neuroprotective function and may instead be detrimental. In this study, we cooled the contralesional hemisphere to determine whether this harms behavioral recovery after cortical injury in rats. All rats were trained on skilled reaching and walking tasks. Rats then received a motor cortex insult contralateral to their dominant paw after which they were randomly assigned to focal contralesional TH (∼33°C) for 1-48, 1-97, or 48-96 hours postinjury, or to a normothermic control group. Contralesional cooling did not impact lesion volume (p = 0.371) and had minimal impact on neurological outcome of the impaired limb. However, rats cooled early were significantly less likely to shift paw preference to the unimpaired paw (p ≤ 0.043), suggesting that cooling reduced learned nonuse. In a second experiment, we tested whether cooling impaired learning of the skilled reaching task in naive rats. Localized TH applied to the hemisphere contralateral or ipsilateral to the preferred paw did not impair learning (p ≥ 0.677) or dendritic branching/length in the motor cortex (p ≥ 0.105). In conclusion, localized TH did not impair learning or plasticity in the absence of neural injury, but contralesional TH may reduce unwanted shifts in limb preference after stroke.

Cocaine Administration and Its Withdrawal Enhance the Expression of Genes Encoding Histone-Modifying Enzymes and Histone Acetylation in the Rat Prefrontal Cortex.

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Sadakierska-Chudy, Anna; Frankowska, Małgorzata; Jastrzębska, Joanna; Wydra, Karolina; Miszkiel, Joanna; Sanak, Marek; Filip, Małgorzata

2017-07-01

Chronic exposure to cocaine, craving, and relapse are attributed to long-lasting changes in gene expression arising through epigenetic and transcriptional mechanisms. Although several brain regions are involved in these processes, the prefrontal cortex seems to play a crucial role not only in motivation and decision-making but also in extinction and seeking behavior. In this study, we applied cocaine self-administration and extinction training procedures in rats with a yoked triad to determine differentially expressed genes in prefrontal cortex. Microarray analysis showed significant upregulation of several genes encoding histone modification enzymes during early extinction training. Subsequent real-time PCR testing of these genes following cocaine self-administration or early (third day) and late (tenth day) extinction revealed elevated levels of their transcripts. Interestingly, we found the enrichment of Brd1 messenger RNA in rats self-administering cocaine that lasted until extinction training during cocaine withdrawal with concomitant increased acetylation of H3K9 and H4K8. However, despite elevated levels of methyl- and demethyltransferase-encoded transcripts, no changes in global di- and tri-methylation of histone H3 at lysine 4, 9, 27, and 79 were observed. Surprisingly, at the end of extinction training (10 days of cocaine withdrawal), most of the analyzed genes in the rats actively and passively administering cocaine returned to the control level. Together, the alterations identified in the rat prefrontal cortex may suggest enhanced chromatin remodeling and transcriptional activity induced by early cocaine abstinence; however, to know whether they are beneficial or not for the extinction of drug-seeking behavior, further in vivo evaluation is required.

Protective Effects Induced by Microwave-Assisted Aqueous Harpagophytum Extract on Rat Cortex Synaptosomes Challenged with Amyloid β-Peptide.

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Ferrante, Claudio; Recinella, Lucia; Locatelli, Marcello; Guglielmi, Paolo; Secci, Daniela; Leporini, Lidia; Chiavaroli, Annalisa; Leone, Sheila; Martinotti, Sara; Brunetti, Luigi; Vacca, Michele; Menghini, Luigi; Orlando, Giustino

2017-08-01

Harpagophytum procumbens is a plant species that displays anti-inflammatory properties in multiple tissues. The iridoid glycosides arpagoside, harpagide, and procumbide appear to be the most therapeutically important constituents. In addition, harpagoside treatment exerted neuroprotective effects both in vitro and in vivo. Considering these findings, the aim of the present work is to explore the possible protective role of the previously described microwave-assisted aqueous extract of H. procumbens on rat hypothalamic (Hypo-E22) cells, and in rat cortex challenged with amyloid β-peptide (1-40). In this context, we assayed the protective effects induced by H. procumbens by measuring the levels of malondialdehyde, 3-hydroxykynurenine (3-HK), brain-derived neurotrophic factor, and tumor necrosis factor-α, 3-HK. Finally, we evaluated the effects of H. procumbens treatment on cortex levels of dopamine, norepinephrine, and serotonin. H. procumbens extract was well tolerated by Hypo-E22 cells and upregulated brain-derived neurotrophic factor gene expression but down-regulated tumor necrosis factor-α gene expression. In addition, the extract reduced amyloid β-peptide stimulation of malondialdehyde and 3-HK and blunted the decrease of dopamine, norepinephrine, and serotonin, in the cortex. In this context, our work supports further studies for the evaluation and confirmation of Harpagophytum in the management of the clinical symptoms related to Alzheimer's disease. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Early continuous white noise exposure alters auditory spatial sensitivity and expression of GAD65 and GABAA receptor subunits in rat auditory cortex.

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Xu, Jinghong; Yu, Liping; Cai, Rui; Zhang, Jiping; Sun, Xinde

2010-04-01

Sensory experiences have important roles in the functional development of the mammalian auditory cortex. Here, we show how early continuous noise rearing influences spatial sensitivity in the rat primary auditory cortex (A1) and its underlying mechanisms. By rearing infant rat pups under conditions of continuous, moderate level white noise, we found that noise rearing markedly attenuated the spatial sensitivity of A1 neurons. Compared with rats reared under normal conditions, spike counts of A1 neurons were more poorly modulated by changes in stimulus location, and their preferred locations were distributed over a larger area. We further show that early continuous noise rearing induced significant decreases in glutamic acid decarboxylase 65 and gamma-aminobutyric acid (GABA)(A) receptor alpha1 subunit expression, and an increase in GABA(A) receptor alpha3 expression, which indicates a returned to the juvenile form of GABA(A) receptor, with no effect on the expression of N-methyl-D-aspartate receptors. These observations indicate that noise rearing has powerful adverse effects on the maturation of cortical GABAergic inhibition, which might be responsible for the reduced spatial sensitivity.

Sequential variation in brain functional magnetic resonance imaging after peripheral nerve injury: A rat study.

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Onishi, Okihiro; Ikoma, Kazuya; Oda, Ryo; Yamazaki, Tetsuro; Fujiwara, Hiroyoshi; Yamada, Shunji; Tanaka, Masaki; Kubo, Toshikazu

2018-04-23

Although treatment protocols are available, patients experience both acute neuropathic pain and chronic neuropathic pain, hyperalgesia, and allodynia after peripheral nerve injury. The purpose of this study was to identify the brain regions activated after peripheral nerve injury using functional magnetic resonance imaging (fMRI) sequentially and assess the relevance of the imaging results using histological findings. To model peripheral nerve injury in male Sprague-Dawley rats, the right sciatic nerve was crushed using an aneurysm clip, under general anesthesia. We used a 7.04T MRI system. T 2 * weighted image, coronal slice, repetition time, 7 ms; echo time, 3.3 ms; field of view, 30 mm × 30 mm; pixel matrix, 64 × 64 by zero-filling; slice thickness, 2 mm; numbers of slices, 9; numbers of average, 2; and flip angle, 8°. fMR images were acquired during electrical stimulation to the rat's foot sole; after 90 min, c-Fos immunohistochemical staining of the brain was performed in rats with induced peripheral nerve injury for 3, 6, and 9 weeks. Data were pre-processed by realignment in the Statistical Parametric Mapping 8 software. A General Linear Model first level analysis was used to obtain T-values. One week after the injury, significant changes were detected in the cingulate cortex, insular cortex, amygdala, and basal ganglia; at 6 weeks, the brain regions with significant changes in signal density were contracted; at 9 weeks, the amygdala and hippocampus showed activation. Histological findings of the rat brain supported the fMRI findings. We detected sequential activation in the rat brain using fMRI after sciatic nerve injury. Many brain regions were activated during the acute stage of peripheral nerve injury. Conversely, during the chronic stage, activation of the amygdala and hippocampus may be related to chronic-stage hyperalgesia, allodynia, and chronic neuropathic pain. Copyright © 2018 Elsevier B.V. All rights reserved.

The prefrontal cortex in the Göttingen minipig brain defined by neural projection criteria and cytoarchitecture

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Jelsing, J; Hay-Schmidt, Anders; Dyrby, Tim

2006-01-01

In an attempt to delineate the prefrontal cortex (PFC) in the Gottingen minipig brain the distribution of reciprocal thalamocortical projections was investigated using anterograde and retrograde tracing techniques and evaluated in relation to the specific cytoarchitectonic organization. Tracers...... the medial and rostral pole of the frontal lobe as well as the anterior cingulate, anterior insular and dorsomedial frontal cortices. Subsequently, the reciprocity and specificity of these connections were tested from injections into the traced frontal cortices indicating that the PFC has cortical...... connections to different parts of the MD nucleus. Although the granular layer IV, characteristic of primate PFC could not be identified, both cytoarchitectonic and connectional data suggests that the Gottingen minipig has a structurally divided prefrontal cortex. Stereological estimates of PFC volume showed...

Scheduling Model for Renewable Energy Sources Integration in an Insular Power System

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Gerardo J. Osório

2018-01-01

Full Text Available Insular power systems represent an asset and an excellent starting point for the development and analysis of innovative tools and technologies. The integration of renewable energy resources that has taken place in several islands in the south of Europe, particularly in Portugal, has brought more uncertainty to production management. In this work, an innovative scheduling model is proposed, which considers the integration of wind and solar resources in an insular power system in Portugal, with a strong conventional generation basis. This study aims to show the benefits of increasing the integration of renewable energy resources in this insular power system, and the objectives are related to minimizing the time for which conventional generation is in operation, maximizing profits, reducing production costs, and consequently, reducing greenhouse gas emissions.

Projection from the prefrontal cortex to histaminergic cell groups in the posterior hypothalamic region of the rat. Anterograde tracing with Phaseolus vulgaris leucoagglutinin combined with immunocytochemistry of histidine decarboxylase

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Wouterlood, F.G.; Steinbusch, H.W.M.; Luiten, P.G.M.; Bol, J.G.J.M.

1987-01-01

We investigated the projection from the infralimbic division of the prefrontal cortex (area 25) to histaminergic neurons in the posterior hypothalamic area. Phaseolus vulgaris-leucoagglutinin (PHA-L) was injected in the prefrontal cortex of rats. Frozen brain sections were subjected to combined

Motor cortex stimulation suppresses cortical responses to noxious hindpaw stimulation after spinal cord lesion in rats.

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Jiang, Li; Ji, Yadong; Voulalas, Pamela J; Keaser, Michael; Xu, Su; Gullapalli, Rao P; Greenspan, Joel; Masri, Radi

2014-01-01

Motor cortex stimulation (MCS) is a potentially effective treatment for chronic neuropathic pain. The neural mechanisms underlying the reduction of hyperalgesia and allodynia after MCS are not completely understood. To investigate the neural mechanisms responsible for analgesic effects after MCS. We test the hypothesis that MCS attenuates evoked blood oxygen-level dependent signals in cortical areas involved in nociceptive processing in an animal model of chronic neuropathic pain. We used adult female Sprague-Dawley rats (n = 10) that received unilateral electrolytic lesions of the right spinal cord at the level of C6 (SCL animals). In these animals, we performed magnetic resonance imaging (fMRI) experiments to study the analgesic effects of MCS. On the day of fMRI experiment, 14 days after spinal cord lesion, the animals were anesthetized and epidural bipolar platinum electrodes were placed above the left primary motor cortex. Two 10-min sessions of fMRI were performed before and after a session of MCS (50 μA, 50 Hz, 300 μs, for 30 min). During each fMRI session, the right hindpaw was electrically stimulated (noxious stimulation: 5 mA, 5 Hz, 3 ms) using a block design of 20 s stimulation off and 20 s stimulation on. A general linear model-based statistical parametric analysis was used to analyze whole brain activation maps. Region of interest (ROI) analysis and paired t-test were used to compare changes in activation before and after MCS in these ROI. MCS suppressed evoked blood oxygen dependent signals significantly (Family-wise error corrected P cortex and the prefrontal cortex. These findings suggest that, in animals with SCL, MCS attenuates hypersensitivity by suppressing activity in the primary somatosensory cortex and prefrontal cortex. Copyright © 2014. Published by Elsevier Inc.

Effect of prenatal exposure to ethanol on the development of cerebral cortex: I. Neuronal generation

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Miller, M.W.

1988-01-01

Prenatal exposure to ethanol causes profound disruptions in the development of the cerebral cortex. Therefore, the effect of in utero ethanol exposure on the generation of neurons was determined. Pregnant rats were fed a liquid diet in which ethanol constituted 37.5% of the total caloric content (Et) or pair-fed an isocaloric control diet (Ct) from gestational day (GD) 6 to the day of birth. The time of origin of cortical neurons was determined in the mature pups of females injected with [3H]thymidine on one day during the period from GD 10 to the day of birth. The brains were processed by standard autoradiographic techniques. Ethanol exposure produced multiple defects in neuronal ontogeny. The period of generation was 1-2 days later for Et-treated rats than for rats exposed prenatally to either control diet. Moreover, the generation period was 1-2 days longer in Et-treated rats. The numbers of neurons generated on a specific day was altered; from GD 12-19 significantly fewer neurons were generated in Et-treated rats than in Ct-treated rats, whereas after GD 19 more neurons were born. The distribution of neurons generated on a specific day was disrupted; most notable was the distribution of late-generated neurons in deep cortex of Et-treated rats rather than in superficial cortex as they are in controls. Cortical neurons in Et-treated rats tended to be smaller than in Ct-treated rats, particularly early generated neurons in deep cortex. The late-generated neurons in Et-treated rats were of similar size to those in Ct-treated rats despite their abnormal position in deep cortex. Neurons in Ct-treated rats tended to be rounder than those in Et-treated rats which were more polarized in the radial orientation

Feedforward motor information enhances somatosensory responses and sharpens angular tuning of rat S1 barrel cortex neurons.

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Khateb, Mohamed; Schiller, Jackie; Schiller, Yitzhak

2017-01-06

The primary vibrissae motor cortex (vM1) is responsible for generating whisking movements. In parallel, vM1 also sends information directly to the sensory barrel cortex (vS1). In this study, we investigated the effects of vM1 activation on processing of vibrissae sensory information in vS1 of the rat. To dissociate the vibrissae sensory-motor loop, we optogenetically activated vM1 and independently passively stimulated principal vibrissae. Optogenetic activation of vM1 supra-linearly amplified the response of vS1 neurons to passive vibrissa stimulation in all cortical layers measured. Maximal amplification occurred when onset of vM1 optogenetic activation preceded vibrissa stimulation by 20 ms. In addition to amplification, vM1 activation also sharpened angular tuning of vS1 neurons in all cortical layers measured. Our findings indicated that in addition to output motor signals, vM1 also sends preparatory signals to vS1 that serve to amplify and sharpen the response of neurons in the barrel cortex to incoming sensory input signals.

Disorganization of Oligodendrocyte Development in the Layer II/III of the Sensorimotor Cortex Causes Motor Coordination Dysfunction in a Model of White Matter Injury in Neonatal Rats.

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Ueda, Yoshitomo; Misumi, Sachiyo; Suzuki, Mina; Ogawa, Shino; Nishigaki, Ruriko; Ishida, Akimasa; Jung, Cha-Gyun; Hida, Hideki

2018-01-01

We previously established neonatal white matter injury (WMI) model rat that is made by right common carotid artery dissection at postnatal day 3, followed by 6% hypoxia for 60 min. This model has fewer oligodendrocyte progenitor cells and reduced myelin basic protein (MBP) positive areas in the sensorimotor cortex, but shows no apparent neuronal loss. However, how motor deficits are induced in this model is unclear. To elucidate the relationship between myelination disturbance and concomitant motor deficits, we first performed motor function tests (gait analysis, grip test, horizontal ladder test) and then analyzed myelination patterns in the sensorimotor cortex using transmission electron microscopy (TEM) and Contactin associated protein 1 (Caspr) staining in the neonatal WMI rats in adulthood. Behavioral tests revealed imbalanced motor coordination in this model. Motor deficit scores were higher in the neonatal WMI model, while hindlimb ladder stepping scores and forelimb grasping force were comparable to controls. Prolonged forelimb swing times and decreased hindlimb paw angles on the injured side were revealed by gait analysis. TEM revealed no change in myelinated axon number and the area g-ratio in the layer II/III of the cortex. Electromyographical durations and latencies in the gluteus maximus in response to electrical stimulation of the brain area were unchanged in the model. Caspr staining revealed fewer positive dots in layers II/III of the WMI cortex, indicating fewer and/or longer myelin sheath. These data suggest that disorganization of oligodendrocyte development in layers II/III of the sensorimotor cortex relates to imbalanced motor coordination in the neonatal WMI model rat.

Protein metabolism in the rat cerebral cortex in vivo and in vitro as affected by the acquisition enhancing drug piracetam

NARCIS (Netherlands)

Nickolson, V.J.; Wolthuis, O.L.

1976-01-01

The effect of Piracetam on rat cerebral protein metabolism in vivo and in vitro was studied. It was found that the drug stimulates the uptake of labelled leucine by cerebral cortex slices, has no effect on the incorporation of leucine into cerebral protein, neither in slices nor in vivo, but

Recovery of motor deficit, cerebellar serotonin and lipid peroxidation levels in the cortex of injured rats.

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Bueno-Nava, Antonio; Gonzalez-Pina, Rigoberto; Alfaro-Rodriguez, Alfonso; Nekrassov-Protasova, Vladimir; Durand-Rivera, Alfredo; Montes, Sergio; Ayala-Guerrero, Fructuoso

2010-10-01

The sensorimotor cortex and the cerebellum are interconnected by the corticopontocerebellar (CPC) pathway and by neuronal groups such as the serotonergic system. Our aims were to determine the levels of cerebellar serotonin (5-HT) and lipid peroxidation (LP) after cortical iron injection and to analyze the motor function produced by the injury. Rats were divided into the following three groups: control, injured and recovering. Motor function was evaluated using the beam-walking test as an assessment of overall locomotor function and the footprint test as an assessment of gait. We also determined the levels of 5-HT and LP two and twenty days post-lesion. We found an increase in cerebellar 5-HT and a concomitant increase in LP in the pons and cerebellum of injured rats, which correlated with their motor deficits. Recovering rats showed normal 5-HT and LP levels. The increase of 5-HT in injured rats could be a result of serotonergic axonal injury after cortical iron injection. The LP and motor deficits could be due to impairments in neuronal connectivity affecting the corticospinal and CPC tracts and dysmetric stride could be indicative of an ataxic gait that involves the cerebellum.

Phencyclidine administration during neurodevelopment alters network activity in prefrontal cortex and hippocampus in adult rats.

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Kjaerby, Celia; Hovelsø, Nanna; Dalby, Nils Ole; Sotty, Florence

2017-08-01

Symptoms of schizophrenia have been linked to insults during neurodevelopment such as NMDA receptor (NMDAR) antagonist exposure. In animal models, this leads to schizophrenia-like behavioral symptoms as well as molecular and functional changes within hippocampal and prefrontal regions. The aim of this study was to determine how administration of the NMDAR antagonist phencyclidine (PCP) during neurodevelopment affects functional network activity within the hippocampus and medial prefrontal cortex (mPFC). We recorded field potentials in vivo after electrical brain stem stimulation and observed a suppression of evoked theta power in ventral hippocampus, while evoked gamma power in mPFC was enhanced in rats administered with PCP neonatally. In addition, increased gamma synchrony elicited by acute administration of the NMDAR antagonist MK-801 was exaggerated in neonatal PCP animals. These data suggest that NMDAR antagonist exposure during brain development alters functional networks within hippocampus and mPFC possibly contributing to the reported behavioral symptoms of this animal model of schizophrenia. NEW & NOTEWORTHY We show that insults with a NMDA receptor antagonist during neurodevelopment lead to suppressed evoked theta oscillations in ventral hippocampus in adult rats, while evoked gamma oscillations are enhanced and hypersensitive to an acute challenge with a NMDA receptor antagonist in prefrontal cortex. These observations reveal the significance of neurodevelopmental disturbances in the evolvement of schizophrenia-like symptoms and contribute to the understanding of the functional deficits underlying aberrant behavior in this disease. Copyright © 2017 the American Physiological Society.

Effect of Electromagnetic Radiation Exposure on Histology and DNA Content of the Brain Cortex and Hypothalamus of Young and Adult Male Albino Rats

International Nuclear Information System (INIS)

Othman, A.I.; Othman, A.I.

2012-01-01

Concerns have been raised regarding the potential adverse effects of exposure to electromagnetic radiation (EMR) arising from mobile phone. The present study investigates the effect of the daily exposure of adult and young rats to EMR for 1 hour (at a frequency of 900 MHz, a power density of 0.02 mW/cm 2 and an average specific absorption rate of 1.165 W/kg) on the DNA content and tissue architecture of the cortex and hypothalamus of the rat brain. Both young and adult rats were sacrificed at two intervals, after 4 months of daily EMR exposure and after 1 month of stopping the exposure. The present results showed a significant increase in the DNA intensity of young and adult rats in both areas after 4 months of daily EMR exposure. However, decreased DNA content around the normal level was observed after one month of stopping the exposure. Light microscopic examination of irradiated rats revealed edema, vacuolation, necrosis and proliferated glial cells. Stopping EMR exposure showed mild amelioration in the structural damage of the cerebral cortex of young animals, however, most drastic changes still persisted in the other animals. In conclusion, these data may confirm the neurotoxic risks arising from the extensive use of mobile phones that may alter the brain histology and impair its function

Catabolism of 6-ketoprostaglandin F1alpha by the rat kidney cortex.

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Pace-Asciak, C R; Domazet, Z; Carrara, M

1977-05-25

Homogenates of the rat kidney cortex converted 5,8,9,11,12,14,15-hepta-tritiated 6-ketoprostaglandin F 1alpha into one major product identified by gas chromatography-mass spectrometry of the methoxime-methyl ester trimethylsilyl ether derivative as 6,15-diketo-9,11-dihydroxyprost-13-enoic acid. The sequence of derivatisation i.e. methoximation prior to methylation, was crucial as methylation of 15-keto catabolites of the E, F and 6-keto-F series affords degradation products. The corresponding 15-keto-13,14-dihydro catabolite was formed in much smaller quantities. Time course studies indicated that 6-keto-prostaglandin F1alpha was catabolised at a slower rate (about 2-5 fold) than prostaglandin F1alpha. The catabolic activity was blocked by NADH.

