Abstract
In contextual fear conditioning, experimental subjects learn to associate a neutral context with an aversive stimulus and display fear responses to a context that predicts danger. Although the hippocampal–amygdala pathway has been implicated in the retrieval of contextual fear memory, the mechanism by which fear memory is encoded in this circuit has not been investigated. Here, we show that activity in the ventral CA1 (vCA1) hippocampal projections to the basal amygdala (BA), paired with aversive stimuli, contributes to encoding conditioned fear memory. Contextual fear conditioning induced selective strengthening of a subset of vCA1–BA synapses, which was prevented under anisomycin-induced retrograde amnesia. Moreover, a subpopulation of BA neurons receives stronger monosynaptic inputs from context-responding vCA1 neurons, whose activity was required for contextual fear learning and synaptic potentiation in the vCA1–BA pathway. Our study suggests that synaptic strengthening of vCA1 inputs conveying contextual information to a subset of BA neurons contributes to encoding adaptive fear memory for the threat-predictive context.
Highlights
In contextual fear conditioning, experimental subjects learn to associate a neutral context with an aversive stimulus and display fear responses to a context that predicts danger
In the anterograde tracing experiment, eYFP-labeled ventral CA1 (vCA1) projections were found in the basolateral (BLA) and basomedial nuclei of the amygdala (BMA), collectively termed the basal amygdala (BA) (Fig. 1a, b)
More vCA1 neurons projecting to the BA expressed the immediate early gene c-fos in mice that were exposed to a novel context or recalled contextual fear memory than in mice left in their home cages (Fig. 1c, d, Supplementary Fig. 1a, and Supplementary Table 1), suggesting that a subset of vCA1: BA projectors can encode contextual representations
Summary
Experimental subjects learn to associate a neutral context with an aversive stimulus and display fear responses to a context that predicts danger. Our study suggests that synaptic strengthening of vCA1 inputs conveying contextual information to a subset of BA neurons contributes to encoding adaptive fear memory for the threat-predictive context. Strengthening of the hippocampal–amygdala pathway as a consequence of learning can facilitate the activation of the amygdala, resulting in conditioned fear responses to the threat-predictive context during the recall of contextual fear memory[6]. We determined the mechanism by which contextual fear memory is encoded in the hippocampal–amygdala circuit by testing our hypothesis that fear memory associated with a particular context is encoded by selective strengthening of hippocampal inputs conveying the contextual information to the amygdala
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