A hippocampal astrocytic sequence emerges during learning and memory

Abstract

Abstract.The dorsal hippocampus is a heterogeneous structure with numerous cell types involved in generating and maintaining detailed representations of space and time. Prior work has established that pyramidal cells contribute to these crucial aspects of associative memory. For example, hippocampal "time cells" encode temporal information through sequential activity. However, the roles of non-neuronal cell types are less often explored. In this study, we investigated dorsal hippocampal CA1 astrocytes using one-photon calcium imaging in freely moving animals during a contextual fear conditioning paradigm, enabling tracking of a population of glial cells across days. In response to foot shock, astrocytes generated robust calcium-event sequences with a time-compressed structure akin to canonical hippocampal time cells. Upon re-exposure to the conditioned context, we again detected astrocytic sequences -- in the absence of shock -- displaying similar time-compressed structure. Importantly, this phenomenon was not observed in a context different from the initial fear conditioning chamber. Lastly, spontaneous astrocytic activity in the initial conditioning context was associated with behavioral state transitions (e.g. freezing), but this was not observed in a novel context. Taken together, these results suggest a direct role for astrocytes in generating hippocampal representations of associative memory, and future work may continue to study how diverse cell types process temporal features of associative memory.