THE EFFECT OF MUSCARINIC ACETLYCHOLINE ANTAGONISM ON VARIANTS OF CONTEXUAL FEAR CONDITIONING
Date
2020-05
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Publisher
University of Delaware
Abstract
The current study focuses on two separate variants of Pavlovian fear conditioning: standard contextual fear conditioning (sCFC) and the Context Preexposure Facilitation Effect (CPFE). In both paradigms, the neutral CS is the context and no discrete cues are presented. During sCFC learning the context and acquiring a context-shock association occur in the same phase of training, with the US presentation appearing immediately after a designated amount of context exposure; in the CPFE paradigm, context preexposure occurs 24hrs prior to immediate-shock training. When systemic scopolamine, a muscarinic acetylcholine receptor (mAChR) antagonist, is administered prior to context preexposure or immediate-shock training during the CPFE adolescent rats display impaired post-shock and retention freezing, suggesting a role of the cholinergic system in acquisition and/or consolidation of the context representation (Experiment 1A) and its later retrieval or association with shock (Experiment 1B). Further, we demonstrated that intra-dHPC infusions of scopolamine prior to the training phase of the CPFE impairs retrieval of the context representation and/or encoding of the context-shock association (Experiment 2). Intra-vHPC infusions of scopolamine prior to training during the CPFE showed similar impairments to that of intra-dHPC infusions suggesting similar roles for muscarinic activity in both the dHPC and vHPC for retrieval of the context memory and/or acquisition of the context-shock association (Experiment 3). During single-trial sCFC, systemic injections of scopolamine prior to training abolished both post-shock and retention freezing (Experiment 4); multiple-trial sCFC conducted under the same
manipulations showed abolished post-shock, but only impaired retention (Experiment 5). These finding suggest an important role for cholinergic functioning in acquisition, consolidation, and retrieval and/or expression of contextual fear memories during sCFC. Experiment 6 investigated the effects of scopolamine when infused directly into the dHPC prior to training in both single (Experiment 6A) and multiple-trial sCFC (Experiment 6B). Single-trial sCFC revealed intact post-shock freezing and abolished retention freezing, suggesting a consolidation deficit. However, multiple-trial sCFC failed to reveal a deficit in acquisition or retention, implying that cholinergic functioning in the dHPC is not required for contextual fear conditioning under multiple-trial conditioning. The current findings suggest that an alternative system, which may require multiple US presentations to acquire, consolidate, and retrieve contextual fear memories in the absence of dHPC cholinergic activity may be compensatory. However, it is likely that this compensatory system requires cholinergic functioning due to impaired contextual fear conditioning through systemic scopolamine.
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Keywords
neuroscience, fear conditioning, muscarinic acetylcholine antagonism