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Orientador: Fabio Papes / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-20T21:10:44Z (GMT). No. of bitstreams: 1 Cardozo_LeonardoMinete_M.pdf: 30220846 bytes, checksum: 6793ed2dd7e959cbc81a5c912cd1c987 (MD5) Previous issue date: 2012 / Resumo: Uma propriedade fundamental do sistema nervoso em todas as espécies animais e a transformação dos estímulos sensoriais em atividade neural, levando a mudanças comportamentais e endócrinas. Dentre os sistemas sensoriais, o Sistema Olfatório destaca-se por sua complexidade molecular, capacidade de detecção de odores e modulação de comportamentos inatos. Entretanto, ainda muito pouco e conhecido sobre como este Sistema detecta, processa e interpreta as informações químicas que recebe do meio externo... Observação: O resumo, na íntegra, poderá ser visualizado no texto completo da tese digital / Abstract: A fundamental property of the nervous system in all animal species is the transformation of sensory stimulation into neural activity, leading to endocrine and behavioral changes. Among the sensory systems, the olfactory system stands out due to its molecular complexity, detection capacity and the modulation of innate behaviors. However, little is known about how this system detects, processes and interprets chemosignals from the environment... Note: The complete abstract is available with the full electronic document / Mestrado / Genetica Animal e Evolução / Mestre em Genética e Biologia Molecular

Bipolar disorder (BD) is a severe psychiatric illness with a consistent genetic influence, involving complex interactions between numerous genes and environmental factors. Immediate early genes (IEGs) are activated in the brain in response to environmental stimuli, such as stress. The potential to translate environmental stimuli into long-term changes in brain has led to increased interest in a potential role for these genes influencing risk for psychiatric disorders. Our recent finding using network-based approach has shown that the regulatory unit of early growth response gene 3 (EGR3) of IEGs family was robustly repressed in postmortem prefrontal cortex of BD patients. As a central transcription factor, EGR3 regulates an array of target genes that mediate critical neurobiological processes such as synaptic plasticity, memory and cognition. Considering that EGR3 expression is induced by brain-derived neurotrophic factor (BDNF) that has been consistently related to BD pathophysiology, we suggest a link between BDNF and EGR3 and their potential role in BD. A growing body of data from our group and others has shown that peripheral BDNF levels are reduced during mood episodes and also with illness progression. In this same vein, BDNF has been proposed as an important growth factor in the impaired cellular resilience related to BD. Taken together with the fact that EGR3 regulates the expression of the neurotrophin receptor p75NTR and may also indirectly induce BDNF expression, here we propose a feed-forward gene regulatory network involving EGR3 and BDNF and its potential role in BD.

Obsessive-compulsive disorder (OCD) is a serious psychiatric condition manifested by repeated thoughts followed by stereotypic compulsive behavior. Alterations to cortico-thalamo-striato- cortical circuits are most often implicated in the pathophysiology of OCD. However, many studies have also found a changed volume, shape and activity of the hippocampus in OCD patients. This work focused on the activity of hippocampal CA1 cells during stereotypical checking behavior and on cognitive flexibility in a quinpirole (QNP) sensitization model of OCD. The activity of CA1 hippocampal cells during stereotypical checking was assessed in an enriched open-field test in QNP sensitized rats. Arc+ (activity-regulated cytoskeletal associated protein, or Arg 3.1) mRNA expression profiles were determined in CA1 coronal hippocampal sections following stereotypical checking. After the establishment of stereotypical checking (10 sessions), rats were exposed to the arena and sacrificed after 5 minutes. QNP sensitized animals visited the same objects with the same frequency as during previous sessions, while control rats did not. Locomotor activity was comparable between QNP treated rats and controls. Following sacrifice, rat brains were flash frozen and sliced to 20 µm thick sections. Sections, mounted on slides, were hybridized...

