PREFRONTAL AND HIPPOCAMPAL ASTROCYTIC AND NEURONAL DYNAMICS ACROSS FEAR LEARNING AND RETRIEVAL

Both the ventral hippocampal CA1 (vCA1) and medial prefrontal cortex (mPFC) are critical for the acquisition and maintenance of fear memories. Our recent findings suggest that these regions exhibit task-specific and affective state-dependent synchrony, underscoring their coordination during memory processes. While much attention has been given to the neuronal circuitry underlying fear memory, much less is known about the contribution of non-neuronal cell types, particularly astrocytes. Astrocytes are emerging as key modulators of neuronal activity, capable of regulating network synchrony and coordinating functionally-relevant neuronal populations. To investigate the real-time dynamics of both astrocytes and neurons in fear memory processing, we employed fiber photometry to simultaneously record activity in the mPFC and vCA1. Mice were subjected to a contextual fear conditioning (CFC) paradigm, including the phases of learning, recent memory recall, and remote memory recall (i.e. 2 weeks post-conditioning). Our findings are twofold: first, we observe robust time-locking of neurons and astrocytes in both brain regions to foot shocks, as well as increased cross-regional cross-correlation of vCA1 astrocytes to mPFC astrocytes. Secondly, astrocytes and neurons display stereotyped calcium transients aligned to freezing onsets. Our ongoing experiments investigate how disturbing astrocytes in vCA1 with a constitutively expressed calcium extruder pump (“Calex”) alters neuronal and astrocytic calcium signaling in upstream mPFC. This work will inform how prefrontal and hippocampal astrocytes and neurons change their dynamics to drive fear acquisition and retrieval, and how perturbing hippocampal astrocytes affects distal cellular dynamics and behavior.