Estrogens regulate neuroinflammatory genes via estrogen receptors α and β in the frontal cortex of middle-aged female rats

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Mahó Sándor

2011-07-01

Full Text Available Abstract Background Estrogens exert anti-inflammatory and neuroprotective effects in the brain mainly via estrogen receptors α (ERα and β (ERβ. These receptors are members of the nuclear receptor superfamily of ligand-dependent transcription factors. This study was aimed at the elucidation of the effects of ERα and ERβ agonists on the expression of neuroinflammatory genes in the frontal cortex of aging female rats. Methods To identify estrogen-responsive immunity/inflammation genes, we treated middle-aged, ovariectomized rats with 17β-estradiol (E2, ERα agonist 16α-lactone-estradiol (16α-LE2 and ERβ agonist diarylpropionitrile (DPN, or vehicle by Alzet minipump delivery for 29 days. Then we compared the transcriptomes of the frontal cortex of estrogen-deprived versus ER agonist-treated animals using Affymetrix Rat230 2.0 expression arrays and TaqMan-based quantitative real-time PCR. Microarray and PCR data were evaluated by using Bioconductor packages and the RealTime StatMiner software, respectively. Results Microarray analysis revealed the transcriptional regulation of 21 immunity/inflammation genes by 16α-LE2. The subsequent comparative real-time PCR study analyzed the isotype specific effects of ER agonists on neuroinflammatory genes of primarily glial origin. E2 regulated the expression of sixteen genes, including down-regulation of complement C3 and C4b, Ccl2, Tgfb1, macrophage expressed gene Mpeg1, RT1-Aw2, Cx3cr1, Fcgr2b, Cd11b, Tlr4 and Tlr9, and up-regulation of defensin Np4 and RatNP-3b, IgG-2a, Il6 and ER gene Esr1. Similar to E2, both 16α-LE2 and DPN evoked up-regulation of defensins, IgG-2a and Il6, and down-regulation of C3 and its receptor Cd11b, Ccl2, RT1-Aw2 and Fcgr2b. Conclusions These findings provide evidence that E2, 16α-LE2 and DPN modulate the expression of neuroinflammatory genes in the frontal cortex of middle-aged female rats via both ERα and ERβ. We propose that ERβ is a promising target to suppress

Alpha2-adrenoceptor modulation of long-term potentiation elicited in vivo in rat occipital cortex.

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Mondaca, Mauricio; Hernández, Alejandro; Pérez, Hernán; Valladares, Luis; Sierralta, Walter; Fernández, Victor; Soto-Moyano, Rubén

2004-09-24

Pretreatment with the alpha(2)-adrenoceptor agonist clonidine (31.25, 62.5, or 125 microg/kg, i.p.) dose-dependently reduced long-term potentiation (LTP) elicited in vivo in the occipital cortex of anesthetized rats, whereas pretreatment with the alpha(2)-adrenoceptor antagonist yohimbine (0.133, 0.4, or 1.2 mg/kg, i.p.) increased neocortical LTP in a dose-dependent fashion. These effects could be related to the reported disruptive and facilitatory actions induced on memory formation by pretreatment with alpha(2)-adrenoceptor agonists and antagonists, respectively.

Adolescent changes in dopamine D1 receptor expression in orbitofrontal cortex and piriform cortex accompany an associative learning deficit.

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Anna K Garske

Full Text Available The orbitofrontal cortex (OFC and piriform cortex are involved in encoding the predictive value of olfactory stimuli in rats, and neural responses to olfactory stimuli in these areas change as associations are learned. This experience-dependent plasticity mirrors task-related changes previously observed in mesocortical dopamine neurons, which have been implicated in learning the predictive value of cues. Although forms of associative learning can be found at all ages, cortical dopamine projections do not mature until after postnatal day 35 in the rat. We hypothesized that these changes in dopamine circuitry during the juvenile and adolescent periods would result in age-dependent differences in learning the predictive value of environmental cues. Using an odor-guided associative learning task, we found that adolescent rats learn the association between an odor and a palatable reward significantly more slowly than either juvenile or adult rats. Further, adolescent rats displayed greater distractibility during the task than either juvenile or adult rats. Using real-time quantitative PCR and immunohistochemical methods, we observed that the behavioral deficit in adolescence coincides with a significant increase in D1 dopamine receptor expression compared to juvenile rats in both the OFC and piriform cortex. Further, we found that both the slower learning and increased distractibility exhibited in adolescence could be alleviated by experience with the association task as a juvenile, or by an acute administration of a low dose of either the dopamine D1 receptor agonist SKF-38393 or the D2 receptor antagonist eticlopride. These results suggest that dopaminergic modulation of cortical function may be important for learning the predictive value of environmental stimuli, and that developmental changes in cortical dopaminergic circuitry may underlie age-related differences in associative learning.

Registration and Analysis of Bioelectric Activity of Sensory-Motor Cortex During the Electrical Stimulation of Nucleus Caudate in Rats

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Snežana Medenica-Milanović

2007-05-01

Full Text Available Background and purposeThe caudate circuit takes part in cognitive control of motor activity The purpose of the present work was registration and analysis of basic bioelectrical activity of ventral and dorsal sensory-motor cortex and nucleus caudate, study of the changes in EEG after nucleus caudate electrical stimulation and to identify of threshold level of electrical stimuli responsible for changes of electrical activity in registered brain area.Materials and methodsWe used 28 albino Wistar rat of both genders. After the animal fixation on stereotaxic apparatus to dry bone, the places for electrode fixation were marked. Two days after the electrodes had been implanted an EEG was registered so that the animals would adjust to the conditions and so they would repair the tissue reactions. EEG was registered with bipolar electrodes with ten-channeled apparatus. For first half an hour spontaneous activity of the brain was registered, and after that the head of nucleus caudate was stimulated with altered impulses of various voltages, frequency and duration.Results and conclusionsThreshold values of electric stimulus intensity from 3 to 5 V, frequency from 3 to 5 Hz, duration from 3 to 5 ms, by stimulation the head of nucleus caudate of rat, lead to the change of basal bioelectric activity of cerebrum. The change of bioelectric activity is firstly recorded in equilateral cortex, and with the higher intensity of the stimulus the changes overtake the contra lateral cortex.

Dyscalculia, Dysgraphia, and Left-Right Confusion from a Left Posterior Peri-Insular Infarct

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S. Bhattacharyya

2014-01-01

Full Text Available The Gerstmann syndrome of dyscalculia, dysgraphia, left-right confusion, and finger agnosia is generally attributed to lesions near the angular gyrus of the dominant hemisphere. A 68-year-old right-handed woman presented with sudden difficulty completing a Sudoku grid and was found to have dyscalculia, dysgraphia, and left-right confusion. Magnetic resonance imaging (MRI showed a focus of abnormal reduced diffusivity in the left posterior insula and temporoparietal operculum consistent with acute infarct. Gerstmann syndrome from an insular or peri-insular lesion has not been described in the literature previously. Pathological and functional imaging studies show connections between left posterior insular region and inferior parietal lobe. We postulate that the insula and operculum lesion disrupted key functional networks resulting in a pseudoparietal presentation.

Dyscalculia, dysgraphia, and left-right confusion from a left posterior peri-insular infarct.

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Bhattacharyya, S; Cai, X; Klein, J P

2014-01-01

The Gerstmann syndrome of dyscalculia, dysgraphia, left-right confusion, and finger agnosia is generally attributed to lesions near the angular gyrus of the dominant hemisphere. A 68-year-old right-handed woman presented with sudden difficulty completing a Sudoku grid and was found to have dyscalculia, dysgraphia, and left-right confusion. Magnetic resonance imaging (MRI) showed a focus of abnormal reduced diffusivity in the left posterior insula and temporoparietal operculum consistent with acute infarct. Gerstmann syndrome from an insular or peri-insular lesion has not been described in the literature previously. Pathological and functional imaging studies show connections between left posterior insular region and inferior parietal lobe. We postulate that the insula and operculum lesion disrupted key functional networks resulting in a pseudoparietal presentation.

Insular threat associations within taxa worldwide.

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Leclerc, Camille; Courchamp, Franck; Bellard, Céline

2018-04-23

The global loss of biodiversity can be attributed to numerous threats. While pioneer studies have investigated their relative importance, the majority of those studies are restricted to specific geographic regions and/or taxonomic groups and only consider a small subset of threats, generally in isolation despite their frequent interaction. Here, we investigated 11 major threats responsible for species decline on islands worldwide. We applied an innovative method of network analyses to disentangle the associations of multiple threats on vertebrates, invertebrates, and plants in 15 insular regions. Biological invasions, wildlife exploitation, and cultivation, either alone or in association, were found to be the three most important drivers of species extinction and decline on islands. Specifically, wildlife exploitation and cultivation are largely associated with the decline of threatened plants and terrestrial vertebrates, whereas biological invasions mostly threaten invertebrates and freshwater fish. Furthermore, biodiversity in the Indian Ocean and near the Asian coasts is mostly affected by wildlife exploitation and cultivation compared to biological invasions in the Pacific and Atlantic insular regions. We highlighted specific associations of threats at different scales, showing that the analysis of each threat in isolation might be inadequate for developing effective conservation policies and managements.

Microsurgery Resection of Intrinsic Insular Tumors via Transsylvian Surgical Approach in 12 Cases

International Nuclear Information System (INIS)

Wang, Peng; Wu, Ming-can; Chen, Shi-jie; Xu, Xian-ping; Yang, Yong; Cai, Jie

2012-01-01

To investigate the clinical characteristics, operative methods, and diffusion tensor imaging (DTI) in the resection of intrinsic insular gliomas via transsylvian approach. From June 2008 to June 2010, 12 patients with intrinsic insular gliomas were treated via transsylvian microsurgical approach, with preoperative magnetic resonance imaging diffusion tensor imaging (MR DTI) evaluation. The data of these patients were retrospectively analyzed. All patients had astrocytoma, including 8 patients of Grades I to II, 2 patients of Grades III to IV, and 2 patients of mixed glial tumors. The insular tumors were completely removed in 9 patients, whereas they were only partially removed from 3 patients. No death was related to the operations. Two patients had transient aphasia, 2 experienced worsened hemiplegia on opposite sides of their bodies, and 2 had mild hemiplegia and language function disturbance. Most of the insular gliomas are of low grade. By evaluating the damage of the corticospinal tract through DTI and using ultrasonography to locate the tumors during operation, microsurgery treatment removes the lesions as much as possible, protects the surrounding areas, reduces the mobility rate, and improves the postoperative quality of life

Perinatal nicotine treatment induces transient increases in NACHO protein levels in the rat frontal cortex

DEFF Research Database (Denmark)

Wichern, Franziska; Jensen, Majbrit M; Christensen, Ditte Z

2017-01-01

The nicotinic acetylcholine receptor (nAChR) regulator chaperone (NACHO) was recently identified as an important regulator of nAChR maturation and surface expression. Here we show that NACHO levels decrease during early postnatal development in rats. This decrease occurs earlier and to a greater...... degree in the frontal cortex (FC) compared with the hippocampus (HIP). We further show that rats exposed to nicotine during pre- and postnatal development exhibit significantly higher NACHO levels in the FC at postnatal day (PND) 21, but not at PND60. Repeated exposure to nicotine selectively during...... a single exposure to a combination of nicotine and the type II α7 nAChR positive allosteric modulator (PAM) PNU-120596, but not the type I PAM AVL-3288. These findings suggest that exposure to nAChR agonism affects NACHO protein levels, and that this effect is more pronounced during pre- or early postnatal...

Repeated forced swim stress enhances CFA-evoked thermal hyperalgesia and affects the expressions of pCREB and c-Fos in the insular cortex.

Science.gov (United States)

Imbe, H; Kimura, A; Donishi, T; Kaneoke, Y

2014-02-14

Stress affects brain activity and promotes long-term changes in multiple neural systems. Exposure to stressors causes substantial effects on the perception and response to pain. In several animal models, chronic stress produces lasting hyperalgesia. The insular (IC) and anterior cingulate cortices (ACC) are the regions exhibiting most reliable pain-related activity. And the IC and ACC play an important role in pain modulation via the descending pain modulatory system. In the present study we examined the expression of phospho-cAMP response element-binding protein (pCREB) and c-Fos in the IC and ACC after forced swim stress (FS) and complete Freund's adjuvant (CFA) injection to clarify changes in the cerebral cortices that affect the activity of the descending pain modulatory system in the rats with stress-induced hyperalgesia. FS (day 1, 10min; days 2-3, 20min) induced an increase in the expression of pCREB and c-Fos in the anterior IC (AIC). CFA injection into the hindpaw after the FS shows significantly enhanced thermal hyperalgesia and induced a decrease in the expression of c-Fos in the AIC and the posterior IC (PIC). Quantitative image analysis showed that the numbers of c-Fos-immunoreactive neurons in the left AIC and PIC were significantly lower in the FS+CFA group (L AIC, 95.9±6.8; L PIC, 181.9±23.1) than those in the naive group (L AIC, 151.1±19.3, pCFA-induced thermal hyperalgesia through dysfunction of the descending pain modulatory system. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

Effect of acute administration of Pistacia lentiscus L. essential oil on rat cerebral cortex following transient bilateral common carotid artery occlusion

Directory of Open Access Journals (Sweden)

Quartu Marina

2012-01-01

Full Text Available Abstract Background Ischemia/reperfusion leads to inflammation and oxidative stress which damages membrane highly polyunsaturated fatty acids (HPUFAs and eventually induces neuronal death. This study evaluates the effect of the administration of Pistacia lentiscus L. essential oil (E.O., a mixture of terpenes and sesquiterpenes, on modifications of fatty acid profile and endocannabinoid (eCB congener concentrations induced by transient bilateral common carotid artery occlusion (BCCAO in the rat frontal cortex and plasma. Methods Adult Wistar rats underwent BCCAO for 20 min followed by 30 min reperfusion (BCCAO/R. 6 hours before surgery, rats, randomly assigned to four groups, were gavaged either with E.O. (200 mg/0.45 ml of sunflower oil as vehicle or with the vehicle alone. Results BCCAO/R triggered in frontal cortex a decrease of docosahexaenoic acid (DHA, the membrane highly polyunsaturated fatty acid most susceptible to oxidation. Pre-treatment with E.O. prevented this change and led further to decreased levels of the enzyme cyclooxygenase-2 (COX-2, as assessed by Western Blot. In plasma, only after BCCAO/R, E.O. administration increased both the ratio of DHA-to-its precursor, eicosapentaenoic acid (EPA, and levels of palmytoylethanolamide (PEA and oleoylethanolamide (OEA. Conclusions Acute treatment with E.O. before BCCAO/R elicits changes both in the frontal cortex, where the BCCAO/R-induced decrease of DHA is apparently prevented and COX-2 expression decreases, and in plasma, where PEA and OEA levels and DHA biosynthesis increase. It is suggested that the increase of PEA and OEA plasma levels may induce DHA biosynthesis via peroxisome proliferator-activated receptor (PPAR alpha activation, protecting brain tissue from ischemia/reperfusion injury.

Motor skills training promotes motor functional recovery and induces synaptogenesis in the motor cortex and striatum after intracerebral hemorrhage in rats.

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Tamakoshi, Keigo; Ishida, Akimasa; Takamatsu, Yasuyuki; Hamakawa, Michiru; Nakashima, Hiroki; Shimada, Haruka; Ishida, Kazuto

2014-03-01

We investigated the effects of motor skills training on several types of motor function and synaptic plasticity following intracerebral hemorrhage (ICH) in rats. Male Wistar rats were injected with collagenase into the left striatum to induce ICH, and they were randomly assigned to the ICH or sham groups. Each group was divided into the motor skills training (acrobatic training) and control (no exercise) groups. The acrobatic group performed acrobatic training from 4 to 28 days after surgery. Motor functions were assessed by motor deficit score, the horizontal ladder test and the wide or narrow beam walking test at several time points after ICH. The number of ΔFosB-positive cells was counted using immunohistochemistry to examine neuronal activation, and the PSD95 protein levels were analyzed by Western blotting to examine synaptic plasticity in the bilateral sensorimotor cortices and striata at 14 and 29 days after ICH. Motor skills training following ICH significantly improved gross motor function in the early phase after ICH and skilled motor coordinated function in the late phase. The number of ΔFosB-positive cells in the contralateral sensorimotor cortex in the acrobatic group significantly increased compared to the control group. PSD95 protein expression in the motor cortex significantly increased in the late phase, and in the striatum, the protein level significantly increased in the early phase by motor skills training after ICH compared to no training after ICH. We demonstrated that motor skills training improved motor function after ICH in rats and enhanced the neural activity and synaptic plasticity in the striatum and sensorimotor cortex. Copyright © 2013 Elsevier B.V. All rights reserved.

Decreased ERp57 Expression in WAG/Rij Rats Thalamus and Cortex; Possible Correlation with Absence Epilepsy.

Science.gov (United States)

Sahin, Deniz; Karadenizli, Sabriye; Kasap, Murat; Oztas, Berrin; Kir, Hale Maral; Akpinar, Gurler; Ates, Nurbay

2018-02-06

The role of intracellular proteins in the pathogenesis of absence epilepsy were mentioned. These proteins are thought to be related to energy generation, signal transduction, inflammation processes and membrane conductance. The investigation of protein profile of the genetically epileptic rat brains was the main subject of this study. For this, a 2D-gel electrophoresis based comparative proteome analysis was performed using thalamus tissue of genetic absence epileptic WAG/Rij and age matched Wistar rats. Regulated spots displaying differences in their abundance were identified using MALDI-TOF/TOF. Among the six spots (DHRS9, BR44, HINT1, CREM, SPRE and PDIA3/ERp57) the highest mascot score was attributed to ERp57 a neuroprotective/neurodegenerative system associated protein. Western Blot analyses were performed to validate changes occurring at ERp57 in thalamus and also identify changes in fronto-parietal cortex. Reductions in the expression levels of ERp57 were detected in the thalamic and the fronto-parietal brain regions of the WAG/Rij rats in comparison to Wistar rats. Such difference might be associated with the pathogenic mechanisms dictating the absence epilepsy. Lower levels of ERp57 may be playing an important role in the development of spontaneous seizures activity seen in the absence epileptic WAG/Rij rats strain. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Texture coarseness responsive neurons and their mapping in layer 2–3 of the rat barrel cortex in vivo

Science.gov (United States)

Garion, Liora; Dubin, Uri; Rubin, Yoav; Khateb, Mohamed; Schiller, Yitzhak; Azouz, Rony; Schiller, Jackie

2014-01-01

Texture discrimination is a fundamental function of somatosensory systems, yet the manner by which texture is coded and spatially represented in the barrel cortex are largely unknown. Using in vivo two-photon calcium imaging in the rat barrel cortex during artificial whisking against different surface coarseness or controlled passive whisker vibrations simulating different coarseness, we show that layer 2–3 neurons within barrel boundaries differentially respond to specific texture coarsenesses, while only a minority of neurons responded monotonically with increased or decreased surface coarseness. Neurons with similar preferred texture coarseness were spatially clustered. Multi-contact single unit recordings showed a vertical columnar organization of texture coarseness preference in layer 2–3. These findings indicate that layer 2–3 neurons perform high hierarchical processing of tactile information, with surface coarseness embodied by distinct neuronal subpopulations that are spatially mapped onto the barrel cortex. DOI: http://dx.doi.org/10.7554/eLife.03405.001 PMID:25233151

Gap detection threshold in the rat before and after auditory cortex ablation.

Science.gov (United States)

Syka, J; Rybalko, N; Mazelová, J; Druga, R

2002-10-01

Gap detection threshold (GDT) was measured in adult female pigmented rats (strain Long-Evans) by an operant conditioning technique with food reinforcement, before and after bilateral ablation of the auditory cortex. GDT was dependent on the frequency spectrum and intensity of the continuously present noise in which the gaps were embedded. The mean values of GDT for gaps embedded in white noise or low-frequency noise (upper cutoff frequency 3 kHz) at 70 dB sound pressure level (SPL) were 1.57+/-0.07 ms and 2.9+/-0.34 ms, respectively. Decreasing noise intensity from 80 dB SPL to 20 dB SPL produced a significant increase in GDT. The increase in GDT was relatively small in the range of 80-50 dB SPL for white noise and in the range of 80-60 dB for low-frequency noise. The minimal intensity level of the noise that enabled GDT measurement was 20 dB SPL for white noise and 30 dB SPL for low-frequency noise. Mean GDT values at these intensities were 10.6+/-3.9 ms and 31.3+/-4.2 ms, respectively. Bilateral ablation of the primary auditory cortex (complete destruction of the Te1 and partial destruction of the Te2 and Te3 areas) resulted in an increase in GDT values. The fifth day after surgery, the rats were able to detect gaps in the noise. The values of GDT observed at this time were 4.2+/-1.1 ms for white noise and 7.4+/-3.1 ms for low-frequency noise at 70 dB SPL. During the first month after cortical ablation, recovery of GDT was observed. However, 1 month after cortical ablation GDT still remained slightly higher than in controls (1.8+/-0.18 for white noise, 3.22+/-0.15 for low-frequency noise, Pdecrease in GDT values during the subsequent months was not observed.

Altered neuronal activity in the primary motor cortex and globus pallidus after dopamine depletion in rats.

Science.gov (United States)

Wang, Min; Li, Min; Geng, Xiwen; Song, Zhimin; Albers, H Elliott; Yang, Maoquan; Zhang, Xiao; Xie, Jinlu; Qu, Qingyang; He, Tingting

2015-01-15

The involvement of dopamine (DA) neuron loss in the etiology of Parkinson's disease has been well documented. The neural mechanisms underlying the effects of DA loss and the resultant motor dysfunction remain unknown. To gain insights into how loss of DA disrupts the electrical processes in the cortico-subcortical network, the present study explores the effects of DA neuron depletion on electrical activity in the primary motor cortex (M1), on the external and the internal segment of the globus pallidus (GPe and GPi respectively), and on their temporal relationships. Comparison of local field potentials (LFPs) in these brain regions from unilateral hemispheric DA neuron depleted rats and neurologically intact rats revealed that the spectrum power of LFPs in 12-70Hz (for M1, and GPe) and in 25-40Hz (for GPi) was significantly greater in the DA depleted rats than that in the control group. These changes were associated with a shortening of latency in LFP activities between M1 and GPe, from several hundred milliseconds in the intact animals to close to zero in the DA depleted animals. LFP oscillations in M1 were significantly more synchronized with those in GPe in the DA depleted rats compared with those in the control rats. By contrast, the synchronization of oscillation in LFP activities between M1 and GPi did not differ between the DA depleted and intact rats. Not surprisingly, rats that had DA neuron depletion spent more time along the ladder compared with the control rats. These data suggest that enhanced oscillatory activity and increased synchronization of LFPs may contribute to movement impairment in the rat model of Parkinson's disease. Copyright © 2014 Elsevier B.V. All rights reserved.

Adrenal-dependent and -independent stress-induced Per1 mRNA in hypothalamic paraventricular nucleus and prefrontal cortex of male and female rats.

