Hippocampal astrocytes contribute to encoding context-specific aversive stimuli to regulate fear-related behavior

Abstract

In contextual fear conditioning, subjects learn to associate a neutral environment with an aversive stimulus and exhibit fear responses to that context, signaling danger. Neuronal activity in hippocampal-amygdala circuits has been shown extensively to underlie the conditioning and recall of contextual fear memories, yet the direct contribution of astrocytes to integrating stimulus and contextual information in this task remains unknown. In this study, we monitor astrocyte activity in real time in the hippocampus and simultaneously during performance in the contextual fear conditioning task. We find that shock-evoked astrocyte responses during conditioning predict the magnitude of freezing during recall in a context-specific manner. Importantly, astrocytic Ca2+ activity progressively precedes freezing onset specifically in the shock-associated context, indicating that hippocampal astrocytes contribute to encoding context-specific shock information. This work reveals an unprecedented contribution of astrocytes to the encoding of context-related information about aversive stimuli in fear-related behavior.