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Mechanisms and functions of amygdala-hippocampus beta synchrony

Award Number: R01MH139220
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 12/01/2024
PERIOD OF PERFORMANCE END DATE: 10/31/2029

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Mechanisms and functions of amygdala-hippocampus beta synchrony - PROJECT SUMMARY Using intracranial EEG (iEEG) recordings from human epilepsy patients, we previously identified a biomarker, based on beta-frequency coherence between the amygdala and hippocampus, that tracks real-time fluctuations in self-reported mood and anxiety. We recently published a study which validates that this same biomarker predicts emotional state in mice, and shows that it is specifically associated with bursts of beta- frequency synchronization between somatostatin (SST)-expressing neurons in the basolateral amygdala (BLA) and ventral hippocampus (vHPC). We further showed that patterns of optogenetic stimulation designed to disrupt or reproduce this cell type-specific pattern of synchronization bidirectionally modulate avoidance and risk-assessment behaviors in the elevated plus maze. Having successfully back-translated this human biomarker to mice, identified associated cell types, and found that it causally influences behavior, we are now poised to understand its mechanisms and functions. Here we propose to identify specific connections between the BLA and vHPC which generate this pattern of synchrony. We will then use voltage indicators, calcium indicators, and electrophysiology to study how these bursts of beta-frequency synchronization dynamically re- organize activity within the BLA-vHPC circuit in a behaviorally-dependent manner. We hypothesize that this facilitates interactions between specific cell types within the BLA-vHPC circuit in order to recruit output pathways that promote particular behaviors. Finally, we will map out the cell type-specific organization of connections within and between the BLA and vHPC. Understanding this pattern of connectivity will help elucidate microcircuit mechanisms through which specific connections generate bursts of beta-frequency synchronization, and through which BLA-vHPC cell types interact during bursts in order to perform specific information processing functions. Results from this project will be broadly useful for understanding the function of these two key nodes in the limbic system, yield insights about the general function of oscillations in brain circuits, and advance the development of strategies for therapeutic modulation targeting this cell type-specific pattern of rhythmic synchronization.


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 = $576,557 )
2026	2026	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Mental Health Research Grants	000	2	11/26/2025	NON-COMPETING CONTINUATION	$576,557
														Subtotal = $576,557

Issue Date FY: 2025 ( Subtotal = $649,965 )
2025	2025	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Mental Health Research Grants	000	1	11/29/2024	NEW	$649,965
														Subtotal = $649,965

Grand Total All Awards = $1,226,522

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Mechanisms and functions of amygdala-hippocampus beta synchrony

Award Number: R01MH139220

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 12/01/2024

PERIOD OF PERFORMANCE END DATE: 10/31/2029

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