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Analyses of the Distributed Representation of Associative-Learning in an Identified Circuit Using a Combination of Single-Cell Electrophysiology and Multicellular Voltage-Sensitive Dye Recordings

Award Number: R01NS101356
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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PROJECT SUMMARY/ABSTRACT Although significant advances have been made in elucidating the cellular, biophysical and molecular mechanisms of learning and memory, much less is known about the ways in which mnemonic processes are embedded in neuronal networks. The overall goal of this proposal is to provide insights into the design principles that govern the implementation of memories within the complex environment of a neural circuit. Studies will focus on an established in vitro analogue of operant conditioning (QC) in a relatively complex circuit, which is amenable to population-wide, cellular, and biophysical analyses. A combination of intra- and extracellular electrophysiological techniques, voltage-sensitive dye (VSD) imaging, dimensionality reduction analysis, and computational modeling will identify and characterize loci of non-synaptic and synaptic plasticity. In addition, the project will examine the extent to which plasticity loci are shared between short- and long-term memory. Aim 1 will use intracellular recording techniques to examine loci of QC-induced plasticity. Previous correlates of OC in this model system were restricted to increases in intrinsic excitability or electrical synapses of key neurons in the circuit. Our recent results indicate QC also decreases the strength of an inhibitory synapse and the excitability of a key neuron in the circuit. Aim 1 will examine other prime candidates of QC-induced synaptic and non-synaptic plasticity, which have an established role in mediating the behavior. In addition, we will use intracellular techniques to examine regions of the circuit that our recent VSD recordings have shown to exhibit QC-induced changes in activity. Computational modeling will assess the ways in which loci work unilaterally or synergistically to mediate the OC phenotype. Aim 2 will use a combination of intracellular recordings, VSD imaging, and dimensionality reduction approaches to expand the search for additional sites of QC-induced plasticity and search for low-dimensional 'signatures' of OC. The combined results from Aims 1 and 2 will provide for an assessment of the scope of plasticity mechanisms associated with OC that is unprecedented in any system. A further important question will be addressed by Aim 3, which will determine the extent to which sites for short-term memory persist during long-term memory and, conversely, which sites of plasticity may be unique to long-term memory. The present proposal will help develop a comprehensive understanding of the ways in which memories are encoded in a relatively complex circuit, elucidate design principles of memory encoding, and provide guidance for similar analyses in more complex systems.


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: 2024 ( Subtotal = $477,488 )
2024	2024	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON	7000 FANNIN ST FL 9	HOUSTON	TX	77030	HARRIS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	7	1/16/2024	NON-COMPETING CONTINUATION	$0
2024	2024	UNIVERSITY OF HEALTH SCIENCE CENTER	7000 FANNIN ST	HOUSTON	TX	77030	HARRIS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	7	11/22/2023	NON-COMPETING CONTINUATION	$351,000
2024	2024	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON	7000 FANNIN ST FL 9	HOUSTON	TX	77030	HARRIS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	7	1/12/2024	SUPPLEMENT FOR EXPANSION	$126,488
														Subtotal = $477,488

Issue Date FY: 2023 ( Subtotal = $390,000 )
2023	2023	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON, THE	7000 FANNIN ST	HOUSTON	TX	77030	HARRIS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	6	12/30/2022	COMPETING CONTINUATION	$390,000
2023	2022	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON, THE	7000 FANNIN ST	HOUSTON	TX	77030	HARRIS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	12/29/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $390,000

Issue Date FY: 2022 ( Subtotal = $334,519 )
2022	2022	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON, THE	7000 FANNIN ST	HOUSTON	TX	77030	HARRIS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	5	3/25/2022	NON-COMPETING CONTINUATION	$33,452
2022	2022	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON, THE	7000 FANNIN ST	HOUSTON	TX	77030	HARRIS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	11/26/2021	NON-COMPETING CONTINUATION	$301,067
														Subtotal = $334,519

Issue Date FY: 2021 ( Subtotal = $334,519 )
2021	2021	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON, THE	7000 FANNIN ST	HOUSTON	TX	77030	HARRIS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	4	1/25/2021	NON-COMPETING CONTINUATION	$33,452
2021	2021	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON, THE	7000 FANNIN ST	HOUSTON	TX	77030	HARRIS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	12/10/2020	NON-COMPETING CONTINUATION	$301,067
														Subtotal = $334,519

Issue Date FY: 2020 ( Subtotal = $334,519 )
2020	2020	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON, THE	7000 FANNIN ST	HOUSTON	TX	77030	HARRIS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	3	2/21/2020	NON-COMPETING CONTINUATION	$33,452
2020	2020	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON, THE	7000 FANNIN ST	HOUSTON	TX	77030	HARRIS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	1/8/2020	NON-COMPETING CONTINUATION	$301,067
														Subtotal = $334,519

Issue Date FY: 2019 ( Subtotal = $334,519 )
2019	2019	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON, THE	7000 FANNIN ST	HOUSTON	TX	77030	HARRIS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	12/11/2018	NON-COMPETING CONTINUATION	$334,519
														Subtotal = $334,519

Issue Date FY: 2018 ( Subtotal = $334,519 )
2018	2018	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON, THE	7000 FANNIN ST	HOUSTON	TX	77030	HARRIS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	1/29/2018	NEW	$334,519
														Subtotal = $334,519

Grand Total All Awards = $2,540,083

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Analyses of the Distributed Representation of Associative-Learning in an Identified Circuit Using a Combination of Single-Cell Electrophysiology and Multicellular Voltage-Sensitive Dye Recordings

Award Number: R01NS101356

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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