Science.gov (United States)

Chun, Lauren E; Christensen, Jenny; Woodruff, Elizabeth R; Morton, Sarah J; Hinds, Laura R; Spencer, Robert L

2018-01-01

Oscillating clock gene expression gives rise to a molecular clock that is present not only in the body's master circadian pacemaker, the hypothalamic suprachiasmatic nucleus (SCN), but also in extra-SCN brain regions. These extra-SCN molecular clocks depend on the SCN for entrainment to a light:dark cycle. The SCN has limited neural efferents, so it may entrain extra-SCN molecular clocks through its well-established circadian control of glucocorticoid hormone secretion. Glucocorticoids can regulate the normal rhythmic expression of clock genes in some extra-SCN tissues. Untimely stress-induced glucocorticoid secretion may compromise extra-SCN molecular clock function. We examined whether acute restraint stress during the rat's inactive phase can rapidly (within 30 min) alter clock gene (Per1, Per2, Bmal1) and cFos mRNA (in situ hybridization) in the SCN, hypothalamic paraventricular nucleus (PVN), and prefrontal cortex (PFC) of male and female rats (6 rats per treatment group). Restraint stress increased Per1 and cFos mRNA in the PVN and PFC of both sexes. Stress also increased cFos mRNA in the SCN of male rats, but not when subsequently tested during their active phase. We also examined in male rats whether endogenous glucocorticoids are necessary for stress-induced Per1 mRNA (6-7 rats per treatment group). Adrenalectomy attenuated stress-induced Per1 mRNA in the PVN and ventral orbital cortex, but not in the medial PFC. These data indicate that increased Per1 mRNA may be a means by which extra-SCN molecular clocks adapt to environmental stimuli (e.g. stress), and in the PFC this effect is largely independent of glucocorticoids.

Glutamine synthetase activity and glutamate uptake in hippocampus and frontal cortex in portal hypertensive rats

Science.gov (United States)

Acosta, Gabriela Beatriz; Fernández, María Alejandra; Roselló, Diego Martín; Tomaro, María Luján; Balestrasse, Karina; Lemberg, Abraham

2009-01-01

AIM: To study glutamine synthetase (GS) activity and glutamate uptake in the hippocampus and frontal cortex (FC) from rats with prehepatic portal vein hypertension. METHODS: Male Wistar rats were divided into sham-operated group and a portal hypertension (PH) group with a regulated stricture of the portal vein. Animals were sacrificed by decapitation 14 d after portal vein stricture. GS activity was determined in the hippocampus and FC. Specific uptake of radiolabeled L-glutamate was studied using synaptosome-enriched fractions that were freshly prepared from both brain areas. RESULTS: We observed that the activity of GS increased in the hippocampus of PH rats, as compared to control animals, and decreased in the FC. A significant decrease in glutamate uptake was found in both brain areas, and was more marked in the hippocampus. The decrease in glutamate uptake might have been caused by a deficient transport function, significantly and persistent increase in this excitatory neurotransmitter activity. CONCLUSION: The presence of moderate ammonia blood levels may add to the toxicity of excitotoxic glutamate in the brain, which causes alterations in brain function. Portal vein stricture that causes portal hypertension modifies the normal function in some brain regions. PMID:19533812

Neuronal codes for the inhibitory control of impulsive actions in the rat infralimbic cortex.

Science.gov (United States)

Tsutsui-Kimura, Iku; Ohmura, Yu; Izumi, Takeshi; Matsushima, Toshiya; Amita, Hidetoshi; Yamaguchi, Taku; Yoshida, Takayuki; Yoshioka, Mitsuhiro

2016-01-01

Poor impulse control is a debilitating condition observed in various psychiatric disorders and could be a risk factor for drug addiction, criminal involvement, and suicide. The rat infralimbic cortex (IL), located in the ventral portion of the medial prefrontal cortex, has been implicated in impulse control. To elucidate the neurophysiological basis of impulse control, we recorded single unit activity in the IL of a rat performing a 3-choiceserial reaction time task (3-CSRTT) and 2-choice task (2-CT), which are animal models for impulsivity. The inactivation of IL neuronal activity with an injection of muscimol (0.1 μg /side) disrupted impulse control in the 3-CSRTT. More than 60% (38/56) of isolated IL units were linked to impulse control, while approximately 30% of all units were linked to attentional function in the 3-CSRTT. To avoid confounding motor-related units with the impulse control-related units, we further conducted the 2-CT in which the animals' motor activities were restricted during recording window. More than 30% (14/44) of recorded IL units were linked to impulse control in the 2-CT. Several types of impulse control-related units were identified. Only 16% of all units were compatible with the results of the muscimol experiment, which showed a transient decline in the firing rate immediately before the release of behavioral inhibition. This is the first study to elucidate the neurophysiological basis of impulse control in the IL and to propose that IL neurons control impulsive actions in a more complex manner than previously considered. Copyright © 2015 Elsevier B.V. All rights reserved.

Women in the Dictionary of Danish Insular Dialects

DEFF Research Database (Denmark)

Hovmark, Henrik

Women in the Dictionary of Danish Insular Dialects In this presentation, I discuss the representation of female domains in the Dictionary of Danish Insular Dialects (DID; Ømålsordbogen ), an historical dictionary giving thorough descriptions of the dialects on the Danish isles 1750-1945. First...... volume appeared in 1992 but data collection and structure of the dictionary date back to the 1920s. It has been pointed out that the language, thoughts and domains of women until recently have been strongly neglected in for instance literary studies and history – and that the representations have been...... characterised by stereotypical images. This point has also been made as regards dictionaries (Hageberg 1990, choice of vocabulary; Mattisson 2006, data and examples). As for DID, however, female domains (‘food’, ‘clothes’, ‘milk’ etc.) are thoroughly registered in the collections and described in the dictionary...

Brain cortex phosphatidylserine inhibits phosphatidylinositol turnover in rat anterior pituitary glands

International Nuclear Information System (INIS)

Bonetti, A.C.; Canonico, P.L.; MacLeod, R.M.

1985-01-01

The in vitro effect of bovine brain cortex phosphatidylserine on 32 Pi incorporation into phosphatidylinositol, phosphatidylcholine, and phosphatidylethanolamine of rat anterior pituitary glands was studied. Phosphatidylserine (0.1 to 66.6 microM) decreased the incorporation of 32 Pi into phosphatidylinositol, but not phosphatidylcholine or phosphatidylethanolamine, in a concentration-related manner. The inhibitory effect of phosphatidylinositol was similar to that of dopamine in the same experimental conditions. The combined effects of submaximal concentrations of dopamine and phosphatidylserine elicited an apparently additive inhibitory effect on phosphatidylinositol synthesis. The inhibitory effect of phosphatidylserine was completely reversed by haloperidol and sulpiride and only partially by pimozide, antidopaminergic agents which per se do not affect phosphatidylinositol synthesis. The stimulatory effect of TRH to increase 32 Pi incorporation into phosphatidylinositol was decreased by phosphatidylserine. These observations suggest that the decrease in prolactin release in the presence of phosphatidylserine may be evoked through a dopaminergic mechanism

Response of the sensorimotor cortex of cerebral palsy rats receiving transplantation of vascular endothelial growth factor 165-transfected neural stem cells

Institute of Scientific and Technical Information of China (English)

Jielu Tan; Xiangrong Zheng; Shanshan Zhang; Yujia Yang; Xia Wang; Xiaohe Yu; Le Zhong

2014-01-01

Neural stem cells are characterized by the ability to differentiate and stably express exogenous ge-nes. Vascular endothelial growth factor plays a role in protecting local blood vessels and neurons of newborn rats with hypoxic-ischemic encephalopathy. Transplantation of vascular endothelial growth factor-transfected neural stem cells may be neuroprotective in rats with cerebral palsy. In this study, 7-day-old Sprague-Dawley rats were divided into ifve groups: (1) sham operation (control), (2) cerebral palsy model alone or with (3) phosphate-buffered saline, (4) vascular en-dothelial growth factor 165 + neural stem cells, or (5) neural stem cells alone. hTe cerebral palsy model was established by ligating the letf common carotid artery followed by exposure to hypox-ia. Phosphate-buffered saline, vascular endothelial growth factor + neural stem cells, and neural stem cells alone were administered into the sensorimotor cortex using the stereotaxic instrument and microsyringe. Atfer transplantation, the radial-arm water maze test and holding test were performed. Immunohistochemistry for vascular endothelial growth factor and histology using hematoxylin-eosin were performed on cerebral cortex. Results revealed that the number of vas-cular endothelial growth factor-positive cells in cerebral palsy rats transplanted with vascular endothelial growth factor-transfected neural stem cells was increased, the time for ifnding water and the ifnding repetitions were reduced, the holding time was prolonged, and the degree of cell degeneration or necrosis was reduced. hTese ifndings indicate that the transplantation of vascu-lar endothelial growth factor-transfected neural stem cells alleviates brain damage and cognitive deifcits, and is neuroprotective in neonatal rats with hypoxia ischemic-mediated cerebral palsy.

Insular species swarm goes underground

DEFF Research Database (Denmark)

P. S. Reboleira, Ana Sofia; Enghoff, Henrik

2014-01-01

Two new species of the genus Cylindroiulus Verhoeff, 1894, C. julesvernei and C. oromii, are described from the subterranean ecosystem of Madeira Island, Portugal. Species are illustrated with photographs and diagrammatic drawings. The new species belong to the Cylindroiulus madeirae......-group, an insular species swarm distributed in the archipelagos of Madeira and the Canary Islands. We discuss the differences between the new species and their relatives and present information on the subterranean environment of Madeira. An updated overview of the subterranean biodiversity of millipedes...

The Role of Primary Motor Cortex (M1) Glutamate and GABA Signaling in l-DOPA-Induced Dyskinesia in Parkinsonian Rats.

Science.gov (United States)

Lindenbach, David; Conti, Melissa M; Ostock, Corinne Y; George, Jessica A; Goldenberg, Adam A; Melikhov-Sosin, Mitchell; Nuss, Emily E; Bishop, Christopher

2016-09-21

Long-term treatment of Parkinson's disease with l-DOPA almost always leads to the development of involuntary movements termed l-DOPA-induced dyskinesia. Whereas hyperdopaminergic signaling in the basal ganglia is thought to cause dyskinesia, alterations in primary motor cortex (M1) activity are also prominent during dyskinesia, suggesting that the cortex may represent a therapeutic target. The present study used the rat unilateral 6-hydroxydopamine lesion model of Parkinson's disease to characterize in vivo changes in GABA and glutamate neurotransmission within M1 and determine their contribution to behavioral output. 6-Hydroxydopamine lesion led to parkinsonian motor impairment that was partially reversed by l-DOPA. Among sham-lesioned rats, l-DOPA did not change glutamate or GABA efflux. Likewise, 6-hydroxydopamine lesion did not impact GABA or glutamate among rats chronically treated with saline. However, we observed an interaction of lesion and treatment whereby, among lesioned rats, l-DOPA given acutely (1 d) or chronically (14-16 d) reduced glutamate efflux and enhanced GABA efflux. Site-specific microinjections into M1 demonstrated that l-DOPA-induced dyskinesia was reduced by M1 infusion of a D1 antagonist, an AMPA antagonist, or a GABAA agonist. Overall, the present study demonstrates that l-DOPA-induced dyskinesia is associated with increased M1 inhibition and that exogenously enhancing M1 inhibition may attenuate dyskinesia, findings that are in agreement with functional imaging and transcranial magnetic stimulation studies in human Parkinson's disease patients. Together, our study suggests that increasing M1 inhibitory tone is an endogenous compensatory response designed to limit dyskinesia severity and that potentiating this response is a viable therapeutic strategy. Most Parkinson's disease patients will receive l-DOPA and eventually develop hyperkinetic involuntary movements termed dyskinesia. Such symptoms can be as debilitating as the disease

A 3 T event-related functional magnetic resonance imaging (fMRI) study of primary and secondary gustatory cortex localization using natural tastants

International Nuclear Information System (INIS)

Smits, Marion; Peeters, Ronald R.; Hecke, Paul van; Sunaert, Stefan

2007-01-01

It is known that taste is centrally represented in the insula, frontal and parietal operculum, as well as in the orbitofrontal cortex (secondary gustatory cortex). In functional MRI (fMRI) experiments activation in the insula has been confirmed, but activation in the orbitofrontal cortex is only infrequently found, especially at higher field strengths (3 T). Due to large susceptibility artefacts, the orbitofrontal cortex is a difficult region to examine with fMRI. Our aim was to localize taste in the human cortex at 3 T, specifically in the orbitofrontal cortex as well as in the primary gustatory cortex. Event-related fMRI was performed at 3 T in seven healthy volunteers. Taste stimuli consisted of lemon juice and chocolate. To visualize activation in the orbitofrontal cortex a dedicated 3D SENSE EPI fMRI sequence was used, in addition to a 2D SENSE EPI fMRI sequence for imaging the entire brain. Data were analyzed using a perception-based model. The dedicated 3D SENSE EPI sequence successfully reduced susceptibility artefacts in the orbitofrontal area. Significant taste-related activation was found in the orbitofrontal and insular cortices. fMRI of the orbitofrontal cortex is feasible at 3 T, using a dedicated sequence. Our results corroborate findings from previous studies. (orig.)

A 3 T event-related functional magnetic resonance imaging (fMRI) study of primary and secondary gustatory cortex localization using natural tastants

Energy Technology Data Exchange (ETDEWEB)

Smits, Marion [Erasmus MC, University Medical Center Rotterdam, Department of Radiology, P.O. Box 2040, CA Rotterdam (Netherlands); K.U.Leuven, Department of Radiology, University Hospitals, Leuven (Belgium); Peeters, Ronald R.; Hecke, Paul van; Sunaert, Stefan [K.U.Leuven, Department of Radiology, University Hospitals, Leuven (Belgium)

2007-01-15

It is known that taste is centrally represented in the insula, frontal and parietal operculum, as well as in the orbitofrontal cortex (secondary gustatory cortex). In functional MRI (fMRI) experiments activation in the insula has been confirmed, but activation in the orbitofrontal cortex is only infrequently found, especially at higher field strengths (3 T). Due to large susceptibility artefacts, the orbitofrontal cortex is a difficult region to examine with fMRI. Our aim was to localize taste in the human cortex at 3 T, specifically in the orbitofrontal cortex as well as in the primary gustatory cortex. Event-related fMRI was performed at 3 T in seven healthy volunteers. Taste stimuli consisted of lemon juice and chocolate. To visualize activation in the orbitofrontal cortex a dedicated 3D SENSE EPI fMRI sequence was used, in addition to a 2D SENSE EPI fMRI sequence for imaging the entire brain. Data were analyzed using a perception-based model. The dedicated 3D SENSE EPI sequence successfully reduced susceptibility artefacts in the orbitofrontal area. Significant taste-related activation was found in the orbitofrontal and insular cortices. fMRI of the orbitofrontal cortex is feasible at 3 T, using a dedicated sequence. Our results corroborate findings from previous studies. (orig.)

Effect of streptozotocin-induced diabetes on motor representations in the motor cortex and corticospinal tract in rats.

Science.gov (United States)

Muramatsu, Ken; Ikutomo, Masako; Tamaki, Toru; Shimo, Satoshi; Niwa, Masatoshi

2018-02-01

Motor disorders in patients with diabetes are associated with diabetic peripheral neuropathy, which can lead to symptoms such as lower extremity weakness. However, it is unclear whether central motor system disorders can disrupt motor function in patients with diabetes. In a streptozotocin-induced rat model of type 1 diabetes, we used intracortical microstimulation to evaluate motor representations in the motor cortex, recorded antidromic motor cortex responses to spinal cord stimulation to evaluate the function of corticospinal tract (CST) axons, and used retrograde labeling to evaluate morphological alterations of CST neurons. The diabetic rats exhibited size reductions in the hindlimb area at 4 weeks and in trunk and forelimb areas after 13 weeks, with the hindlimb and trunk area reductions being the most severe. Other areas were unaffected. Additionally, we observed reduced antidromic responses in CST neurons with axons projecting to lumbar spinal segments (CST-L) but not in those with axons projecting to cervical segments (CST-C). This was consistent with the observation that retrograde-labeled CST-L neurons were decreased in number following tracer injection into the spinal cord in diabetic animals but that CST-C neurons were preserved. These results show that diabetes disrupts the CST system components controlling hindlimb and trunk movement. This disruption may contribute to lower extremity weakness in patients. Copyright © 2017 Elsevier B.V. All rights reserved.

Serotonin-stimulated phosphoinositide turnover: mediation by the S2 binding site in rat cerebral cortex but not in subcortical regions

International Nuclear Information System (INIS)

Conn, P.J.; Sanders-Bush, E.

1985-01-01

In rat cerebral cortex, serotonin (5-HT) stimulates phosphoinositide turnover with an EC50 of 1 microM in the presence of pargyline. The EC50 is 16-fold higher in the absence of pargyline. Selective S2 antagonists inhibit 5-HT-stimulated phosphoinositide turnover. Schild analysis of the blockade by ketanserin of the 5-HT effect gives an estimated Kd of ketanserin for the phosphoinositide-linked receptor of 11.7 nM, which agrees with the Kd (3.5 nM) of [ 3 H]ketanserin for the S2 site. Furthermore, MK-212, 5-HT and 5-fluorotryptamine stimulate phosphoinositide turnover with potencies that resemble their potencies at the S2 but not the S1 binding site. Of 11 agonists tested, the tryptamine derivatives tend to be more efficacious than the piperazine derivatives. The selective S1 agonist 8-hydroxy-2-(di-N-propylamino)tetralin is inactive at stimulating phosphoinositide turnover. No significant relationship exists between the regional distributions of 5-HT-stimulated phosphoinositide turnover and S2 binding sites. Furthermore, the S2 antagonist ketanserin is less potent and less efficacious in hippocampus and limbic forebrain than in cerebral cortex. These data suggest that 5-HT-stimulated phosphoinositide turnover is linked to the S2 binding site in rat cerebral cortex. However, 5-HT increases phosphoinositide turnover in subcortical regions by mechanisms other than stimulation of the S2 receptor

Acute stress exposure preceding transient global brain ischemia exacerbates the decrease in cortical remodeling potential in the rat retrosplenial cortex.

Science.gov (United States)

Kutsuna, Nobuo; Yamashita, Akiko; Eriguchi, Takashi; Oshima, Hideki; Suma, Takeshi; Sakatani, Kaoru; Yamamoto, Takamitsu; Yoshino, Atsuo; Katayama, Yoichi

2014-01-01

Doublecortin (DCX)-immunoreactive (-ir) cells are candidates that play key roles in adult cortical remodeling. We have previously reported that DCX-ir cells decrease after stress exposure or global brain ischemia (GBI) in the cingulate cortex (Cg) of rats. Herein, we investigate whether the decrease in DCX-ir cells is exacerbated after GBI due to acute stress exposure preconditioning. Twenty rats were divided into 3 groups: acute stress exposure before GBI (Group P), non-stress exposure before GBI (Group G), and controls (Group C). Acute stress or GBI was induced by a forced swim paradigm or by transient bilateral common carotid artery occlusion, respectively. DCX-ir cells were investigated in the anterior cingulate cortex (ACC) and retrosplenial cortex (RS). The number of DCX-ir cells per unit area (mm(2)) decreased after GBI with or without stress preconditioning in the ACC and in the RS (ANOVA followed by a Tukey-type test, P<0.001). Moreover, compared to Group G, the number in Group P decreased significantly in RS (P<0.05), though not significantly in ACC. Many of the DCX-ir cells were co-localized with the GABAergic neuronal marker parvalbumin. The present study indicates that cortical remodeling potential of GABAergic neurons of Cg decreases after GBI, and moreover, the ratio of the decrease is exacerbated by acute stress preconditioning in the RS. Copyright © 2013 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

[Food-procuring stereotype movements is accompanied by changes of c-Fos gene expression in the amygdala and modulation of heart rate in rats].

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Dovgan', O V; Vlasenko, O V; Buzyka, T V; Maĭs'kyĭ, V O; Piliavs'kyĭ, O I; Maznychenko, A V

2012-01-01

The distribution of Fos-immunoreactive (Fos-ir) and NADPH Diaphorase reactive (NADPH-dr-) neurons in the different subnuclei of amygdala and insular cortex (on the level -2,12 to -3,14 mm from bregma), and the associated changes of heart rate (HR) in intact, food-deprivated and executed food-procuring movements of rats were studied. In comparison with other groups of animals, the mean number of the Fos-ir neurons in the central nucleus of amygdala (Ce) and the insular cortex (GI/DI) at all studied levels was significantly greater in the executed food-procuring movements in rats. The main focus of localization of the Fos-ir neurons was found in lateral part of the Ce (58.5 +/- 1.9 units in 40-microm-thick section) at the level -2.56 mm. The mean number of Fos-ir neurons was significantly greater also in the lateral and capsular parts of the Ce. The mean number of Fos-ir neurons in the GI/DI was 165.5 +/- 3.2 cells in section. The number and density of NADPH-d reactive neurons was not significantly different in the brain structures of all animal groups studied. The double stained neurons (Fos-ir + NADPH-dr) were registered in medial, basolateral, anterior cortical amygdaloid nuclei and substantia innominata (SI) in rats after realization food-procuring movements. It was found that realization of food-procuring movements by the forelimb during repeated sessions was accompanied with the gradual decline of mean values of the HR (from 5% to 12% of control level) with subsequent renewal of them to the initial values (tonic component). The analysis of dynamics of the HR changes during realization of separate purposeful motion has shown the transient period of the HR suppression (500 ms), which coincided with the terminal phase of grasping of food pellet (phasic component). We suggest that the revealed focuses of localization of Fos-ir neurons in the lateral and medial subregions of amigdaloid Ce and also GI/DI, and SI testified that these structures of brain are involved

Preventive Effects of Resveratrol on Endocannabinoid System and Synaptic Protein Modifications in Rat Cerebral Cortex Challenged by Bilateral Common Carotid Artery Occlusion and Reperfusion

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Gianfranca Carta

2018-01-01

Full Text Available This study aims to evaluate the putative roles of a single acute dose of resveratrol (RVT in preventing cerebral oxidative stress induced by bilateral common carotid artery occlusion, followed by reperfusion (BCCAO/R and to investigate RVT’s ability to preserve the neuronal structural integrity. Frontal and temporal-occipital cortices were examined in two groups of adult Wistar rats, sham-operated and submitted to BCCAO/R. In both groups, 6 h before surgery, half the rats were gavage-fed with a single dose of RVT (40 mg/per rat in 300 µL of sunflower oil as the vehicle, while the second half received the vehicle alone. In the frontal cortex, RVT pre-treatment prevented the BCCAO/R-induced increase of lipoperoxides, augmented concentrations of palmitoylethanolamide and docosahexaenoic acid, increased relative levels of the cannabinoid receptors type 1 (CB1 and 2 (CB2, and peroxisome-proliferator-activated-receptor (PPAR-α proteins. Increased expression of CB1/CB2 receptors mirrored that of synaptophysin and post-synaptic density-95 protein. No BCCAO/R-induced changes occurred in the temporal-occipital cortex. Collectively, our results demonstrate that, in the frontal cortex, RVT pre-treatment prevents the BCCAO/R-induced oxidative stress and modulates the endocannabinoid and PPAR-α systems. The increased expression of synaptic structural proteins further suggests the possible efficacy of RVT as a dietary supplement to preserve the nervous tissue metabolism and control the physiological response to the hypoperfusion/reperfusion challenge.

