Project Summary: Memory consolidation is an indispensable function for everyday experiences that becomes compromised in many prevalent memory disorders such as post-traumatic stress disorder and dementia. Understanding the underlying process of memory consolidation is essential for the development of therapeutics and treatment interventions for pervasive memory disorders. Systems consolidation, memory consolidation across neural networks, involves the transformation of impermanent, hippocampus-dependent memories, into permanent long-term memories stored throughout cortical regions. During this consolidation process, sharp-wave ripples (SPWs), neural oscillations originating from the dorsal CA1 of the hippocampus during slow wave sleep (SWS), have emerged as a key mediator. These oscillations facilitate systems consolidation through the reactivation of hippocampal and cortical neurons previously active during wakefulness. Recently, researcher have identified two anatomically distinct CA1 pyramidal sublayers that differ in function during SPWs: superficial and deep. Superficial neurons (CA1sup) display more stable firings rates exhibiting little change in response to learning, whereas deep neurons (CA1deep) are less stable exhibiting dynamic changes to learning. While these differences have been uncovered, much remains unknown on how sublayers are selectively recruited during SPWs. The anterior cingulate cortex (ACC), a cortical region involved long-term memory, emerges as a possible candidate in driving CA1 activity. The ACC exhibits increased activity immediately preceding SPWs and dCA1 neuronal firings, suggesting a potential ACC → dCA1 influence. Our results revealed that ACC neural activity immediately preceding SPWs (~200ms prior) preferentially predicts CA1deep neuron activity during SPWs. Prediction success increases following learning, suggesting a role of ACC → CA1deep communication in learning. Additionally, we show that stimulation of ACC excitatory neurons specifically increases the activity of CA1deep, but not CA1sup, during SWS. Given these findings, I hypothesize that ACC neurons selectively communicate with CA1deep activity during SPWs post-learning, and this communication is necessary for consolidation of newly-acquired memories. I will test this hypothesis through the following two aims. Aim 1 will utilize dual-site extracellular in vivo electrophysiology to determine how the ACC and dCA1 neurons communicate during SPW events for memory consolidation. Aim 2 will implement closed-loop optogenetics to investigate the causal role ACC → CA1deep communication during SPWs in memory consolidation. Findings from this proposal will advance our understanding of systems consolidation and how the brain stores long-term memories. Results from this study would lay the framework for the development of future therapeutic interventions targeted towards memory disorders.