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Acetylcholinergic Neurotransmission During Aging

Award Number: K01AG049055
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 09/01/2015
PERIOD OF PERFORMANCE END DATE: 12/31/2022

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Acetylcholinergic Neurotransmission During Aging - Project Summary This proposal is aimed at determining the role of changes in acetylcholinergic neurotransmission on synaptic physiology and behavior during aging. Acetylcholine regulation has long been thought to play a crucial role in the mediation of cognitive and behavioral function as an organism ages, yet the precise function of acetylcholine in this process has, till date remained poorly elucidated. We are using a subtle mutation in the vesicular acetylcholine transporter (VAChT) the protein responsible for the packaging of ACh for exocytotic release to determine the role of cholinergic neurotransmission during aging. The short life span of the fly coupled, with additional genetic tools unique to this system will allow us to assess the impact of altered ACh release on behavior and synaptic physiology throughout the lifespan of the animal. Our preliminary data show for the first time action potential firing in aged Drosophila cholinergic neurons; we also show that Vacht mutations have a differential effect on organismal survival with the most severe mutation have a significantly shorter lifespan than wildtype. These and other results have allowed us to advance the central hypothesis that a decrease in VAChT function produce a corresponding decrease in neuronal excitability and behavior that are amplified with age In Aim 1, we will determine the effect of a relatively mild reduction decrease in VAChT function on synaptic physiology at central cholinergic synapses during aging. In Aim 2, we will measure whether the reduction in Vacht affects cognition at defined points across the lifespan. Future studies will be aimed at using the system that we have developed here to understand the mechanisms behind the preferential susceptibility of cholinergic neurons in pathological conditions such as Alzheimer’s disease.


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 = -$41,770 )
2024	2022	DELAWARE STATE UNIVERSITY	1200 N DUPONT HWY	DOVER	DE	19901	KENT	USA	Aging Research	000	5	10/16/2023	SUPPLEMENT FOR EXPANSION	-$41,770
														Subtotal = -$41,770

Issue Date FY: 2022 ( Subtotal = $92,952 )
2022	2022	DELAWARE STATE UNIVERSITY	1200 N DUPONT HWY	DOVER	DE	19901	KENT	USA	Aging Research	000	5	6/27/2022	SUPPLEMENT FOR EXPANSION	$92,952
2022	2019	DELAWARE STATE UNIVERSITY	1200 N DUPONT HWY	DOVER	DE	19901	KENT	USA	Aging Research	001	5	7/13/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $92,952

Issue Date FY: 2021 ( Subtotal = $0 )
2021	2019	DELAWARE STATE UNIVERSITY	1200 N DUPONT HWY	DOVER	DE	19901	KENT	USA	Aging Research	000	5	4/23/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2019 ( Subtotal = $139,140 )
2019	2019	DELAWARE STATE UNIVERSITY	1200 N DUPONT HWY	DOVER	DE	19901	KENT	USA	Aging Research	000	5	5/27/2019	NON-COMPETING CONTINUATION	$139,140
														Subtotal = $139,140

Issue Date FY: 2018 ( Subtotal = $353,139 )
2018	2018	DELAWARE STATE UNIVERSITY	1200 N DUPONT HWY	DOVER	DE	19901	KENT	USA	Aging Research	001	4	9/12/2018	SUPPLEMENT FOR EXPANSION	$213,999
2018	2018	DELAWARE STATE UNIVERSITY	1200 N DUPONT HWY	DOVER	DE	19901	KENT	USA	Aging Research	000	4	5/18/2018	NON-COMPETING CONTINUATION	$139,140
														Subtotal = $353,139

Issue Date FY: 2017 ( Subtotal = $139,140 )
2017	2017	DELAWARE STATE UNIVERSITY	1200 N DUPONT HWY	DOVER	DE	19901	KENT	USA	Aging Research	000	3	5/15/2017	NON-COMPETING CONTINUATION	$139,140
														Subtotal = $139,140

Issue Date FY: 2016 ( Subtotal = $139,140 )
2016	2016	DELAWARE STATE UNIVERSITY	1200 NORTH DUPONT HIGHWAY	DOVER	DE	19901	KENT	USA	Aging Research	000	2	5/26/2016	NON-COMPETING CONTINUATION	$139,140
														Subtotal = $139,140

Issue Date FY: 2015 ( Subtotal = $139,140 )
2015	2015	DELAWARE STATE UNIVERSITY	1200 NORTH DUPONT HIGHWAY	DOVER	DE	19901	KENT	USA	Aging Research	000	1	8/20/2015	NEW	$139,140
														Subtotal = $139,140

Grand Total All Awards = $960,881

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Acetylcholinergic Neurotransmission During Aging

Award Number: K01AG049055

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 09/01/2015

PERIOD OF PERFORMANCE END DATE: 12/31/2022

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