The effects of low dose ionizing radiation on the development of rat cerebral cortex, (1)

International Nuclear Information System (INIS)

Matsushita, Koji

1993-01-01

We obtained the following results with regards to the effects of low dose ionizing radiation (5, 10, 15 and 20 cGy) on neuronal migration of developing rat cerebral cortex. Neuronal migration delay was found by autoradiography after intraperitoneal labeling with 3 H-thymidine to pregnant Wistar rats embryonic 16, and low dose radiation an hour or 48 hours after labeling. In 15-20 cGy, N-CAM (neural cell adhesion molecules) staining patterns changed with immunohistochemical method, whereas those of L1 and cytoskeleton neurofilament (160 KD), tauprotein, MAP2 (microtubule associated protein 2) did not. After 24-48 hours of radiation, N-CAM were not detected on the matrix cell layer. After 72-96 hours of radiation, N-CAM staining recovered to a normal pattern. In conclusion, low dose radiation of 15-20 cGy gave rise to neuronal migration delay and it was suggested that N-CAM may be related to neuronal migration as one of the mechanisms involved. (author)

Cellular properties of principal neurons in the rat entorhinal cortex. I. The lateral entorhinal cortex

NARCIS (Netherlands)

Canto, C.B.; Witter, M.P.

2012-01-01

The lateral entorhinal cortex (LEC) provides a major cortical input to the hippocampal formation, equaling that of the medial entorhinal cortex (MEC). To understand the functional contributions made by LEC, basic knowledge of individual neurons, in the context of the intrinsic network, is needed.

Effect of cortex mori on pharmacokinetic profiles of main isoflavonoids from pueraria lobata in rat plasma.

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Xiao, Bingxin; Sun, Zengxian; Sun, Shu Yang; Dong, Jie; Li, Yanli; Gao, Shan; Pang, Jie; Chang, Qi

2017-09-14

Radix pueraria (the root of pueraria lobata (Wild.) Ohwi.), which contains a class of isoflavonoids as the main active components, as well as cortex mori (the root bark of Morus alba L), which contains abundant active alkaloids, have been employed for the treatment of diabetes in traditional Chinese medicine for centuries. In previous studies, pharmacodynamic synergistic reactions have been observed in compatible application of pueraria lobata isoflavonoids extracts (PLF) and cortex mori alkaloids extracts (CME) for inhibiting α-glycosidase activity. It has also been demonstrated that PLF can effectively slow down the absorption of active alkaloid from CME, so as to produce a higher effective concentration in small intestine for depressing the elevation of postprandial blood glucose through inhibiting α-glycosidase activity. In this study, the hypoglycemic effect of PLF, CME or CME-PLF mixture (the mixture of CME and PLF at a ratio of 1:6.3) was further evaluated through in vivo glucose tolerance studies. And the effect of CME on pharmacokinetic profiles of main isoflavonoids from PLF in rat plasma was investigated to further underlie compatibility mechanism of the two herbs. Four groups of rats received an oral dose of starch solution alone or simultaneously with drugs by gavage feeding. The blood samples were collected to determine glucose concentrations by glucose oxidase method. In addition, another two groups of rats were orally administered with PLF or CME-PLF. The plasma samples were collected and assayed using an LC/MS/MS method for comparatively pharmacokinetic studies of five main isoflavonoids. For starch loading, co-administration of CME-PLF resulted in more potent inhibition effects on glucose responses compared to those by CME or PLF in rat. The isoflavonoids from PLF were rapidly absorbed, presenting similarly low concentrations in plasma. When CME was added, the C max and AUC of all the five isoflavonoids were increased. A phenomenon of double

The biogeography of threatened insular iguanas and opportunities for invasive vertebrate management

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Tershy, Bernie R.; Newton, Kelly M.; Spatz, Dena R.; Swinnerton, Kirsty; Iverson, John B.; Fisher, Robert N.; Harlow, Peter S.; Holmes, Nick D.; Croll, Donald A.; Iverson, J.B.; Grant, T. D.; Knapp, C. R.; Pasachnik, S. A.

2016-01-01

Iguanas are a particularly threatened group of reptiles, with 61% of species at risk of extinction. Primary threats to iguanas include habitat loss, direct and indirect impacts by invasive vertebrates, overexploitation, and human disturbance. As conspicuous, charismatic vertebrates, iguanas also represent excellent flagships for biodiversity conservation. To assist planning for invasive vertebrate management and thus benefit threatened iguana recovery, we identified all islands with known extant or extirpated populations of Critically Endangered and Endangered insular iguana taxa as recognized by the International Union for Conservation of Nature (IUCN) Red List of Threatened Species. For each island, we determined total area, sovereignty, the presence of invasive alien vertebrates, and human population. For the 23 taxa of threatened insular iguanas we identified 230 populations, of which iguanas were extant on 185 islands and extirpated from 45 islands. Twenty-one iguana taxa (91% of all threatened insular iguana taxa) occurred on at least one island with invasive vertebrates present; 16 taxa had 100% of their population(s) on islands with invasive vertebrates present. Rodents, cats, ungulates, and dogs were the most common invasive vertebrates. We discuss biosecurity, eradication, and control of invasive vertebrates to benefit iguana recovery: (1) on islands already free of invasive vertebrates; (2) on islands with high iguana endemicity; and (3) for species and subspecies with small total populations occurring across multiple small islands. Our analyses provide an important first step toward understanding how invasive vertebrate management can be planned effectively to benefit threatened insular iguanas.

Protective effect and its mechanism of curcumin on ischemia-reperfusion injury of cerebral cortex in rats

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Li LIU

2013-03-01

Full Text Available Objective 　To investigate the effect of curcumin pretreatment on the expression of uncoupling protein 2 (UCP2 and mitochondrial transcription factor A (MTFA in rats' cerebral cortex against focal ischemia reperfusion injury. Methods 　Eighty male SD rats weighed 220g–300g were randomly divided into 4 groups: sham-operated group, ischemia/reperfusion (I/R group, curcumine 50mg/kg+I/R (low dose group, and curcumine 100mg/kg+I/R (high dose group. The common carotid artery, external carotid artery and internal carotid artery on the right side were exposed in the sham-operated group. Animals of the other groups were subjected to a 2-hour period of right middle cerebral artery occlusion, followed by 24 hours of reperfusion, and then they were sacrificed. Curcumin was administered (ip in a dose of 50mg/kg (low dose group or 100mg/kg (high dose group for 5 days, respectively, prior to arterial occlusion. The pathological changes in neurons and their mitochondria in the cerebral cortex supplied by middle cerebral artery were observed with Nissl staining and electron microscope, respectively. The expressions of UCP2 and MTFA in corresponding cotex were assessed by immunohistochemistry and RT-PCR. Results 　Compared with sham-operated group, animals in I/R group presented edema of neurons in the corresponding cortex, reduction in the number of Nissl bodies, and swelling of mitochondria with broken, even lysis of cristae. Low dose and high dose of curcumin pretreatment before brain ischemia significantly alleviated the loss of neurons and the damage of mitochondria, accompanied with an increase in the expression of UCP2 and TFAM (P<0.05, and the changes appeared a dose-dependent manner (P<0.05. Conclusions 　Curcumin may prevent neurons from focal cerebral ischemia reperfusion injury by up-regulating UCP2 and MTFA. Regulation of mitochondrial biogenesis may probably be a potential target of curcumin as a neuroprotective drug.

Impaired GABAergic inhibition in the prefrontal cortex of early postnatal phencyclidine (PCP)-treated rats.

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Kjaerby, Celia; Broberg, Brian V; Kristiansen, Uffe; Dalby, Nils Ole

2014-09-01

A compromised γ-aminobutyric acid (GABA)ergic system is hypothesized to be part of the underlying pathophysiology of schizophrenia. N-methyl-D-aspartate (NMDA) receptor hypofunction during neurodevelopment is proposed to disrupt maturation of interneurons causing an impaired GABAergic transmission in adulthood. The present study examines prefrontal GABAergic transmission in adult rats administered with the NMDA receptor channel blocker, phencyclidine (PCP), for 3 days during the second postnatal week. Whole-cell patch-clamp recordings from pyramidal cells in PCP-treated rats showed a 22% reduction in the frequency of miniature inhibitory postsynaptic currents in layer II/III, but not in layer V pyramidal neurons of the prefrontal cortex. Furthermore, early postnatal PCP treatment caused insensitivity toward effects of the GABA transporter 1 (GAT-1) inhibitor, 1,2,5,6-tetrahydro-1-[2-[[(diphenyl-methylene)amino]oxy]ethyl]-3-pyridinecarboxylic acid, and also diminished currents passed by δ-subunit-containing GABAA receptors in layer II/III pyramidal neurons. The observed impairments in GABAergic function are compatible with the alteration of GABAergic markers as well as cognitive dysfunction observed in early postnatal PCP-treated rats and support the hypothesis that PCP administration during neurodevelopment affects the functionality of interneurons in later life. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Protective role of curcumin against sulfite-induced structural changes in rats' medial prefrontal cortex.

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Noorafshan, Ali; Asadi-Golshan, Reza; Abdollahifar, Mohammad-Amin; Karbalay-Doust, Saied

2015-08-01

Sodium metabisulfite as a food preservative can affect the central nervous system. Curcumin, the main ingredient of turmeric has neuroprotective activity. This study was designed to evaluate the effects of sulfite and curcumin on the medial prefrontal cortex (mPFC) using stereological methods. Thirty rats were randomly divided into five groups. The rats in groups I-V received distilled water, olive oil, curcumin (100 mg/kg/day), sodium metabisulfite (25 mg/kg/day), and sulfite + curcumin, respectively, for 8 weeks. The brains were subjected to the stereological methods. Cavalieri and optical disector techniques were used to estimate the total volume of mPFC and the number of neurons and glial cells. Intersections counting were applied on the thick vertical uniform random sections to estimate the dendrites length, and classify the spines. Non-parametric tests were used to analyze the data. The mean mPFC volume, neurons number, glia number, dendritic length, and total spines per neuron were 3.7 mm(3), 365,000, 180,000, 1820 µm, and 1700 in distilled water group, respectively. A reduction was observed in the volume of mPFC (∼8%), number of neurons (∼15%), and number of glia (∼14%) in mPFC of the sulfite group compared to the control groups (P curcumin had a protective role against the changes in the rats.

Application of Awake Craniotomy and Intraoperative Brain Mapping for Surgical Resection of Insular Gliomas of the Dominant Hemisphere.

Science.gov (United States)

Alimohamadi, Maysam; Shirani, Mohammad; Shariat Moharari, Reza; Pour-Rashidi, Ahmad; Ketabchi, Mehdi; Khajavi, Mohammadreza; Arami, Mohamadali; Amirjamshidi, Abbas

2016-08-01

Radical resection of dominant insular gliomas is difficult because of their close vicinity with internal capsule, basal ganglia, and speech centers. Brain mapping techniques can be used to maximize the extent of tumor removal and to minimize postoperative morbidities by precise localization of eloquent cortical and subcortical areas. Patients with newly diagnosed gliomas of dominant insula were enrolled. The exclusion criteria were severe cognitive disturbances, communication difficulty, age greater than 75 years, severe obesity, difficult airways for intubation and severe cardiopulmonary diseases. All were evaluated preoperatively with contrast-enhanced brain magnetic resonance imaging (MRI), functional brain MRI, and diffusion tensor tractography of language and motor systems. All underwent awake craniotomy with the same anesthesiology protocol. Intraoperative monitoring included continuous motor-evoked potential, electromyography, electrocorticography, direct electrical stimulation of cortex, and subcortical tracts. The patients were followed with serial neurologic examination and imaging. Ten patients were enrolled (4 men, 6 women) with a mean age of 43.6 years. Seven patients suffered from low-grade glioma, and 3 patients had high-grade glioma. The most common clinical presentation was seizure followed by speech disturbance, hemiparesis, and memory loss. Extent of tumor resection ranged from 73% to 100%. No mortality or new major postoperative neurologic deficit was encountered. Seizure control improved in three fourths of patients with medical refractory epilepsy. In one patient with speech disorder at presentation, the speech problem became worse after surgery. Brain mapping during awake craniotomy helps to maximize extent of tumor resection while preserving neurologic function in patients with dominant insular lobe glioma. Copyright © 2016. Published by Elsevier Inc.

Layer-specific high-frequency spiking in the prefrontal cortex of awake rats

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Zimbo Saroeni Raymond Maria Boudewijns

2013-06-01

Full Text Available Cortical pyramidal neurons show irregular in vivo action potential (AP spiking with high frequency bursts occurring on sparse background activity. Somatic APs can backpropagate from soma into basal and apical dendrites and locally generate dendritic calcium spikes. The critical AP frequency for generation of such dendritic calcium spikes can be very different depending on cell-type or brain area involved. Previously, it was shown in vitro that calcium electrogenesis can also be induced in L(ayer 5 pyramidal neurons of prefrontal cortex (PFC. It remains an open question whether somatic burst spiking and resulting dendritic calcium electrogenesis also occur in morphologically more compact L2/3 pyramidal neurons. Furthermore, it is not known whether critical frequencies that trigger dendritic calcium electrogenesis occur in PFC under awake conditions in vivo. Here, we addressed these issues and found that pyramidal neurons in both PFC L2/3 and L5 in awake rats spike APs in short bursts, but with different probabilities. The critical frequency for calcium electrogenesis in vitro was layer-specific and lower in L5 neurons compared to L2/3. Taking the in vitro critical frequency as predictive measure for dendritic electrogenesis during in vivo spontaneous activity, supracritical bursts in vivo were observed in a larger fraction of L5 neurons compared to L2/3 neurons but with similar incidence within these subpopulations. Together, these results show that in PFC of awake rats, AP spiking occurs at frequencies that are relevant for dendritic calcium electrogenesis and suggest that in awake rat PFC, dendritic calcium electrogenesis may be involved in neuronal computation.

The effects of low dose ionizing radiation on the development of rat cerebral cortex, (2); In vitro study with regards to neuronal migration

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Matsushita, Koji [Kyoto Prefectural Univ. of Medicine (Japan)

1993-03-01

In order to study the molecular mechanisms of neuronal migration on developing rat cerebral cortex, we need a tissue culture system in which neuronal migration can be observed. We prepared a tissue culture system of embryonic rat cerebral cortex starting on embryonic day 16 and cultivating it for 48 hours. The autoradiographic study in this system revealed not only the migration of [sup 3]H-thymidine labeled neurons but also neuronal migration delays from low doses of ionizing radiation of more than 10 cGy. In addition, on immunohistochemical study, cell-cell adhesion molecule N-CAM staining was remarkably decreased in the matrix cell layer. In the tissue culture system where monoclonal anti-N-CAM antibodies were added, neuronal migration delay comparable to that of 20 cGy radiation was found. In conclusion, it was speculated that neuronal migration delay might be caused by disturbed N-CAM synthesis in matrix cells after low dose ionizing radiation. (author).

Effect of early and late rehabilitation onset in a chronic rat model of ischemic stroke- assessment of motor cortex signaling and gait functionality over time.

Science.gov (United States)

Nielsen, Rasmus K; Samson, Katrine L; Simonsen, Daniel; Jensen, Winnie

2013-11-01

The aim of the present study was to investigate the effects of ischemic stroke and onset of subsequent rehabilitation of gait function in rats. Nine male Sprague-Dawley rats were instrumented with a 16-channel intracortical (IC) electrode array. An ischemic stroke was induced within the hindlimb area of the left motor cortex. The rehabilitation consisted of a repetitive training paradigm over 28 days, initiated on day one ("Early-onset", 5 rats) and on day seven, ("Late-onset", 4 rats). Data were obtained from IC microstimulation tests, treadmill walking tests, and beam walking tests. Results revealed an expansion of the hindlimb representation within the motor cortex area and an increased amount of cortical firing rate modulation for the "Early-onset" group but not for the "Late-onset" group. Kinematic data revealed a significant change for both intervention groups. However, this difference was larger for the "Early-onset" group. Results from the beam walking test showed functional performance deficits following stroke which returned to pre-stroke level after the rehabilitative training. The results from the present study indicate the existence of a critical time period following stroke where onset of rehabilitative training may be more effective and related to a higher degree of true recovery.

Age-related decrease in the mitochondrial sirtuin deacetylase Sirt3 expression associated with ROS accumulation in the auditory cortex of the mimetic aging rat model.

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Zeng, Lingling; Yang, Yang; Hu, Yujuan; Sun, Yu; Du, Zhengde; Xie, Zhen; Zhou, Tao; Kong, Weijia

2014-01-01

Age-related dysfunction of the central auditory system, also known as central presbycusis, can affect speech perception and sound localization. Understanding the pathogenesis of central presbycusis will help to develop novel approaches to prevent or treat this disease. In this study, the mechanisms of central presbycusis were investigated using a mimetic aging rat model induced by chronic injection of D-galactose (D-Gal). We showed that malondialdehyde (MDA) levels were increased and manganese superoxide dismutase (SOD2) activity was reduced in the auditory cortex in natural aging and D-Gal-induced mimetic aging rats. Furthermore, mitochondrial DNA (mtDNA) 4834 bp deletion, abnormal ultrastructure and cell apoptosis in the auditory cortex were also found in natural aging and D-Gal mimetic aging rats. Sirt3, a mitochondrial NAD+-dependent deacetylase, has been shown to play a crucial role in controlling cellular reactive oxygen species (ROS) homeostasis. However, the role of Sirt3 in the pathogenesis of age-related central auditory cortex deterioration is still unclear. Here, we showed that decreased Sirt3 expression might be associated with increased SOD2 acetylation, which negatively regulates SOD2 activity. Oxidative stress accumulation was likely the result of low SOD2 activity and a decline in ROS clearance. Our findings indicate that Sirt3 might play an essential role, via the mediation of SOD2, in central presbycusis and that manipulation of Sirt3 expression might provide a new approach to combat aging and oxidative stress-related diseases.

Topography and collateralization of dopaminergic projections to primary motor cortex in rats.

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Hosp, Jonas A; Nolan, Helen E; Luft, Andreas R

2015-05-01

Dopaminergic signaling within the primary motor cortex (M1) is necessary for successful motor skill learning. Dopaminergic neurons projecting to M1 are located in the ventral tegmental area (VTA, nucleus A10) of the midbrain. It is unknown which behavioral correlates are encoded by these neurons. The objective here is to investigate whether VTA-M1 fibers are collaterals of projections to prefrontal cortex (PFC) or nucleus accumbens (NAc) or if they form a distinct pathway. In rats, multiple-site retrograde fluorescent tracers were injected into M1, PFC and the core region of the NAc and VTA sections investigated for concomitant labeling of different tracers. Dopaminergic neurons projecting to M1, PFC and NAc were found in nucleus A10 and to a lesser degree in the medial nucleus A9. Neurons show high target specificity, minimal collateral branching to other than their target area and hardly cross the midline. Whereas PFC- and NAc-projecting neurons are indistinguishably intermingled within the ventral portion of dopaminergic nuclei in middle and caudal midbrain, M1-projecting neurons are only located within the dorsal part of the rostral midbrain. Within M1, the forelimb representation receives sevenfold more dopaminergic projections than the hindlimb representation. This strong rostro-caudal gradient as well as the topographical preference to dorsal structures suggest that projections to M1 emerged late in the development of the dopaminergic systems in and form a functionally distinct system.

Asymmetric multisensory interactions of visual and somatosensory responses in a region of the rat parietal cortex.

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Michael T Lippert

Full Text Available Perception greatly benefits from integrating multiple sensory cues into a unified percept. To study the neural mechanisms of sensory integration, model systems are required that allow the simultaneous assessment of activity and the use of techniques to affect individual neural processes in behaving animals. While rodents qualify for these requirements, little is known about multisensory integration and areas involved for this purpose in the rodent. Using optical imaging combined with laminar electrophysiological recordings, the rat parietal cortex was identified as an area where visual and somatosensory inputs converge and interact. Our results reveal similar response patterns to visual and somatosensory stimuli at the level of current source density (CSD responses and multi-unit responses within a strip in parietal cortex. Surprisingly, a selective asymmetry was observed in multisensory interactions: when the somatosensory response preceded the visual response, supra-linear summation of CSD was observed, but the reverse stimulus order resulted in sub-linear effects in the CSD. This asymmetry was not present in multi-unit activity however, which showed consistently sub-linear interactions. These interactions were restricted to a specific temporal window, and pharmacological tests revealed significant local intra-cortical contributions to this phenomenon. Our results highlight the rodent parietal cortex as a system to model the neural underpinnings of multisensory processing in behaving animals and at the cellular level.

The blockade of the transient receptor potential vanilloid type 1 and fatty acid amide hydrolase decreases symptoms and central sequelae in the medial prefrontal cortex of neuropathic rats

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Di Marzo Vincenzo

2011-01-01

Full Text Available Abstract Background Neuropathic pain is a chronic disease resulting from dysfunction within the "pain matrix". The basolateral amygdala (BLA can modulate cortical functions and interactions between this structure and the medial prefrontal cortex (mPFC are important for integrating emotionally salient information. In this study, we have investigated the involvement of the transient receptor potential vanilloid type 1 (TRPV1 and the catabolic enzyme fatty acid amide hydrolase (FAAH in the morphofunctional changes occurring in the pre-limbic/infra-limbic (PL/IL cortex in neuropathic rats. Results The effect of N-arachidonoyl-serotonin (AA-5-HT, a hybrid FAAH inhibitor and TPRV1 channel antagonist, was tested on nociceptive behaviour associated with neuropathic pain as well as on some phenotypic changes occurring on PL/IL cortex pyramidal neurons. Those neurons were identified as belonging to the BLA-mPFC pathway by electrical stimulation of the BLA followed by hind-paw pressoceptive stimulus application. Changes in their spontaneous and evoked activity were studied in sham or spared nerve injury (SNI rats before or after repeated treatment with AA-5-HT. Consistently with the SNI-induced changes in PL/IL cortex neurons which underwent profound phenotypic reorganization, suggesting a profound imbalance between excitatory and inhibitory responses in the mPFC neurons, we found an increase in extracellular glutamate levels, as well as the up-regulation of FAAH and TRPV1 in the PL/IL cortex of SNI rats. Daily treatment with AA-5-HT restored cortical neuronal activity, normalizing the electrophysiological changes associated with the peripheral injury of the sciatic nerve. Finally, a single acute intra-PL/IL cortex microinjection of AA-5-HT transiently decreased allodynia more effectively than URB597 or I-RTX, a selective FAAH inhibitor or a TRPV1 blocker, respectively. Conclusion These data suggest a possible involvement of endovanilloids in the cortical

Effect of donepezil hydrochloride (E2020) on extracellular acetylcholine concentration in the cerebral cortex of rats.

