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CRCNS: Role of mAChRs on CA 1 pyramidal neurons in memory formation and stability

Award Number: R01AG085899
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/15/2023
PERIOD OF PERFORMANCE END DATE: 04/30/2027

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CRCNS: Role of mAChRs on CA 1 pyramidal neurons in memory formation and stability - The formation and retention of memories of our daily experiences depend on a brain region called the hippocampus. Among the extensive neuromodulatory inputs the hippocampus receives, cholinergic inputs from the basal forebrain are crucial for learning and memory. These same inputs elicit reduced neuronal response with aging, and degenerate in patients suffering from Alzheimer's disease. Despite its critical role in memory formation and stability, how cholinergic modulation mediates memory functions through individual circuit elements in the hippocampus remains largely unknown. In CA 1, the major output of the hippocampus, acetylcholine receptors are expressed in multiple cell types and cellular compartments. Until now, it has been difficult to determine the contribution of individual elements to the overall network effects of acetylcholine. In this project, we will study the role of muscarinic cholinergic receptors located on the pyramidal neurons of the CA1 region in the formation and long-term stability of Internally Generated Sequences (IGS), the sequences generated during locomotion while sensory cues are held constant and as animals perform memory tasks. We will use IGS as a representative of memory-related activity patterns to reveal how cholinergic activity modulates the formation of and the long timescale drift in the hippocampal code and in turn refines the behavior by activating cell-type-specific acetylcholine receptors. Our experimental approach is to manipulate the strength and locus of cholinergic modulation in CA1 while imaging large numbers of neurons in awake head-fixed mice engaged in a hippocampus-dependent memory task. Specifically, we will selectively modulate the CA1 pyramidal neurons with cell-type specific neuropharmacological tools. Integrating computational modeling with findings from experiments, we will elucidate possible plasticity and network mechanisms responsible for the observed neuronal dynamics. By combining experimental and computational approaches to elucidate the cholinergic control of plasticity over memory formation and stability across the cellular, circuit, and behavioral levels, we will contribute novel insights into the effects of a disruption in cholinergic signaling. Our results may indicate which physiological parameters could be altered to compensate for the loss of cholinergic signals, and lead to the development of new treatment options for memory disorders.


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	MAX PLANCK FLORIDA CORP	1 MAX PLANCK WAY	JUPITER	FL	33458	PALM BEACH	USA	Aging Research	001	2	4/1/2025	NON-COMPETING CONTINUATION	$0
2025	2024	MAX PLANCK FLORIDA CORP	1 MAX PLANCK WAY	JUPITER	FL	33458	PALM BEACH	USA	Aging Research	000	2	3/28/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $334,693 )
2024	2024	MAX PLANCK FLORIDA CORP	1 MAX PLANCK WAY	JUPITER	FL	33458	PALM BEACH	USA	Aging Research	000	2	5/24/2024	NON-COMPETING CONTINUATION	$334,693
														Subtotal = $334,693

Issue Date FY: 2023 ( Subtotal = $347,238 )
2023	2023	MAX PLANCK FLORIDA CORP	1 MAX PLANCK WAY	JUPITER	FL	33458	PALM BEACH	USA	Aging Research	000	1	8/14/2023	NEW	$347,238
2023	2023	MAX PLANCK FLORIDA CORP	1 MAX PLANCK WAY	JUPITER	FL	33458	PALM BEACH	USA	Aging Research	001	1	9/12/2023	NEW	$0
														Subtotal = $347,238

Grand Total All Awards = $681,931

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CRCNS: Role of mAChRs on CA 1 pyramidal neurons in memory formation and stability

Award Number: R01AG085899

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/15/2023

PERIOD OF PERFORMANCE END DATE: 04/30/2027

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