Ablation of suprachiasmatic nucleus alters timing of hibernation in ground squirrels.

Hibernation patterns were monitored continuously for 2.5 years in female squirrels that were neurologically intact or in which the hypothalamic suprachiasmatic nucleus (SCN) was completely ablated (SCNx). The number of hibernation bouts in SCNx squirrels increased by 159%, total hibernation time increased by 58%, and periodic arousals from hibernation were 47% longer in SCNx than in control squirrels; the duration of individual torpor bouts was 2 days shorter and far more variable in SCNx than in control animals. Some SCNx squirrels cycled through bouts of torpor continuously for nearly 2 years. The SCN appears to be part of the mechanism that controls the duration of the hibernation season and the temporal structure of individual torpor bouts.

Medial prefrontal cortex suppression of the hypothalamic–pituitary–adrenal axis response to a physical stressor, systemic delivery of interleukin-1β

Previous studies have shown that the medial prefrontal cortex can suppress the hypothalamic-pituitary-adrenal axis response to stress. However, this effect appears to vary with the type of stressor. Furthermore, the absence of direct projections between the medial prefrontal cortex and corticotropin-releasing factor cells at the apex of the hypothalamic-pituitary-adrenal axis suggest that other brain regions must act as a relay when this inhibitory mechanism is activated. In the present study, we first established that electrolytic lesions involving the prelimbic and infralimbic medial prefrontal cortex increased plasma adrenocorticotropic hormone levels seen in response to a physical stressor, the systemic delivery of interleukin-1beta. However, medial prefrontal cortex lesions did not alter plasma adrenocorticotropic hormone levels seen in response to a psychological stressor, noise. To identify brain regions that might mediate the effect of medial prefrontal cortex lesions on hypothalamic-pituitary-adrenal axis responses to systemic interleukin-1beta, we next mapped the effects of similar lesions on interleukin-1beta-induced Fos expression in regions previously shown to regulate the hypothalamic-pituitary-adrenal axis response to this stressor. It was found that medial prefrontal cortex lesions reduced the number of Fos-positive cells in the ventral aspect of the bed nucleus of the stria terminalis. However, the final experiment, which involved combining retrograde tracing with Fos immunolabelling, revealed that bed nucleus of the stria terminalis-projecting medial prefrontal cortex neurons were largely separate from medial prefrontal cortex neurons recruited by systemic interleukin-1beta, an outcome that is difficult to reconcile with a simple medial prefrontal cortex-bed nucleus of the stria terminalis-corticotropin-releasing factor cell control circuit.

A critical role for the parabrachial nucleus in generating central nervous system responses elicited by a systemic immune challenge

Using Fos immunolabelling as a marker of neuronal activation, we investigated the role of the parabrachial nucleus in generating central neuronal responses to the systemic administration of the proinflarnmatory cytokine interleukin-1beta (1 mug/kg, i.a.). Relative to intact animals, parabrachial nucleus lesions significantly reduced the number of Fos-positive cells observed in the central amygdala (CeA), the bed nucleus of the stria terminalis (BNST), and the ventrolateral medulla (VLM) after systemic interleukin-1beta. In a subsequent experiment in which animals received parabrachial-directed deposits of a retrograde tracer, it was found that many neurons located in the nucleus tractus solitarius (NTS) and the VLM neurons were both retrogradely labelled and Fos-positive after interleukin-1beta administration. These results suggest that the parabrachial nucleus plays a critical role in interleukin-1beta-induced Fos expression in CeA, BNST and VLM neurons and that neurons of the NTS and VLM may serve to trigger or at least influence changes in parabrachial nucleus activity that follows systemic interleukin-1beta administration. (C) 2004 Elsevier B.V. All rights reserved.