Science.gov (United States)

Kosasa, T; Kuriya, Y; Yamanishi, Y

1999-10-01

Donepezil hydrochloride (donepezil), a potent and selective acetylcholinesterase inhibitor, has been developed for the treatment of Alzheimer's disease. We studied the effect of oral administration of this drug on the extracellular acetylcholine (ACh) concentration in the cerebral cortex of rats using microdialysis. We also observed fasciculation, a peripheral cholinergic sign induced by activation of neuromuscular transmission, after oral administration of the drug as an index of peripheral cholinergic activation. Other cholinesterase inhibitors, tacrine, ENA-713 and TAK-147, were used as reference drugs. Donepezil significantly and dose-dependently increased the extracellular ACh concentration in the rat cerebral cortex within the dose range of 2.5-10 mg/kg. Tacrine, ENA-713 and TAK-147 also elevated the extracellular concentration of ACh. The minimum effective doses of donepezil, tacrine, ENA-713 and TAK-147 were (< or = 2.5, 10, 10 and < or = 10 mg/kg, respectively. Donepezil produced fasciculation at doses of 2.5 mg/kg and above, with a dose-dependent increase in incidence and intensity. The reference compounds also induced fasciculation in a dose-dependent manner. The threshold doses of tacrine, ENA-713 and TAK-147 for fasciculation were 5, 2.5 and 2.5 mg/kg, respectively. The values of the ratio of the minimum effective dose for the ACh-increasing action to that for the fasciculation-producing action were: donepezil, < or = 1; tacrine, 2; ENA-713, 4; TAK-147, < or = 4. These results indicate that orally administered donepezil has a potent and selective activity on the central cholinergic system.

Development of neuropeptide Y (NPY) immunoreactive neurons in the rat occipital cortex: A combined immunohistochemical-autoradiographic study

International Nuclear Information System (INIS)

Cavanagh, M.E.; Parnavelas, J.G.

1990-01-01

The postnatal development of neuropeptide Y (NPY)-immunoreactive neurons, previously labeled with [3H]thymidine on embryonic days E14-E21, has been studied in the rat occipital cortex. Immunohistochemistry combined with autoradiography showed evidence of a modified inside-out pattern of maturation. NPY-neurons are generated between E14 and E20 and are found in layers II-VI of the cortex and the subcortical white matter. NPY neurons from all these birthdates are overproduced at first, although cells generated at E16 produce the greatest excess, followed by E15 and E17. Some of these transient neurons are found in the wrong layer for their birthdates, and their elimination produces a more correct alignment at maturity. However, most of the NPY neurons that survive are generated at E17, and these cells are found throughout layers II-VI with a preponderance in layer VI. This evidence is strongly suggestive of cell death rather than merely cessation of production of NPY

Circadian oscillations of molecular clock components in the cerebellar cortex of the rat

DEFF Research Database (Denmark)

Rath, Martin Fredensborg; Rohde, Kristian; Møller, Morten

2012-01-01

these genes, Per1, Per2, Per3, Cry1, Arntl, Nr1d1, and Dbp were found to exhibit circadian rhythms in a sequential temporal manner similar to that of the SCN, but with several hours of delay. The results of lesion studies indicate that the molecular oscillatory profiles of Per1, Per2, and Cry1......The central circadian clock of the mammalian brain resides in the suprachiasmatic nucleus (SCN) of the hypothalamus. At the molecular level, the circadian clockwork of the SCN constitutes a self-sustained autoregulatory feedback mechanism reflected by the rhythmic expression of clock genes. However...... in the cerebellum are controlled, though possibly indirectly, by the central clock of the SCN. These data support the presence of a circadian oscillator in the cortex of the rat cerebellum....

Opioid-receptor (OR) signaling cascades in rat cerebral cortex and model cell lines: the role of plasma membrane structure

Czech Academy of Sciences Publication Activity Database

Ujčíková, Hana; Brejchová, Jana; Vošahlíková, Miroslava; Kagan, Dmytro; Dlouhá, Kateřina; Sýkora, Jan; Merta, Ladislav; Drastichová, Z.; Novotný, J.; Ostašov, Pavel; Roubalová, Lenka; Parenti, M.; Hof, Martin; Svoboda, Petr

2014-01-01

Roč. 63, Suppl.1 (2014), S165-S176 ISSN 0862-8408 R&D Projects: GA ČR(CZ) GAP207/12/0919; GA ČR(CZ) GBP304/12/G069 Institutional support: RVO:67985823 ; RVO:61388955 Keywords : GPCR * morphine * mu-OR, delta-OR and kappa-OR * rat brain cortex * adenylyl cyclase I and II * proteomic analysis Subject RIV: CE - Biochemistry; CF - Physical ; Theoretical Chemistry (UFCH-W) Impact factor: 1.293, year: 2014

The R-enantiomer of citalopram counteracts escitalopram-induced increase in extracellular 5-HT in the frontal cortex of freely moving rats

DEFF Research Database (Denmark)

Mørk, A; Kreilgaard, Mads; Sánchez, C

2003-01-01

The selective serotonin (5-HT) reuptake inhibitor, citalopram, is a racemic mixture of an S(+)- and R(-)-enantiomer, escitalopram and R-citalopram, respectively. The present study compares the effects of escitalopram, R-citalopram and citalopram on extracellular levels of 5-HT in the frontal cortex...... of freely moving rats. In addition, co-injection of escitalopram and R-citalopram (ratios 1:2 and 1:4) were assessed. In some experiments escitalopram and R-citalopram were infused into the frontal cortex by reverse microdialysis. Finally, the extracellular level of escitalopram in the frontal cortex...... was studied after administration of escitalopram alone or in combination with R-citalopram. Escitalopram (1.0-3.9 mg/kg, s.c.) produced a greater maximal increase in extracellular 5-HT than citalopram (2.0-8.0 mg/kg, s.c.). R-citalopram (15.6 mg/kg s.c.) did not affect the 5-HT levels. When co-injected, R...

Effect of chronic usage of tramadol on motor cerebral cortex and testicular tissues of adult male albino rats and the effect of its withdrawal: histological, immunohistochemical and biochemical study.

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Ghoneim, Fatma M; Khalaf, Hanaa A; Elsamanoudy, Ayman Z; Helaly, Ahmed N

2014-01-01

This study was designed to demonstrate the histopathological and biochemical changes in rat cerebral cortex and testicles due to chronic usage of tramadol and the effect of withdrawal. Thirty adult male rats weighing 180-200 gm were classified into three groups; group I (control group) group II (10 rats received 50 mg/kg/day of tramadol intraperitoneally for 4 weeks) and group III (10 rats received the same dose as group II then kept 4 weeks later to study the effect of withdrawal). Histological and immunohistochemical examination of cerebral cortex and testicular specimens for Bax (apoptotic marker) were carried out. Testicular specimens were examined by electron microscopy. RT-PCR after RNA extraction from both specimens was done for the genes of some antioxidant enzymes .Also, malondialdehyde (MDA) was measured colourimetrically in tissues homogenizate. The results of this study demonstrated histological changes in testicular and brain tissues in group II compared to group I with increased apoptotic index proved by increased Bax expression. Moreover in this group increased MDA level with decreased gene expression of the antioxidant enzymes revealed oxidative stress. Group III showed signs of improvement but not returned completely normal. It could be concluded that administration of tramadol have histological abnormalities on both cerebral cortex and testicular tissues associated with oxidative stress in these organs. Also, there is increased apoptosis in both organs which regresses with withdrawal. These findings may provide a possible explanation for delayed fertility and psychological changes associated with tramadol abuse.

The insular cortex: relationship to skin conductance responses to facial expression of emotion in temporal lobe epilepsy.

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Banks, Sarah J; Bellerose, Jenny; Douglas, Danielle; Jones-Gotman, Marilyn

2014-03-01

The insula plays an important role both in emotion processing and in the generation of epileptic seizures. In the current study we examined thickness of insular cortices and bilateral skin conductance responses (SCR) in healthy subjects in addition to a small number of patients with temporal lobe epilepsy. SCR measures arousal and is used to assess non-conscious responses to emotional stimuli. We used two emotion tasks, one explicitly about emotion and the other implicit. The explicit task required judgments about emotions being expressed in photographs of faces, while the implicit one required judgments about the age of the people in the photographs. Patients and healthy differed in labeling neutral faces, but not other emotions. They also differed in their SCR to emotions, though the profile depended on which hand the recordings were from. Finally, we found relationships between the thickness of the insula and SCR to each task: in the healthy group the thickness of the left insula was related to SCR to the emotion-labeling task; in the patient group it was between the thickness of the right insula and SCR in the age-labeling task. These patterns were evident only for the right hand recordings, thus underscoring the importance of bilateral recordings.

Brain imaging signatures of the relationship between epidermal nerve fibers and heat pain perception.

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Tseng, Ming-Tsung; Kong, Yazhuo; Chiang, Ming-Chang; Chao, Chi-Chao; Tseng, Wen-Yih I; Hsieh, Sung-Tsang

2015-11-15

Although the small-diameter primary afferent fibers in the skin promptly respond to nociceptive stimuli and convey sensory inputs to the central nervous system, the neural signatures that underpin the relationship between cutaneous afferent fibers and pain perception remain elusive. We combined skin biopsy at the lateral aspect of the distal leg, which is used to quantify cutaneous afferent fibers, with fMRI, which is used to assess brain responses and functional connectivity, to investigate the relationship between cutaneous sensory nerves and the corresponding pain perception in the brain after applying heat pain stimulation to the dorsum of the right foot in healthy subjects. During painful stimulation, the degree of cutaneous innervation, as measured by epidermal nerve fiber density, was correlated with individual blood oxygen level-dependent (BOLD) signals of the posterior insular cortex and of the thalamus, periaqueductal gray, and rostral ventromedial medulla. Pain perception was associated with the activation of the anterior insular cortex and with the functional connectivity from the anterior insular cortex to the primary somatosensory cortex during painful stimulation. Most importantly, both epidermal nerve fiber density and activity in the posterior insular cortex showed a positive correlation with the strength of coupling under pain between the anterior insular cortex and the primary somatosensory cortex. Thus, our findings support the notion that the neural circuitry subserving pain perception interacts with the cerebral correlates of peripheral nociceptive fibers, which implicates an indirect role for skin nerves in human pain perception. Copyright © 2015 Elsevier Inc. All rights reserved.

The flexible use of multiple cue relationships in spatial navigation : A comparison of water maze performance following hippocampal, medial septal, prefrontal cortex, or posterior parietal cortex lesions

NARCIS (Netherlands)

Compton, DM; Griffith, HR; McDaniel, WF; Foster, RA; Davis, BK

Rats prepared with lesions of the prefrontal cortex, posterior parietal cortex, hippocampus, or medial septal area were tested for acquisition of a number of variations of the open-field water maze using a version of place learning assessment described by Eichenbaum, Stewart, and Morris (1991).

Hepatoprotective activity of Rhus oxyacantha root cortex extract against DDT-induced liver injury in rats.

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Ben Miled, Hanène; Barka, Zaineb Ben; Hallègue, Dorsaf; Lahbib, Karima; Ladjimi, Mohamed; Tlili, Mounira; Sakly, Mohsen; Rhouma, Khémais Ben; Ksouri, Riadh; Tebourbi, Olfa

2017-06-01

The present investigation aimed to study the antioxidant activity and hepatoprotective effects of ethyl acetate extract of R. oxyacantha root cortex (RE) against DDT-induced liver injury in male rats. The RE exhibited high total phenolic, flavonoid and condensed tannins contents. The antioxidant activity in vitro systems showed a significant potent free radical scavenging activity of the extract. The HPLC finger print of R. oxyacantha active extract showed the presence of five phenolic compounds with higher amounts of catechol and gallic acid. The in vivo results showed that a single intraperitoneal administration of DDT enhanced levels of hepatic markers (ALT, AST and LDH) in serum of experimental animals. It also increased the oxidative stress markers resulting in increased levels of the lipid peroxidation with a significant induction of SOD and GPx, metallothioneins (MTs) and a concomitant decrease of non protein thiols (NPSH) in liver. However, pretreatment of rats with RE at a dose of 150 and 300mg/kg body weight significantly lowered serum transaminases and LDH in treated rats. A significant reduction in hepatic thiobarbituric reactive substances and a decrease in antioxidant enzymes activities and hepatic MTs levels by treatment with plant extract against DDT, were observed. These biochemical changes were consistent with histopathological observations, suggesting marked hepatoprotective effect of RE with the two doses used. These results strongly suggest that treatment with ethyl acetate extract normalizes various biochemical parameters and protects the liver against DDT-induced oxidative damage in rats and thus help in evaluation of traditional claim on this plant. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Purification of lysosomal phospholipase A and demonstration of proteins that inhibit phospholipase A in a lysosomal fraction from rat kidney cortex

International Nuclear Information System (INIS)

Hostetler, K.Y.; Gardner, M.F.; Giordano, J.R.

1986-01-01

Phospholipase A has been isolated from a crude lysosomal fraction from rat kidney cortex and purified 7600-fold with a recovery of 9.8% of the starting activity. The purified enzyme is a glycoprotein having an isoelectric point of pH 5.4 and an apparent molecular weight of 30,000 by high-pressure liquid chromatography gel permeation. Naturally occurring inhibitors of lysosomal phospholipase A are present in two of the lysosomal-soluble protein fractions obtained in the purification. They inhibit hydrolysis of 1,2-di[1- 14 C]oleoylphosphatidylcholine by purified phospholipase A 1 with IC 50 values of 7-11 μg. The inhibition is abolished by preincubation with trypsin at 37 0 C, but preincubation with trypsin at 4 0 C has no effect, providing evidence that the inhibitors are proteins. The results suggest that the activity of lysosomal phospholipase A may be regulated in part by inhibitory proteins. Lysosomal phospholipase A from rat kidney hydrolyzes the sn-1 acyl group of phosphatidylcholine, does not require divalent cations for full activity, and is not inhibited by ethylenediaminetetraacetic acid. It has an acid pH optimum of 3.6-3.8. Neither rho-bromophenacyl bromide, diisopropyl fluorophosphate, nor mercuric ion inhibits phospholipase A 1 . In contrast to rat liver, which has two major isoenzymes of acid phospholipase A 1 , kidney cortex has only one isoenzyme of lysosomal phospholipase A 1

Purification of lysosomal phospholipase A and demonstration of proteins that inhibit phospholipase A in a lysosomal fraction from rat kidney cortex

Energy Technology Data Exchange (ETDEWEB)

Hostetler, K.Y.; Gardner, M.F.; Giordano, J.R.

1986-10-21

Phospholipase A has been isolated from a crude lysosomal fraction from rat kidney cortex and purified 7600-fold with a recovery of 9.8% of the starting activity. The purified enzyme is a glycoprotein having an isoelectric point of pH 5.4 and an apparent molecular weight of 30,000 by high-pressure liquid chromatography gel permeation. Naturally occurring inhibitors of lysosomal phospholipase A are present in two of the lysosomal-soluble protein fractions obtained in the purification. They inhibit hydrolysis of 1,2-di(1-/sup 14/C)oleoylphosphatidylcholine by purified phospholipase A/sub 1/ with IC/sub 50/ values of 7-11 ..mu..g. The inhibition is abolished by preincubation with trypsin at 37/sup 0/C, but preincubation with trypsin at 4/sup 0/C has no effect, providing evidence that the inhibitors are proteins. The results suggest that the activity of lysosomal phospholipase A may be regulated in part by inhibitory proteins. Lysosomal phospholipase A from rat kidney hydrolyzes the sn-1 acyl group of phosphatidylcholine, does not require divalent cations for full activity, and is not inhibited by ethylenediaminetetraacetic acid. It has an acid pH optimum of 3.6-3.8. Neither rho-bromophenacyl bromide, diisopropyl fluorophosphate, nor mercuric ion inhibits phospholipase A/sub 1/. In contrast to rat liver, which has two major isoenzymes of acid phospholipase A/sub 1/, kidney cortex has only one isoenzyme of lysosomal phospholipase A/sub 1/.

Effects of chronic REM sleep restriction on D1 receptor and related signal pathways in rat prefrontal cortex.

Science.gov (United States)

Han, Yan; Wen, Xiaosa; Rong, Fei; Chen, Xinmin; Ouyang, Ruying; Wu, Shuai; Nian, Hua; Ma, Wenling

2015-01-01

The prefrontal cortex (PFC) mediates cognitive function that is sensitive to disruption by sleep loss, and molecular mechanisms regulating neural dysfunction induced by chronic sleep restriction (CSR), particularly in the PFC, have yet to be completely understood. The aim of the present study was to investigate the effect of chronic REM sleep restriction (REM-CSR) on the D1 receptor (D1R) and key molecules in D1R' signal pathways in PFC. We employed the modified multiple platform method to create the REM-CSR rat model. The ultrastructure of PFC was observed by electron microscopy. HPLC was performed to measure the DA level in PFC. The expressions of genes and proteins of related molecules were assayed by real-time PCR and Western blot, respectively. The general state and morphology of PFC in rats were changed by CSR, and DA level and the expression of D1R in PFC were markedly decreased (P CSR rats (P CSR induced cognitive dysfunction, and the PKA pathway of D1R may play an important role in the impairment of advanced neural function.

Multiphysics and Thermal Response Models to Improve Accuracy of Local Temperature Estimation in Rat Cortex under Microwave Exposure

Science.gov (United States)

Kodera, Sachiko; Gomez-Tames, Jose; Hirata, Akimasa; Masuda, Hiroshi; Arima, Takuji; Watanabe, Soichi

2017-01-01

The rapid development of wireless technology has led to widespread concerns regarding adverse human health effects caused by exposure to electromagnetic fields. Temperature elevation in biological bodies is an important factor that can adversely affect health. A thermophysiological model is desired to quantify microwave (MW) induced temperature elevations. In this study, parameters related to thermophysiological responses for MW exposures were estimated using an electromagnetic-thermodynamics simulation technique. To the authors’ knowledge, this is the first study in which parameters related to regional cerebral blood flow in a rat model were extracted at a high degree of accuracy through experimental measurements for localized MW exposure at frequencies exceeding 6 GHz. The findings indicate that the improved modeling parameters yield computed results that match well with the measured quantities during and after exposure in rats. It is expected that the computational model will be helpful in estimating the temperature elevation in the rat brain at multiple observation points (that are difficult to measure simultaneously) and in explaining the physiological changes in the local cortex region. PMID:28358345

Age-related decrease in the mitochondrial sirtuin deacetylase Sirt3 expression associated with ROS accumulation in the auditory cortex of the mimetic aging rat model.

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Lingling Zeng

Full Text Available Age-related dysfunction of the central auditory system, also known as central presbycusis, can affect speech perception and sound localization. Understanding the pathogenesis of central presbycusis will help to develop novel approaches to prevent or treat this disease. In this study, the mechanisms of central presbycusis were investigated using a mimetic aging rat model induced by chronic injection of D-galactose (D-Gal. We showed that malondialdehyde (MDA levels were increased and manganese superoxide dismutase (SOD2 activity was reduced in the auditory cortex in natural aging and D-Gal-induced mimetic aging rats. Furthermore, mitochondrial DNA (mtDNA 4834 bp deletion, abnormal ultrastructure and cell apoptosis in the auditory cortex were also found in natural aging and D-Gal mimetic aging rats. Sirt3, a mitochondrial NAD+-dependent deacetylase, has been shown to play a crucial role in controlling cellular reactive oxygen species (ROS homeostasis. However, the role of Sirt3 in the pathogenesis of age-related central auditory cortex deterioration is still unclear. Here, we showed that decreased Sirt3 expression might be associated with increased SOD2 acetylation, which negatively regulates SOD2 activity. Oxidative stress accumulation was likely the result of low SOD2 activity and a decline in ROS clearance. Our findings indicate that Sirt3 might play an essential role, via the mediation of SOD2, in central presbycusis and that manipulation of Sirt3 expression might provide a new approach to combat aging and oxidative stress-related diseases.

Hydrocephalus compacted cortex and hippocampus and altered their output neurons in association with spatial learning and memory deficits in rats.

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Chen, Li-Jin; Wang, Yueh-Jan; Chen, Jeng-Rung; Tseng, Guo-Fang

2017-07-01

Hydrocephalus is a common neurological disorder in children characterized by abnormal dilation of cerebral ventricles as a result of the impairment of cerebrospinal fluid flow or absorption. Clinical presentation of hydrocephalus varies with chronicity and often shows cognitive dysfunction. Here we used a kaolin-induction method in rats and studied the effects of hydrocephalus on cerebral cortex and hippocampus, the two regions highly related to cognition. Hydrocephalus impaired rats' performance in Morris water maze task. Serial three-dimensional reconstruction from sections of the whole brain freshly froze in situ with skull shows that the volumes of both structures were reduced. Morphologically, pyramidal neurons of the somatosensory cortex and hippocampus appear to be distorted. Intracellular dye injection and subsequent three-dimensional reconstruction and analyses revealed that the dendritic arbors of layer III and V cortical pyramid neurons were reduced. The total dendritic length of CA1, but not CA3, pyramidal neurons was also reduced. Dendritic spine densities on both cortical and hippocampal pyramidal neurons were decreased, consistent with our concomitant findings that the expressions of both synaptophysin and postsynaptic density protein 95 were reduced. These cortical and hippocampal changes suggest reductions of excitatory connectivity, which could underlie the learning and memory deficits in hydrocephalus. © 2016 International Society of Neuropathology.

Effects of medial prefrontal cortex lesions in rats on the what-where-when memory of a fear conditioning event.

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Li, Jay-Shake; Hsiao, Kun-Yuan; Chen, Wei-Min

2011-03-17

Previous animal studies have defined the ability to remember the details of what, where, and when of an event as an episodic-like memory to be used to model episodic memory in humans. Numerous findings indicate that the hippocampal-frontal cortical circuitry plays a major part in its neural mechanism. Researchers have intensively studied roles of diverse hippocampus sub-regions using animal models. By contrast, the impact of prefrontal cortex lesions on episodic-like memory in animals is still unknown. Here we show that Wistar rats with bilateral medial prefrontal cortex lesions failed to use the temporal-contextual information to retrieve memory of a fear-conditioning event, indicating impairments in their episodic-like memory. Subsequent experiments excluded alternative interpretations that the manipulation impaired the fear-conditioning per se, or interfered with the sensory preconditioning process. We concluded that damages in this area might impair temporal information processing, or interfere with integrating temporal and contextual elements of fear-conditioning events to form a conjunctive entity. These findings can help understand how the medial prefrontal cortex contributes to episodic-like memory. Copyright © 2010 Elsevier B.V. All rights reserved.

