Time Cells in the Hippocampus Are Neither Dependent on Medial Entorhinal Cortex Inputs nor Necessary for Spatial Working Memory.

A key function of the hippocampus and entorhinal cortex is to bridge events that are discontinuous in time, and it has been proposed that medial entorhinal cortex (mEC) supports memory retention by sustaining the sequential activity of hippocampal time cells. Therefore, we recorded hippocampal neuronal activity during spatial working memory and asked whether time cells depend on mEC inputs. Working memory was impaired in rats with mEC lesions, but the occurrence of time cells and of trajectory-coding cells in the stem did not differ from controls. Rather, the main effect of mEC lesions was an extensive spatial coding deficit of CA1 cells, which included inconsistency over time and reduced firing differences between positions on the maze. Therefore, mEC is critical for providing stable and distinct spatial information to hippocampus, while working memory (WM) maintenance is likely supported either by local synaptic plasticity in hippocampus or by activity patterns elsewhere in the brain.

Dentate network activity is necessary for spatial working memory by supporting CA3 sharp-wave ripple generation and prospective firing of CA3 neurons.

Complex spatial working memory tasks have been shown to require both hippocampal sharp-wave ripple (SWR) activity and dentate gyrus (DG) neuronal activity. We therefore asked whether DG inputs to CA3 contribute to spatial working memory by promoting SWR generation. Recordings from DG and CA3 while rats performed a dentate-dependent working memory task on an eight-arm radial maze revealed that the activity of dentate neurons and the incidence rate of SWRs both increased during reward consumption. We then found reduced reward-related CA3 SWR generation without direct input from dentate granule neurons. Furthermore, CA3 cells with place fields in not-yet-visited arms preferentially fired during SWRs at reward locations, and these prospective CA3 firing patterns were more pronounced for correct trials and were dentate-dependent. These results indicate that coordination of CA3 neuronal activity patterns by DG is necessary for the generation of neuronal firing patterns that support goal-directed behavior and memory.