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

NCAM drives synaptic remodeling in developing GABAergic neurons in C. elegans

Award Number: F31NS134292
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 12/01/2023
PERIOD OF PERFORMANCE END DATE: 10/31/2026

Group Awards By:

View Award Description

NCAM drives synaptic remodeling in developing GABAergic neurons in C. elegans - Neural circuits are actively restructured during development as synapses are dismantled in some locations and assembled in others. Despite the importance of synaptic remodeling to circuit function, the underlying mechanisms are largely unknown. To investigate this question, we are exploiting the DD GABAergic motor neurons in C. elegans which undergo synaptic remodeling during larval development. In newly hatched larvae, DD presynaptic boutons are initially positioned on ventral muscles but are then relocated over a ~5 hr period to the dorsal DD neurite for input to dorsal muscles. DD remodeling is transcriptionally regulated by the Iroquois-type homeodomain protein, IRX-1. IRX-1 directs synaptic remodeling by upregulating UNC-8, a sodium epithelial channel (ENaC), which triggers a Ca2+-dependent mechanism of presynaptic disassembly. Additional downstream effectors are likely required, however, because UNC-8 dismantles a subset of presynaptic components (RAB3, v-SNARE, liprin-, endophilin) whereas IRX-1 also acts in a parallel pathway to remove additional presynaptic proteins (UNC13, ELKS, Clarinet). To identify additional IRX-1 targets, we used single-cell RNA-Sequencing (scRNA-Seq) to detect transcripts that are upregulated in remodeling DD neurons. An RNAi screen of this dataset detected a necessary role for the neural cell adhesion protein, NCAM-1, in DD synaptic remodeling. A genetic mutant of NCAM-1 impairs both the removal of ventral synapses as well as their reassembly in dorsal DD neurites, thus confirming that NCAM-1 normally promotes remodeling. Considering the established roles of NCAM in vertebrate neural development, my studies of the C. elegans NCAM homolog could reveal conserved mechanisms for synaptic plasticity that also operate in the brain. I hypothesize that NCAM-1 mediates presynaptic disassembly in remodeling GABAergic neurons in parallel to UNC-8. In Aim 1, I will test the role of NCAM-1 as a regulator of presynaptic remodeling using (A) smFISH to determine if ncam-1 is regulated by IRX-1, (B) live-cell imaging of GFP tagged Clarinet in ncam-1 mutants to determine if NCAM-1 functions in a parallel to UNC-8, and (C) GFP-tagged NCAM-1 to determine its location in remodeling DD neurons. In Aim 2, I will use genome-engineering to identify NCAM-1 structural domains that are required for presynaptic disassembly. Additionally, I will use cell-specific RNAi (csRNAi) to determine if ncam-1 function is required in DD neurons for synaptic disassembly. Finally, in Aim 3, I will determine if NCAM-1 is required for recycling of photoconverted (red) dendra2::RAB-3 from ventral to dorsal synapses in remodeling DD neurons. Because the vertebrate homolog of NCAM-1 mediates the removal of GABAergic inputs in the developing cortex, we suggest that the underlying mechanism may be conserved and thus can be molecularly defined by studies in C. elegans.


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 = $32,220 )
2026	2026	VANDERBILT UNIVERSITY	110 21ST AVE S	NASHVILLE	TN	37203	DAVIDSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	1/14/2026	NON-COMPETING CONTINUATION	$32,220
														Subtotal = $32,220

Issue Date FY: 2025 ( Subtotal = $34,851 )
2025	2025	VANDERBILT UNIVERSITY	110 21ST AVE S	NASHVILLE	TN	37203	DAVIDSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	12/19/2024	NON-COMPETING CONTINUATION	$34,287
2025	2025	VANDERBILT UNIVERSITY	110 21ST AVE S	NASHVILLE	TN	37203	DAVIDSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	2	8/5/2025	NON-COMPETING CONTINUATION	$564
														Subtotal = $34,851

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2023	VANDERBILT UNIVERSITY	110 21ST AVE S	NASHVILLE	TN	37203	DAVIDSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	12/27/2023	NEW	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $32,989 )
2023	2023	VANDERBILT UNIVERSITY	110 21ST AVE S	NASHVILLE	TN	37203	DAVIDSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	1	7/18/2023	NEW	$0
2023	2023	VANDERBILT UNIVERSITY	110 21ST AVE S	NASHVILLE	TN	37203	DAVIDSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	7/18/2023	NEW	$32,989
														Subtotal = $32,989

Grand Total All Awards = $100,060

Top

All Categories

About

Search

Reports

Data Submission

Award Information

NCAM drives synaptic remodeling in developing GABAergic neurons in C. elegans

Award Number: F31NS134292

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 12/01/2023

PERIOD OF PERFORMANCE END DATE: 10/31/2026

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer