UCLA

Memories are temporally organized. When recalling an event, we also recall the relative timing it was experienced. How does the brain compute and store this temporal representation of memory? The hippocampus is important to the temporal organization of memories. Hippocampal CA1 or CA3 lesions cause impaired coding of sequential events separated by time. The hippocampus bridges stimuli-free gaps between sequential events through neural ensembles that fire sequentially during the delay. These “time cells” fire sequentially encoding successive moments during the delay. Recent work has found that the CA1 region of the hippocampus contains neurons that display stimulus-specific sequential firing patterns during the delay period of a working memory task. CA1 largely lacks recurrent connectivity, so it is unlikely that it generates these sequential firing patterns on its own. CA3 is an upstream region with direct connections through the Schaffer collaterals to CA1. CA3 has extensive recurrent connections and is a likely candidate that generates these stimulus-specific sequential firing patterns. The recurrent connections in CA3 are well-suited for storing and processing temporal information because they allow for rapid associations. CA3 also receives input from the lateral entorhinal cortex, which processes nonspatial sensory information and receives direct connects from the olfactory bulb. To date, it is unknown where and how sensory and temporal information is integrated. Given the unique attributes of CA3, we propose that CA3 is where sensory and temporal information is integrated and that this code is then passed onto CA1. To test this hypothesis, we used cutting-edge chronic in vivo two-photon calcium imaging to monitor CA3 neuronal populations during a working memory task. We demonstrate that CA3 contains populations of cells that hold time and odor information. These cells fired in a stimuli-specific sequential manner during a working memory task. Though these odor-specific sequence cells were found to have low odor selectivity, we were able to decode odor and time from their firing activity. The odor-specific time cells in CA3 did not increase in numbers across days. These experiments help shed light on how elements of a memory are unified and coded within CA3.