Η ντοπαμινεργική νεύρωση είναι πολύ σημαντική για τις μακροχρόνιες αλλαγές της συναπτικής πλαστικότητας στον ιππόκαμπο και στον προμετωπιαίο φλοιό, καθώς και για την έκφραση των πρώιμων γονιδίων που σχετίζονται με τη μνήμη και τη μάθηση. Πολλές εργασίες έχουν δείξει ότι οι αλληλεπιδράσεις μεταξύ ντοπαμινεργικών και γλουταμινεργικών υποδοχέων είναι ιδιαίτερα σημαντικές για τις γνωστικές λειτουργίες του ιππόκαμπου και του προμετωπιαίου φλοιού. Προκειμένου να μελετήσουμε το μοριακό υπόβαθρο των αλληλεπιδράσεων μεταξύ των ντοπαμινεργικών και γλουταμινεργικών υποδοχέων στο ιππόκαμπο και τον προμετωπιαίο φλοιό του επίμυος, εξετάσαμε «in vitro» την επίδραση της ενεργοποίησης των D1 υποδοχέων ντοπαμίνης στο επίπεδο φωσφορυλίωσης των υπομονάδων των NMDA και AMPA υποδοχέων γλουταμινικού οξέος., καθώς στην φωσφορυλίωση/ ενεργοποίηση του σηματοδοτικού μονοπατιού της ERK1/2 κινάσης (Extracellular Regulated Kinase1/2) και της DARPP-32 (Dopamine-and cyclicAMP-Regulated PhosphoProtein-32). Επιπλέον, συγκρίναμε τις αλληλεπιδράσεις των D1/NMDA/AMPA υποδοχέων που παρατηρούνται στον ιππόκαμπο και στον προμετωπιαίο φλοιό με αυτές που εμφανίζονται στο ραβδωτό σώμα, στο οποίο η πυκνότητα των D1 υποδοχέων είναι η μέγιστη στον εγκέφαλο. Τα αποτελέσματά μας δείχνουν ότι η ενεργοποίηση των D1 υποδοχέων από τον ειδικό αγωνιστή τους SKF38393 (10 μΜ) στις τομές του ιππόκαμπου και του προμετωπιαίου φλοιού έχει ως αποτέλεσμα μια σημαντική αύξηση των επιπέδων φωσφορυλίωσης: α) της σερίνης-897 της NR1 υπομονάδας και της σερίνης-1303 της NR2B υπομονάδας του NMDA υποδοχέα, οι οποίες επάγουν τη διακίνηση των υποδοχέων στην μεμβρανική επιφάνεια (trafficking) και την ενίσχυση των ρευμάτων του ιοντικού διαύλου, αντίστοιχα, β) των σερινών-831 και -845 της GLUR1 υπομονάδας του AMPA υποδοχέα, οι οποίες ενισχύουν τα ρεύματα του ιοντικού διαύλου και αυξάνουν την πιθανότητα ανοίγματος του καναλιού, αντίστοιχα και γ) της ERK1/2 κινάσης, αλλά όχι της DARPP-32. Είναι ενδιαφέρον το γεγονός ότι η συνενεργοποίηση των D1 και NMDA υποδοχέων με ανενεργές δόσεις των ειδικών αγωνιστών τους SKF38393 (2 μΜ) και NMDA (5 μΜ), αντίστοιχα έχει ως αποτέλεσμα μια περαιτέρω αύξηση των επιπέδων φωσφορυλίωσης των υπομονάδων των NMDA και AMPA υποδοχέων, καθώς και της ERK1/2 κινάσης, αλλά όχι της DARPP-32. Οι παραπάνω επαγόμενες από την ενεργοποίηση των D1 υποδοχέων και την συνενεργοποίηση των D1/ NMDA υποδοχέων φωσφορυλιώσεις αναστέλλονται πλήρως από τον ειδικό αναστολέα της ενεργοποίησης της ERK1/2 κινάσης, SL327. Αντίθετα, στο ραβδωτό σώμα τα αποτελέσματα επιβεβαιώνουν ότι η επαγόμενη από τους D1 υποδοχείς φωσφορυλίωση των υπομονάδων των NMDA και AMPA υποδοχέων βασίζεται στο καλά περιγραμμένο σηματοδοτικό μονοπάτι D1/PKA/DARPP-32. Συμπερασματικά, τα «in vitro» πειράματα δείχνουν στον ιππόκαμπο και στον προμετωπιαίο φλοιό να υφίσταται ισχυρή συνεργιστική αλληλεπίδραση μεταξύ των D1 και των NMDA υποδοχέων, η οποία οδηγεί στην ενεργοποίηση του σηματοδοτικού μονοπατιού της ΕΡΚ1/2 κινάσης. Επιπλέον, η επαγόμενη από την διέγερση των D1 υποδοχέων και από τη συνδιέγερση των D1/ NMDA υποδοχέων φωσφορυλίωση