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Uncovering the Dynamics of Hippocampal-Neocortical Coupling in Humans and Mice

Award Number: F30MH143505
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 10/06/2026
PERIOD OF PERFORMANCE END DATE: 10/05/2027

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Uncovering the Dynamics of Hippocampal-Neocortical Coupling in Humans and Mice - PROJECT SUMMARY Hippocampal sharp-wave ripples (SWRs) are high-frequency bursts of pyramidal cell activity that facilitate communication between the hippocampus and neocortex, primarily during non-rapid eye movement (NREM) sleep. These bursts drive neural representations of experience across the neocortical mantle, supporting long- term memory consolidation through synaptic strengthening. Numerous studies have highlighted the importance of hippocampal-neocortical coupling in memory, implicating SWRs in animal models of Alzheimer’s, epilepsy, autism, schizophrenia, and depression. Recent work from our lab revealed that not all SWRs serve the same function. Researchers identified four distinct SWR types based on their timing relative to neocortical UP and DOWN state transitions, suggesting that different SWR types play specialized roles in memory processing. Here, I propose a series of studies to clarify the mechanisms underlying SWR-dependent consolidation in both rodents and humans. First, I will test the hypothesis that the timing of SWR-dependent hippocampal-neocortical coupling and the spread of ripple activity across the cortex are conserved between rodents and humans. I will use a novel human SWR detection pipeline, combined with current source localization and time-locked averaging, to analyze stereo- EEG data from epilepsy patients. Second, I will investigate whether hippocampal-neocortical coupling is bi- directional by using optogenetics to silence the entorhinal cortex, a key input to the hippocampus. This will allow me to assess changes in SWR timing and content relative to cortical state transitions during NREM sleep. Finally, I will probe the functional significance of different SWR types in mice by selectively suppressing SWRs with optogenetics and testing their impact on memory retention in a cheeseboard maze task. Successful completion of these studies will clarify the conserved role of SWRs in memory consolidation across species and provide a framework for targeting SWR-related mechanisms in memory-related disorders such as epilepsy and Alzheimer’s disease.


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: 2026 ( Subtotal = $55,114 )
2026	2026	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Mental Health Research Grants	000	1	4/9/2026	NEW	$55,114
														Subtotal = $55,114

Grand Total All Awards = $55,114

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Uncovering the Dynamics of Hippocampal-Neocortical Coupling in Humans and Mice

Award Number: F30MH143505

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 10/06/2026

PERIOD OF PERFORMANCE END DATE: 10/05/2027

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