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Retrosplenial Down state assembly facilitates memory consolidation during slow-wave sleep

Award Number: R21MH134016
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/01/2025
PERIOD OF PERFORMANCE END DATE: 04/30/2027

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Retrosplenial Down state assembly facilitates memory consolidation during slow-wave sleep - PROJECT SUMMARY/ABSTRACT System consolidation of memory involves a cortical-hippocampal-cortical loop of information processing; however, it remains unclear how this process is initiated. Converging evidence suggests that slow-wave sleep (SWS) plays an essential role in memory consolidation. During SWS, various cortical regions exhibit a prominent delta oscillation (0.5–6 Hz) that enables coordinated interactions across the brain via synchrony. This delta wave exhibits a cyclic Up and Down pattern: the Up state corresponds to high cortical activity, whereas the Down state coincides with near-total cortical silence. Therefore, each Down state functions as a reset to position key cortical regions for information exchange during the subsequent Up state. One key unanswered question is whether there is a unique group of cortical neurons that primarily drive SWS Down-to-Up transitions for memory consolidation. Utilizing large-scale in vivo recording and advanced analysis techniques, we recently discovered that a distinct subpopulation (~20%) of retrosplenial cortex (RSC) layer-5 neurons initiates firing during SWS Down states. We termed these neurons RSC Down-state assembly (DSA) neurons. Preliminary results revealed that RSC DSA neurons exhibit robust synchrony at SWS Down-to-Up transitions, which precedes the activity of other RSC neurons. Moreover, RSC DSA neurons increased their activity between pre- and post-training sleep after a new learning experience, indicating their role in memory consolidation. The central objective of this proposal is to test our hypothesis that RSC layer-5 DSA neurons play a key role in initiating SWS Up states to drive memory consolidation. Supported by considerable preliminary data, we propose to pursue this objective through the following two specific aims. Aim 1 investigates the neural dynamics of RSC layer-5 neurons in memory consolidation. Aim 2 investigates the connectivity and causal role of RSC DSA neurons in memory consolidation. Results from this study will advance our understanding of RSC neuronal activity dynamics and the delta oscillation generation mechanisms underlying memory consolidation. This could provide insight into the improvement of memory and interventions in memory disorders such as post-traumatic stress disorder.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $408,541 )
2025	2025	DREXEL UNIVERSITY	3141 CHESTNUT ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Mental Health Research Grants	000	1	4/21/2025	NEW	$408,541
														Subtotal = $408,541

Grand Total All Awards = $408,541

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Retrosplenial Down state assembly facilitates memory consolidation during slow-wave sleep

Award Number: R21MH134016

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 05/01/2025

PERIOD OF PERFORMANCE END DATE: 04/30/2027

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