PROJECT SUMMARY The primary goal of the present proposal is to explore the role of pathway-specific RE neurons in the synchronized activity of the prefrontal-hippocampal circuit (mPFC-HC) and memory related rhythms in wake (episodic-like sequence memory) and in sleep states (REM/NREM). To accomplish this, Aim1 will determine if and how excitation of RE neurons can drive memory related mPFC-HC coherent states. The first experiment will test a range of relevant frequencies in RE-pathway specific neurons to identify a stimulation capable of driving mPFC-HC coherent modes in freely behaving rats. Using a closed-loop optogenetic approach, the second experiment will stimulate RE neurons to induce mPFC-HC coherence during different endogenous coherence states to boost memory performance while rats perform in a nonspatial sequence memory task. As I transition to my independent career (R00), Aim2 will explore the role of pathway-specific RE neurons in driving theta and delta related sleep oscillations (REM/NREM) using a closed-loop setup. Two new technical skills will be acquired during the K99 training phase which include 1) learning to run a sophisticated rodent sequence memory task capable of testing multiple RE-dependent memory dimensions, and 2) implementing a cutting edge closed-loop optogenetic control system capable of detecting neurophysiological coherence modes between the hippocampus and medial prefrontal cortex in `real-time' to trigger RE optogenetic stimulations. My previous training in anatomy, optogenetics, multisite electrophysiological recordings, and my theoretical background on RE-related mnemonic processes and arousal provides me with the foundation and technical skills necessary to pursue these goals with this additional training. Florida International University, a research- intensive and Hispanic-serving institution, is the ideal place to complete my training because it offers all the resources (mentor, equipment, facilities, and professional development programs) necessary to carry out the proposed experiments and training plan. The mentoring team is composed of two well-established and highly successful scientists, who together are committed to my success and will adequately prepare me for a career as an independent research investigator. The K99 phase of this award would allow me to enter the independent stage of my career with the theoretical, technical, methodological, networking, and laboratory management skills necessary to answer scientific questions at the circuit and network level, establish my own laboratory, and independently pursue future scientific directions. As a MOSAIC awardee and future principal investigator, one of my goals is to become a role model and mentor to other underrepresented students and scientists, so that I can enhance diversity, equality, and inclusion in the biomedical field. Overall, this research will shed new light on the role of RE in driving network-wide memory states, while the training p...