Patterns of neuronal activation in the rat brain and spinal cord in response to increasing durations of restraint stress

By most accounts the psychological stressor restraint produces a distinct pattern of neuronal activation in the brain. However, some evidence is incongruous with this pattern, leading us to propose that the restraint- induced pattern in the central nervous system might depend on the duration of restraint used. We therefore determined the pattern of neuronal activation ( as indicated by the presence of Fos protein) seen in the paraventricular nucleus (PVN), bed nucleus of the stria terminalis, amygdala, locus coeruleus, nucleus tractus solitarius (NTS), ventrolateral medulla (VLM) and thoracic spinal cord of the rat in response to 0, 15, 30 or 60 min periods of restraint. We found that although a number of cell groups displayed a linear increase in activity with increasing durations of restraint ( e. g. hypothalamic corticotrophin-releasing factor (CRF) cells, medial amygdala neurons and sympathetic preganglionic neurons of the thoracic spinal cord), a number of cell groups did not. For example, in the central amygdala restraint produced both a decrease in CRF cell activity and an increase in non-CRF cell activity. In the locus coeruleus, noradrenergic neurons did not display Fos in response to 15 min of restraint, but were significantly activated by 30 or 60 min restraint. After 30 or 60 min restraint a greater degree of activation of more rostral A1 noradrenergic neurons was observed compared with the pattern of A1 noradrenergic neurons in response to 15 min restraint. The results of this study demonstrate that restraint stress duration determines the amount and the pattern of neuronal activation seen in response to this psychological stressor.

Central proopiomelanocortin but not neuropeptide Y mediates sympathoexcitation and hypertension in fat fed conscious rabbits

OBJECTIVE: High-fat diet (HFD)-induced hypertension in rabbits is neurogenic because of the central sympathoexcitatory actions of leptin. Hypothalamic melanocortin and neuropeptide Y (NPY) neurons are recognized as the major signalling pathways through which leptin exerts its central effects. In this study, we assessed the effects of specific antagonists and agonists to melanocortin and NPY receptors on HFD-induced sympathoexcitation and hypertension. METHODS: Rabbits were instrumented with intracerebroventricular cannula, renal sympathetic nerve activity (RSNA) electrode, and blood pressure telemetry transmitter. RESULTS: After 3 weeks HFD (13.5% fat, n = 12) conscious rabbits had higher RSNA (+3.8  nu, P = 0.02), blood pressure (+8.6  mmHg, P < 0.001) and heart rate (+15  b/min, P = 0.01), and brain-derived neurotrophic factor levels in the hypothalamus compared with rabbits fed a control diet (4.2% fat, n = 11). Intracerebroventricular administration of the melanocortin receptor antagonist SHU9119 reduced RSNA (-2.7  nu) and blood pressure (-8.5  mmHg) in HFD but not control rabbits, thus reversing 100% of the hypertension and 70% of the sympathoexcitation induced by a HFD. By contrast, blocking central NPY Y1 receptors with BVD10 increased RSNA only in HFD rabbits. Intracerebroventricular α-melanocortin stimulating hormone increased RSNA and heart rate (P < 0.001) in HFD rabbits but had no effect in control rabbits. CONCLUSION: These findings suggest that obesity-induced hypertension and increased RSNA are dependent on the balance between greater activation of melanocortin signalling through melanocortin receptors and lesser activation of NPY sympathoinhibitory signalling. The amplification of the sympathoexcitatory effects of α-melanocortin stimulating hormone also indicates that the underlying mechanism is related to facilitation of leptin-melanocortin signalling, possibly involving chronic activation of brain-derived neurotrophic factor.

Effects of sucrose on opioid gene expression in the rat brain.

Opioid peptide neurotransmitters stimulate feeding and are involved in mediating the rewarding aspects of feeding, as well as in energy regulation in the brain. The effects of sucrose diets on opioid peptide gene expression were measured in the arcuate nucleus (ARC) and the paraventricular nucleus (PVN) of the rat. Rats were fed a cornstarch-based diet or a low (16.7%), medium (33.4%), or high (50%) sucrose containing diet for 7 days. Analyses of the ARC and PVN demonstrated that sucrose in the diet had no effect on mRNA levels of opioid peptides. The lack of an opioid response in the ARC and PVN suggests that opioids in the ARC and PVN are involved in energy regulation rather than in mediating hedonic aspects of feeding.

