Rede córtico-amigdalar envolvida na compensação do hipocampo dorsal na aprendizagem do medo contextual

• Ano de defesa: 2017
• Autor(a) principal: Coelho, Cesar Augusto de Oliveira [UNIFESP]
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de São Paulo (UNIFESP)
• Palavras-chave em Português: Teoria de grafos; Condicionamento de medo; Aprendizagem e memória; pCREB; Retroesplenial; Learning; Memory; Fear; CREB-binding protein; Graph theory
• Link de acesso: https://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=5072688; http://repositorio.unifesp.br/handle/11600/50411

The hippocampus is a central region in the medial temporal lobe memory system and its lesion results in a marked retrograde and anterograde amnesia. Many hippocampal manipulations show that despite hippocampal engagement in various learning and memory paradigms, hippocampal lesions can be compensated and allow some learning in these tasks. One of them in the contextual fear conditioning (CMC), in which hippocampal lesions do not result in anterograde amnesia. Among the questions raised in the literature about this is which regions are compensating hippocampal loss and what is learned by them. A myriad of regions has been observed to participate in CMC, comprising cortices that also compose the medial temporal lobe, pre-frontal cortices and subcortical regions such as the amygdala nuclei. However, the traditional methods of investigation do not assess a kind of information critical to understand learning and memory: the brain interactivity during a cognitive process. Methods capable of assessing the complexity of interactions of the brain, such as the network analysis or graph theory, have increasingly gained the favor of neuroscientific community for its simplicity in capturing complex interactions information and test hypotheses about them. This thesis employed large scale pCREB expression mapping after CMC learning to investigate neural changes that might be underlying dorsal hippocampal compensation in CMC. The pCREB activity analysis did not reveal grupo differences that could help to explain hippocampal compensation. The network analysis showed that hippocampal lesion did not alter the network topology, maintaining its interactivity concomitantly highly widespread and clustered. However, the compensatory network showed differences compared to the control group network in the most central regions of the network (hubs) and in the strength of many connections. Further experiments tested if the double lesion of the hippocampus and one of the identified hubs was sufficient to affect CMC. Only the lesions involving hippocampus and RSC resulted in memory impairment. This is in accordance with current models proposing the RSC as part of a circuit involved in spatial processing, whereas PER-36 is involved in a pathway involved in object processing. Further, the results also corroborate current theories on changes of connectivity after brain lesions in human patients.