Sensorimotor circuit integration: 5-HTR6+ interneurons in spinal cord function and adaptation - sensorimotor circuit integration in the spinal cord is crucial for normal motor function and…

The National Institute of Neurological Disorders and Stroke awarded Rutgers, The State University $118,593 on September 1, 2026, under the Extramural Research Programs in the Neurosciences and Neurological Disorders program (CFDA 93.853, Assistance Listing).

The award funds research investigating the role of dorsal horn interneurons expressing the serotonin 6 receptor (5HTR6+ interneurons) in sensorimotor integration within the spinal cord under both normal conditions and following spinal cord injury. The research employs mouse genetics, chemogenetics, and behavioral analysis to explore how these interneurons contribute to sensory processing and motor output in intact and injured spinal cords. The hypothesis is that 5HTR6+ interneurons contribute to sensorimotor integration in normal conditions and are remodeled during rehabilitation following spinal cord injury to promote adaptive plasticity and improve motor function. Research activities include mapping the functional connectivity of 5HTR6+ interneurons in normal and injured spinal cords using targeted neural tracing techniques and synaptic analysis methods.

The period of performance runs from September 1, 2026, through August 31, 2029. Work is performed in Piscataway, New Jersey.

Sensorimotor circuit integration: 5-HTR6+ interneurons in spinal cord function and adaptation - sensorimotor circuit integration in the spinal cord is crucial for normal motor function and adaptation after spinal cord injury (SCI). Post-SCI rehabilitation enhances functional motor recovery and is associated with the plasticity of spared spinal circuits. Understanding the complex sensorimotor networks within the spinal cord is crucial for advancing our knowledge of system-level integration of sensory processing and motor control. This proposal aims to investigate the role of dorsal horn interneurons expressing the serotonin 6 receptor (5HTR6+ interneurons) in sensorimotor integration under both normal conditions and following SCI. 5HTR6+ interneurons, located at the nexus of descending serotonergic modulation, sensory afferent input, and premotor network communication, are uniquely positioned to influence sensorimotor circuits. Using a combination of mouse genetics, chemogenetics, and behavioral analysis, we will explore how these interneurons contribute to sensory processing and motor output in intact and injured spinal cords. The hypothesis of this proposal is that 5HTR6+ interneurons contribute to sensorimotor integration in normal conditions and are influenced by rehabilitation to promote adaptive plasticity post-SCI. Aim 1 both aims complement each other synergistically while maintaining their individual significance. Will test the hypothesis that the functional input and output connectivity of these interneurons is remodeled during rehabilitation following SCI improving motor function. This will provide insights into how these interneurons integrate sensory and modulatory information in both intact and reorganized circuits. Aim 1's training potential functional connectivity of 5HTR6+ interneurons in normal and injured spinal cords using lies in mapping the targeted neural tracing techniques, synaptic analysis methods, and interpretation of complex neuroanatomical data. In aim 2 ,i hypothesize that the manipulation of the interneuron's activity in intact spinal cords will modulate corrective motor responses while during rehabilitation post SCI IT will improve functional recovery whilst promoting adaptive plasticity. Aim 2's training potential is rooted in chemogenetic manipulation of 5HTR6+ interneurons along with advanced behavioral analyses, computerized gait assessments, and balance beam testing in intact, post-injury, and rehabilitation states. Together, these aims provide a comprehensive understanding of these interneurons' importance in sensorimotor integrations and SCI recovery, yet each aim can yield valuable insights independently of the other. Overall, this research will elucidate fundamental mechanisms of sensorimotor circuit function and plasticity, focusing on system-level integration rather than cellular or molecular mechanisms. The high training potential of these aims has been carefully designed to fill my GAP based knowledge. This work deepens our understanding of spinal cord circuitry and adaptability, informing future research on motor control and sensory processing across various contexts while aligning closely with the ninds mission to reduce neurological diseases burden and potentially improving therapeutic strategies.