Interneuron circuits in the spinal motor system

Project Summary:
Neural circuits in the spinal cord serve as the conduit through which the nervous system controls muscle
contraction to implement behavior. Defining spinal circuit organization is therefore central to understanding
the neural control of movement. One major challenge in resolving how spinal circuits direct motor output is
the highly heterogeneous nature of spinal interneurons, which shape fundamental elements of limb movement
underlying locomotion and skilled forelimb behaviors. Because our ability to resolve distinct interneuron cell
types remains limited, little is known about the synaptic and circuit organization of spinal interneurons or their
functional contributions to motor output. We recently discovered that spinal V1 interneurons, the largest
inhibitory interneuron population in the spinal motor system, constitute a molecularly heterogeneous group
that can be segregated into at least four mutually exclusive subsets (clades) defined by expression of the
transcription factors Foxp2, MafA, Pou6f2, and Sp8. V1 clades exhibit restricted and highly stereotyped
positions in the spinal cord, and several show distinct electrophysiological signatures. As such, V1
interneurons represent an ideal system in which to explore general principles of interneuron identity and
circuitry governing motor output, of relevance to other classes of spinal interneurons. Motivated by our
discovery of V1 interneuron diversity, this proposal aims to (1) define the molecular and cellular identity of
these clades and the mechanisms through which this diversity arises, (2) test the hypothesis that descending
motor pathways from the brain differentially innervate V1 clades, and (3) investigate how V1 interneurons
influence one key aspect of motor control – the speed of rhythmic locomotor output. Together, the proposed
experiments address a fundamental gap in knowledge about the identity, circuit organization, and function of
interneurons in the spinal motor system, and serve as a foundation for future efforts aimed at dissecting the
contributions of specific interneuron cell types to motor behavior, of relevance for developmental motor
disorders and spinal cord injury.

Grant Number: 5R01NS123116-05
NIH Institute/Center: NIH
Principal Investigator: Jay Bikoff