Ventral hippocampal shock encoding modulates the expression of trace cued fear

Abstract

The hippocampus is crucial for associative fear learning when the anticipation of threat requires temporal or contextual binding of predictive stimuli as in trace and contextual fear conditioning. Compared with the dorsal hippocampus, far less is known about the contribution of the ventral hippocampus to fear learning. The ventral hippocampus, which is highly interconnected with defensive and emotional networks, has a prominent role in both innate and learned affective behaviors including anxiety, fear, and reward. Lesions or temporary inactivation of the ventral hippocampus impair both cued and contextual fear learning, but whether the ventral hippocampal role in learning is driven by affective processing, associative encoding, or both is not clear. Here, we used trace fear conditioning in mixed sex cohorts to assess the contribution of shock-encoding to the acquisition of cued and contextual fear memories. Trace conditioning requires subjects to associate an auditory conditional stimulus (CS) with a shock unconditional stimulus (UCS) that are separated in time by a 20-s trace interval. We first recorded neuronal activity in the ventral hippocampus during trace fear conditioning and found that ventral CA1 predominantly encoded the shock reinforcer. Potentiated firing to the CS was evident at testing, but no encoding of the trace interval was observed. We then tested the necessity of shock encoding for conditional fear acquisition by optogenetically silencing ventral hippocampal activity during the UCS on each trial of training. Contrary to our predictions, preventing hippocampal shock-evoked firing did not impair associative fear. Instead, it led to a more prolonged expression of CS freezing across test trials, an effect observed in males, but not females. Contextual fear learning was largely intact, although a subset of animals in each sex were differentially affected by shock-silencing. Taken together, the results show that shock encoding in the ventral hippocampus modulates the expression of learned fear in a sex-specific manner.