Study of neural activity correlates of contextual fear memory recall in dorsal CA1 of mouse hippocampus by using microendoscopic in vivo calcium imaging

Abstract

The hippocampus is crucial for the 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 employed 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 an overall increase in the response of the neuronal population compared with simple context exposure. Such an increased response was specific to the conditioned context as it disappeared in a neutral context. The magnitude of the 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 due to the 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 a proportionally more similar level of freezing. Furthermore, these patterns initially appear during post-learning sessions, which suggest possibility that synchronous pattern are critical to consolidation. Together, these results indicate that increase in responses of individual neurons and synchronous cell activity patterns in the dCA1 neuronal network is critically involved in representing a contextual memory recall.