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Presynaptic forms of long-term plasticity in the CNS

Award Number: R01MH125772
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/24/2003
PERIOD OF PERFORMANCE END DATE: 06/30/2031

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Presynaptic forms of long-term plasticity in the CNS - Synapses can change their functional and structural properties in response to activity, a phenomenon known as synaptic plasticity, which is essential for experience-dependent adjustments in brain function. A widely recognized mechanism of synaptic plasticity in the central nervous system (CNS) involves long-term changes in neurotransmitter release. Dysregulation of presynaptic plasticity has been linked to the pathophysiology of various neuropsychiatric conditions, including cognitive disorders, autism spectrum disorders (ASD), intellectual disabilities, mood disorders, schizophrenia, epilepsy, and drug addiction. Despite significant advancements in the molecular understanding of neurotransmission, the long-term modification of transmitter release remains largely unknown. We hypothesize that presynaptic local protein synthesis (LPS) in the mature mammalian brain mediates functional and structural plasticity, playing a critical role in behavior and brain disorders. To test our hypothesis, we will employ multiple complementary approaches that specifically target the presynaptic neurons or the presynaptic compartment, focusing on hippocampal synapses that express mechanistically similar forms of presynaptic plasticity. We seek to determine how activity and experiences induce presynaptic local protein synthesis (Aim 1), the impact of presynaptic local protein synthesis on structural and functional synaptic plasticity and behavior (Aim 2), and identify changes in the presynaptic transcriptome, translatome, and proteome induced by activity, experiences, and brain disorders (Aim 3). Completing the proposed studies will likely provide mechanistic insights into how presynaptic LPS is induced, its precise role in synaptic function and behavior, and how its disruption contributes to brain disorders such as intellectual disabilities, ASD, depression, and epilepsy. A better understanding of local protein synthesis at the synapse may help develop novel targets for treating these 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: 2026 ( Subtotal = $741,480 )
2026	2026	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Mental Health Research Grants	001	22	9/2/2026	COMPETING CONTINUATION	$741,766
2026	2024	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Mental Health Research Grants	000	21	1/7/2026	NON-COMPETING CONTINUATION	-$286
														Subtotal = $741,480

Issue Date FY: 2024 ( Subtotal = $574,933 )
2024	2024	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Mental Health Research Grants	000	21	7/16/2024	NON-COMPETING CONTINUATION	$574,933
														Subtotal = $574,933

Issue Date FY: 2023 ( Subtotal = $574,933 )
2023	2023	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Mental Health Research Grants	001	20	7/6/2023	NON-COMPETING CONTINUATION	$574,933
2023	2022	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Mental Health Research Grants	000	19	7/5/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $574,933

Issue Date FY: 2022 ( Subtotal = $574,934 )
2022	2022	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Mental Health Research Grants	001	19	7/19/2022	NON-COMPETING CONTINUATION	$574,933
2022	2020	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Mental Health Research Grants	000	17	11/2/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$1
														Subtotal = $574,934

Issue Date FY: 2021 ( Subtotal = $574,933 )
2021	2021	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Mental Health Research Grants	000	18	7/13/2021	NON-COMPETING CONTINUATION	$574,933
														Subtotal = $574,933

Issue Date FY: 2020 ( Subtotal = $608,199 )
2020	2020	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Mental Health Research Grants	000	17	9/18/2020	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$608,199
														Subtotal = $608,199

Grand Total All Awards = $3,649,412

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Presynaptic forms of long-term plasticity in the CNS

Award Number: R01MH125772

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/24/2003

PERIOD OF PERFORMANCE END DATE: 06/30/2031

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