Internal representation of hippocampal neuronal population span a time-distance continuum

Abstract

The hippocampus plays a critical role in episodic memory: the sequential representation of visited places and experienced events. This function is mirrored by hippocampal activity that self organizes into sequences of neuronal activation that integrate spatio-temporal information. What are the underlying mechanisms of such integration is still unknown. Single cell activity was recently shown to combine time and distance information; however, it remains unknown whether a degree of tuning between space and time can be defined at the network level. Here, combining daily calcium imaging of CA1 sequence dynamics in running head-fixed mice and network modeling, we show that CA1 network activity tends to represent a specific combination of space and time at any given moment, and that the degree of tuning can shift within a continuum from one day to the next. Our computational model shows that this shift in tuning can happen under the control of the external drive power. We propose that extrinsic global inputs shape the nature of spatio-temporal integration in the hippocampus at the population level depending on the task at hand, a hypothesis which may guide future experimental studies.\n\nSignificance StatementThe hippocampus organizes experience in sequences of events that form episodic memory. How are time and space internally computed in the hippocampus in the absence of sequential external inputs? Here we show that time and space are integrated together within the hippocampal network with different degrees of tuning across days. This was found by recording the activity of hundreds of pyramidal cells for several days. We also propose a mechanism supporting such spatio-temporal integration based on a ring attractor network model: the degree of tuning between space and time can be adjusted by modulating the power of a non-sequential external excitatory drive. In this way, the hippocampus is able to generate a spatio-temporal representation tuned to the task at hand.