Forelimb training drives transient map reorganization in ipsilateral motor cortex.

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Pruitt, David T; Schmid, Ariel N; Danaphongse, Tanya T; Flanagan, Kate E; Morrison, Robert A; Kilgard, Michael P; Rennaker, Robert L; Hays, Seth A

2016-10-15

Skilled motor training results in reorganization of contralateral motor cortex movement representations. The ipsilateral motor cortex is believed to play a role in skilled motor control, but little is known about how training influences reorganization of ipsilateral motor representations of the trained limb. To determine whether training results in reorganization of ipsilateral motor cortex maps, rats were trained to perform the isometric pull task, an automated motor task that requires skilled forelimb use. After either 3 or 6 months of training, intracortical microstimulation (ICMS) mapping was performed to document motor representations of the trained forelimb in the hemisphere ipsilateral to that limb. Motor training for 3 months resulted in a robust expansion of right forelimb representation in the right motor cortex, demonstrating that skilled motor training drives map plasticity ipsilateral to the trained limb. After 6 months of training, the right forelimb representation in the right motor cortex was significantly smaller than the representation observed in rats trained for 3 months and similar to untrained controls, consistent with a normalization of motor cortex maps. Forelimb map area was not correlated with performance on the trained task, suggesting that task performance is maintained despite normalization of cortical maps. This study provides new insights into how the ipsilateral cortex changes in response to skilled learning and may inform rehabilitative strategies to enhance cortical plasticity to support recovery after brain injury. Copyright © 2016 Elsevier B.V. All rights reserved.

Motor cortex is required for learning but not for executing a motor skill.

Science.gov (United States)

Kawai, Risa; Markman, Timothy; Poddar, Rajesh; Ko, Raymond; Fantana, Antoniu L; Dhawale, Ashesh K; Kampff, Adam R; Ölveczky, Bence P

2015-05-06

Motor cortex is widely believed to underlie the acquisition and execution of motor skills, but its contributions to these processes are not fully understood. One reason is that studies on motor skills often conflate motor cortex's established role in dexterous control with roles in learning and producing task-specific motor sequences. To dissociate these aspects, we developed a motor task for rats that trains spatiotemporally precise movement patterns without requirements for dexterity. Remarkably, motor cortex lesions had no discernible effect on the acquired skills, which were expressed in their distinct pre-lesion forms on the very first day of post-lesion training. Motor cortex lesions prior to training, however, rendered rats unable to acquire the stereotyped motor sequences required for the task. These results suggest a remarkable capacity of subcortical motor circuits to execute learned skills and a previously unappreciated role for motor cortex in "tutoring" these circuits during learning. Copyright © 2015 Elsevier Inc. All rights reserved.

Postnatal changes in the nitric oxide system of the rat cerebral cortex after hypoxia during delivery.

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Fernández, Ana Patricia; Alonso, David; Lisazoaín, Ignacio; Serrano, Julia; Leza, Juan Carlos; Bentura, María Luisa; López, Juan Carlos; Manuel Encinas, Juan; Fernández-Vizarra, Paula; Castro-Blanco, Susana; Martínez, Alfredo; Martinez-Murillo, Ricardo; Lorenzo, Pedro; Pedrosa, Juan Angel; Peinado, María Angeles; Rodrigo, José

2003-05-14

The impact of hypoxia in utero during delivery was correlated with the immunocytochemistry, expression and activity of the neuronal (nNOS) and inducible (iNOS) isoforms of the nitric oxide synthase enzyme as well as with the reactivity and expression of nitrotyrosine as a marker of protein nitration during early postnatal development of the cortex. The expression of nNOS in both normal and hypoxic animals increased during the first few postnatal days, reaching a peak at day P5, but a higher expression was consistently found in hypoxic brain. This expression decreased progressively from P7 to P20, but was more prominent in the hypoxic group. Immunoreactivity for iNOS was also higher in the cortex of the hypoxic rats and was more evident between days P0 and P5, decreasing dramatically between P10 and P20 in both groups of rats. Two nitrated proteins of 52 and 38 kDa, were also identified. Nitration of the 52-kDa protein was more intense in the hypoxic animals than in the controls, increasing from P0 to P7 and then decreasing progressively to P20. The 38-kDa nitrated protein was seen only from P10 to P20, and its expression was more intense in control than in the hypoxic group. These results suggest that the NO system may be involved in neuronal maturation and cortical plasticity over postnatal development. Overproduction of NO in the brain of hypoxic animals may constitute an effort to re-establish normal blood flow and may also trigger a cascade of free-radical reactions, leading to modifications in the cortical plasticity.

Activation of 5-HT2 receptors enhances the release of acetylcholine in the prefrontal cortex and hippocampus of the rat.

Science.gov (United States)

Nair, Sunila G; Gudelsky, Gary A

2004-09-15

The role of 5-HT2 receptors in the regulation of acetylcholine (ACh) release was examined in the medial prefrontal cortex and dorsal hippocampus using in vivo microdialysis. The 5-HT(2A/2C) agonist +/-1-(2,5-dimethoxy-4-iodophenyl) -2- aminopropane hydrochloride (DOI) (1 and 2 mg/kg, i.p.) significantly increased the extracellular concentration of ACh in both brain regions, and this response was attenuated in rats treated with the 5-HT(2A/2B/2C) antagonist LY-53,857 (3 mg/kg, i.p.). Treatment with LY-53,857 alone did not significantly alter ACh release in either brain region The 5-HT(2C) agonist 6-chloro-2-(1-piperazinyl)-pyrazine) (MK-212) (5 mg/kg, i.p.) significantly enhanced the release of ACh in both the prefrontal cortex and hippocampus, whereas the 5-HT2 agonist mescaline (10 mg/kg, i.p.) produced a 2-fold increase in ACh release only in the prefrontal cortex. Intracortical, but not intrahippocampal, infusion of DOI (100 microM) significantly enhanced the release of ACh, and intracortical infusion of LY-53,857 (100 microM) significantly attenuated this response. These results suggest that the release of ACh in the prefrontal cortex and hippocampus is influenced by 5-HT2 receptor mechanisms. The increase in release of ACh induced by DOI in the prefrontal cortex, but not in the hippocampus, appears to be due to 5-HT2 receptor mechanisms localized within this brain region. Furthermore, it appears that the prefrontal cortex is more sensitive than the dorsal hippocampus to the stimulatory effect of 5-HT2 agonists on ACh release.

Distinct GABAergic targets of feedforward and feedback connections between lower and higher areas of rat visual cortex.

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Gonchar, Yuri; Burkhalter, Andreas

2003-11-26

Processing of visual information is performed in different cortical areas that are interconnected by feedforward (FF) and feedback (FB) pathways. Although FF and FB inputs are excitatory, their influences on pyramidal neurons also depend on the outputs of GABAergic neurons, which receive FF and FB inputs. Rat visual cortex contains at least three different families of GABAergic neurons that express parvalbumin (PV), calretinin (CR), and somatostatin (SOM) (Gonchar and Burkhalter, 1997). To examine whether pathway-specific inhibition (Shao and Burkhalter, 1996) is attributable to distinct connections with GABAergic neurons, we traced FF and FB inputs to PV, CR, and SOM neurons in layers 1-2/3 of area 17 and the secondary lateromedial area in rat visual cortex. We found that in layer 2/3 maximally 2% of FF and FB inputs go to CR and SOM neurons. This contrasts with 12-13% of FF and FB inputs onto layer 2/3 PV neurons. Unlike inputs to layer 2/3, connections to layer 1, which contains CR but lacks SOM and PV somata, are pathway-specific: 21% of FB inputs go to CR neurons, whereas FF inputs to layer 1 and its CR neurons are absent. These findings suggest that FF and FB influences on layer 2/3 pyramidal neurons mainly involve disynaptic connections via PV neurons that control the spike outputs to axons and proximal dendrites. Unlike FF input, FB input in addition makes a disynaptic link via CR neurons, which may influence the excitability of distal pyramidal cell dendrites in layer 1.

A new and specific non-NMDA receptor antagonist, FG 9065, blocks L-AP4-evoked depolarization in rat cerebral cortex.

Science.gov (United States)

Sheardown, M J

1988-04-13

L(+)-AP4 (2-amino-4-phosphonobutyrate) depolarized slices of rat cerebral cortex, when applied following a 2 min priming application of quisqualate. This response diminishes with time and is not seen after NMDA application. A new selective non-N-methyl-D-aspartate (NMDA) antagonist, 6-cyano-7-nitro-2,3-dihydroxyquinoxaline (FG 9065), inhibits the L(+)-AP4 depolarization. It is argued that the response is mediated indirectly by postsynaptic quisqualate receptors.

Substance P signalling in primary motor cortex facilitates motor learning in rats.

Directory of Open Access Journals (Sweden)

Benjamin Hertler

Full Text Available Among the genes that are up-regulated in response to a reaching training in rats, Tachykinin 1 (Tac1-a gene that encodes the neuropeptide Substance P (Sub P-shows an especially strong expression. Using Real-Time RT-PCR, a detailed time-course of Tac1 expression could be defined: a significant peak occurs 7 hours after training ended at the first and second training session, whereas no up-regulation could be detected at a later time-point (sixth training session. To assess the physiological role of Sub P during movement acquisition, microinjections into the primary motor cortex (M1 contralateral to the trained paw were performed. When Sub P was injected before the first three sessions of a reaching training, effectiveness of motor learning became significantly increased. Injections at a time-point when rats already knew the task (i.e. training session ten and eleven had no effect on reaching performance. Sub P injections did not influence the improvement of performance within a single training session, but retention of performance between sessions became strengthened at a very early stage (i.e. between baseline-training and first training session. Thus, Sub P facilitates motor learning in the very early phase of skill acquisition by supporting memory consolidation. In line with these findings, learning related expression of the precursor Tac1 occurs at early but not at later time-points during reaching training.

Substance P signalling in primary motor cortex facilitates motor learning in rats.

Science.gov (United States)

Hertler, Benjamin; Hosp, Jonas Aurel; Blanco, Manuel Buitrago; Luft, Andreas Rüdiger

2017-01-01

Among the genes that are up-regulated in response to a reaching training in rats, Tachykinin 1 (Tac1)-a gene that encodes the neuropeptide Substance P (Sub P)-shows an especially strong expression. Using Real-Time RT-PCR, a detailed time-course of Tac1 expression could be defined: a significant peak occurs 7 hours after training ended at the first and second training session, whereas no up-regulation could be detected at a later time-point (sixth training session). To assess the physiological role of Sub P during movement acquisition, microinjections into the primary motor cortex (M1) contralateral to the trained paw were performed. When Sub P was injected before the first three sessions of a reaching training, effectiveness of motor learning became significantly increased. Injections at a time-point when rats already knew the task (i.e. training session ten and eleven) had no effect on reaching performance. Sub P injections did not influence the improvement of performance within a single training session, but retention of performance between sessions became strengthened at a very early stage (i.e. between baseline-training and first training session). Thus, Sub P facilitates motor learning in the very early phase of skill acquisition by supporting memory consolidation. In line with these findings, learning related expression of the precursor Tac1 occurs at early but not at later time-points during reaching training.

Low level postnatal methylmercury exposure in vivo alters developmental forms of short-term synaptic plasticity in the visual cortex of rat

International Nuclear Information System (INIS)

Dasari, Sameera; Yuan, Yukun

2009-01-01

Methylmercury (MeHg) has been previously shown to affect neurotransmitter release. Short-term synaptic plasticity (STP) is primarily related to changes in the probability of neurotransmitter release. To determine if MeHg affects STP development, we examined STP forms in the visual cortex of rat following in vivo MeHg exposure. Neonatal rats received 0 (0.9% NaCl), 0.75 or 1.5 mg/kg/day MeHg subcutaneously for 15 or 30 days beginning on postnatal day 5, after which visual cortical slices were prepared for field potential recordings. In slices prepared from rats treated with vehicle, field excitatory postsynaptic potentials (fEPSPs) evoked by paired-pulse stimulation at 20-200 ms inter-stimulus intervals showed a depression (PPD) of the second fEPSP (fEPSP2). PPD was also seen in slices prepared from rats after 15 day treatment with 0.75 or 1.5 mg/kg/day MeHg. However, longer duration treatment (30 days) with either dose of MeHg resulted in paired-pulse facilitation (PPF) of fEPSP2 in the majority of slices examined. PPF remained observable in slices prepared from animals in which MeHg exposure had been terminated for 30 days after completion of the initial 30 day MeHg treatment, whereas slices from control animals still showed PPD. MeHg did not cause any frequency- or region-preferential effect on STP. Manipulations of [Ca 2+ ] e or application of the GABA A receptor antagonist bicuculline could alter the strength and polarity of MeHg-induced changes in STP. Thus, these data suggest that low level postnatal MeHg exposure interferes with the developmental transformation of STP in the visual cortex, which is a long-lasting effect.

The action of piracetam on 14C-glucose metabolism in normal and posthypoxic rat cerebral cortex slices

International Nuclear Information System (INIS)

Domanska-Janik, K.; Zaleska, M.

1977-01-01

The stimulating effect of piracetam on the respiration and glycolysis was observed in rat brain cortex slices incubated under oxygen atmosphere. After preincubation of the slices under pure nitrogen atmosphere, piracetam influenced also decarboxylation of the C 1 -glucose carbon, indicating stimulation of the pentose cycle. Any significant effect of piracetam on the lowered by anoxia incorporation of 14 C from U- 14 C-glucose into macromolecular fractions was not observed. The results have supported a protective effect of piracetam against oxygen deficiency, caused mainly by stimulation of metabolic glucose pathways, connected with energy production in CNS. (author)

Brain Responses during the Anticipation of Dyspnea.

Science.gov (United States)

Stoeckel, M Cornelia; Esser, Roland W; Gamer, Matthias; Büchel, Christian; von Leupoldt, Andreas

2016-01-01

Dyspnea is common in many cardiorespiratory diseases. Already the anticipation of this aversive symptom elicits fear in many patients resulting in unfavorable health behaviors such as activity avoidance and sedentary lifestyle. This study investigated brain mechanisms underlying these anticipatory processes. We induced dyspnea using resistive-load breathing in healthy subjects during functional magnetic resonance imaging. Blocks of severe and mild dyspnea alternated, each preceded by anticipation periods. Severe dyspnea activated a network of sensorimotor, cerebellar, and limbic areas. The left insular, parietal opercular, and cerebellar cortices showed increased activation already during dyspnea anticipation. Left insular and parietal opercular cortex showed increased connectivity with right insular and anterior cingulate cortex when severe dyspnea was anticipated, while the cerebellum showed increased connectivity with the amygdala. Notably, insular activation during dyspnea perception was positively correlated with midbrain activation during anticipation. Moreover, anticipatory fear was positively correlated with anticipatory activation in right insular and anterior cingulate cortex. The results demonstrate that dyspnea anticipation activates brain areas involved in dyspnea perception. The involvement of emotion-related areas such as insula, anterior cingulate cortex, and amygdala during dyspnea anticipation most likely reflects anticipatory fear and might underlie the development of unfavorable health behaviors in patients suffering from dyspnea.

The medial prefrontal cortex and nucleus accumbens mediate the motivation for voluntary wheel running in the rat.

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Basso, Julia C; Morrell, Joan I

2015-08-01

Voluntary wheel running in rats provides a preclinical model of exercise motivation in humans. We hypothesized that rats run because this activity has positive incentive salience in both the acquisition and habitual stages of wheel running and that gender differences might be present. Additionally, we sought to determine which forebrain regions are essential for the motivational processes underlying wheel running in rats. The motivation for voluntary wheel running in male and female Sprague-Dawley rats was investigated during the acquisition (Days 1-7) and habitual phases (after Day 21) of running using conditioned place preference (CPP) and the reinstatement (rebound) response after forced abstinence, respectively. Both genders displayed a strong CPP for the acquisition phase and a strong rebound response to wheel deprivation during the habitual phase, suggesting that both phases of wheel running are rewarding for both sexes. Female rats showed a 1.5 times greater rebound response than males to wheel deprivation in the habitual phase of running, while during the acquisition phase, no gender differences in CPP were found. We transiently inactivated the medial prefrontal cortex (mPFC) or the nucleus accumbens (NA), hypothesizing that because these regions are involved in the acquisition and reinstatement of self-administration of both natural and pharmacological stimuli, they might also serve a role in the motivation to wheel run. Inactivation of either structure decreased the rebound response in the habitual phase of running, demonstrating that these structures are involved in the motivation for this behavior. (c) 2015 APA, all rights reserved).

Susceptibility to infection and immune response in insular and continental populations of Egyptian vulture: implications for conservation.

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Laura Gangoso

Full Text Available BACKGROUND: A generalized decline in populations of Old World avian scavengers is occurring on a global scale. The main cause of the observed crisis in continental populations of these birds should be looked for in the interaction between two factors -- changes in livestock management, including the increased use of pharmaceutical products, and disease. Insular vertebrates seem to be especially susceptible to diseases induced by the arrival of exotic pathogens, a process often favored by human activities, and sedentary and highly dense insular scavengers populations may be thus especially exposed to infection by such pathogens. Here, we compare pathogen prevalence and immune response in insular and continental populations of the globally endangered Egyptian vulture under similar livestock management scenarios, but with different ecological and evolutionary perspectives. METHODS/PRINCIPAL FINDINGS: Adult, immature, and fledgling vultures from the Canary Islands and the Iberian Peninsula were sampled to determine a the prevalence of seven pathogen taxa and b their immunocompetence, as measured by monitoring techniques (white blood cells counts and immunoglobulins. In the Canarian population, pathogen prevalence was higher and, in addition, an association among pathogens was apparent, contrary to the situation detected in continental populations. Despite that, insular fledglings showed lower leukocyte profiles than continental birds and Canarian fledglings infected by Chlamydophila psittaci showed poorer cellular immune response. CONCLUSIONS/SIGNIFICANCE: A combination of environmental and ecological factors may contribute to explain the high susceptibility to infection found in insular vultures. The scenario described here may be similar in other insular systems where populations of carrion-eaters are in strong decline and are seriously threatened. Higher susceptibility to infection may be a further factor contributing decisively to the extinction

Electrical stimulation of motor cortex in the uninjured hemisphere after chronic unilateral injury promotes recovery of skilled locomotion through ipsilateral control.

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Carmel, Jason B; Kimura, Hiroki; Martin, John H

2014-01-08

Partial injury to the corticospinal tract (CST) causes sprouting of intact axons at their targets, and this sprouting correlates with functional improvement. Electrical stimulation of motor cortex augments sprouting of intact CST axons and promotes functional recovery when applied soon after injury. We hypothesized that electrical stimulation of motor cortex in the intact hemisphere after chronic lesion of the CST in the other hemisphere would restore function through ipsilateral control. To test motor skill, rats were trained and tested to walk on a horizontal ladder with irregularly spaced rungs. Eight weeks after injury, produced by pyramidal tract transection, half of the rats received forelimb motor cortex stimulation of the intact hemisphere. Rats with injury and stimulation had significantly improved forelimb control compared with rats with injury alone and achieved a level of proficiency similar to uninjured rats. To test whether recovery of forelimb function was attributable to ipsilateral control, we selectively inactivated the stimulated motor cortex using the GABA agonist muscimol. The dose of muscimol we used produces strong contralateral but no ipsilateral impairments in naive rats. In rats with injury and stimulation, but not those with injury alone, inactivation caused worsening of forelimb function; the initial deficit was reinstated. These results demonstrate that electrical stimulation can promote recovery of motor function when applied late after injury and that motor control can be exerted from the ipsilateral motor cortex. These results suggest that the uninjured motor cortex could be targeted for brain stimulation in people with large unilateral CST lesions.

G-protein activity in Percoll-purified plasma membranes, bulk plasma membranes, and low-density plasma membranes isolated from rat cerebral cortex

Czech Academy of Sciences Publication Activity Database

Bouřová, Lenka; Stöhr, Jiří; Lisý, Václav; Rudajev, Vladimír; Novotný, Jiří; Svoboda, Petr

2009-01-01

Roč. 15, č. 4 (2009), BR111-BR122 ISSN 1234-1010 R&D Projects: GA MŠk(CZ) LC554; GA MŠk(CZ) LC06063; GA ČR(CZ) GA309/06/0121; GA AV ČR(CZ) IAA500110606 Institutional research plan: CEZ:AV0Z50110509 Keywords : rat cerebral cortex * plasma membrane * G-protein activity Subject RIV: CE - Biochemistry Impact factor: 1.543, year: 2009

Vocabular Clarity and Insular Scandinavian: A response

OpenAIRE

Enger, Hans-Olav

2017-01-01

In his article “Testing Vocabular Clarity in insular Scandinavian”, Haukur Þorgeirsson (HT) discusses the analysis of Faroese noun inflection presented in Enger (2013a). It is rewarding to see that the NBP/VC motivates careful consideration of alternative analyses and additional facts. HT raises valid questions and interesting challenges, including issues that were not dealt with in sufficient detail by Enger (2013a); yet I cannot agree with his main conclusions. Given space limitations, this...

Metabolic activity in the insular cortex and hypothalamus predicts hot flashes: an FDG-PET study.

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Joffe, Hadine; Deckersbach, Thilo; Lin, Nancy U; Makris, Nikos; Skaar, Todd C; Rauch, Scott L; Dougherty, Darin D; Hall, Janet E

2012-09-01

Hot flashes are a common side effect of adjuvant endocrine therapies (AET; leuprolide, tamoxifen, aromatase inhibitors) that reduce quality of life and treatment adherence in breast cancer patients. Because hot flashes affect only some women, preexisting neurobiological traits might predispose to their development. Previous studies have implicated the insula during the perception of hot flashes and the hypothalamus in thermoregulatory dysfunction. The aim of the study was to understand whether neurobiological factors predict hot flashes. [18F]-Fluorodeoxyglucose (FDG) positron emission tomography (PET) brain scans coregistered with structural magnetic resonance imaging were used to determine whether metabolic activity in the insula and hypothalamic thermoregulatory and estrogen-feedback regions measured before and in response to AET predict hot flashes. Findings were correlated with CYP2D6 genotype because of CYP2D6 polymorphism associations with tamoxifen-induced hot flashes. We measured regional cerebral metabolic rate of glucose uptake (rCMRglu) in the insula and hypothalamus on FDG-PET. Of 18 women without hot flashes who began AET, new-onset hot flashes were reported by 10 (55.6%) and were detected objectively in nine (50%) participants. Prior to the use of all AET, rCMRglu in the insula (P ≤ 0.01) and hypothalamic thermoregulatory (P = 0.045) and estrogen-feedback (P = 0.007) regions was lower in women who reported developing hot flashes. In response to AET, rCMRglu was further reduced in the insula in women developing hot flashes (P ≤ 0.02). Insular and hypothalamic rCMRglu levels were lower in intermediate than extensive CYP2D6 metabolizers. Trait neurobiological characteristics predict hot flashes. Genetic variability in CYP2D6 may underlie the neurobiological predisposition to hot flashes induced by AET.