των υπομονάδων των NMDA και AMΡΑ υποδοχέων φαίνεται να οφείλεται στο σηματοδοτικό μονοπάτι της ERK1/2 κινάσης και πιθανώς αποτελεί το μοριακό υπόβαθρο της ενίσχυσης των ρευμάτων των NMDA και AMPA υποδοχέων από την ενεργοποίηση των D1 υποδοχέων. Προκειμένου να διερευνήσουμε εάν αυτή η συνεργιστική αλληλεπίδραση των D1/ NMDA υποδοχέων υφίσταται και «in vivo» και να εξετάσουμε περαιτέρω τη λειτουργική της σημασία, επιλέξαμε ένα φυσικό συμπεριφορικό τεστ, την εισαγωγή των πειραματόζωων σε «πρωτόγνωρο» περιβάλλον (ελεύθερη εξερεύνηση του χώρου). Η δοκιμασία αυτή είναι γνωστό ότι επάγει την αύξηση των επιπέδων ντοπαμίνης στον ιππόκαμπο και τον προμετωπιαίο φλοιό και κατ’επέκταση επάγει την ενεργοποίηση των D1 υποδοχέων. Τα αποτελέσματα μας δείχνουν ότι η εισαγωγή των επίμυων στο «καινούργιο» περιβάλλον επάγει στον ιππόκαμπο και στον προμετωπιαίο φλοιό: α) μια σημαντική αύξηση των επιπέδων φωσφορυλίωσης των υπομονάδων των NMDA και ΑΜPA υποδοχέων, καθώς και ισχυρή φωσφορυλίωση/ ενεργοποίηση του σηματοδοτικού μονοπατιού της ERK1/2 κινάσης. Τα φαινόμενα αυτά όπως δείξαμε μετά τη χορήγηση ειδικών ανταγωνιστών εξαρτώνται από τη σύγχρονη ενεργοποίηση των D1/ NMDA υποδοχέων και οφείλονται στο «νέο» ερέθισματα, δεδομένου ότι δεν εμφανίζονται μετά από δοκιμασία «εξοικείωσης» των επίμυων στο «καινούργιο» περιβάλλον, β) επιγεννετικές τροποποιήσεις (φωσφορυλίωση/ ακετυλίωση της ιστόνης Η3) και γ) αύξηση των πρωτεϊνικών επιπέδων έκφρασης των πρώιμων γονιδίων cFos και zif268 επιλεκτικά στη CA1 περιοχή του ιπποκάμπου, φαινόμενα τα οποία εξαρτώνται από την συνενεργοποίηση των D1/ NMDA υποδοχέων, καθώς και των μουσκαρινικών υποδοχέων ακετυλοχολίνης. Συμπερασματικά τα αποτελέσματα μας δείχνουν ότι: α) η φωσφορυλίωση των υπομονάδων των NMDA και AMPA υποδοχέων πιθανώς δρα ως «δείκτης του πρωτόγνωρου ερεθίσματος», δεδομένου ότι δεν εμφανίζονται μετά την «εξοικείωση» των επίμυων στο «καινούργιο» περιβάλλον, β) η ισχυρή ενεργοποίηση του σηματοδοτικού μονοπατιού της ERK1/2 κινάσης που επάγεται από το «νέο» ερέθισμα απαιτεί τη συνεργιστική αλληλεπίδραση των D1/ NMDA υποδοχέων και γ) η ενεργοποίηση του μονοπατιού μεταγωγής σήματος της ERK1/2 κινάσης οδηγεί σε επιγεννετικές αλλαγές και αύξηση της έκφρασης των πρώιμων γονιδίων cFos και zif268, φαινόμενα τα οποία απαιτούνται στη ρύθμιση της συναπτικής πλαστικότητας, καθώς και στις διαδικασίες της μνήμης και της μάθησης. / Dopaminergic innervation is critical for long term changes in synaptic efficacy in hippocampus and prefrontal cortex (PFC), as well as for learning-associated immediate-early gene expression. Many studies have demonstrated that the interactions between dopamine and glutamate receptors are essential for the prefrontal cortical (PFC) and hippocampal cognitive functions. In order to understand the molecular basis of dopamine/glutamate interactions in rat PFC and hippocampus, we investigated the effect of “in vitro” dopamine D1 receptor stimulation on glutamate NMDA and AMPA receptor subunits’ phosphorylation, as well as on ERK1/2 (Extracellular Regulated Kinase1/2) and DARPP-32 (Dopamine-and cyclicAMP-Regulated