Effects of social context on endocrine function and Zif268 expression in response to an acute stressor in adolescent and adult rats

There is a paucity of studies comparing social buffering in adolescents and adults, despite their marked differences in social behaviour. I investigated whether greater effects of social buffering on plasma corticosterone concentrations and expression of Zif268 in neural regions after an acute stressor would be found in adolescent compared with adult rats. Samples were obtained before and after one hour of isolation stress and after either one or three hours of recovery back in the colony with either a familiar or unfamiliar cage partner. Adolescent and adult rats did not differ in plasma concentrations of corticosterone at any time point. Corticosterone concentrations were higher after one hour isolation than at baseline (p < 0.001), and rats with a familiar partner during the recovery phase had lower corticosterone concentrations than did rats with an unfamiliar partner (p = 0.02). Zif268 immunoreactive cell counts were higher in the arcuate nucleus in both age groups after isolation (p = 0.007) and higher in the paraventricular nucleus of adolescents compared with adults during the recovery phase irrespective of partner familiarity. There was a significant decrease in immunoreactive cell counts after one hour isolation compared to baseline in the basolateral amygdala, central nucleus of the amygdala, and in the pyramidal layer of the hippocampus (all p < 0.05). An effect of partner familiarity on Zif268 immunoreactive cell counts was found in the granule layer of the dentate gyrus irrespective of age (higher in those with a familiar partner, p = 0.03) and in the medial prefrontal cortex in adolescents (higher with an unfamiliar partner, p = 0.02). Overall, the acute stress and partner familiarity produced a similar pattern of results in adolescents and adults, with both age groups sensitive to the social context.

Impact de l'haploinsuffisance du gène Sim1 sur le développement et la fonction du noyau paraventriculaire de l'hypothalamus