EARLY MIOCENE INSULAR VERTEBRATES FROM LAERRU (SARDINIA, ITALY: PRELIMINARY NOTE

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DANIEL ZOBOLI

2017-01-01

Full Text Available A new vertebrate assemblage was discovered in an Early  Miocene lacustrine deposit near the village of Laerru (northern Sardinia, Italy. The assemblage is composed by mammals, reptiles and a bird. The mammals are represented by three ruminants (cf. Sardomeryx oschiriensis, Pecora indet. small size and Pecora indet. very small size and one dormouse (Peridyromys aff. murinus while reptiles are represented by turtles (Trionychidae? and crocodiles (cf. Diplocynodon sp.. A bird bone fragment is also reported and referred to Palaeortyx cf. brevipes (Galliformes. The assemblage can be related to the “Oschiri fauna”, one of the oldest endemic insular fauna known in the Mediterranean. The age of the Laerru vertebrates is early-middle Burdigalian, between 18.8 and 18.3 Ma, corresponding to the mammal unit of the main land MN3. The predominance of ruminants confirms the good capacity of these mammals to colonize insular environments.

Effect of chronic restraint stress on inhibitory gating in the auditory cortex of rats.

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Ma, Lanlan; Li, Wai; Li, Sibin; Wang, Xuejiao; Qin, Ling

2017-05-01

A fundamental adaptive mechanism of auditory function is inhibitory gating (IG), which refers to the attenuation of neural responses to repeated sound stimuli. IG is drastically impaired in individuals with emotional and cognitive impairments (i.e. posttraumatic stress disorder). The objective of this study was to test whether chronic stress impairs the IG of the auditory cortex (AC). We used the standard two-tone stimulus paradigm and examined the parametric qualities of IG in the AC of rats by recording the electrophysiological signals of a single-unit and local field potential (LFP) simultaneously. The main results of this study were that most of the AC neurons showed a weaker response to the second tone than to the first tone, reflecting an IG of the repeated input. A fast negative wave of LFP showed consistent IG across the sampled AC sites, whereas a slow positive wave of LFP had less IG effect. IG was diminished following chronic restraint stress at both, the single-unit and LFP level, due to the increase in response to the second tone. This study provided new evidence that chronic stress disrupts the physiological function of the AC. Lay Summary The effects of chronic stress on IG were investigated by recording both, single-unit spike and LFP activities, in the AC of rats. In normal rats, most of the single-unit and N25 LFP activities in the AC showed an IG effect. IG was diminished following chronic restraint stress at both, the single-unit and LFP level.

Beta-amyloid-induced cholinergic denervation correlates with enhanced nitric oxide synthase activity in rat cerebral cortex: Reversal by NMDA receptor blockade : Reversal by NMDA receptor blockade

NARCIS (Netherlands)

O’Mahony, S.; Harkany, T.; Ábrahám, I.; Jong, G.I. de; Varga, J.L.; Zarándi, M.; Penke, B.; Nyakas, C.; Luiten, P.G.M.; Leonard, B.E.

1998-01-01

Ample experimental evidence indicates that acute beta-amyloid infusion into the nucleus basalis of rats elicits abrupt degeneration of the magnocellular cholinergic neurons projecting to the cerebral cortex, In fact, involvement of a permanent Ca2+ overload, partially via N-methyl-D-aspartate (NMDA)

Towards grid parity in insular energy systems: The case of photovoltaics (PV) in Cyprus

International Nuclear Information System (INIS)

Fokaides, Paris A.; Kylili, Angeliki

2014-01-01

Grid parity is defined as the threshold at which a grid-connected renewable energy sources (RES) system supplies electricity to the end user at the same price as grid-supplied electricity. Predictions from the 2006 time-frame expected retail grid parity for solar in the 2016 to 2020 era, but due to rapid downward pricing changes, more recent calculations have forced dramatic reductions in time scale, and the suggestion that solar has already reached grid parity in a wide variety of locations. This study presents aspects of achieving grid parity in insular energy systems, based on a case study applied in Cyprus. The analysis presents the variation of the manufacturing cost, the selling price of the produced energy, and the performance of the solar panels to examine the conditions of accomplishing grid parity event. It is also concluded that grid parity may be easier achieved in insular energy systems due to the higher cost of primary energy. - Highlights: • This study presents aspects of achieving grid parity in insular energy systems, based on a case study applied in Cyprus. • The impact of the manufacturing cost and the feed in tariff on accomplishing grid parity event is analysed. • A sensitivity analysis is conducted to define the parameters that strongly affect the goal of grid parity. • It is concluded that grid parity may be easier achieved in insular energy systems due to the higher cost of primary energy

Motor cortex is required for learning but not executing a motor skill

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Kawai, Risa; Markman, Timothy; Poddar, Rajesh; Ko, Raymond; Fantana, Antoniu; Dhawale, Ashesh; Kampff, Adam R.; Ölveczky, Bence P.

2018-01-01

Motor cortex is widely believed to underlie the acquisition and execution of motor skills, yet its contributions to these processes are not fully understood. One reason is that studies on motor skills often conflate motor cortex’s established role in dexterous control with roles in learning and producing task-specific motor sequences. To dissociate these aspects, we developed a motor task for rats that trains spatiotemporally precise movement patterns without requirements for dexterity. Remarkably, motor cortex lesions had no discernible effect on the acquired skills, which were expressed in their distinct pre-lesion forms on the very first day of post-lesion training. Motor cortex lesions prior to training, however, rendered rats unable to acquire the stereotyped motor sequences required for the task. These results suggest a remarkable capacity of subcortical motor circuits to execute learned skills and a previously unappreciated role for motor cortex in ‘tutoring’ these circuits during learning. PMID:25892304

Asymmetrical expression of BDNF and NTRK3 genes in frontoparietal cortex of stress-resilient rats in an animal model of depression.

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Farhang, Sara; Barar, Jaleh; Fakhari, Ali; Mesgariabbasi, Mehran; Khani, Sajjad; Omidi, Yadollah; Farnam, Alireza

2014-09-01

The current study is based on the "approach-withdrawal" theory of emotional regulation and lateralization of brain function in rodents, which has little been studied. The aim was to indentify asymmetry in hemispheric genes expression during depression. Depressive-like symptoms were induced in rats using chronic mild stress protocol. The sucrose consumption test was performed to identify the anhedonic and stress-resilient rats. After decapitation, RNA was extracted from frontotemporal cortex of both hemispheres of anhedonic and stress-resilient rats. The pattern of gene expression in these samples was compared with controls by real-time polymerase chain reaction. A linear mixed model analysis of variance was fitted to the data to estimate the effect of rat line. From the total of 30 rats in the experimental group, five rats were identified to be anhedonic and five were stress-resilient, according to the result of sucrose-consumption test. BDNF and NTRK-3 were expressed at significantly lower levels in the right hemisphere of anhedonic rats compared with stress-resilient rats. No significant difference was found between left hemispheres. Hemispheric asymmetry in the level of gene expression was only observed for the BDNF gene in stress-resilient rats, upregulated in right hemisphere compared with the left. Expression of NTRK3, HTR2A, COMT, and SERT was not lateralized. There was no significant asymmetry between hemispheres of anhedonic rats. This study supports the evidence for the role of genes responsible for neural plasticity in pathophysiology of depression, emphasizing probable hemispheric asymmetry at level of gene expression. Copyright © 2014 Wiley Periodicals, Inc.

Sex differences in social interaction behaviors in rats are mediated by extracellular signal-regulated kinase 2 expression in the medial prefrontal cortex

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Carrier, Nicole; Kabbaj, Mohamed

2012-01-01

Considerable sex differences occur in the incidence and prevalence of anxiety disorders where women are more anxious than men, particularly in situations where social interaction is required. In preclinical studies, the social interaction test represents a valid animal model to study sex differences in social anxiety. Indeed, female rats engage less in conspecific interactions than their male counterparts, which are behaviors indicative of higher social anxiety in female rats. In this work, we implicated extracellular signal regulated kinase 2 (ERK2) in the medial prefrontal cortex (mPFC) in mediating social interaction. Indeed, female rats’ had lower ERK2 expression compared to male rats, and overexpression of ERK2 in the mPFC increases their social interaction to the level seen in their male counterparts. These data indicate that the sexually dimorphic expression of ERK2 mediates social anxiety-like behaviors. PMID:22521590

Ethanol intake and 3H-serotonin uptake I: A study in Fawn-Hooded rats

International Nuclear Information System (INIS)

Daoust, M.; Compagnon, P.; Legrand, E.; Boucly, P.

1991-01-01

Ethanol intake and synaptosomal 3 H-serotonin uptake were studied in male Fawn-Hooded and Sprague-Dawley rats. Fawn-Hooded rats consumed more alcohol and more water than Sprague-Dawley rats. Plasma alcohol levels of Sprague-Dawley rats were not detectable but were about 5 mg/dl in Fawn-Hooded rats. Ethanol intake increased the Vmax of serotonin uptake in Fawn-Hooded rats in hippocampus and cortex, but not in thalamus. In Fawn-Hooded rats, serotonin uptake (Vmax) was higher than in Sprague-Dawley rats cortex. Ethanol intake reduced the Vmax of serotonin uptake in Fawn-Hooded rats in hippocampus and cortex. In cortex, the carrier affinity for serotonin was increased in alcoholized Fawn-Hooded rats. These results indicate that synaptosomal 3 H-serotonin uptake is affected by ethanol intake. In Fawn-Hooded rats, high ethanol consumption is associated with high serotonin uptake. In rats presenting high serotonin uptake, alcoholization reduces 3 H-serotonin internalization in synaptosomes, indicating a specific sensitivity to alcohol intake of serotonin uptake system

Total Phenolic Content and Antioxidant Activity of Different Types of Chocolate, Milk, Semisweet, Dark, and Soy, in Cerebral Cortex, Hippocampus, and Cerebellum of Wistar Rats

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Niara da Silva Medeiros

2015-01-01

Full Text Available Chocolate is a product consumed worldwide and it stands out for presenting an important amount of phenolic compounds. In this study, the total phenolic content and antioxidant activity in the cerebral cortex, hippocampus, and cerebellum of male Wistar rats when consuming different types of chocolate, including milk, semisweet, dark, and soy, was evaluated. The total polyphenols concentration and antioxidant activity in vitro by the method of DPPH radical-scavenging test were evaluated in chocolate samples. Lipid peroxidation (TBARS, protein oxidation (carbonyl, sulfhydryl groups, and activity of SOD enzyme in cerebral cortex, hippocampus, and cerebellum of rats treated or not with hydrogen peroxide and/or chocolate were also evaluated. The dark chocolate demonstrated higher phenolic content and antioxidant activity, followed by semisweet, soy, and milk chocolates. The addition of chocolate in the diet of the rats reduced lipid peroxidation and protein oxidation caused by hydrogen peroxide. In the sulfhydryl assay, we observed that the levels of nonenzymatic defenses only increased with the chocolate treatments The SOD enzyme activity was modulated in the tissues treated with the chocolates. We observed in the samples of chocolate a significant polyphenol content and an important antioxidant activity; however, additional studies with different chocolates and other tissues are necessary to further such findings.

Total Phenolic Content and Antioxidant Activity of Different Types of Chocolate, Milk, Semisweet, Dark, and Soy, in Cerebral Cortex, Hippocampus, and Cerebellum of Wistar Rats

Science.gov (United States)

da Silva Medeiros, Niara; Koslowsky Marder, Roberta; Farias Wohlenberg, Mariane; Funchal, Cláudia; Dani, Caroline

2015-01-01

Chocolate is a product consumed worldwide and it stands out for presenting an important amount of phenolic compounds. In this study, the total phenolic content and antioxidant activity in the cerebral cortex, hippocampus, and cerebellum of male Wistar rats when consuming different types of chocolate, including milk, semisweet, dark, and soy, was evaluated. The total polyphenols concentration and antioxidant activity in vitro by the method of DPPH radical-scavenging test were evaluated in chocolate samples. Lipid peroxidation (TBARS), protein oxidation (carbonyl), sulfhydryl groups, and activity of SOD enzyme in cerebral cortex, hippocampus, and cerebellum of rats treated or not with hydrogen peroxide and/or chocolate were also evaluated. The dark chocolate demonstrated higher phenolic content and antioxidant activity, followed by semisweet, soy, and milk chocolates. The addition of chocolate in the diet of the rats reduced lipid peroxidation and protein oxidation caused by hydrogen peroxide. In the sulfhydryl assay, we observed that the levels of nonenzymatic defenses only increased with the chocolate treatments The SOD enzyme activity was modulated in the tissues treated with the chocolates. We observed in the samples of chocolate a significant polyphenol content and an important antioxidant activity; however, additional studies with different chocolates and other tissues are necessary to further such findings. PMID:26649198

Effect of hyperbaric oxygenation on mitochondrial function of neuronal cells in the cortex of neonatal rats after hypoxic-ischemic brain damage

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L. Yang

2016-01-01

Full Text Available The timing and mechanisms of protection by hyperbaric oxygenation (HBO in hypoxic-ischemic brain damage (HIBD have only been partially elucidated. We monitored the effect of HBO on the mitochondrial function of neuronal cells in the cerebral cortex of neonatal rats after HIBD. Neonatal Sprague-Dawley rats (total of 360 of both genders were randomly divided into normal control, HIBD, and HIBD+HBO groups. The HBO treatment began immediately after hypoxia-ischemia (HI and continued once a day for 7 consecutive days. Animals were euthanized 0, 2, 4, 6, and 12 h post-HI to monitor the changes in mitochondrial membrane potential (ΔΨm occurring soon after a single dose of HBO treatment, as well as 2, 3, 4, 5, 6, and 7 days post-HI to study ΔΨm changes after a series of HBO treatments. Fluctuations in ΔΨm were observed in the ipsilateral cortex in both HIBD and HIBD+HBO groups. Within 2 to 12 h after HI insult, the ΔΨm of the HIBD and HIBD+HBO groups recovered to some extent. A secondary drop in ΔΨm was observed in both groups during the 1-4 days post-HI period, but was more severe in the HIBD+HBO group. There was a secondary recovery of ΔΨm observed in the HIBD+HBO group, but not in the HIBD group, during the 5-7 days period after HI insult. HBO therapy may not lead to improvement of neural cell mitochondrial function in the cerebral cortex in the early stage post-HI, but may improve it in the sub-acute stage post-HI.

Influence of bushenhuoxue on primary visual cortex' BDNF damage in rat model of chronic elevated intraocular pressure

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Xiang Li

2013-04-01

Full Text Available AIM: To observe the effect of traditional Chinese medicine(TCMof bushenhuoxue on primary visual cortex(PVCbrain-derived neurotrophic factor(BDNFin rat model of chronic elevated intraocular pressure(EIOP, and explore the mechanism of it initially. METHODS: The rat model of chronic EIOP was established by unilaterally cauterizing 3 episcleral veins, then 30 rats were divided into 3 groups randomly: control group, model group, and treatment group. After given drugs or normal saline for 8 weeks, the rats were put to death. The effect of intraocular pressure(IOP, expression of BDNF and ultrastructure of neuron cell in the PVC was observed. RESULTS: Unilaterally cauterizing episcleral veins increased IOP of the rat model obviously, there was significant difference compared with pre-operation(P<0.01. Semi-quantitative pathological analysis on PVC showed that BDNF of total area in the model group was(82438±2597.39S/μm2,mean optical density was(1155.9±123.14, integrated optical density was(12915±673.28, compared with the control group {total area was(132370±7588.47S/μm2, mean optical density was(5365±379.65, integrated optical density was(35102±2648.5}, there were statistical differences(all P<0.05,there was statistical difference in BDNF of total area between model group and treatment group{(108980±9126.77S/μm2, P<0.05}, significant difference in mean optical density between the model group and treatment group(3220.4±413.67, P<0.05, statistical difference in integrated optical density between the model group and treatment group(23821±3431.68, P<0.05. CONCLUSION: TCM of bushenhuoxue can repair the PVC damage in the rat model of chronic EIOP by enhancing expression of BDNF, improving ultrastructure of neuron cell.

Alterations in neuronal morphology in infralimbic cortex predict resistance to fear extinction following acute stress

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Kelly M. Moench

2016-06-01

Full Text Available Dysfunction in corticolimbic circuits that mediate the extinction of learned fear responses is thought to underlie the perseveration of fear in stress-related psychopathologies, including post-traumatic stress disorder. Chronic stress produces dendritic hypertrophy in basolateral amygdala (BLA and dendritic hypotrophy in medial prefrontal cortex, whereas acute stress leads to hypotrophy in both BLA and prelimbic cortex. Additionally, both chronic and acute stress impair extinction retrieval. Here, we examined the effects of a single elevated platform stress on extinction learning and dendritic morphology in infralimbic cortex, a region considered to be critical for extinction. Acute stress produced resistance to extinction, as well as dendritic retraction in infralimbic cortex. Spine density on apical and basilar terminal branches was unaffected by stress. However, animals that underwent conditioning and extinction had decreased spine density on apical terminal branches. Thus, whereas dendritic morphology in infralimbic cortex appears to be particularly sensitive to stress, changes in spines may more sensitively reflect learning. Further, in stressed rats that underwent conditioning and extinction, the level of extinction learning was correlated with spine densities, in that rats with poorer extinction retrieval had more immature spines and fewer thin spines than rats with better extinction retrieval, suggesting that stress may have impaired learning-related spine plasticity. These results may have implications for understanding the role of medial prefrontal cortex in learning deficits associated with stress-related pathologies.

Proteomic analysis of post-nuclear supernatant fraction and percoll-purified membranes prepared from brain cortex of rats exposed to increasing doses of morphine

Czech Academy of Sciences Publication Activity Database

Ujčíková, Hana; Eckhardt, Adam; Kagan, Dmytro; Roubalová, Lenka; Svoboda, Petr

2014-01-01

Roč. 12, Feb 14 (2014), s. 11 ISSN 1477-5956 R&D Projects: GA ČR(CZ) GAP207/12/0919; GA ČR(CZ) GBP304/12/G069 Institutional support: RVO:67985823 Keywords : morphine * long-term exposure * rat brain cortex * isolated plasma membranes * post-nuclear supernatant * 2D electrophoresis Subject RIV: CE - Biochemistry Impact factor: 1.725, year: 2014

Vitamin E can improve behavioral tests impairment, cell loss, and dendrite changes in rats' medial prefrontal cortex induced by acceptable daily dose of aspartame.

Science.gov (United States)

Rafati, Ali; Noorafshan, Ali; Jahangir, Mahboubeh; Hosseini, Leila; Karbalay-Doust, Saied

2018-01-01

Aspartame is an artificial sweetener used in about 6000 sugar-free products. Aspartame consumption could be associated with various neurological disorders. This study aimed to evaluate the effect of aspartame onmedial Prefrontal Cortex (mPFC) as well as neuroprotective effects of vitamin E. The rats were divided into seven groups, including distilled water, corn oil, vitamin E (100mg/kg/day), and low (acceptable daily dose) and high doses of aspartame (40 and 200mg/kg/day) respectively, with or without vitamin E consumption, for 8 weeks. Behavioral tests were recorded and the brain was prepared for stereological assessments. Novel objects test and eight-arm radial maze showed impairmentoflong- and short-termmemoriesin aspartame groups. Besides, mPFC volume, infralimbic volume, neurons number, glial cells number, dendrites length per neuron,and number of spines per dendrite length were decreased by 7-61% in the rats treated with aspartame. However, neurons' number, glial cells number, and rats' performance in eight-arm radial mazes were improved by concomitant consumption of vitamin E and aspartame. Yet, the mPFC volume and infralimbic cortex were protected only in the rats receiving the low dose of aspartame+vitamin E. On the other hand, dendrites length, spines number,and novel object recognition were not protected by treatment with vitamin E+aspartame. The acceptable daily dose or higher doses of aspartame could induce memory impairments and cortical cells loss in mPFC. However, vitamin E could ameliorate some of these changes. Copyright © 2017 Elsevier GmbH. All rights reserved.

Sympathetic regulation and anterior cingulate cortex volume are altered in a rat model of chronic back pain.

Science.gov (United States)

Touj, Sara; Houle, Sébastien; Ramla, Djamel; Jeffrey-Gauthier, Renaud; Hotta, Harumi; Bronchti, Gilles; Martinoli, Maria-Grazia; Piché, Mathieu

2017-06-03

Chronic pain is associated with autonomic disturbance. However, specific effects of chronic back pain on sympathetic regulation remain unknown. Chronic pain is also associated with structural changes in the anterior cingulate cortex (ACC), which may be linked to sympathetic dysregulation. The aim of this study was to determine whether sympathetic regulation and ACC surface and volume are affected in a rat model of chronic back pain, in which complete Freund Adjuvant (CFA) is injected in back muscles. Sympathetic regulation was assessed with renal blood flow (RBF) changes induced by electrical stimulation of a hind paw, while ACC structure was examined by measuring cortical surface and volume. RBF changes and ACC volume were compared between control rats and rats injected with CFA in back muscles segmental (T10) to renal sympathetic innervation or not (T2). In rats with CFA, chronic inflammation was observed in the affected muscles in addition to increased nuclear factor-kappa B (NF-kB) protein expression in corresponding spinal cord segments (p=0.01) as well as decreased ACC volume (pchronic pain at T2 (p'schronic back pain alters sympathetic functions through non-segmental mechanisms, possibly by altering descending regulatory pathways from ACC. Yet, segmental somato-sympathetic reflexes may compete with non-segmental processes depending on the back region affected by pain and according to the segmental organization of the sympathetic nervous system. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Both Hypo-Connectivity and Hyper-Connectivity of the Insular Subregions Associated With Severity in Children With Autism Spectrum Disorders

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Jinping Xu

2018-04-01

Full Text Available Some studies identified hypo-connectivity, while others showed hyper-connectivity of the insula in the autism spectrum disorders (ASD. These contradictory findings leave open the question of whether and to what extent functional connectivity of the insula is altered and how functional connectivity of the insula is associated with the severity of ASD. A newly emerging insular atlas that comprises multiple functionally differentiated subregions provides a new framework to interpret the functional significance of insular findings and uncover the mechanisms underlying the severity of ASD. Using the new insular atlas, the present study aimed to investigate the distinct functional connectivity of the insular subregions and their associations with ASD severity in a cohort of 49 children with ASD and 33 typically developing (TD subjects. We found that compared with TD group, the ASD group showed different connectivity patterns in the left ventral agranular insula, right ventral dysgranular and granular insula, and dorsal dysgranular insula, characterized by significant hyper-connectivity and/or hypo-connectivity with special brain regions. Furthermore, both the hypo-connectivity and hyper-connectivity patterns of the insular subregions were significantly associated with the severity of ASD symptoms. Our research demonstrated distinct functional connectivity patterns of the insular subregions and emphasized the importance of the subdivisions within the insula to the potential impact of functional difference in children with ASD. Moreover, these results might help us to better understand the mechanisms underlying the symptoms in children with ASD and might elucidate potential biomarkers for clinical applications.