PhosphoProtein-32) phosphorylation/activation. Furthermore, we compared the D1/NMDA/AMPA receptor interactions seen in PFC and hippocampus with those appearing in striatum, in which the D1 receptors’ density is the highest within the mammalian brain. Our results showed that stimulation of D1 receptor by the specific agonist SKF38393 (10μM) in PFC and hippocampal slices significantly increased the phosphorylation state of: a) NR1ser897 and NR2Bser1303 subunits of NMDA receptor, which promotes the trafficking and enhances the ionic currents, respectively, b) of GLUR1(ser831 and ser845) subunit of AMPA receptor, which enhances the receptor currents and the open probability of the receptor channel and c) of ERK1/2, but not of DARPP-32. Interestingly, co-stimulation of D1 and NMDA receptors with an ineffective dose of SKF38393(2μM) and NMDA(5μM) respectively, elevated further the phosphorylation level of NMDA and AMPA receptor subunits, as well as of ERK1/2, but not of DARPP-32. The D1- and D1/NMDA-induced phosphorylations were totally inhibited by SL327 (specific ERK1/2 inhibitor). Conversely, in striatal slices our data confirm that the D1-mediated phosphorylation of NMDA and AMPA receptor subunits relies on D1/PKA/DARPP-32 signalling. In conclusion, in PFC and hippocampus: a) a strong synergistic interaction of D1 and NMDA receptors exists, which results in a significant ERK1/2 pathway activation, b) The D1 and the D1/NMDA receptor induced phosphorylation of NMDA and AMPA receptor subunits seems to rely on ERK1/2 signalling and could to some extend underlie the enhancement of NMDA and AMPA receptor currents mediated by D1 receptor activation. In order to investigate whether this synergistic interaction occurs also “in vivo” and to further examine its functional significance, we exposed the rats to a novel environment (open field exploration), which is known to evoke dopamine release in hippocampus and PFC. Our results showed that the “spatial” novelty stimulus induced in rat hippocampus and PFC: a) a significant increase in phosphorylation of NMDA and AMPA receptor subunits, as well as a robust phosphorylation/activation of ERK1/2 signalling, which are both dependent on the concomitant stimulation of D1/NMDA receptors and are both abolished by habituation, b) chromatin remodeling events (phosphorylation-acetylation of histone H3) and c) an increase in the immediate early genes cFos and zif268 expression in the CA1 region of hippocampus, which is dependent on the coactivation of D1/NMDA and muscarinic acetylcholine receptors. Our results indicate that: a) the phosphorylation of NMDA and AMPA receptor subunits could act as a ‘novelty detector’, since it is absent after habituation, b) the robust activation of ERK1/2 signalling elicited by “spatial” novelty, demands the synergistic interaction of D1/NMDA receptors and c) the activation of ERK1/2 pathway leads to chromatin remodeling events and expression of the immediate early genes cFos and zif268, which are required for the regulation of synaptic plasticity and memory consolidation.

