| Episodic memory, the ability to store and later recall individual experiences, plays a fundamental role in our day-to-day lives, and reflects a temporal organization of events that form an experience. Numerous studies have shown that the hippocampus plays a crucial role in episodic memory. Recent studies have reported the existence of hippocampal "time cells", neurons that fire at particular moments during temporally extended periods when behavior and location are relatively constant. However, the origin of these hippocampal firing patterns, and the extent to which they are primarily determined by time, or instead by variations in behavior, location, or distance traveled over time, remains uncertain. Here we introduce a novel behavioral paradigm that allowed us to investigate firing patterns in the hippocampus and medial entorhinal cortex (MEC) as rats ran in place on a treadmill, thus "clamping" behavior and location while varying treadmill speed to distinguish time and distance traveled.;We recorded activity in dorsal hippocampal CA1 and showed that "time cells" exist in this task and that their firing could not be explained by movement through space alone. Instead, we found that hippocampal neurons were heavily influenced by both time and distance, with different neurons reflecting these parameters to varying extents. These findings demonstrated that hippocampal neuronal networks capture the organization of time and distance in situations where these dimensions dominate an ongoing experience.;We next recorded neural activity in the MEC, a dominant source of input into the hippocampus, to determine whether the MEC is also involved in temporal processing. We found many MEC neurons exhibiting temporally-modulated firing that could not be explained by either movement through space or changes in head direction. This included neurons with single and multiple temporal firing fields, as well as neurons exhibiting temporally-periodic firing during treadmill running. In addition, we found that neurons classified as grid cells during open-field foraging often fired with one or more temporal firing fields during treadmill running.;Together, these findings suggest that both hippocampal and MEC neurons code for temporal, as well as spatial and other environmental regularities. |
