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A novel form of proprioception mediated by piezo2b-expressing premotor neurons in larval zebrafish

Award Number: R21NS153150
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/10/2026
PERIOD OF PERFORMANCE END DATE: 08/31/2028

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A novel form of proprioception mediated by piezo2b-expressing premotor neurons in larval zebrafish - PROJECT SUMMARY Proprioceptive sensing of the position, movement, and force experienced by one’s body is essential for coordinated behavior. While mammalian proprioceptors that innervate skeletal muscle and joints have been thoroughly studied, the recent discovery of two previously unknown proprioceptive pathways in zebrafish highlights the possibility that additional mechanisms remain to be identified. This idea gains additional support from the observation that mechanosensitive ion channels, including members of the Piezo receptor family, are expressed and confer pressure sensitivity to a much broader range of cell types than initially thought, including many neurons with no known sensory function. In characterizing the molecular features of a population of premotor reticulospinal neurons (RSNs) in the zebrafish brainstem, we discovered a subset of cells that is uniquely defined by expression of piezo2b, the fish ortholog of mammalian Piezo2. In situ hybridization revealed that this cell group includes neurons located in the nucleus of the medial longitudinal fascicle (nMLF), which project to distal regions of the spinal cord and directly control swim velocity and tail deflection amplitude in proportion to their firing rate. Because Piezo receptors confer mechanical sensitivity to every cell in which they have been investigated, our observations strongly suggest that the nMLF is capable of sensing physical forces, possibly including those exerted on its descending axons as the animal bends its tail laterally while swimming. We hypothesize that piezo2b enables a novel and cell-intrinsic form of proprioception mediated by the premotor neurons in nMLF, in which cell firing is enhanced by pressure generated due to axonal bending during tail movement. To test this idea we will determine whether piezo2b renders nMLF neurons sensitive to pressure applied to their cell soma or axons, measure the behavioral effects of pharmacological and genetic perturbations of piezo2b function, and create new transgenic lines to allow conditional manipulation of piezo2b function and of the neurons that express it. The outcomes of this award will include a clear demonstration of piezo2b’s ability to encode pressure within an ostensibly “non-sensory” premotor network, essential evidence for a novel proprioceptive function of these cells, and a new set of genetic tools that will enable more detailed mechanistic investigation of our central hypotheses, as well as piezo2b’s other physiological and behavioral functions.


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 = $423,500 )
2026	2026	UNIVERSITY OF UTAH	201 PRESIDENTS CIR	SALT LAKE CITY	UT	84112	SALT LAKE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	9/10/2026	NEW	$423,500
														Subtotal = $423,500

Grand Total All Awards = $423,500

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A novel form of proprioception mediated by piezo2b-expressing premotor neurons in larval zebrafish

Award Number: R21NS153150

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/10/2026

PERIOD OF PERFORMANCE END DATE: 08/31/2028

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