La formation des souvenirs repose sur un dialogue entre l’hippocampe et le cortex préfrontal médian (CPFm) qui se met en place progressivement et durablement après l’encodage de l’information. La lésion des noyaux reuniens et rhomboïde (ReRh), relai anatomo-fonctionnel entre ces deux structures, perturbe la consolidation à long terme d’un souvenir spatial. A ce jour, les mécanismes mis en jeu ne sont, pas connus. Nous avons donc étudié les processus moléculaires impliqués dans la formation d’un souvenir spatial, au sein de l’hippocampe et du CPFm, et les conséquences induites par la lésion des noyaux ReRh. Pour cela, nous avons lésé les noyaux ReRh de rats, puis nous les testés dans une tâche de piscine de Morris pendant trois jours. Nous avons alors effectué un séquençage des ARNm des sous-régions hippocampiques CA1 dorsale et ventrale, une analyse par RT-qPCR des ARNm du CPFm, ainsi qu’une analyse de l’activation de ces structures par quantification de la protéine issue du gène immédiat c-fos. Nos résultats montrent que la lésion des noyaux ReRh modifie les processus transcriptionnels et traductionnels qui prennent place dans l’hippocampe et le CPFm, dès trois jours d’apprentissage spatial. Ces résultats pourraient expliquer la non persistance d’un souvenir spatial et les déficits comportementaux qui en résultent à la suite d’une lésion des noyaux ReRh. / Memorization relies on a dialogue between the hippocampus and the medial prefrontal cortex (mPFC). This dialog takes place progressively after the encoding of an event. Given their connectivity, the thalamic nuclei named reuniens and rhomboid (ReRh) may modulate the functional loop between these two structures. Indeed, a lesion of these nuclei impairs the persistence of a spatial memory. The mechanisms underlying this process are still unknown. Therefore, we analyzed the molecular mechanisms underlying spatial memory consolidation within the hippocampus and the mPFC, and the consequences of a lesion of the ReRh nuclei. After a stereotaxic lesion of the ReRh nuclei, rats were subjected to three days of a spatial training in the Morris water maze. We then performed a RNA sequencing of the dorsal and ventral hippocampus (CA1 regions), RT-qPCR analysis of the mPCF, and a quantification of the expression of c-fos in these two structures. Results show that ReRh nuclei lesion impairs the transcriptional and translational mechanisms within the hippocampus and the mPFC as soon as after three days of a spatial learning. These alterations could lead to the retrieval deficit observed after a long post-acquisition delay.

