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Local Circuit Control of Rapid Plasticity and Tunable Ensemble Formation in the Hippocampus

Award Number: R01NS133381
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: 09/01/2023
PERIOD OF PERFORMANCE END DATE: 08/31/2028

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Local Circuit Control of Rapid Plasticity and Tunable Ensemble Formation in the Hippocampus - Project Summary/Abstract Neural representations supporting spatial and episodic learning form, and transform rapidly in the mammalian hippocampus. Individual hippocampal pyramidal cells each fire at a specific location in an environment and together these place cells provide a striking substrate for a cognitive map. A critical step in achieving a mechanistic understanding of how place cell dynamics support hippocampal learning and memory is to be able to re-create endogenous neuronal representations experimentally, and test their behavioral relevance. However, it has not previously been possible to generate lasting hippocampal place cell maps through controlled manipulations of hippocampal plasticity. Our groups have recently identified key potential controllers of hippocampal ensemble formation, raising the intriguing possibility that stable place cell maps can be synthetically generated and allocated by manipulating these controllers. In particular, we demonstrated that any individual, arbitrarily chosen pyramidal cell in the mouse hippocampal area CA1 can be reliably induced to become lasting place cells, using all-optical plasticity induction. Here, we propose to determine if targeted in vivo manipulations of feedback inhibitory (Aim 1), recurrent excitatory (Aim 2), and cell-intrinsic retrograde (Aim 3) local circuit control mechanisms enable the specific generation and allocation of behaviorally relevant neural representation by scaling single-cell optogenetic place cell induction to multi-cellular ensembles. We will test our hypothesis in the hippocampal area CA1 of mice navigating and learning in a virtual reality environment, utilizing a variety of innovative in vivo calcium-imaging, optogenetic, electrophysiology, statistical data analysis, and modeling approaches. We anticipate that our project will have a significant, potentially translatable impact by overcoming major knowledge gaps about cellular and local circuit determinants of neuronal plasticity, while also supporting rapid induced plasticity of neuronal representations. Our research can thereby accelerate the development of neural modulation strategies to study, modify, or improve memory-related behaviors.


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 = $752,108 )
2026	2026	THE UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	21st Century Cures Act -Brain Research through Advancing Innovative Neurotechnologies	000	2	8/27/2026	EXTENSION WITH OR WITHOUT FUNDS	$752,108
														Subtotal = $752,108

Grand Total All Awards = $752,108

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Local Circuit Control of Rapid Plasticity and Tunable Ensemble Formation in the Hippocampus

Award Number: R01NS133381

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: 09/01/2023

PERIOD OF PERFORMANCE END DATE: 08/31/2028

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