Probing of cortical-hippocampal dialogue using light-mediated circuit monitoring in vivo

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We spend about one third of our lives sleeping. Perhaps surprisingly, our brain never rests and neurons remain continually active during sleep. One can reason that neurons responsible for autonomic functions such as respiration should be active in both sleep and wakefulness, however, why would neurons in other parts of the brain remain active, often in a highly synchronous and rhythmic fashion during sleep? One proposed idea is that neural activity during sleep may allow for the rewiring of neural connections and that this synaptic rewiring is relevant for storing memories. My focus is on understanding memories that require medial temporal lobe structures like the hippocampus (eg. episodic memory) and the memory-enhancing role of particular patterns of spontaneous activity that appear during sleep in neocortex (NC) and hippocampus (HPC). The central goal of my research is to provide new information regarding the interaction of HPC and NC during sleep. Although evidence indicates that these memories are formed through a functional coupling between hippocampal sharp-wave (SPW) and cortical slow-wave oscillations (SO), how they interact to subserve a transfer of information is still unclear. To provide new insight regarding the interaction of HPC and NC during sleep, we will combine novel imaging technologies with the most advanced genetic, molecular and electrophysiological technologies. This will allow us to interrogate the cortical circuits at the level of individual synapses and function with millisecond temporal resolution across the entire cortex with information from the hippocampus. The primary aim of my research will be to examine how SO and SPW-, and other events (i.e. spindles, gamma oscillations) are embedded in larger cortical networks. By selectively and temporarily inactivating SPW, I will test a causal link between HPC activity and NC distinct network activity patterns. Further, I will dissect how HPC output to NC contributes significantly to experience-dependent dendritic spine turnover and plasticity. Performing these experiments will provide a deeper understanding of the functional relationship between hippocampus and neocortex and information processing and long-term memory storage.