Made available in DSpace on 2014-12-17T15:36:52Z (GMT). No. of bitstreams: 1 NelsonAML.pdf: 877661 bytes, checksum: 9f0e44b26c1eea9bd528ee3676051107 (MD5) Previous issue date: 2008-04-17 / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico / In the behavioral paradigm of discriminative avoidance task, both short and long-term memories have been extensively investigated with behavioral and pharmacological approaches. The aim of the present study was to evaluate, using the abovementioned model, the hippocampal expression of zif-268 - a calcium-dependent immediate early gene involved with synaptic plasticity process - throughout several steps of memory formation, such as acquisition, evocation and extiction. The behavioral apparatus consisted of a modified elevaated plus-maze, with their enclosed arms disposed in "L". A pre-exposure to the maze was made with the animal using all arms enclosed, for 30 minutes, followed by training and test, during 10 minutes each. The between sections interval was 24h. During training, aversive stimuli (bright light and loud noise) were actived whenever the animals entered one of the enclosed armas (aversive arm). Memory acquisiton, retention and extinction were evaluated by the percentage of the total time spent exploring the aversive arm. The parameters evaluated (time spent in the arms and total distance traveled) were estimated with an animal tracking software (Anymaze, Stoelting, USA). Learning during training was estimated by the decrease of the time spent exploring the aversive arm. One hour after the beginning of each section, animals were anaesthetized with sodium-thiopental (i.p.) and perfused with 0.9% heparinized saline solution followed by 4% paraformaldehyde. Brains were cryoprotected with 20% sucrose, separeted in three blocks and frozen. The middle block, containing the hippocampus, was sectioned at 20 micro meters in the coronal plane and the resutant sections were submitted to zif-268 immunohistochemistry. Our results show an increased expression of zif-268 in the dentate gyrus (DG) during the evocation and extinction stages. There is a distinct participation of the DG during the memory evocation, but not during its acquisition. Inaddition, all hippocampal regions (CA1, CA3 and DG) presented an increased zif-268 expression during the process of extinction. / No paradigma comportamental da esquiva discriminativa, as mem?rias de curto e de longo prazo t?m sido extensivamente estudadas tanto comportamental quanto farmacologicamente. O objetivo do presente estudo foi avaliar, usando o modelo supracitado, a express?o hipocampal de zif-268 - gene imediato dependente de c?lcio implicado em processos de plasticidade sin?ptica - ao longo das diversas etapas da forma??o da mem?ria, como aquisi??o, evoca??o e extin??o. O aparato comportamental consistiu de um labirinto em crum elevado modificado, com seus bra?os fechados dispostos em "L". Uma pr?-exposi??o ao labirinto foi feita com os animais usando os quatro bra?os fechados, com dura??o de 30 minutos, seguida de um treino e de um teste, cada qual com dura??o de 10 minutos. O intervalo entre as sess?es foi de 24 horas. Durante o treino, um est?mulo aversivo (luz e ru?do intensos) era acionado sempre que os animais entravam em um dos bra?os fechados (bra?o aversivo). A aquisi??o, reten??o e extin??o da mem?ria foram avaliados pelo percentual de tempo total gasto explorando o bra?o aversivo. Os par?metros avaliados (tempo nos bra?os e dist?ncia percorrida) foram registrados por um software de rastreamento de animais (Anymaze, Stoelting, USA). O aprendizado durante o treino foi estimado pelo decr?scimo do tempo gasto explorando o bra?o aversivo. Uma hora ap?s o in?cio de cada sess?o, os animais foram anestesiados com uma overdose de tiopental s?dico (i.p.) e perfundidos com solu??o salina heparinizada 0.9% seguida de paraformalde?do a 4%. Os enc?falos foram crioprotegidos com solu??o de sacorose a 20%, separados em tr?s blocos e congelados. O bloco do meio, contendo o hipocampo, foi seccionado a 20 micro metros no plano coronal e as sec??es resultantes foram ent?o submetidas ? imunohistoqu?mica para zif-268. Nossos resultados evidenciam um aumento da express?o de zif-268 no giro denteado (GD) durante asetapas de evoca??o e extins?o. H? uma participa??o distinta no GD durante a evoca??o e extin??o da mem?ria, mas n?o durante a aquisi??o. Al?m disso, todas as ?reas hipocampais (CA1, CA3 e GD) apresentam uma eleva??o da express?o de zif-268 durante o processo de extin??o