L’obésité provient d’un déséquilibre de l’homéostasie énergétique, c’est-à-dire une augmentation des apports caloriques et/ou une diminution des dépenses énergétiques. Plusieurs données, autant anatomiques que physiologiques, démontrent que l’hypothalamus est un régulateur critique de l’appétit et des dépenses énergétiques. En particulier, le noyau paraventriculaire (noyau PV) de l’hypothalamus intègre plusieurs signaux provenant du système nerveux central (SNC) et/ou de la périphérie, afin de contrôler l’homéostasie énergétique via des projections axonales sur les neurones pré-ganglionnaires du système autonome situé dans le troc cérébral et la moelle épinière. Plusieurs facteurs de transcription, impliqués dans le développement du noyau PV, ont été identifiés. Le facteur de transcription SIM1, qui est produit par virtuellement tous les neurones du noyau PV, est requis pour le développement du noyau PV. En effet, lors d’une étude antérieure, nous avons montré que le noyau PV ne se développe pas chez les souris homozygotes pour un allèle nul de Sim1. Ces souris meurent à la naissance, probablement à cause des anomalies du noyau PV. Par contre, les souris hétérozygotes survivent, mais développent une obésité précoce. De façon intéressante, le noyau PV des souris Sim1+/- est hypodéveloppé, contenant 24% moins de cellules. Ces données suggèrent fortement que ces anomalies du développement pourraient perturber le fonctionnement du noyau PV et contribuer au développement du phénotype d’obésité. Dans ce contexte, nous avons entrepris des travaux expérimentaux ayant pour but d’étudier l’impact de l’haploinsuffisance de Sim1 sur : 1) le développement du noyau PV et de ses projections neuronales efférentes; 2) l’homéostasie énergétique; et 3) les voies neuronales physiologiques contrôlant l’homéostasie énergétique chez les souris Sim1+/-. A cette fin, nous avons utilisé : 1) des injections stéréotaxiques combinées à des techniques d’immunohistochimie afin de déterminer l’impact de l’haploinsuffisance de Sim1 sur le développement du noyau PV et de ses projections neuronales efférentes; 2) le paradigme des apports caloriques pairés, afin de déterminer l’impact de l’haploinsuffisance de Sim1 sur l’homéostasie énergétique; et 3) une approche pharmacologique, c’est-à-dire l’administration intra- cérébroventriculaire (i.c.v.) et/ou intra-péritonéale (i.p.) de peptides anorexigènes, la mélanotane II (MTII), la leptine et la cholécystokinine (CCK), afin de déterminer l’impact de l’haploinsuffisance de Sim1 sur les voies neuronales contrôlant l’homéostasie énergétique. Dans un premier temps, nous avons constaté une diminution de 61% et de 65% de l’expression de l’ARN messager (ARNm) de l’ocytocine (Ot) et de l’arginine-vasopressine (Vp), respectivement, chez les embryons Sim1+/- de 18.5 jours (E18.5). De plus, le nombre de cellules produisant l’OT et la VP est apparu diminué de 84% et 41%, respectivement, chez les souris Sim1+/- adultes. L’analyse du marquage axonal rétrograde des efférences du noyau PV vers le tronc cérébral, en particulier ses projections sur le noyau tractus solitaire (NTS) aussi que le noyau dorsal moteur du nerf vague (X) (DMV), a permis de démontrer une diminution de 74% de ces efférences. Cependant, la composition moléculaire de ces projections neuronales reste inconnue. Nos résultats indiquent que l’haploinsuffisance de Sim1 : i) perturbe spécifiquement le développement des cellules produisant l’OT et la VP; et ii) abolit le développement d’une portion importante des projections du noyau PV sur le tronc cérébral, et notamment ses projections sur le NTS et le DMV. Ces observations soulèvent donc la possibilité que ces anomalies du développement du noyau PV contribuent au phénotype d’hyperphagie des souris Sim1+/-. En second lieu, nous avons observé que la croissance pondérale des souris Sim1+/- et des souris Sim1+/+ n’était pas significativement différente lorsque la quantité de calories présentée aux souris Sim1+/- était la même que celle consommée par les souris Sim1+/+. De plus, l’analyse qualitative et quantitative des tissus adipeux blancs et des tissus adipeux bruns n’a démontré aucune différence significative en ce qui a trait à la taille et à la masse de ces tissus chez les deux groupes. Finalement, au terme de ces expériences, les souris Sim1+/--pairées n’étaient pas différentes des souris Sim1+/+ en ce qui a trait à leur insulinémie et leur contenu en triglycérides du foie et des masses adipeuses, alors que tous ces paramètres étaient augmentés chez les souris Sim1+/- nourries ad libitum. Ces résultats laissent croire que l’hyperphagie, et non une diminution des dépenses énergétiques, est la cause principale de l’obésité des souris Sim1+/-. Par conséquent, ces résultats suggèrent que : i) l’haploinsuffisance de Sim1 est associée à une augmentation de l’apport calorique sans toutefois moduler les dépenses énergétiques; ii) l’existence d’au moins deux voies neuronales issues du noyau PV : l’une qui régule la prise alimentaire et l’autre la thermogénèse; et iii) l’haploinsuffisance de Sim1 affecte spécifiquement la voie neuronale qui régule la prise alimentaire. En dernier lieu, nous avons montré que l’injection de MTII, de leptine ainsi que de CCK induit une diminution significative de la consommation calorique des souris des deux génotypes, Sim1+/+ et Sim1+/-. De fait, la consommation calorique cumulative des souris Sim1+/- et Sim1+/+ est diminuée de 37% et de 51%, respectivement, durant les 4 heures suivant l’administration i.p. de MTII comparativement à l’administration d’une solution saline. Lors de l’administration i.c.v. de la leptine, la consommation calorique cumulative des souris Sim1+/- et Sim1+/+ est diminuée de 47% et de 32%, respectivement. Finalement, l’injection i.p. de CCK diminue la consommation calorique des souris Sim1+/- et Sim1+/+ de 52% et de 36%, respectivement. L’ensemble des résultats suggère ici que l’haploinsuffisance de Sim1 diminue l’activité de certaines voies neuronales régulant l’homéostasie énergétique, et particulièrement de celles qui contrôlent la prise alimentaire. En résumé, ces travaux ont montré que l’haploinsuffisance de Sim1 affecte plusieurs processus du développement au sein du noyau PV. Ces anomalies du développement peuvent conduire à des dysfonctions de certains processus physiologiques distincts régulés par le noyau PV, et notamment de la prise alimentaire, et contribuer ainsi au phénotype d’obésité. Les souris hétérozygotes pour le gène Sim1 représentent donc un modèle animal unique, où l’hyperphagie, et non les dépenses énergétiques, est la principale cause de l’obésité. En conséquence, ces souris pourraient représenter un modèle expérimental intéressant pour l’étude des mécanismes cellulaires et moléculaires en contrôle de la prise alimentaire.

