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

Synaptic function programs in neuron-astrocyte co-cultures from human post-mortem brain tissue

Award Number: R21MH141189
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2026
PERIOD OF PERFORMANCE END DATE: 08/31/2028

Group Awards By:

View Award Description

Synaptic function programs in neuron-astrocyte co-cultures from human post-mortem brain tissue - Compelling evidence establishes synaptic pathology as a central convergence point for a growing number of psychiatric, neurodevelopmental and neurodegenerative brain disorders. While there is broad agreement that synaptic functions require cooperation between neurons and astrocytes, investigations on synaptic pathology have largely focused on distinct cellular components. We showed multicellular, concerted gene expression programs supporting synaptic functions in neurons and astrocytes. We call these coordinated gene expression programs ‘Synaptic Neuron Astrocyte Program’ (SNAP). SNAP is enriched in risk variants for schizophrenia and is reduced in this disorder and in aging. SNAP points to the importance of investigating synaptic dysfunction in the context of multicellular interactions between neurons and glial cells. Given the complexity and heterogeneity of brain disorders, human-derived models of the brain such as induced Pluripotent Stem Cells (iPSCs), that can be manipulated in experiments, are uniquely informative to understand brain disease biology. However, the extent to which cells in culture recapitulate human brain biology remains unresolved. At least in part, this is due to challenges in studying cell interactions under different experimental paradigms yet in the same persons. Here, we combine state-of-the-art approaches developed by our groups to generate primary human astrocyte cultures as well as human iPSC-derived astrocytes and neurons from the same human postmortem brain tissue. Primary astrocytes are isolated from the frontal lobe, dura mater-derived fibroblasts from the same donor are reprogrammed into iPSCs (dm-iPSCs) and differentiated into astrocytes and neurons Our long-term goal is to illuminate the role of multicellular programs involved in human brain biology and disease, including synaptic functions in the health brain and disease. Our hypothesis is that gene expression programs supporting synaptic functions are dynamically orchestrated across neurons and astrocytes. Built in these experiments is a rigorous validation of human-derived neuron-astrocyte co-cultures as a tool for investigations on cell-to-cell synaptic mechanisms and synaptopathology in brain disorders. In Aim 1 we will use single nucleus RNA sequencing to compare mono-cultures of human primary astrocytes and dm-iPSC-derived astrocytes and neurons to their cell counterparts in cortical tissue from the same donors. In Aim 2, similar assays will be carried out on co-cultures of human astrocytes (primary and dm-iPSCs) and dm-iPSC-Neurons from the same donors. These studies will offer the first evidence for the feasibility and relevance of human-derived primary and iPSC- derived multicellular models of synaptic functions. Their rigor will be supported by direct comparison of gene expression programs and canonical protein expression from the same donors and specific brain regions of origin. Their broad impact and applicability reside in the convergence of synaptopathies in a growing number of brain disorders and in their potential to further validate and enhance the use of iPSCs from live donors.


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 = $463,229 )
2026	2026	THE MCLEAN HOSPITAL CORPORATION	115 MILL ST	BELMONT	MA	02478	MIDDLESEX	USA	Mental Health Research Grants	000	1	8/28/2026	NEW	$463,229
														Subtotal = $463,229

Grand Total All Awards = $463,229

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Synaptic function programs in neuron-astrocyte co-cultures from human post-mortem brain tissue

Award Number: R21MH141189

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/01/2026

PERIOD OF PERFORMANCE END DATE: 08/31/2028

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer