Activity Patterns of Individual Neurons and Ensembles Correlated with Retrieval of a Contextual Memory in the Dorsal CA1 of Mouse Hippocampus.

Abstract

The hippocampus is crucial for retrieval of contextual memories. The activation of a subpopulation of neurons in the dorsal CA1 (dCA1) of the hippocampus is required for memory retrieval. Given that hippocampal neurons exhibit distinct patterns of response during memory retrieval, the activity patterns of individual neurons or ensembles may be critically involved in memory retrieval. However, this relation has been unclear. To investigate this question, we used an in vivo microendoscope calcium imaging technique to optically record neuronal activity in the dCA1 of male and female mice. We observed that a portion of dCA1 neurons increased their responses to the learned context after contextual fear conditioning (FC), resulting in overall increase in response of neuronal population compared with simple context exposure. Such increased response was specific to the conditioned context as it disappeared in neutral context. The magnitude of increase in neuronal responses by FC was proportional to memory strength during retrieval. The increases in activity preferentially occurred during the putative sharp wave ripple events and were not simply because of animal's movement and immobility. At the ensemble level, synchronous cell activity patterns were associated with memory retrieval. Accordingly, when such patterns were more similar between conditioned and neutral context, animals displayed proportionally more similar level of freezing. Together, these results indicate that increase in responses of individual neurons and synchronous cell activity patterns in the dCA1 neuronal network are critically involved in representing a contextual memory recall.SIGNIFICANCE STATEMENT Neurons in the dorsal CA1 of the hippocampus are crucial for memory retrieval. By using in vivo calcium imaging methods for recording neuronal activity, we demonstrate that dCA1 neurons increased their responses to the learned context specifically by FC and such changes correlated with memory strength during retrieval. Moreover, distinct synchronous cell activity patterns were formed by FC and involved in representing contextual memory retrieval. These findings reveal dynamic activity features of dCA1 neurons that are involved in contextual memory retrieval.