Sleep is critical to memory and learning. During rapid eye movement (REM) or non-REM (NREM) sleep, subgroups of cell assemblies in hippocampal and sensory cortical circuits are reactivated in a temporally coordinated manner, forming a cortical-hippocampal-cortical loop of information processing during memory consolidation. Deciphering neural codes of hippocampal-neocortical memories during sleep would reveal important circuit mechanisms of memory consolidation. To date, a complete understanding of the mechanisms of hippocampal-neocortical memory processing and the interaction of their specific spatial/non­ spatial memory representations during sleep is lacking. Furthermore, little is known about the causal impact of the hippocampal-neocortical interactions on subsequent memory reactivation or post-sleep learning. In this proposal, we will dissect representations of spatial ("where") and visual ("what") memory in the rodent hippocampal CA1 and primary visual cortex (V1) during sleep. We will combine electrophysiology, population-decoding methods, optogenetics and closed-loop neural interface to decipher sleep-associated CA1-V1 population codes in memory coding. In Aim 1, we will identify visual cortical representations in a spatial navigation task and determine visual cortical neuronal firing dependency on space, experiences and visual cues. In Aim 2, we will uncover "where" (spatial) and "what" (visual) representations of CA1-V1 memory reactivations during sleep. In Aim 3, we will determine the causal role of the hippocampus in the V1-CA1-V1 loop of memory consolidation during sleep. Together, these results will enable us to casually dissect circuit mechanisms of hippocampal-neocortical memory coding during sleep, and to establish a new analysis paradigm to identify the contents of hippocampal-memory reactivations during sleep. Our project will provide further insight into memory-related neurological and psychiatric disorders and potential therapeutic treatment for targeted memory reactivation or enhancement.

The study of hippocampal-neocortical memory coding during sleep is aimed at identifying a more complete answer to the "where", "what" and "when" questions related to memory processing. We will combine electrophysiology, population-decoding methods, optogenetics and closed-loop neural interface to uncover sleep-associated memory contents of neural codes in the hippocampus and visual cortex and to dissect the circuit mechanisms of hippocampal­ neocortical interaction and memory consolidation during various stages of sleep. The proposed project will provide valuable insight into targeted memory reactivation during sleep for memory enhancement or therapeutic applications.