Sex differences in neural activation following different routes of oxytocin administration in awake adult rats.

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Dumais, Kelly M; Kulkarni, Praveen P; Ferris, Craig F; Veenema, Alexa H

2017-07-01

The neuropeptide oxytocin (OT) regulates social behavior in sex-specific ways across species. OT has promising effects on alleviating social deficits in sex-biased neuropsychiatric disorders. However little is known about potential sexually dimorphic effects of OT on brain function. Using the rat as a model organism, we determined whether OT administered centrally or peripherally induces sex differences in brain activation. Functional magnetic resonance imaging was used to examine blood oxygen level-dependent (BOLD) signal intensity changes in the brains of awake rats during the 20min following intracerebroventricular (ICV; 1μg/5μl) or intraperitoneal (IP; 0.1mg/kg) OT administration as compared to baseline. ICV OT induced sex differences in BOLD activation in 26 out of 172 brain regions analyzed, with 20 regions showing a greater volume of activation in males (most notably the nucleus accumbens and insular cortex), and 6 regions showing a greater volume of activation in females (including the lateral and central amygdala). IP OT also elicited sex differences in BOLD activation with a greater volume of activation in males, but this activation was found in different and fewer (10) brain regions compared to ICV OT. In conclusion, exogenous OT modulates neural activation differently in male versus female rats with the pattern and magnitude, but not the direction, of sex differences depending on the route of administration. These findings highlight the need to include both sexes in basic and clinical studies to fully understand the role of OT on brain function. Copyright © 2017 Elsevier Ltd. All rights reserved.

La proyección colonial de Chile a la Patagonia Insular en el siglo XVIII

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Urbina Carrasco, María Ximena

2011-01-01

In this article, the geopolitical consequences of the shipwreck of the English frigate Wager and the landfall of the ship Anna into the coasts of the Western Insular Patagonia in 1741 are presented, which were part of the fleet of George Anson. The news reporting the English presence in the deserted and unknown insular and coastal territory southernmost Chiloé, and which had disseminated towards the end of the continent, promoted the deployment of different actions tending to make presence no...

Associative learning changes cross-modal representations in the gustatory cortex.

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Vincis, Roberto; Fontanini, Alfredo

2016-08-30

A growing body of literature has demonstrated that primary sensory cortices are not exclusively unimodal, but can respond to stimuli of different sensory modalities. However, several questions concerning the neural representation of cross-modal stimuli remain open. Indeed, it is poorly understood if cross-modal stimuli evoke unique or overlapping representations in a primary sensory cortex and whether learning can modulate these representations. Here we recorded single unit responses to auditory, visual, somatosensory, and olfactory stimuli in the gustatory cortex (GC) of alert rats before and after associative learning. We found that, in untrained rats, the majority of GC neurons were modulated by a single modality. Upon learning, both prevalence of cross-modal responsive neurons and their breadth of tuning increased, leading to a greater overlap of representations. Altogether, our results show that the gustatory cortex represents cross-modal stimuli according to their sensory identity, and that learning changes the overlap of cross-modal representations.

High-Frequency Stimulation of the Subthalamic Nucleus Activates Motor Cortex Pyramidal Tract Neurons by a Process Involving Local Glutamate, GABA and Dopamine Receptors in Hemi-Parkinsonian Rats.

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Chuang, Chi-Fen; Wu, Chen-Wei; Weng, Ying; Hu, Pei-San; Yeh, Shin-Rung; Chang, Yen-Chung

2018-04-30

Deep brain stimulation (DBS) is widely used to treat advanced Parkinson’s disease (PD). Here, we investigated how DBS applied on the subthalamic nucleus (STN) influenced the neural activity in the motor cortex. Rats, which had the midbrain dopaminergic neurons partially depleted unilaterally, called the hemi-Parkinsonian rats, were used as a study model. c-Fos expression in the neurons was used as an indicator of neural activity. Application of high-frequency stimulation (HFS) upon the STN was used to mimic the DBS treatment. The motor cortices in the two hemispheres of hemi-Parkinsonian rats were found to contain unequal densities of c-Fos-positive (Fos+) cells, and STN-HFS rectified this bilateral imbalance. In addition, STN-HFS led to the intense c-Fos expression in a group of motor cortical neurons which exhibited biochemical and anatomical characteristics resembling those of the pyramidal tract (PT) neurons sending efferent projections to the STN. The number of PT neurons expressing high levels of c-Fos was significantly reduced by local application of the antagonists of non-N-methyl-D-aspartate (non-NMDA) glutamate receptors, gammaaminobutyric acid A (GABAA) receptors and dopamine receptors in the upper layers of the motor cortex. The results indicate that the coincident activations of synapses and dopamine receptors in the motor cortex during STN-HFS trigger the intense expression of c-Fos of the PT neurons. The implications of the results on the cellular mechanism underlying the therapeutic effects of STN-DBS on the movement disorders of PD are also discussed.

Corticofugal projections induce long-lasting effects on somatosensory responses in the trigeminal complex of the rat

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Angel eNunez

2014-05-01

Full Text Available The sensory information flow at subcortical relay stations is controlled by the action of topographic connections from the neocortex. To determinate the functional properties of the somatosensory corticofugal projections to the principal (Pr5 and caudal spinal (Sp5C trigeminal nuclei, we performed unitary recordings in anesthetized rats. To examine the effect of these cortical projections we used tactile stimulation of the whisker and electrical stimulation of somatosensory cortices. Corticofugal anatomical projections to Pr5 and Sp5C nuclei were detected by using retrograde fluorescent tracers. Neurons projecting exclusively to Pr5 were located in the cingulate cortex while neurons projecting to both Sp5C and Pr5 nuclei were located in the somatosensory and insular cortices (>75% of neurons. Physiological results indicated that primary somatosensory cortex produced a short-lasting facilitating or inhibiting effects (< 5 minutes of tactile responses in Pr5 nucleus through activation of NMDA glutamatergic or GABAA receptors since effects were blocked by iontophoretically application of APV and bicuculline, respectively. In contrast, stimulation of secondary somatosensory cortex did not affect most of the Pr5 neurons; however both cortices inhibited the nociceptive responses in the Sp5C nucleus through activation of glycinergic or GABAA receptors because effects were blocked by iontophoretically application of strychnine and bicuculline, respectively. These and anatomical results demonstrated that the somatosensory cortices projects to Pr5 nucleus to modulate tactile responses by excitatory and inhibitory actions, while projections to the Sp5C nucleus control nociceptive sensory transmission by only inhibitory effects. Thus, somatosensory cortices may modulate innocuous and noxious inputs simultaneously, contributing to the perception of specifically tactile or painful sensations.

Activation of cannabinoid system in anterior cingulate cortex and orbitofrontal cortex modulates cost-benefit decision making.

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Khani, Abbas; Kermani, Mojtaba; Hesam, Soghra; Haghparast, Abbas; Argandoña, Enrike G; Rainer, Gregor

2015-06-01

Despite the evidence for altered decision making in cannabis abusers, the role of the cannabinoid system in decision-making circuits has not been studied. Here, we examined the effects of cannabinoid modulation during cost-benefit decision making in the anterior cingulate cortex (ACC) and orbitofrontal cortex (OFC), key brain areas involved in decision making. We trained different groups of rats in a delay-based and an effort-based form of cost-benefit T-maze decision-making task. During test days, the rats received local injections of either vehicle or ACEA, a cannabinoid type-1 receptor (CB1R) agonist in the ACC or OFC. We measured spontaneous locomotor activity following the same treatments and characterized CB1Rs localization on different neuronal populations within these regions using immunohistochemistry. We showed that CB1R activation in the ACC impaired decision making such that rats were less willing to invest physical effort to gain high reward. Similarly, CB1R activation in the OFC induced impulsive pattern of choice such that rats preferred small immediate rewards to large delayed rewards. Control tasks ensured that the effects were specific for differential cost-benefit tasks. Furthermore, we characterized widespread colocalizations of CB1Rs on GABAergic axonal ends but few colocalizations on glutamatergic, dopaminergic, and serotonergic neuronal ends. These results provide first direct evidence that the cannabinoid system plays a critical role in regulating cost-benefit decision making in the ACC and OFC and implicate cannabinoid modulation of synaptic ends of predominantly interneurons and to a lesser degree other neuronal populations in these two frontal regions.

Sex-specific effects of early life stress on social interaction and prefrontal cortex dendritic morphology in young rats.

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Farrell, M R; Holland, F H; Shansky, R M; Brenhouse, H C

2016-09-01

Early life stress has been linked to depression, anxiety, and behavior disorders in adolescence and adulthood. The medial prefrontal cortex (mPFC) is implicated in stress-related psychopathology, is a target for stress hormones, and mediates social behavior. The present study investigated sex differences in early-life stress effects on juvenile social interaction and adolescent mPFC dendritic morphology in rats using a maternal separation (MS) paradigm. Half of the rat pups of each sex were separated from their mother for 4h a day between postnatal days 2 and 21, while the other half remained with their mother in the animal facilities and were exposed to minimal handling. At postnatal day 25 (P25; juvenility), rats underwent a social interaction test with an age and sex matched conspecific. Distance from conspecific, approach and avoidance behaviors, nose-to-nose contacts, and general locomotion were measured. Rats were euthanized at postnatal day 40 (P40; adolescence), and randomly selected infralimbic pyramidal neurons were filled with Lucifer yellow using iontophoretic microinjections, imaged in 3D, and then analyzed for dendritic arborization, spine density, and spine morphology. Early-life stress increased the latency to make nose-to-nose contact at P25 in females but not males. At P40, early-life stress increased infralimbic apical dendritic branch number and length and decreased thin spine density in stressed female rats. These results indicate that MS during the postnatal period influenced juvenile social behavior and mPFC dendritic arborization in a sex-specific manner. Copyright © 2016 Elsevier B.V. All rights reserved.

Stimulus-dependent modulation of spontaneous low-frequency oscillations in the rat visual cortex.

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Huang, Liangming; Liu, Yadong; Gui, Jianjun; Li, Ming; Hu, Dewen

2014-08-06

Research on spontaneous low-frequency oscillations is important to reveal underlying regulatory mechanisms in the brain. The mechanism for the stimulus modulation of low-frequency oscillations is not known. Here, we used the intrinsic optical imaging technique to examine stimulus-modulated low-frequency oscillation signals in the rat visual cortex. The stimulation was presented monocularly as a flashing light with different frequencies and intensities. The phases of low-frequency oscillations in different regions tended to be synchronized and the rhythms typically accelerated within a 30-s period after stimulation. These phenomena were confined to visual stimuli with specific flashing frequencies (12.5-17.5 Hz) and intensities (5-10 mA). The acceleration and synchronization induced by the flashing frequency were more marked than those induced by the intensity. These results show that spontaneous low-frequency oscillations can be modulated by parameter-dependent flashing lights and indicate the potential utility of the visual stimulus paradigm in exploring the origin and function of low-frequency oscillations.

Medial Orbitofrontal Cortex Mediates Effort-related Responding in Rats.

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Münster, Alexandra; Hauber, Wolfgang

2017-11-17

The medial orbitofrontal cortex (mOFC) is known to support flexible control of goal-directed behavior. However, limited evidence suggests that the mOFC also mediates the ability of organisms to work with vigor towards a selected goal, a hypothesis that received little consideration to date. Here we show that excitotoxic mOFC lesion increased responding under a progressive ratio (PR) schedule of reinforcement, that is, the highest ratio achieved, and increased the preference for the high effort-high reward option in an effort-related decision-making task, but left intact outcome-selective Pavlovian-instrumental transfer and outcome-specific devaluation. Moreover, pharmacological inhibition of the mOFC increased, while pharmacological stimulation reduced PR responding. In addition, pharmacological mOFC stimulation attenuated methylphenidate-induced increase of PR responding. Intact rats tested for PR responding displayed higher numbers of c-Fos positive mOFC neurons than appropriate controls; however, mOFC neurons projecting to the nucleus accumbens did not show a selective increase in neuronal activation implying that they may not play a major role in regulating PR responding. Collectively, these results suggest that the mOFC plays a major role in mediating effort-related motivational functions. Moreover, our data demonstrate for the first time that the mOFC modulates effort-related effects of psychostimulant drugs. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

[Effect of electric acupuncture on the expression of NgR in the cerebral cortex, the medulla oblongata, and the spinal cord of hypertensive rats after cerebral infarction].

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Tan, Feng; Chen, Jie; Liang, Yan-Gui; Li, Yan-Ping; Wang, Xue-Wen; Meng, Di; Cheng, Nan-Fang

2014-03-01

To observe the effect of electric acupuncture (EA) on the Nogo receptors (NgR) protein expression in the cerebral cortex, the medulla oblongata, and the spinal cord of cerebral ischemia-reperfusion (I/R) stroke-prone renovascular hypertensive rats (RHRSP) with middle cerebral artery occlusion (MCAO) at different time points, and to investigate its possible mechanisms for remote-organ injury of acute cerebral infarction (ACI). The RHRSP model was duplicated in male SPF grade SD rats. Then the MCAO model was prepared by a thread stringing method. Rats were divided into the hypertension group,the sham-operation group, the MCAO group, the EA group, and the sham-acupoint group by random number table method, 60 in each group. Rats in the MCAO group only received MCAO reperfusion treatment. Those in the sham-operation group only received surgical trauma. Baihui (DU20) and Dazhui (DU14) were needled in the EA group, once daily for a total of 28 days.The needles were acupunctured at the skin one cun distant from Baihui (DU20) and Dazhui (DU14) and then the same EA treatment was performed in the sham-acupoint group. At day 1, 7, 14, 28 after treatment, six rats were executed from each group, and their right cortex and medulla oblongata, and the left spinal cord were isolated. The infarct volume was detected by Nissl's staining method. The NgR expression was detect by Western blot. (1) In the cortex area: compared with the hypertension group,the NgR expression increased in the MCAO group at day 1,7,14,and 28 after MCAO (P 0.05). At day 7, 14,and 28 after MCAO, the NgR expression decreased in the EA group (P 0.05). (2) In the medulla oblongata area: compared with the hypertension group, the NgR expression was equivalent in the sham-operation group. the MCAO group,the EA group, and the sham-acupoint group at 1 day after MCAO (P > 0.05). At day 7.14, and 28 after MCAO, the NgR expression increased in the MCAO group (P 0.05). (3) In the spinal cord area: compared with the

5HT(1A) and 5HT(1B) receptors of medial prefrontal cortex modulate anxiogenic-like behaviors in rats.

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Solati, Jalal; Salari, Ali-Akbar; Bakhtiari, Amir

2011-10-31

Medial prefrontal cortex (MPFC) is one of the brain regions which play an important role in emotional behaviors. The purpose of the present study was to evaluate the role of 5HT(1A) and 5HT(1B) receptors of the MPFC in modulation of anxiety behaviors in rats. The elevated plus maze (EPM) which is a useful test to investigate the effects of anxiogenic or anxiolytic drugs in rodents, was used. Bilateral intra-MPFC administration of 5HT(1A) receptor agonist, 8-OH-DPAT (5, 10, and 50 ng/rat) decreased the percentages of open arm time (OAT%) and open arm entries (OAE%), indicating an anxiogenic response. Moreover, administration of 5HT(1A) receptor antagonist, NAN-190 (0.25, 0.5, and 1 μg/rat) significantly increased OAT% and OAE%. Pre-treatment administration of NAN-190 (0.5 μg/rat), which was injected into the MPFC, reversed the anxiogenic effects of 8-OH-DPAT (5, 10, and 50 ng/rat). Intra-MPFC microinjection of 5HT(1B) receptor agonist, CGS-12066A (0.25, 0.5, and 1 μg/rat) significantly decreased OAT% and OAE%, without any change in locomotor activity, indicating an anxiogenic effect. However, injection of 5HT(1B) receptor antagonist, SB-224289 (0.5, 1, and 2 μg/rat) into the MPFC showed no significant effect. In conclusion, these findings suggest that 5HT(1A) and 5HT(1B) receptors of the MPFC region modulate anxiogenic-like behaviors in rats. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Ontogeny of neuro-insular complexes and islets innervation in the human pancreas.

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Alexandra E. Proshchina

2014-04-01

Full Text Available The ontogeny of the neuro-insular complexes (NIC and the islets innervation in human pancreas has not been studied in detail. Our aim was to describe the developmental dynamics and distribution of the nervous system structures in the endocrine part of human pancreas. We used doublestaining with antibodies specific to pan-neural markers (neuron-specific enolase (NSE and S100 protein and to hormones of pancreatic endocrine cells. NSE and S100-positive nerves and ganglia were identified in the human fetal pancreas from gestation week (gw 10 onwards. Later the density of S100 and NSE-positive fibers increased. In adults this network was sparse. The islets innervation started to form from gw 14. NSE-containing endocrine cells were identified from gw 12 onwards. Additionally, S100-positive cells were detected both in the periphery and within some of the islets starting at gw 14. The analysis of islets innervation has shown that the fetal pancreas contained neuro-insular complexes and the number of these complexes was reduced in adults. The highest density of neuro-insular complexes is detected during middle and late fetal periods, when the mosaic islets, typical for adults, form. The close integration between the developing pancreatic islets and the nervous system structures may play an important role not only in the hormone secretion, but also in the islets morphogenesis.

Proteomic profiling of the rat cerebral cortex in sleep and waking.

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Cirelli, C; Pfister-Genskow, M; McCarthy, D; Woodbury, R; Tononi, G

2009-09-01

Transcriptomic studies have shown that hundreds of genes change their expression levels across the sleep/waking cycle, and found that waking-related and sleep-related mRNAs belong to different functional categories. Proteins, however, rather than DNA or RNA, carry out most of the cellular functions, and direct measurements of protein levels and activity are required to assess the effects of behavioral states on the overall functional state of the cell. Here we used surface-enhanced laser desorption-ionization (SELDI), followed by time-of-flight mass spectrometry, to obtain a large-scale profiling of the proteins in the rat cerebral cortex whose expression is affected by sleep, spontaneous waking, short (6 hours) and long (7 days) sleep deprivation. Each of the 94 cortical samples was profiled in duplicate on 4 different ProteinChip Array surfaces using 2 different matrix molecules. Overall, 1055 protein peaks were consistently detected in cortical samples and 15 candidate biomarkers were selected for identification based on significant changes in multiple conditions (conjunction analysis): 8 "sleep" peaks, 4 "waking" peaks, and 4 "long sleep deprivation" peaks. Four candidate biomarkers were purified and positively identified. The 3353 Da candidate sleep marker was identified as the 30 amino acid C-terminal fragment of rat histone H4. This region encompasses the osteogenic growth peptide, but a possible link between sleep and this peptide remains highly speculative. Two peaks associated with short and long sleep deprivation were identified as hemoglobin alpha1/2 and beta, respectively, while another peak associated with long sleep deprivation was identified as cytochrome C. The upregulation of hemoglobins and cytochrome C may be part of a cellular stress response triggered by even short periods of sleep loss.

Task-specific compensation and recovery following focal motor cortex lesion in stressed rats.

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Kirkland, Scott W; Smith, Lori K; Metz, Gerlinde A

2012-03-01

One reason for the difficulty to develop effective therapies for stroke is that intrinsic factors, such as stress, may critically influence pathological mechanisms and recovery. In cognitive tasks, stress can both exaggerate and alleviate functional loss after focal ischemia in rodents. Using a comprehensive motor assessment in rats, this study examined if chronic stress and corticosterone treatment affect skill recovery and compensation in a task-specific manner. Groups of rats received daily restraint stress or oral corticosterone supplementation for two weeks prior to a focal motor cortex lesion. After lesion, stress and corticosterone treatments continued for three weeks. Motor performance was assessed in two skilled reaching tasks, skilled walking, forelimb inhibition, forelimb asymmetry and open field behavior. The results revealed that persistent stress and elevated corticosterone levels mainly limit motor recovery. Treated animals dropped larger amounts of food in successful reaches and showed exaggerated loss of forelimb inhibition early after lesion. Stress also caused a moderate, but non-significant increase in infarct size. By contrast, stress and corticosterone treatments promoted reaching success and other quantitative measures in the tray reaching task. Comparative analysis revealed that improvements are due to task-specific development of compensatory strategies. These findings suggest that stress and stress hormones may partially facilitate task-specific and adaptive compensatory movement strategies. The observations support the notion that hypothalamic-pituitary-adrenal axis activation may be a key determinant of recovery and motor system plasticity after ischemic stroke.

Reorganization of Motor Cortex by Vagus Nerve Stimulation Requires Cholinergic Innervation.

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Hulsey, Daniel R; Hays, Seth A; Khodaparast, Navid; Ruiz, Andrea; Das, Priyanka; Rennaker, Robert L; Kilgard, Michael P

2016-01-01

Vagus nerve stimulation (VNS) paired with forelimb training drives robust, specific reorganization of movement representations in the motor cortex. The mechanisms that underlie VNS-dependent enhancement of map plasticity are largely unknown. The cholinergic nucleus basalis (NB) is a critical substrate in cortical plasticity, and several studies suggest that VNS activates cholinergic circuitry. We examined whether the NB is required for VNS-dependent enhancement of map plasticity in the motor cortex. Rats were trained to perform a lever pressing task and then received injections of the immunotoxin 192-IgG-saporin to selectively lesion cholinergic neurons of the NB. After lesion, rats underwent five days of motor training during which VNS was paired with successful trials. At the conclusion of behavioral training, intracortical microstimulation was used to document movement representations in motor cortex. VNS paired with forelimb training resulted in a substantial increase in the representation of proximal forelimb in rats with an intact NB compared to untrained controls. NB lesions prevent this VNS-dependent increase in proximal forelimb area and result in representations similar to untrained controls. Motor performance was similar between groups, suggesting that differences in forelimb function cannot account for the difference in proximal forelimb representation. Together, these findings indicate that the NB is required for VNS-dependent enhancement of plasticity in the motor cortex and may provide insight into the mechanisms that underlie the benefits of VNS therapy. Copyright © 2016 Elsevier Inc. All rights reserved.