Our cognition is heavily dependent on our ability to form memories out of our experiences. The hippocampus is necessary for the formation of new memories and their retrieval for planning our future behavior. Hippocampal area CA1 local field potential (LFP) exhibits high frequency (100- 250 Hz) events known as sharp-wave ripples (SWRs). These events that occur during slow-wave sleep and awake restfulness have been shown to be important for the consolidation of spatial memory. During exploration, CA1 pyramidal cells, which receive excitatory inputs from entorhinal cortex (EC) and hippocampal area CA3, show location-specific activity known as place fields. However, the mechanism of formation of SWRs and place fields in the presence of these two inputs is not yet well understood. Using high-density multi-tetrode recording and reversible optogenetic manipulation, I found that the silencing of hippocampal area CA3’s Schafer collateral (SC) projections to CA1 decimates SWRs. Furthermore, SC silencing substantially suppresses hippocampal place cell activity during exploration but does not change the position of place fields. Moreover, temporal coding in CA1 place cells, as reflected in their theta phase precession ability, remains intact without CA3 input. These findings shed light on the functional interconnections between hippocampal subregions that support episodic memory.
Hippocampal structure and function is disrupted in several psychiatric disorders such as schizophrenia. The calcineurin mouse model of schizophrenia whose synaptic activity is impaired by deleting the calcineurin phosphatase gene in its forebrain shows behavioral and cognitive abnormalities recapitulating symptoms of schizophrenia and is therefore a good candidate for examining hippocampal neural circuit dysfunctions. Using multi-tetrode recording, we found that CA1 SWRs in these mice become overabundant and the reactivation of place cells during SWRs is abolished. However, place cells preserve their normal activity during exploration. This selective disruption in SWRs provides a mechanism for underlying impairments in information processing that may contribute to the cognitive impairments in schizophrenia. Overall, the research and technical advances described in this dissertation represent a step towards understanding hippocampal neural ensemble activity as is reflected in SWRs and place cell responses