Régulation transcriptionelle du développement de l'hypothalamus chez l'amphibien

Le noyau paraventriculaire (PVN) de l'hypothalamus régule une série de phénomènes physiologiques incluant l'équilibre énergétique et la pression artérielle. Nous avons identifié une cascade de facteurs de transcription qui contrôle le développement du PVN. SIM1 et OTP agissent en parallèle pour contrôler la différenciation d'au moins cinq types de neurones identifiables par la production d'OT, AVP, CRH, SS et TRH. Ces Facteurs de transcriptions contrôlent le développement des lignées CRH, AVP et OT en maintenant l'expression de Brn2 qui à son tour est nécessaire pour la différenciation terminale de ces neurones. L'analyse du transcriptome du PVN nous a permis d'identifier plusieurs gènes qui ont le potentiel de contrôler le développement du PVN. Nous voulons développer un paradigme de perte de fonction qui permettrait l'étude de ces gènes candidats sur une grande échelle. Le but de ce projet est de caractériser le PVN en développement de l'amphibien en vue de l'utilisation de ce modèle pour des études fonctionnelles. Nous avons cloné des fragments de cDNA de Sim1, OTP, Brn2, Sim2, CRH, Ot, AVP et TRH à partir de l'ARN total de Xenopus Laevis. Nous avons adapté notre technique d'hybridation in situ pour caractériser l'expression de ces gènes chez l'amphibien aux stades 33-39, 44, 51, 54, 60, et chez l'adulte. Résultats. Les Facteurs de transcription Sim1, OTP, et Brn2 commencent à être exprimés dans le PVN prospectif au stade 33. L'expression des marqueurs de différenciation terminale devient détectable entre les stades 37 et 39. De façon intéressante, le PVN occupe initialement un domaine de forme globulaire puis à partir du stade 44 s'allonge le long de l’axe dorso-ventral. Cet allongement se traduit par une organisation en colonnes des cellules du PVN que nous n'avons pas observée chez les rongeurs. Le développement du PVN est conservé chez l'amphibien dans la mesure où la relation entre l'expression des facteurs de transcription et des marqueurs de différenciation terminale est conservée. Il existe par ailleurs des différences entre la topographie des PVN des mammifères et de l'amphibien. L'organisation en colonnes de cellules pourrait correspondre à des mouvements de migration tangentielle. Nous sommes maintenant en mesure de tester la fonction des facteurs de transcription dans le PVN par l'approche d'invalidation par morpholinos.

The cannabinoid CB1 receptor antagonist SR141716 blocks the orexigenic effects of intrahypothalamic ghrelin

The paraventricular nucleus (PVN) of the hypothalamus plays a key role in the control of appetite and energy balance. Both ghrelin and cannabinoid receptor agonists increase food intake when administered into this nucleus: this study investigated possible interactions between the two systems in relation to eating. The orexigenic effect of ghrelin (100 pmol) when infused in to the PVN was reversed by a small, systemic dose of the CB1 cannabinoid receptor antagonist SR141716 (1 mg kg(-1)). This is the first demonstration of a functional relationship between brain ghrelin and endocannabinoid systems, and, although it needs to be further investigated, the effect of ghrelin on food intake when injected into the PVN seems to be mediated by stimulation of cannabinoid release.

