MECHANISMS OF LOCOMOTOR RHYTHM GENERATION IN RODENT SPINAL CORD
NIH/NINDS R01 NS130799; 09/30/2022 - 07/31/2027
PIs: Dougherty KJ, Rybak IA
Locomotion is a fundamental behavior that allows humans and animals to move through their environments and is critically involved in all aspects of life. This behavior is impeded in a number of diseases, disorders, and injuries, including spinal cord injury, stroke, and various ataxias. All of the essential circuity to generate locomotor rhythm and pattern is located in the thoracolumbar spinal cord, most often below the level of neural damage. These circuits can be accessed directly via various central and peripheral stimulation methods, including but not limited to epidural stimulation.
CRCNS US-FRENCH RESEARCH PROPOSAL: BRAINSTEM-SPINAL CIRCUITS FOR CONTROL OF LOCOMOTOR STEERING
NSF 2113069; 10/01/2021 - 09/30/2025
PIs: Ausborn J, Bouvier J; Co-PI: Rybak IA
The ability to move within the environment is essential for the survival of all animals, including humans. In mammals, the neurons that generate and drive locomotor movements reside in the spinal cord, and these spinal networks are controlled by upstream signals from the brainstem. Most studies of neural control of locomotion in mammals have focused on straight-trajectory forward locomotion. However, how brainstem and spinal neural networks control turning movements remains poorly understood. This study will investigate this question, using a combination of experimental and computational approaches.
IMPROVING BREATHING WITH LIMB MUSCLE STIMULATION AFTER CERVICAL SCI
Pennsylvania Department of Health, SAP # 4100089343; 6/01/2021- 5/31/2023
PI: Bezdudnaya T; Co-PI: Rybak IA
The long-term goals of this project are to investigate the organization of spinal respiratory circuits, evaluate conditions for activation of breathing by stimulation of limb muscle afferents in intact and injured spinal cord, and develop a novel computational model of the respiratory system. This model will include both supraspinal and spinal levels of respiratory control, afferent inputs from limb muscles, and reproduce all experimental data. The experiments will be performed in adult decerebrate rats in vivo in close interaction with computational modeling studies conducted in parallel.
PROPRIOPSINAL NEURON FUNCTION IN NORMAL AND POST-SCI LOCOMOTION
NIH/NINDS R01 NS112304; 03/15/2021 - 01/31/2026
PIs: Danner SM, Magnuson DS, Whittemore SR
Despite the more than 100 years since the recognition of intrinsic spinal locomotor circuits, many of the functional details of those circuits and their contributions to recovery following spinal cord injury (SCI) remain to be determined. Recent development of powerful molecular tools enables functional dissection of neural circuitry via reversibly silencing neurotransmission and trans-synaptic labeling. We will combine these tools with sophisticated gait and kinematic analyses, that includes the full repertoire of speed dependent gaits, to provide the functional and anatomical information necessary for building and refining an advanced neurobiomechanical computer model of the rat spinal cord, body and limbs.
Spinal circuits for sensorimotor integration and interlimb coordination during locomotion
NIH/NINDS R01 NS115900; 09/21/2020 - 06/30/2025
PI: Danner SM; Co-PI: Akay T
Somatosensory feedback from the limbs is essential for locomotion and its recovery after spinal cord injury. To achieve stable locomotion, the spinal cord needs to process afferent feedback signals and properly adjust muscle activation and interlimb coordination. But the interactions of somatosensory feedback with the spinal circuitry during locomotion have yet to be understood on the same level of detail.
Limb coordination during locomotion before and after spinal cord injury
NIH/NINDS R01 NS110550; 02/15/2020 - 01/31/2025
PIs: Rybak IA, Frigon A, Prilutsky BI
Interlimb coordination is essential for maintaining balance when navigating in complex and/or changing environments. It involves complex dynamic interactions between neural circuits at different levels of the nervous system and biomechanical properties of the musculoskeletal system to allow animals to adjust locomotor speed and gait for goal-oriented behaviors. Interactions within the nervous system include those between the spinal circuits controlling each limb, supraspinal inputs and sensory feedback from the limbs.