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Regulation of synaptic plasticity by BDNF-endocannabinoid interactions

Award Number: R01NS111986
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: 12/01/2019
PERIOD OF PERFORMANCE END DATE: 11/30/2025

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Regulation of synaptic plasticity by BDNF-endocannabinoid interactions - PROJECT SUMMARY The goal of this project is to explore the functional relevance of interactions between brain-derived neurotrophic factor (BDNF) and endogenous cannabinoids (eCB) in regulating activity-dependent synaptic plasticity in the neocortex and hippocampus. Although there is growing evidence for crosstalk between BDNF and eCBs, little is known regarding potential synaptic interactions. We have previously characterized the synaptic effects of eCBs and BDNF in layer 2/3 and layer 5 of somatosensory cortex as well as the CA1 area of hippocampus, and we have recently shown that the presynaptic effects of BDNF at cortical and hippocampal inhibitory synapses are mediated by the BDNF-induced release of eCBs from postsynaptic pyramidal cells. We have also found that BDNF causes release of eCBs at excitatory synapses, and this eCB signaling mitigates the direct facilitatory effects of BDNF at these synapses. We are now poised to explore the functional relevance of these interactions in regulating activity-dependent synaptic plasticity. In particular, we will examine the interactions between endogenous BDNF-induced eCB release and activity-dependent eCB release in regulating the magnitude and direction of plasticity at excitatory and inhibitory synapses. These studies will combine electrophysiology and calcium imaging with pharmacological and genetic approaches to manipulate these signaling systems. We will also examine these signaling interactions using mice engineered to express common human single-nucleotide polymorphisms (SNPs) that affect either endogenous BDNF or anandamide levels. Importantly, we will carry out parallel studies using cultured human induced pluripotent stem cell (iPSC)-derived neurons generated from individuals who carry these same SNPs.


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 = $486,967 )
2025	2025	UNIVERSITY OF CONNECTICUT HEALTH CENTER	263 FARMINGTON AVE	FARMINGTON	CT	06030	CAPITOL	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	11/27/2024	NON-COMPETING CONTINUATION	$486,967
														Subtotal = $486,967

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2023	UNIVERSITY OF CONNECTICUT HEALTH CENTER	263 FARMINGTON AVE	FARMINGTON	CT	06030	CAPITOL	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	12/13/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $541,075 )
2023	2023	UNIVERSITY OF CONNECTICUT	263 FARMINGTON AVE, ASB #3	FARMINGTON	CT	06032	CAPITOL	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	11/24/2022	NON-COMPETING CONTINUATION	$486,967
2023	2023	UNIVERSITY OF CONNECTICUT	263 FARMINGTON AVE, ASB #3	FARMINGTON	CT	06032	CAPITOL	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	4	1/31/2023	NON-COMPETING CONTINUATION	$54,108
														Subtotal = $541,075

Issue Date FY: 2022 ( Subtotal = $541,075 )
2022	2022	UNIVERSITY OF CONNECTICUT	263 FARMINGTON AVE, ASB #3	FARMINGTON	CT	06032	CAPITOL	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	11/23/2021	NON-COMPETING CONTINUATION	$486,967
2022	2022	UNIVERSITY OF CONNECTICUT	263 FARMINGTON AVE, ASB #3	FARMINGTON	CT	06032	CAPITOL	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	3	6/23/2022	NON-COMPETING CONTINUATION	$54,108
														Subtotal = $541,075

Issue Date FY: 2021 ( Subtotal = $541,075 )
2021	2021	UNIVERSITY OF CONNECTICUT	263 FARMINGTON AVE, ASB #3	FARMINGTON	CT	06032	CAPITOL	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	2	4/5/2021	NON-COMPETING CONTINUATION	$54,108
2021	2021	UNIVERSITY OF CONNECTICUT	263 FARMINGTON AVE, ASB #3	FARMINGTON	CT	06032	CAPITOL	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	11/23/2020	NON-COMPETING CONTINUATION	$486,967
														Subtotal = $541,075

Issue Date FY: 2020 ( Subtotal = $538,369 )
2020	2020	UNIVERSITY OF CONNECTICUT	263 FARMINGTON AVE, ASB #3	FARMINGTON	CT	06032	CAPITOL	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	11/15/2019	NEW	$538,369
														Subtotal = $538,369

Grand Total All Awards = $2,648,561

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Regulation of synaptic plasticity by BDNF-endocannabinoid interactions

Award Number: R01NS111986

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: 12/01/2019

PERIOD OF PERFORMANCE END DATE: 11/30/2025

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