The Immune-Pineal Axis Stress as a Modulator of Pineal Gland Function

The temporal organization of mammals presents a daily adjustment to the environmental light/dark cycle. The environmental light detected by the retina adjusts the central clock in the suprachiasmatic nuclei, which innervate the pineal gland through a polysynaptic pathway. During the night, this gland produces and releases the nocturnal hormone melatonin, which circulates throughout the whole body and adjusts several bodily functions according to the existence and duration of darkness. We have previously shown that during the time frame of an inflammatory response, pro-inflammatory cytokines, such as tumor necrosis factor-a, inhibit while anti-inflammatory mediators, such as glucocorticoids, enhance the synthesis of melatonin, interfering in the daily adjustment of the light/dark cycle. Therefore, injury disconnects the organism from environmental cycling, while recovery restores the light/dark information to the whole organism. Here, we extend these observations by evaluating the effect of a mild restraint stress, which did not induce macroscopic gastric lesions. After 2 h of restraint, there was an increase in circulating corticosterone, indicating activation of the hypothalamus-pituitary-adrenal (HPA) axis. In parallel, an increase in melatonin production was observed. Taking into account the data obtained with models of inflammation and stress, we reinforce the hypothesis that the activity of the pineal gland is modulated by the state of the immune system and the HPA axis, implicating the darkness hormone melatonin as a modulator of defense responses.

Differential regulation of the renin-angiotensin system by nicotine in WKY and SHR glia

Given that (1) the renin-angiotensin system (RAS) is compartmentalized within the central nervous system in neurons and glia (2) the major source of brain angiotensinogen is the glial cells, (3) the importance of RAS in the central control of blood pressure, and (4) nicotine increases the probability of development of hypertension associated to genetic predisposition; the objective of the present study was to evaluate the effects of nicotine on the RAS in cultured glial cells from the brainstem and hypothalamus of Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats. Ligand binding, real-time PCR and western blotting assays were used to compare the expression of angiotensinogen, angiotensin converting enzyme, angiotensin converting enzyme 2 and angiotensin II type1 receptors. We demonstrate, for the first time, that there are significant differences in the basal levels of RAS components between WKY and SHR rats in glia from 1-day-old rats. We also observed that nicotine is able to modulate the renin-angiotensin system in glial cells from the brainstem and hypothalamus and that the SHR responses were more pronounced than WKY ones. The present data suggest that nicotine effects on the RAS might collaborate to the development of neurogenic hypertension in SHR through modulation of glial cells.

mRNA expression of corticotropin-releasing factor and urocortin 1 after restraint and foot shock together with alprazolam administration

Corticotropin-releasing factor (CRF) is expressed in the paraventricular nucleus of the hypothalamus (PVN), and act centrally to provoke stress-like autonomic and behavioral responses. Urocortins 1-3 are additional ligands to the CRF receptors 1 and 2. Ucn 1 neurons are primarily concentrated in the Edinger-Westphal (EW) nucleus and also have been associated with stress responses. It is also known that UCN 1 respond in different ways depending on the stressor presented. Benzodiazepines can act via the CRF peptidergic system and chronic administration of alprazolam does not interfere with CRF mRNA expression in the PVN, but significantly increase Ucn 1 mRNA expression in the EW. The aim of our study was to investigate the relationship between different stressor stimuli, foot shock (FS) and restraint (R), and the mRNA expression of CRF and Ucn 1 in the PVN and EW using alprazolam (A). We employed fos activation and in situ hybridization. Restraint group presented increased fos-ir and CRF mRNA expression in the PVN compared to FS group. The stress responses of R group were prevented by A. In the EW,fos-ir was higher in the FS group than in the R group, whereas Ucn 1 mRNA expression was higher in the R group than in the FS group. Alprazolam significantly increased fos-ir and Ucn 1 mRNA expression in both groups. Our results show that PVN and EW respond in different ways to the same stressors. Furthermore, EW of stressed animals replies in a complementary way comparing to PVN with the use of Alprazolam. (C) 2010 Elsevier Inc. All rights reserved.

