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The role of the ventral CA1 in distinct social representations

Award Number: R01MH142589
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/24/2026
PERIOD OF PERFORMANCE END DATE: 01/31/2031

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The role of the ventral CA1 in distinct social representations - Project Summary Deficiencies in interpretation and memory of emotional social interactions are debilitating symptoms in many neuropsychiatric disorders including autism and schizophrenia and lack effective treatment. This is largely due to a poor understanding of the neural basis underlying valence-association of social memories which enables normal functioning of these processes. While neutral social memory (novel versus familiar) has been extensively explored, the circuit and synaptic underpinnings of valence-associated social memories are largely unknown. Recent findings indicate that distinct neural circuits mediate social and non-social memory. Moreover, due to the dynamic nature of social relationships, social valance representation requires more flexible updating compared to object valence and thus likely underlies distinct mechanisms. Therefore, there is an urgent need to investigate social memory valence in order to understand the pathogenesis of maladaptive social behaviors. The hippocampal subregion ventral CA1 (vCA1) has been found to regulate neutral social memory and non-social valence and indeed hippocampal abnormalities are prevalent in autism spectrum disorder (ASD). To address this knowledge gap, our overall objective is to uncover the circuits mediating positive and negative social memories and identify hippocampal cell types supporting the distinct valence representations and valence updating. Our preliminary data show several vCA1 input regions with differential activity following a positive or negative social interaction. Further, inhibition of the vCA1 impaired valence-associated social memories, which is likely dependent on differential neuromodulation. Based on those results, we hypothesize that differential inputs activate selective cell types in the vCA1 to mediate the formation and updating of specific social emotional memories. Therefore, we will pursue three Specific Aims: 1) Identify and manipulate neuromodulatory inputs into the vCA1 which selectively mediate positive social memory, 2) Uncover and manipulate neuromodulator inputs into the vCA1 which selectively control negative social memory, 3) Identify vCA1 cell type interactions involved in positive and negative social memory updating. In Aim 1 and 2 we will use optogenetics in Cre-driver lines to manipulate neuromodulatory inputs into the vCA1 as well as in vivo fiber photometry to record neuromodulator activity during positive and negative social interactions. In addition, we will use conditional knockout lines to delete neuromodulators in vCA1 input projections and assay the effect on valence-associated social memories. In Aim 3 we will combine TRAP2;Ai14 with RNAscope to identify distinct vCA1 cell types involved in positive and negative social memory representations and use slice electrophysiology to elucidate synaptic interactions between “positive” and “negative” ensembles. Since impaired social memory and emotional processing of social interactions are prevalent symptoms of ASD, research elucidating the neural basis of these social cognitive processes is essential for the much-needed therapeutic progress.


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 = $701,763 )
2026	2026	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	1 GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Mental Health Research Grants	000	1	4/28/2026	NEW	$701,763
														Subtotal = $701,763

Grand Total All Awards = $701,763

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The role of the ventral CA1 in distinct social representations

Award Number: R01MH142589

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 04/24/2026

PERIOD OF PERFORMANCE END DATE: 01/31/2031

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