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Characterizing the underlying population code to understand the functional organization of the hippocampus and the lateral hypothalamus

Award Number: R00DA053388
ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/01/2023
PERIOD OF PERFORMANCE END DATE: 07/31/2026

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Characterizing the underlying population code to understand the functional organization of the hippocampus and the lateral hypothalamus - Project Summary/Abstract Recent advancements in neural recording/imaging technologies and computational methods have generated a renewed interest in studying coordinated population activity. Understanding the population code can help us better understand the complex mechanisms behind substance use disorders (SUD). One leading idea is that high-dimensional neural activity, such as simultaneous recordings from hundreds to thousands of cells, can lie on low-dimensional manifolds, such that a handful of latent variables can accurately describe the activity of all recorded neurons. The lateral hypothalamus (LH) is a brain area well-known for its functional diversity – individual cells respond with great heterogeneity to a wide range of appetitive behaviors, and LH stimulation can evoke a variety of actions ranging from feeding to social interaction. This project proposes to use the latest nonlinear dimensionality reduction techniques to extract the low-dimensional manifolds representing population activity patterns that geometrically organize the heterogeneous single neuron activity. These manifolds can then be used to achieve this project’s main goal – differentiating LH neural population encoding of natural reward-seeking behaviors and maladaptive drug-seeking behaviors. In addition, novel computational modeling methods will be used to perform unsupervised detection of internal neural states that guide animals switching between these two reward-seeking behaviors. Finally, state-of-the-art cellular-resolution simultaneous stimulation and imaging microscopy will be used to casually perturb animal behavior and/or neural activity patterns by activating sequences of neurons along trajectories on the low-dimensional manifolds. Importantly, Aims 1 and 2 support these goals by offering training in the use of the necessary computational and instrumentation techniques. Ultimately, results obtained from this project will advance our understanding of the neural mechanisms separating harmful drug-seeking behaviors and useful natural reward-seeking behaviors, such that SUD treatments with more precise targets can be developed that minimize unwanted side effects.


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 = $249,000 )
2025	2025	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 EMMET ST N	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Drug Use and Addiction Research Programs	000	5	6/25/2025	NON-COMPETING CONTINUATION	$249,000
														Subtotal = $249,000

Issue Date FY: 2024 ( Subtotal = $390,429 )
2024	2024	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 EMMET ST N	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Drug Use and Addiction Research Programs	001	4	7/3/2024	NON-COMPETING CONTINUATION	$248,999
2024	2023	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 EMMET ST N	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Drug Use and Addiction Research Programs	000	3	12/20/2023	EXTENSION WITH OR WITHOUT FUNDS	$141,430
														Subtotal = $390,429

Issue Date FY: 2023 ( Subtotal = $248,999 )
2023	2023	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Drug Use and Addiction Research Programs	000	3	7/27/2023	EXTENSION WITH OR WITHOUT FUNDS	$248,999
														Subtotal = $248,999

Grand Total All Awards = $888,428

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Characterizing the underlying population code to understand the functional organization of the hippocampus and the lateral hypothalamus

Award Number: R00DA053388

ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/01/2023

PERIOD OF PERFORMANCE END DATE: 07/31/2026

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