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Control of CA2 by its cortico-hippocampal inputs and local inhibition in social information processing and learning

Award Number: R01MH104602
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/11/2014
PERIOD OF PERFORMANCE END DATE: 10/31/2028

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Control of CA2 by its cortico-hippocampal inputs and local inhibition in social information processing and learning - PROJECT SUMMARY The neural mechanisms by which the hippocampus encodes social memory, the ability to recognize and recall encounters with a conspecific, remain largely unexplored. As social dysfunction and social memory impairment are associated with a number of neuropsychiatric disorders, a deeper understanding of the neural bases of social memory is needed to enhance our understanding of disease mechanisms. Here, we focus on the hippocampal CA2 region, as CA2 pyramidal neurons have recently been found to play a central role in social memory in mice. Moreover, CA2 abnormalities have been identified in several human diseases and their mouse models. Although progress has been made in defining the role of CA2 in a simple form of social memory—the ability of a mouse to distinguish a novel from a familiar individual—a number of fundamental questions remain. What social sensory information is encoded in CA2? How is social information relayed to CA2 through its cortical-hippocampal inputs? Does CA2 participate in forms of social memory more complex than social familiarity? Here we address such questions by examining neural representations of the most salient social cue for mice, mouse urine, and how those representations are modified by odor-reward learning. We use 2-photon calcium imaging in head-fixed mice to assess CA2 neuron responses to social and non-social odors in an odor-reward learning paradigm in which a mouse is trained to associate one of two odors with a water reward. We find that social-odor reward learning both requires CA2 and enhances the ability of CA2 pyramidal neuron activity to distinguish between rewarded and unrewarded social odors. Although CA2 also distinguishes non- social odors, non-social odor learning neither requires CA2 nor enhances CA2 non-social odor discrimination. Thus, CA2 is specialized for the encoding of associations between a social stimulus and reward, and this encoding is behaviorally relevant. Here we ask how social information is delivered to CA2 and whether odor classification and odor- reward learning are computed locally in CA2 or inherited from CA2 inputs. We will address these questions using optogenetic inhibition of the three major cortico-hippocampal inputs to CA2: entorhinal cortex, dentate gyrus, and CA3. We will perform two-photon calcium imaging from these regions to examine and compare their representations of social and non-social odors, before and after odor-reward learning, with our results in CA2. Finally, we will use optogenetics and two photon imaging to characterize the odor representations and role in odor learning of three distinct populations of CA2 inhibitory neurons that have been implicated in social memory. Through this comprehensive analysis, we aim to provide the first detailed examination of how social odors and odor-reward learning is processed through the cortico-hippocampal circuit to allow socially-relevant experiences to be incorporated into social memory representations.


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 = $499,416 )
2025	2025	THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Mental Health Research Grants	000	12	12/9/2024	NON-COMPETING CONTINUATION	$499,416
2025	2024	THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Mental Health Research Grants	002	11	2/20/2025	COMPETING CONTINUATION	$8
2025	2023	THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Mental Health Research Grants	001	10	2/20/2025	NON-COMPETING CONTINUATION	-$8
														Subtotal = $499,416

Issue Date FY: 2024 ( Subtotal = $587,549 )
2024	2024	THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Mental Health Research Grants	001	11	12/13/2023	COMPETING CONTINUATION	$528,794
2024	2024	THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Mental Health Research Grants	002	11	6/12/2024	COMPETING CONTINUATION	$58,755
2024	2023	THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Mental Health Research Grants	000	10	12/6/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $587,549

Issue Date FY: 2023 ( Subtotal = $414,840 )
2023	2023	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, THE	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Mental Health Research Grants	000	10	1/25/2023	NON-COMPETING CONTINUATION	$414,840
														Subtotal = $414,840

Issue Date FY: 2022 ( Subtotal = $414,840 )
2022	2022	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, THE	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Mental Health Research Grants	000	9	2/1/2022	NON-COMPETING CONTINUATION	$373,354
2022	2022	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, THE	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Mental Health Research Grants	001	9	5/12/2022	NON-COMPETING CONTINUATION	$41,486
														Subtotal = $414,840

Issue Date FY: 2021 ( Subtotal = $414,840 )
2021	2021	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, THE	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Mental Health Research Grants	000	8	2/26/2021	NON-COMPETING CONTINUATION	$414,840
														Subtotal = $414,840

Issue Date FY: 2020 ( Subtotal = $414,797 )
2020	2020	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Mental Health Research Grants	000	7	1/27/2020	NON-COMPETING CONTINUATION	$414,797
														Subtotal = $414,797

Issue Date FY: 2019 ( Subtotal = $434,592 )
2019	2019	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Mental Health Research Grants	002	6	7/25/2019	COMPETING CONTINUATION	$121,876
2019	2019	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Mental Health Research Grants	000	6	3/8/2019	COMPETING CONTINUATION	$434,592
2019	2019	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Mental Health Research Grants	003	6	9/24/2019	COMPETING CONTINUATION	$0
2019	2018	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Mental Health Research Grants	001	5	7/25/2019	NON-COMPETING CONTINUATION	-$121,876
														Subtotal = $434,592

Issue Date FY: 2018 ( Subtotal = $400,000 )
2018	2018	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Mental Health Research Grants	000	5	4/26/2018	NON-COMPETING CONTINUATION	$400,000
														Subtotal = $400,000

Issue Date FY: 2017 ( Subtotal = $400,000 )
2017	2017	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Mental Health Research Grants	000	4	3/24/2017	NON-COMPETING CONTINUATION	$360,000
2017	2017	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Mental Health Research Grants	001	4	8/4/2017	NON-COMPETING CONTINUATION	$40,000
														Subtotal = $400,000

Issue Date FY: 2016 ( Subtotal = $400,000 )
2016	2016	COLUMBIA UNIVERSITY	615 WEST 131ST ST, 4TH FLOOR	NEW YORK	NY	10027	NEW YORK	USA	Mental Health Research Grants	000	3	3/22/2016	NON-COMPETING CONTINUATION	$400,000
														Subtotal = $400,000

Issue Date FY: 2015 ( Subtotal = $400,000 )
2015	2015	COLUMBIA UNIVERSITY	615 WEST 131ST ST, 4TH FLOOR	NEW YORK	NY	10027	NEW YORK	USA	Mental Health Research Grants	000	2	7/29/2015	NON-COMPETING CONTINUATION	$400,000
														Subtotal = $400,000

Issue Date FY: 2014 ( Subtotal = $400,000 )
2014	2014	COLUMBIA UNIVERSITY	615 WEST 131ST ST, 4TH FLOOR	NEW YORK	NY	10027	NEW YORK	USA	Mental Health Research Grants	000	1	7/3/2014	NEW	$400,000
														Subtotal = $400,000

Grand Total All Awards = $5,180,874

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Control of CA2 by its cortico-hippocampal inputs and local inhibition in social information processing and learning

Award Number: R01MH104602

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/11/2014

PERIOD OF PERFORMANCE END DATE: 10/31/2028

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