Made available in DSpace on 2014-12-17T15:36:52Z (GMT). No. of bitstreams: 1 CristianoSS.pdf: 703357 bytes, checksum: 61a9f2f7ebf9d69474aa37bec7180627 (MD5) Previous issue date: 2008-04-23 / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico / Immediate-early genes (IEGs) expression has been widely used as a valuable tool to investigate brain areas activated by specific stimuli. Studies of natural vocalizations, specially in songbirds, have largely benefited from this tool. Here we used IEGs expression to investigate brain areas activated by the hearing of conspecific common marmoset (Callithrix jacchus) vocalizations and/or utterance of antiphonal vocalizations. Nine adult male common marmosets were housed in sound-attenuating cages. Six animals were stimulated with playbacks of freely recorded natural long distance vocalizations (phee calls and twitters; 45 min. total duration). Three of them vocalized in response (O/V group) and three did not (O/n group). The control group (C) was composed by the remaining animals, which neither heard the playbacks nor spontaneously vocalized. After one hour of the stimulation onset (or no stimulation, in the case of the C group), animals were perfused with 0,9% phosphate-saline buffer and 4% paraformaldehyde. The tissue was coronally sectioned at 20 micro meter in a cryostat and submitted to immunohistochemistry for the IEGs egr-1 and c-fos. Marked immunoreactivity was observed in the auditory cortex of O/V and O/n subjects and in the anterior cingulate cortex, the dorsomedial prefrontal cortex and the ventrolateral prefrontal cortex of O/V subjects. In this study, brain areas activated by vocalizations of common marmosets were investigated using IEGs expression for the first time. Our results with the egr-1 gene indicate that potential plastic phenomena occur in areas related to hearing and uttering conspecific vocalizations. / A express?o de genes imediatos tem sido largamente utilizada na investiga??o de ?reas cerebrais ativadas por est?mulos espec?ficos. Estudos de comunica??o vocal, especialmente em aves canoras, t?m se beneficiado enormemente dessa ferramente. Neste trabalho, utilizamos a express?o de genes imediatos para identificar as ?reas corticiais ativadas pela audi??o e express?o de vocaliza??es co-espec?ficas de sag?is comuns (Callithrix jacchus). Nove sag?is comuns machos adultos foram mantidos em caixas de atenua??o ac?stica. Seis animais foram expostos a playbacks de vocaliza??es co-espec?ficas naturais (phee calls e twitters; total de 45 minutos). Tr?s deles vocalizaram em resposta, compondo o grupo que "ouviu e vocalizou" (O/V), e tr?s permaneceram em sil?ncio (grupo O/n). O grupo controle (C) foi composto pelos tr?s animais restantes, que n?o foram expostos ao est?mulo e nem vocalizaram espontaneamente. Depois de uma hora do in?cio do est?mulo, (ou nenhum est?mulo, no caso do grupo C), os animais foram perfundidos com solu??o salina 0,9%, seguida de paraformalde?do 4%. Os c?rebros foram removidos e cortados coronalmente a 20 micro metros com o aux?lio de um criostato e submetidos a imunohistoqu?mica para os genes imediatos egr-1 and c-fos. Maior imunorreatividade foi observada no c?rtex auditivo prim?rio dos animais dos grupos O/V e O/n e no c?rtex cingulado anterior, c?rtex pr?-frontal dorso-medial e c?rtex pr?-frontal ventro-lateral dos animais do grupo O/V. Este trabalho foi o primeiro a utilizar a express?o de genes imediatos no estudo das ?reas corticais envolvidas na comunica??o de sag?is comuns. Nossos resultados, especialmente em rela??o ao gene egr-1, indicam que eventos potencialmente pl?sticos ocorrem nas ?reas relacionadas ? audi??o e emiss?o de vocaliza??es co-espec?ficas.Express?o de genes imediatos induzidos por vocaliza??es em sag?is-comuns (Callithrix jacchus)

