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Molecular mechanisms of somatosensory adaptation to prolonged hypothermia

Award Number: R01NS132868
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: 12/21/2023
PERIOD OF PERFORMANCE END DATE: 11/30/2028

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Molecular mechanisms of somatosensory adaptation to prolonged hypothermia - Project Summary/Abstract Mechanosensitivity and mechanotransduction are fundamental processes that affect virtually all aspects of human physiology. Sensitivity to mechanical stimuli ranges from light touch to unpleasant or painful and relies on the ability of primary sensory afferents to transduce these stimuli into electrical signaling. In humans, dysfunctions of the somatosensory system have only symptomatic or palliative care, largely because the molecular and cellular aspects of mechanosensitivity and mechanotransduction, and the sequence of events that underlies somatosensory tuning remain enigmatic. Our long-term goal is to understand general principles somatosensory mechanotransduction under normal, adaptive, and pathological conditions. In this collaborative basic scientific proposal, we seek to uncover the mechanism underlying adaptations of mammalian mechanosensory system to cold. We will approach this problem using a novel model organism— hibernating thirteen-lined ground squirrel (Ictidomys tridecemlineatus). Despite the prolonged severe hypothermia during hibernation, when body temperature drops to less than 10°C, squirrels maintain the ability to detect mechanical force and can be aroused by touch and vibration. The endurance of the sense of touch despite prolonged hypothermia supports the existence of specific molecular and cellular adaptations at the level of peripheral mechanoreceptors. We seek to uncover these adaptations by biophysical analysis of ion channels in peripheral mechanoreceptors that determine baseline excitability, convert touch into excitation and generate and propagate action potential, implementing a mechanosensory tune-up that preserve touch sensitivity despite prolonged exposure to cold. This proposal will elucidate tunable molecular pathways in mammalian mechanosensory neurons to inform clinical practices mitigating somatosensory dysfunctions following hypothermia or nerve damage.


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 = $490,732 )
2026	2026	YALE UNIV	150 MUNSON ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	12/23/2025	NON-COMPETING CONTINUATION	$490,732
														Subtotal = $490,732

Issue Date FY: 2025 ( Subtotal = $490,660 )
2025	2025	YALE UNIV	150 MUNSON ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	11/22/2024	NON-COMPETING CONTINUATION	$490,660
														Subtotal = $490,660

Issue Date FY: 2024 ( Subtotal = $556,452 )
2024	2024	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	12/22/2023	NEW	$556,452
														Subtotal = $556,452

Grand Total All Awards = $1,537,844

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Molecular mechanisms of somatosensory adaptation to prolonged hypothermia

Award Number: R01NS132868

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: 12/21/2023

PERIOD OF PERFORMANCE END DATE: 11/30/2028

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