The highly orchestrated muscle activation sequences during motor behaviors are achieved directly through the fine-tuned firing of motor neurons in the ventral spinal cord. These motor neurons are mainly regulated by spinal interneurons present in all mammals, which are, in turn, connected to other spinal neurons as well as various types of descending neurons from the brain, such as corticospinal (CS), reticulospinal and rubrospinal neurons. Until recently, the identities and functioning of the interneuron subtypes and descending neurons participating in individual circuits had remained elusive. What remains lacking is knowledge of the arrangement and functional role of the spinal interneuron subtypes in individual circuits. There is, therefore, a critical need to determine the anatomical and functional connectivity of these spinal interneuron subtypes and how they regulate motor behaviors. Our overall objectives in this application are to (i) map anatomical and functional connectivity of different classes of spinal interneurons (Aims 1 & 2), and (ii) elucidate how those interneurons effect motor behaviors (Aim 3). Our central hypothesis is that each interneuron subtype will exhibit preferential connections with distinct descending neurons to control discrete forms of locomotor and skilled movements.
Motor circuits such as corticospinal circuits are essential for skilled movement, and spinal interneurons mediate the information to motor neurons. In humans, interruption of motor circuits caused by spinal cord injury, stroke, or other disorders results in severe deficits in most fine motor skills. Therefore, understanding the cellular and molecular mechanisms underlying motor circuits including spinal interneurons will provide important information for developing new therapeutic avenues for addressing diseases and injuries related to motor or spinal circuits in humans.