Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Changes in cortical silent synapses and cognitive flexibility over the lifespan of humans and mice

Award Number: R01AG102702
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/20/2026
PERIOD OF PERFORMANCE END DATE: 06/30/2031

Group Awards By:

View Award Description

Changes in cortical silent synapses and cognitive flexibility over the lifespan of humans and mice - Age is the primary risk factor for cognitive decline. With the number of Americans over the age of 65 projected to almost double in the next 25 years, there is an urgent need to address and mitigate brain health issues associated with both normal and pathological aging. Despite immense public investment and decades of intensive research, critical gaps in our understanding of the causes of cognitive decline have precluded the development of effective treatments. Synaptic dysfunction is strongly implicated as the critical player in aging- related cognitive changes. Alterations in synapse density, morphology, and protein expression have all been linked to age and associated diseases, and the leading hypothesis for age-related cognitive change is a general loss of synapses. However, the field lacks a detailed understanding of the types of synapses that change during aging, how they change, and how those changes relate to decline in cognition, particularly in humans. We propose that a new model of how synapses change across brain aging is needed. The central objective of this proposal is to provide the first characterization of cortical silent synapse structure, function, and protein expression across aging in both humans and mice. We propose that aging preferentially decreases filopodia, the structural substrate of silent synapses in the adult cortex. We will harness a novel combination of super- resolution imaging, physiological techniques, and artificial neural networks to evaluate filopodial silent synapses over the course of aging. To maximize translational impact, we will compare synapses in non-pathological human tissue with comparable cortical regions in mice using Patch2MAP, a novel method we developed to directly link physiological properties with nanoscale protein expression and morphology. We will execute the following Specific Aims: 1) Evaluate the prevalence of filopodial silent synapses over the course of aging in mice; 2) Define the structural, protein, and physiological properties of human silent synapses; and 3) Establish the relationship between filopodial silent synapses and age-related cognitive decline. The project team’s expertise in cutting- edge physiology and anatomy across species and the MIT/MGH/BWH research environment will ensure successful completion of the proposed experiments. Results from this project have the potential to provide transformative insights into cognitive decline and synaptic function in the aging human brain. They will produce functional, anatomical, and protein expression datasets that will help identify putative drug targets for future pharmacological interventions. Thus, this proposal furthers the mission of the National Institute on Aging, revealing new biological principles for aging-related synaptic changes in the mammalian cortex to facilitate the development of new therapeutic approaches for cognitive decline.


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 = $682,537 )
2026	2026	MASSACHUSETTS INSTITUTE OF TECHNOLOGY	77 MASSACHUSETTS AVE	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Aging Research	000	1	9/17/2026	NEW	$682,537
														Subtotal = $682,537

Grand Total All Awards = $682,537

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Changes in cortical silent synapses and cognitive flexibility over the lifespan of humans and mice

Award Number: R01AG102702

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/20/2026

PERIOD OF PERFORMANCE END DATE: 06/30/2031

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer