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

Author(s)

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

Affiliation

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

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

• Document type: Journal article
• Source: NEUROBIOLOGY OF LEARNING AND MEMORY; v. 171, MAY 2020.
• Web of Science Citations: 0

Abstract

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)

• FAPESP's process: 17/25917-5 - Effect of functional disconnection between hippocampus and pre-limbic cortex on the acquisition of contextual fear conditioning and contextual fear conditioning with temporal discontinuity
• Grantee: Andreia Eleutério Wallau
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 16/13027-2 - Neural network underlying fear conditioning acquisition with temporal and spatial discontinuity: interactions of prelimbic cortex
• Grantee: Thays Brenner dos Santos
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 16/25755-2 - Neural network underlying fear conditioning acquisition with temporal and spatial discontinuity: interactions of prelimbic cortex
• Grantee: Maria Gabriela Menezes de Oliveira
• Support Opportunities: Regular Research Grants