Une mémoire émotionnelle normale se base sur la sélection de stimuli prédictifs d’un événement important pour l’individu. Cependant, ce processus de sélection peut être compromis en situation de forte intensité émotionnelle. En particulier, la sélection d’un élément saillant non nécessairement prédictif, associée à une amnésie de type déclaratif pour les éléments contextuels, caractérise les altérations mnésiques de l’état de stress post-traumatique (ESPT). Les données de la littérature suggèrent que l’action de glucocorticoïdes dans l’hippocampe serait l’une des causes possibles du développement de troubles mnésiques de type ESPT. Nos travaux ont porté sur les conditions dans lesquelles les glucocorticoïdes dans l’hippocampe peuvent altérer les fonctions mnésiques chez la souris.En utilisant des procédures de conditionnement classique aversif, nous montrons que l’injection post-apprentissage de corticostérone dans l’hippocampe dorsal, en situation de forte intensité émotionnelle, conduit (1) à une sélection incorrecte du stimulus saillant non prédictif du choc électrique au détriment des éléments contextuels (2) et à des dysfonctionnements d’activité neuronale au sein du circuit hippocampo-amygdalien (expression de c-Fos). De façon intéressante, par une action sur le même type de récepteurs (aux glucocorticoïdes, GR), l’injection de corticostérone dans l’hippocampe ventral conduit également à un processus incorrect de sélection du stimulus prédictif mais en faveur des éléments contextuels. Enfin, un apprentissage en labyrinthe radiaire révèle que l’injection de corticostérone dans l’hippocampe dorsal altère spécifiquement la mémoire relationnelle, analogue de la mémoire déclarative humaine, uniquement chez les animaux ayant été au préalable exposés à un stress.L’ensemble de nos données révèlent qu’un excès de glucocorticoïdes dans l’hippocampe contribue (1) à des déficits de mémoires émotionnelle et relationnelle, (2) à la sélection inadaptée de stimuli non prédictifs d’un événement aversif (3) reposant sur des dysfonctionnements du circuit hippocampo-amygdalien, le tout, correspondant à des altérations mnésiques de type ESPT. / Normal emotional memory is based on the selection of cues predicting threatening events. However, exposure to extreme threatening situation can compromise the selection of the correct cues. In particular, selection of a salient not necessarily predictive cue, associated with declarative amnesia for peritraumatic contextual cues, characterizes the memory disturbances of posttraumatic stress disorder (PTSD). Accumulating evidence suggest that action of glucocorticoids into the hippocampus could be a potential mechanism for PTSD-related memory disturbances. Hence, we studied the conditions for which glucocorticoids into the hippocampus can alter memory functions in mice.Using Pavlovian fear conditioning, we showed that post-training infusion of glucocorticoids in the dorsal hippocampus, in stressful situation, resulted in (1) selection of a salient non predictive cue instead of contextual cues and in (2) dysfunctions of neural activity of the hippocampal-amygdalar circuit (c-Fos expression). Interestingly, via action on the same receptor subtype (glucocorticoid receptors, GR), infusion of glucocorticoids in the ventral hippocampus also resulted in incorrect selection of predictive cue but in favor of contextual cues. Finally, using radial-maze task, we showed that infusion of glucocorticoids in the dorsal hippocampus specifically impaired relational declarative-like memory, only in mice previously exposed to stress.Altogether, our findings reveal that excess glucocorticoids in the hippocampus contributes to (1) deficits in emotional and relational memories, (2) incorrect selection of predictive cues (3) based to dysfunctions of the hippocampal-amygdalar circuit, all, corresponding to PTSD-related memory disturbances.

The ability to perceive the Earth's magnetic field has been demonstrated in a variety of animals, including representatives of all five classes of vertebrates. The physiological mechanisms underlying magnetic field sensation, however, remain largely unknown. Behavioral, physiological, neuroethological studies and studies using early response genes as neuronal activation markers indicated that a major role in the perception and processing of magnetic information play trigeminal, vestibular and visual systems. Subsequently, magnetic information seem to be integrated with multimodal sensory and motor information within the hippocampal-entorhinal system. In the majority of studies, however, birds have been used as model organisms. In this work I analyzed the neural substrate of magnetic compass orientation in the mouse strain C57BL/6J using markers c-Fos and Egr1. I found that all the aforementioned systems contain neurons responsive to the experimental magnetic fields. This finding demonstrates a complex processing of the magnetic information at level of the central nervous system.