Thursday, July 3, 2025 7/3/2025

Serotonergic modulation of excitatory synapse formation and maturation during development

Award Number: R01MH124778
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 12/01/2020
PERIOD OF PERFORMANCE END DATE: 10/31/2025

Group Awards By:

View Award Description

Serotonergic modulation of excitatory synapse formation and maturation during development - Project Summary Autism Spectrum Disorders (ASDs) comprise a group of severe neurodevelopmental disorders that are typified by communication deficits and social impairment. Given that the onset of symptoms occurs by the age of 3, it is largely agreed that neuronal dysfunction arises during early brain development. A developing brain shows a remarkable capacity for plastic changes in response to experiences; thus, its development is most vulnerable to the environmental factors that can derail normal brain function. In utero exposure to drugs that raise blood 5HT levels, including selective serotonin reuptake inhibitors (SSRIs), has demonstrated behavioral and psychological deficits in offspring that closely resemble autistic symptoms in both animals models and human studies. In order to understand how these alterations arise, it is necessary to first understand the basic mechanisms of serotonergic modulation of brain function. Formation and stabilization of excitatory synapses are known to be essential for the initial establishment of functional neural circuits. Conversely, disrupted synapse development impairs neuron function and is thought to underlie the pathology of multiple neurodevelopmental disorders. PFC is densely innervated by serotonergic axon terminals and associated with higher cognitive processes that may be disrupted in illnesses such as ASDs. Despite a wealth of literature examining the role of 5HT in modulating behavior and in the pathogenesis of brain disorders, little is known at the cellular and molecular level about the role of 5HT in early cortical development, and particularly the postsynaptic 5HT mechanisms that modulate synapse development in the developing PFC. In the present study, we utilize a novel combination of tools including two-color, two-photon uncaging that enables precise release of 5HT and glutamate neurotransmitters, calcium imaging, electrophysiology, and optogenetic stimulation of genetically-targeted 5HT neurons to test our central hypothesis that 5HT signaling promotes the initiation of excitatory synapse formation and controls the maturation of excitatory synapses during brain development. Guided by strong preliminary data, we will examine this hypothesis in two specific aims: 1) Determine the role of 5HT signaling in lowering the threshold for induction of activity-dependent synapse formation. 2) Define the actions of 5HT on activity-dependent, input-specific and heterosynaptic spine stabilization. Results from these studies will further our understanding of the unique and detailed mechanisms by which 5HT regulates brain development, with critical relevance to cellular underpinnings of neurodevelopmental disorders. In the U.S., approximately 13% of pregnant women use SSRIs, which typically increase fetal 5HT levels. We expect that our results will highlight new avenues into the investigation of the pathophysiology underlying neurodevelopmental disorders resulting from early perturbation of 5HT signaling.


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 = $326,145 )
2025	2025	THE REGENTS OF THE UNIVERSITY OF COLORADO	13001 E 17TH PL STE F428	AURORA	CO	80045	ADAMS	USA	Mental Health Research Grants	000	5	11/25/2024	NON-COMPETING CONTINUATION	$326,145
														Subtotal = $326,145

Issue Date FY: 2024 ( Subtotal = $383,700 )
2024	2024	THE REGENTS OF THE UNIVERSITY OF COLORADO	13001 E 17TH PL STE F428	AURORA	CO	80045	ADAMS	USA	Mental Health Research Grants	001	4	8/15/2024	NON-COMPETING CONTINUATION	$38,370
2024	2024	REGENTS OF THE UNIVERSITY OF COLORADO, THE	13001 E 17TH PLACE F428	AURORA	CO	80045	ADAMS	USA	Mental Health Research Grants	000	4	12/14/2023	NON-COMPETING CONTINUATION	$345,330
														Subtotal = $383,700

Issue Date FY: 2023 ( Subtotal = $383,700 )
2023	2023	REGENTS OF THE UNIVERSITY OF COLORADO, THE	13001 E 17TH PLACE F428	AURORA	CO	80045	ADAMS	USA	Mental Health Research Grants	000	3	11/4/2022	NON-COMPETING CONTINUATION	$345,330
2023	2023	REGENTS OF THE UNIVERSITY OF COLORADO, THE	13001 E 17TH PLACE F428	AURORA	CO	80045	ADAMS	USA	Mental Health Research Grants	001	3	3/6/2023	NON-COMPETING CONTINUATION	$38,370
														Subtotal = $383,700

Issue Date FY: 2022 ( Subtotal = $383,700 )
2022	2022	REGENTS OF THE UNIVERSITY OF COLORADO, THE	13001 E 17TH PLACE F428	AURORA	CO	80045	ADAMS	USA	Mental Health Research Grants	001	2	6/21/2022	NON-COMPETING CONTINUATION	$38,370
2022	2022	REGENTS OF THE UNIVERSITY OF COLORADO, THE	13001 E 17TH PLACE F428	AURORA	CO	80045	ADAMS	USA	Mental Health Research Grants	000	2	10/22/2021	NON-COMPETING CONTINUATION	$345,330
														Subtotal = $383,700

Issue Date FY: 2021 ( Subtotal = $383,700 )
2021	2021	REGENTS OF THE UNIVERSITY OF COLORADO, THE	13001 E 17TH PLACE F428	AURORA	CO	80045	ADAMS	USA	Mental Health Research Grants	000	1	11/23/2020	NEW	$383,700
														Subtotal = $383,700

Grand Total All Awards = $1,860,945

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Serotonergic modulation of excitatory synapse formation and maturation during development

Award Number: R01MH124778

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 12/01/2020

PERIOD OF PERFORMANCE END DATE: 10/31/2025

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer