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Molecular Dissection of Proprioceptor Subclass Identity

Award Number: R01NS106715
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: 03/01/2019
PERIOD OF PERFORMANCE END DATE: 11/30/2029

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Molecular Dissection of Proprioceptor Subclass Identity - SUMMARY The proprioceptive sense relies on multiple sensory subtypes that relay information from skin, joint, or muscle, to best estimate changes in limb dynamics. Proprioceptive muscle afferents - arguably representing the primary input into this sensory system – derive their sensory feedback information from two specialized mechano- receptive end-organs in skeletal muscle: muscle spindles (MSs), and Golgi tendon organs (GTOs). These end- organs respond to changes in muscle length or tension, respectively, and this information is routed to spinal and supraspinal motor centers through MS-groups Ia and II afferents, and GTO-group Ib afferents, which each relay qualitatively distinct features of limb state (e.g., movement speed, position, effort). The combined afferent feedback is used by central somatosensory and motor circuits to compute changes in limb state during passive or voluntary movement, and to correct the motor plan if needed. Despite their importance in movement control, how individual proprioceptor subtypes emerge during development remains poorly understood. Two opposing ideas are considered. First, it has been postulated that proprioceptive muscle afferent subtypes are genetically predetermined, meaning that their MS-group Ia or II, or GTO-group Ib identity, is fixed from the moment these neurons become post-mitotic. Recent data however, including from our lab, have led to the hypothesis that proprioceptive neurons adopt their specific subtype identity only after they innervate their cognate peripheral receptors, possibly instructed by signals from nascent MS or GTO end-organs or through activity-dependent mechanisms. This proposal aims to test this idea through three parallel aims that examine intrinsic proprioceptor transcriptomic and epigenetic dynamics i) prior to and just following end-organ innervation, ii) in the absence of extrinsic end-organs derived signals, or iii) when neural activity is compromised. Together, these experiments will identify the transcriptional and epigenetic signatures of proprioceptors as they undergo their developmental transitions to assume MS- or GTO-afferent subtype identities, and provide insight into the relevant signals that are needed to coordinate this process or to maintain these identities. The results should lead to an expansion of the genetic and molecular tools to study proprioceptor function. Moreover, given recent demonstrations that epidural stimulation of proprioceptive pathways benefits patients suffering from spinal cord injury, a better understanding of the developmental cues that promote one proprioceptor subtype over another may permit the selective stimulation/repurposing of those proprioceptor subtypes that are especially beneficial for recovery.


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 = $559,578 )
2026	2026	THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	7	1/15/2026	NON-COMPETING CONTINUATION	$559,578
														Subtotal = $559,578

Issue Date FY: 2025 ( Subtotal = $605,429 )
2025	2025	THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	6	11/29/2024	COMPETING CONTINUATION	$605,429
2025	2023	THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	5	5/14/2025	NON-COMPETING CONTINUATION	$0
2025	2023	THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	11/21/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $605,429

Issue Date FY: 2023 ( Subtotal = $354,375 )
2023	2023	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, THE	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	5	3/8/2023	NON-COMPETING CONTINUATION	$354,375
2023	2022	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, THE	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	3/8/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $354,375

Issue Date FY: 2022 ( Subtotal = $354,375 )
2022	2022	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, THE	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	2/17/2022	NON-COMPETING CONTINUATION	$318,938
2022	2022	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, THE	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	4	3/24/2022	NON-COMPETING CONTINUATION	$35,437
														Subtotal = $354,375

Issue Date FY: 2021 ( Subtotal = $354,375 )
2021	2021	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, THE	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	2/23/2021	NON-COMPETING CONTINUATION	$354,375
														Subtotal = $354,375

Issue Date FY: 2020 ( Subtotal = $354,375 )
2020	2020	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	2/21/2020	NON-COMPETING CONTINUATION	$354,375
														Subtotal = $354,375

Issue Date FY: 2019 ( Subtotal = $354,375 )
2019	2019	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	2/7/2019	NEW	$354,375
														Subtotal = $354,375

Grand Total All Awards = $2,936,882

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Molecular Dissection of Proprioceptor Subclass Identity

Award Number: R01NS106715

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: 03/01/2019

PERIOD OF PERFORMANCE END DATE: 11/30/2029

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