Effects of extinction on cellular activity in the dorsal and ventral hippocampus

University Of Pennsylvania, Philadelphia PA

Investigators

Linked publications, trials & patents

Abstract

? DESCRIPTION (provided by applicant): Emotion has a powerful impact on memory, with fearful memories in particular maintaining a strong foothold long after the actual event. However, because continued fearful responding in the absence of danger can be detrimental, the ability to extinguish fearful memories is extremely important. During extinction, the fear response is reduced through repeated exposures without consequences to a stimulus previously associated with a fearful event. Many psychopathologies such as post-traumatic stress disorder and specific phobias are characterized by failures of extinction, resulting in persistent fearful responding. Extinction is widely believed to be a form of new learning rather than memory erasure, and it is context-specific; indeed, one limitation of traditional exposure therapies is the difficulty patients have in generalizing their new learning outside of the therapy context. The hippocampus is well-established as a region critical for contextual learning, and it may provide context-dependent gating of fear and extinction through its projections to the prelimbic and infralimbic regions of the medial prefrontal cortex, respectively. The objective of this application is to investigate how cellular firing patterns change during fear conditioning and extinction by analyzing the individual and population activity of place cells in the dorsal (Specifc Aim 1) and ventral (Specific Aim 2) hippocampus. Additionally, I will investigate how changes in hippocampal firing patterns affect phase locking and neuronal coherence along the hippocampal longitudinal axis and between the hippocampus and the mPFC (Specific Aim 3). Data for these Aims will be collected using in vivo single-unit and local field potential (LFP) recordings in awake, behaving C57bl/6 mice undergoing a fear conditioning and extinction paradigm. I hypothesize that both dorsal and ventral place cells will show changes in firing patterns after fear conditioning and extinction, suggesting that distinct representations are formed in the hippocampus to encode specific contexts for fearful and safe situations. Moreover, I predict that these changes will lead to increased coherence between the hippocampus and the prelimbic region during retrieval of the fearful representation, and increased coherence between the hippocampus and the infralimbic region during retrieval of the safe representation. In this way, the changes in firing pattern seen in the hippocampus can modulate communication between the hippocampus and other brain regions in order to provide contextual gating of behavior during fear and extinction. Understanding the neural substrates underlying these forms of learning may provide insights for creating more effective and targeted therapies.