Calcium-binding proteins in the circadian centers of the common marmoset (Callithrix jacchus) and the rock cavy (Kerodon rupestris) brains

The hypothalamic suprachiasmatic nucleus (SCN) and the thalamic intergeniculate leaflet (IGL) are considered to be the main centers of the mammalian circadian timing system. In primates, the IGL is included as part of the pregeniculate nucleus (PGN), a cell group located mediodorsally to the dorsal lateral geniculate nucleus. This work was carried out to comparatively evaluate the immunohistochemical expression of the calcium-binding proteins calbindin D-28k (CB), parvalbumin (PV), and calretinin (CR) into the circadian brain districts of the common marmoset and the rock cavy. In both species, although no fibers, terminals or perikarya showed PV-immunoreaction (IR) into the SCN, CB-IR perikarya labeling was detected throughout the SCN rostrocaudal extent, Seeming to delimit its cytoarchitectonic borders. CR-IR perikarya and neuropil were noticed into the ventral and dorsal portions of the SCN, lacking immunoreactivity in the central core of the marmoset and filling the entire nucleus in the rockcavy. The PGN of the marmoset presented a significant number of CB-, PV-, and CR-IR perikarya throughout the nucleus. The IGL of the rocky cavy exhibited a prominent CB- and CR-IR neuropil, showing similarity to the pattern found in other rodents. By comparing with literature data from other mammals, the results of the present study suggest that CB, PV, and CR are differentially distributed into the SCN and IGL among species. They may act either in concert or in a complementary manner in the SCN and IGL, so as to participate in specific aspects of the circadian regulation. (c) 2008 Elsevier Inc. All rights reserved.

AMYGDALAR ROLES DURING EXPOSURE TO A LIVE PREDATOR AND TO A PREDATOR-ASSOCIATED CONTEXT

The amygdala plays a critical role in determining the emotional significance of sensory stimuli and the production of fear-related responses. Large amygdalar lesions have been shown to practically abolish innate defensiveness to a predator; however, it is not clear how the different amygdalar systems participate in the defensive response to a live predator. Our first aim was to provide a comprehensive analysis of the amygdalar activation pattern during exposure to a live cat and to a predator-associated context. Accordingly, exposure to a live predator up-regulated Fos expression in the medial amygdalar nucleus (MEA) and in the lateral and posterior basomedial nuclei, the former responding to predator-related pheromonal information and the latter two nuclei likely to integrate a wider array of predatory sensory information, ranging from olfactory to non-olfactory ones, such as visual and auditory sensory inputs. Next, we tested how the amygdalar nuclei most responsive to predator exposure (i.e. the medial, posterior basomedial and lateral amygdalar nuclei) and the central amygdalar nucleus (CEA) influence both unconditioned and contextual conditioned anti-predatory defensive behavior. Medial amygdalar nucleus lesions practically abolished defensive responses during cat exposure, whereas lesions of the posterior basomedial or lateral amygdalar nuclei reduced freezing and increased risk assessment displays (i.e. crouch sniff and stretch postures), a pattern of responses compatible with decreased defensiveness to predator stimuli. Moreover, the present findings suggest a role for the posterior basomedial and lateral amygdalar nuclei in the conditioning responses to a predator-related context. We have further shown that the CEA does not seem to be involved in either unconditioned or contextual conditioned anti-predatory responses. Overall, the present results help to clarify the amygdalar systems involved in processing predator-related sensory stimuli and how they influence the expression of unconditioned and contextual conditioned anti-predatory responses. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.