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Activity-Dependent Transcriptional Pathways Underlying Synaptic Mechanisms for Memory Discrimination and Generalization

Award Number: R01NS115543
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/02/2024
PERIOD OF PERFORMANCE END DATE: 12/31/2025

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Activity-Dependent Transcriptional Pathways Underlying Synaptic Mechanisms for Memory Discrimination and Generalization - PROJECT SUMMARY The ability of the brain to utilize information from past experiences to guide future decisions, termed adaptive behavior, is critical for survival. To effectively adapt behaviors, the brain applies stored memory to new but similar situations (generalization), while also maintaining the capacity to distinguish unique stimuli (discrimination). When these critical processes (memory generalization or discrimination) go awry, it can lead to maladaptive disorders such as post-traumatic stress disorder (PTSD) and panic disorder. Despite their importance, mechanisms underlying memory discrimination and generalization remain largely unknown. This proposal will investigate the dynamic processes that underlie the utilization of an encoded memory to guide future behaviors, in particular the molecular, synaptic, and circuit mechanisms that govern the balance between discrimination and generalization. We have collected very exciting preliminary data showing that individual contextual fear memories are represented in the dentate gyrus (DG) by multiple functionally distinct neuronal ensembles defined by different activity-dependent transcriptional pathways, and that these ensembles bi-directionally regulate the discrimination-generalization balance. Based on these exciting findings, we hypothesize that the activity- dependent pathways target specific synaptic inputs on DG granule cells to differentially control memory discrimination and generalization. We aim to (1) uncover novel forms of learning-induced synaptic plasticity; (2) reveal underlying circuit mechanisms for memory discrimination and generalization; and (3) identify the molecular players important for this experience-dependent behavioral adaptation. The proposed research is both conceptually and technically innovative. It will experimentally demonstrate for the first time functionally distinct active neuronal ensembles coexisting within the memory engram, shed light on the synaptic and circuit mechanisms by which encoded memories directly drive experience-dependent behavioral outputs, and may lead to new treatment strategies for neuropsychiatric disorders, such as PTSD and panic disorder, which are caused by the imbalance between memory discrimination and generalization.


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 = $0 )
2025	2024	THE UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	6	2/21/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$165,588
2025	2024	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	750 E ADAMS ST	SYRACUSE	NY	13210	ONONDAGA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	5	2/21/2025	NON-COMPETING CONTINUATION	-$40,629
2025	2023	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	750 E ADAMS ST	SYRACUSE	NY	13210	ONONDAGA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	2/21/2025	NON-COMPETING CONTINUATION	-$124,959
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $568,238 )
2024	2024	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	750 E ADAMS ST	SYRACUSE	NY	13210	ONONDAGA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	12/30/2023	NON-COMPETING CONTINUATION	$522,374
2024	2024	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	750 E ADAMS ST	SYRACUSE	NY	13210	ONONDAGA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	5	4/10/2024	NON-COMPETING CONTINUATION	$40,629
2024	2024	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	750 E ADAMS ST	SYRACUSE	NY	13210	ONONDAGA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	5	8/5/2024	NON-COMPETING CONTINUATION	-$522,374
2024	2024	THE UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	003	6	8/6/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$527,609
														Subtotal = $568,238

Issue Date FY: 2023 ( Subtotal = $581,361 )
2023	2023	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	750 E ADAMS ST	SYRACUSE	NY	13210	ONONDAGA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	12/12/2022	NON-COMPETING CONTINUATION	$523,226
2023	2023	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	750 E ADAMS ST	SYRACUSE	NY	13210	ONONDAGA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	4	1/30/2023	NON-COMPETING CONTINUATION	$58,135
														Subtotal = $581,361

Issue Date FY: 2022 ( Subtotal = $625,543 )
2022	2022	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	750 E ADAMS ST	SYRACUSE	NY	13210	ONONDAGA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	3	1/14/2022	SUPPLEMENT FOR EXPANSION	$44,182
2022	2022	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	750 E ADAMS ST	SYRACUSE	NY	13210	ONONDAGA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	11/19/2021	NON-COMPETING CONTINUATION	$523,226
2022	2022	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	750 E ADAMS ST	SYRACUSE	NY	13210	ONONDAGA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	3	3/29/2022	NON-COMPETING CONTINUATION	$58,135
														Subtotal = $625,543

Issue Date FY: 2021 ( Subtotal = $594,726 )
2021	2021	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	750 E ADAMS ST	SYRACUSE	NY	13210	ONONDAGA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	2	1/11/2021	NON-COMPETING CONTINUATION	$59,472
2021	2021	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	750 E ADAMS ST	SYRACUSE	NY	13210	ONONDAGA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	12/18/2020	NON-COMPETING CONTINUATION	$535,254
														Subtotal = $594,726

Issue Date FY: 2020 ( Subtotal = $610,894 )
2020	2020	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	750 E ADAMS ST	SYRACUSE	NY	13210	ONONDAGA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	2/20/2020	NEW	$566,359
2020	2020	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	750 E ADAMS ST	SYRACUSE	NY	13210	ONONDAGA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	1	7/21/2020	NEW	$44,535
														Subtotal = $610,894

Grand Total All Awards = $2,980,762

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Activity-Dependent Transcriptional Pathways Underlying Synaptic Mechanisms for Memory Discrimination and Generalization

Award Number: R01NS115543

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 05/02/2024

PERIOD OF PERFORMANCE END DATE: 12/31/2025

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