Dynamic representations of valence in anterior cingulate cortex in mice.

While the contributions of hippocampus and amygdala to fear memory are well established, the role of anterior cingulate cortex in recall of recent fear memory remains unclear. Here we longitudinally recorded anterior cingulate cortex neural activity using single-photon calcium imaging in freely-moving male mice undergoing auditory fear conditioning. During pre-exposure to the conditioned stimulus, neural responses were strongest to novel conditioned stimulus presentations and declined with repetition. During acquisition, responses emerged late in training as the conditioned stimulus became shock-predictive. Ensemble analysis identified subpopulations of "freezing on" and "freezing off" cells whose activation coincided with decreased population activity and increased neural synchrony. During 24 and 48-h recall, responses were robust during early unreinforced conditioned stimulus presentations and declined with repetition; similarly, a subpopulation of neurons emerged that was consistently upmodulated by the conditioned stimulus in early 24 and 48-h recall and suppressed in late epochs. Our results demonstrate that the anterior cingulate cortex neural response to a cue reorganizes within and across sessions, with dynamic changes in population activity, recruitment, and synchrony that mirror changes in salience relative to novelty and both conditioned and unconditioned negative valence. This response pattern is consistent with a role for anterior cingulate cortex as a flexible hub that dynamically represents cue salience.