Thursday, July 3, 2025 7/3/2025

The encoding of proprioceptive signaling by Nav1.6

Award Number: F31NS134241
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: 05/01/2024
PERIOD OF PERFORMANCE END DATE: 04/30/2026

Group Awards By:

View Award Description

The encoding of proprioceptive signaling by Nav1.6 - Project Summary: The long-term objective of this work is to define the molecular mechanisms underlying proprioceptive signaling that are required for sensory-driven motor behaviors. Proprioception encodes body and limb position, which is essential for purposeful movement. Yet, the lack of tools to selectively target genes in proprioceptors, the sensory neurons that carry proprioceptive signals, has impeded our understanding of the molecular mechanisms underlying this vital sixth sense. Voltage-gated sodium channels (NaVs) are critical for neuronal signaling in the nervous system, and proprioceptors express three isoforms: NaV1.1, NaV1.6, and NaV1.7. We recently discovered that loss of NaV1.1 in sensory neurons causes ataxic-like behaviors and abnormal limb positioning and impaired proprioceptor transmission during static muscle stretch. While loss of NaV1.7 has no impact on motor function in mice or humans, NaV1.6 is known to contribute to the function of brain neurons involved in motor control. Thus, our lab created a sensory neuron-wide knock out of NaV1.6 and found that these animals have extremely severe motor coordination deficits distinct from those observed in NaV1.1 conditional knockout animals. This proposal will uncover the mechanistic role of NaV1.6 in proprioceptive signaling by developing the first CRISPR/Cas9 intersectional genetic and viral strategy to manipulate genes in selectively proprioceptors. The work outlined herein will test the central hypothesis that the unique cellular localization patterns and intrinsic properties of NaV1.6 underly the transmission of proprioceptive signals to spinal motor circuits for motor behaviors. I test this hypothesis using the following mechanistic aims: Aim 1 will analyze the cellular distribution patterns of NaV1.6 channels in proprioceptive sensory neurons. Aim 2 will investigate how loss of NaV1.6 changes proprioceptor biophysical properties and excitability. Aim 3 will leverage an intersectional gene knock out model to investigate how acute deletion of NaV1.6 proprioceptors affects sensory-motor circuit function and motor behaviors, overcoming a long-standing challenge in the field. NaV1.6 is associated with brain-related diseases like epilepsy and autism spectrum disorder. Symptoms of these diseases include motor-related deficits; however, our understanding of the mechanisms that give rise to these comorbidities outside the brain is understudied. The proposed herein are directly in line with the goals of NINDS as it will 1) advance our knowledge about mammalian proprioception and 2) shed new light on critical roles of peripheral sensory neuron signaling in neurological disorders. Furthermore, this proposal will not only provide critical me new training in molecular biology and biochemistry techniques, but also offer the scientific community a new and exciting approach to gene manipulation in challenging- to-target neuronal populations.


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 = $22,871 )
2025	2025	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR STE 300	DAVIS	CA	95618	YOLO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	5/30/2025	NON-COMPETING CONTINUATION	$22,871
														Subtotal = $22,871

Issue Date FY: 2024 ( Subtotal = $41,972 )
2024	2024	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR STE 300	DAVIS	CA	95618	YOLO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	1	5/8/2024	NEW	$0
2024	2024	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR STE 300	DAVIS	CA	95618	YOLO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	1	5/8/2024	NEW	$1,280
2024	2024	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	4/11/2024	NEW	$40,692
														Subtotal = $41,972

Grand Total All Awards = $64,843

Top

All Categories

About

Search

Reports

Data Submission

Award Information

The encoding of proprioceptive signaling by Nav1.6

Award Number: F31NS134241

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: 05/01/2024

PERIOD OF PERFORMANCE END DATE: 04/30/2026

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer