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The role of Renshaw cells and recurrent inhibition during motor behaviors

Award Number: R56NS147432
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: 09/01/2026
PERIOD OF PERFORMANCE END DATE: 08/31/2027

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The role of Renshaw cells and recurrent inhibition during motor behaviors - SUMMARY Motor output from the spinal cord directs coordinated limb movements and is ultimately controlled by a local output-regulating microcircuit that includes flexor and extensor motoneurons, Ia reciprocal inhibitory interneurons and Renshaw cells. Despite decades of accrued knowledge on connectivity, synaptic interactions and recruitment of interneurons within this microcircuit there is still a surprising lack of validated hypothesis describing their contribution during motor actions in freely behaving animals. This gap in knowledge has gained increased relevance recently as these interneurons have been implicated in many motor dysfunctions, including spasticity or ineffective posture and balance in older age, as well as motor deficits after stroke, spinal cord injury, and amyotrophic lateral sclerosis. Particularly surprising is that the role(s) played by Renshaw cells in motor control are still open to debate, despite being the first inhibitory interneuron ever discovered and placed in a well-defined synaptic circuit of the mammalian central nervous system. Renshaw cells mediate recurrent inhibition of motoneurons and their connectivity has been thoroughly described, including their modulation of Ia inhibitory interneurons mediating reciprocal inhibition between antagonists at single joints. Nevertheless, Renshaw cells influence during the execution of motor actions is still debated, leading some to even question whether they have a discernable function at all. We suggest the principal reason for slow progress has been the lack of methods to interfere with their function while recording motoneuron activity and movement in unrestrained behaving animals. This capability would allow to move from correlative hypotheses to causality demonstrations of their exact impact controlling motor output and movement. Two recent methodological developments overcome these limitations. First, the Alvarez lab generated several new mouse models to manipulate the function of Renshaw cells in adult animals. Second, the Sober lab developed new Myomatrix flexible multielectrode arrays that can be chronically implanted in the small muscles of mice to record electromyographic activity in unanesthetized behaving animals. These devices can be employed alongside new spike sorting algorithms that improve extraction of single motor unit activity and with machine-learning methods to describe in detail ongoing movement kinematics. Using these tools the Alvarez-Sober team proposes to investigate the action of Renshaw cells on modulating motor unit output during behavior, using treadmill locomotion and postural adjustments as valuable motor tasks. The main hypothesis is that Renshaw cells are multiplexing interneurons controlling motor output across several spatial and time scales while being modulated by descending inputs in a task-dependent manner. We will analyze in three Aims their roles in motor unit recruitment and millisecond spike timing (Aim 1), motor pool recruitment and shaping of muscle sequential activation (Aim 2) and control of co-contraction of antagonists during postural adjustments (Aim 3). The results will lend experimental support to past and new theories about their roles during motor function and dysfunction to finally move forward the debate on Renshaw cells actions.


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 = $534,557 )
2026	2026	EMORY UNIVERSITY	201 DOWMAN DR NE	ATLANTA	GA	30322	DEKALB	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	8/13/2026	NEW	$534,557
														Subtotal = $534,557

Grand Total All Awards = $534,557

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The role of Renshaw cells and recurrent inhibition during motor behaviors

Award Number: R56NS147432

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: 09/01/2026

PERIOD OF PERFORMANCE END DATE: 08/31/2027

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