Functional interaction of ventral hippocampal CA1 region and prelimbic cortex contributes to the encoding of contextual fear association of stimuli separated in time

Autor(es)

Santos, Thays Brenner ^[1] ; Wallau, Andreia Eleuterio ^[1] ; Kramer-Soares, Juliana Carlota ^{[1, 2]} ; Menezes Oliveira, Maria Gabriela ^[1]

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo UNIFESP, Dept Psicobiol, BR-04023062 Sao Paulo - Brazil

^[2] Univ Ibirapuera UNIB, Dept Psicol, BR-04661100 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: NEUROBIOLOGY OF LEARNING AND MEMORY; v. 171, MAY 2020.
• Citações Web of Science: 0

Resumo

Although stimuli that are associated often overlap in time, previous events can also predict the occurrence of a later aversive stimulus and be associated with it to better guide future behavior. Associations of stimuli separated in time have been studied using discrete stimulus as the conditioned stimulus (CS) in trace conditioning or, more recently in our lab, using the context as the CS in contextual fear conditioning with temporal discontinuity (CFC-5s), a task that simultaneously includes the processing of time and space components. It is thought that fear memories are encoded by the strengthening of synaptic connections in a distributed neural network. However, it is unclear how this temporal factor, which may differentially require the maintenance of the stimulus over time, affects the interactivity between brain regions to form the association. Because the prelimbic cortex (PL) and the hippocampus have been individually engaged in trace conditioning, they may functionally interact to encode associations separated in time. This is anatomically supported by direct ipsilateral projections from the ventral hippocampal CAl region (vCA1) to PL. The aim of the present study was to investigate the effect of the functional disconnection of vCA1 and PL on CFC-5s using pre-training asymmetric reversible inactivation with muscimol. For comparison, we also observed its effect on contextual fear conditioning (CFC). Results showed that the functional disconnection impaired the encoding of the CFC-5s, an association of stimuli separated in time, while did not affect the CFC, an association of stimuli overlapped in time. In addition, the preserved connection in one hemisphere was sufficient to support the encoding of CFC-5s. The time interval by itself did not increase freezing responses and both CFC and CFC tasks had similar generalization and higher freezing responses than unconditioned groups. These findings suggest that the time factor alters the requirement of the interactivity of the brain regions underlying fear conditioning and extend the relevance of hippocampal-prefrontal interactions in memory. (AU)

• Processo FAPESP: 17/25917-5 - Efeito da desconexão funcional entre hipocampo e córtex pré-límbico na aquisição do condicionamento de medo ao contexto e condicionamento de medo ao contexto em descontinuidade temporal
• Beneficiário: Andreia Eleutério Wallau
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 16/13027-2 - Rede neural subjacente à aquisição do condicionamento de medo em descontinuidade temporal e espacial: interações do córtex pré-límbico
• Beneficiário: Thays Brenner dos Santos
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 16/25755-2 - Rede neural subjacente à aquisição do condicionamento de medo em descontinuidade temporal e espacial: interações do córtex pré-límbico
• Beneficiário: Maria Gabriela Menezes de Oliveira
• Modalidade de apoio: Auxílio à Pesquisa - Regular