Electrophysiological properties of neurons in the intermediate thoracolumbar spinal cord mediating proprioception.

Abstract

Animals must know where their body is in relationship to their environment to move appropriately. Proprioception, the sense of limb and body position, is required to produce feedforward predictions of future movement as well as provide feedback information during movement to update the system. How proprioception is processed at the level of the spinal cord is not well understood. Most work has focused on Clarkes column (CC) neurons, a component of the dorsal spinocerebellar tract (DSCT). CC neurons receive hindlimb proprioceptive information and send it directly to the cerebellum with no axon collaterals to other neurons in the spinal cord. In contrast to CC neurons, we previously found that a subset of thoracolumbar Atoh1-lineage neurons also receives proprioceptive afferent inputs, but project locally within the spinal cord including synapsing on motor neurons. We set out to understand how CC and Atoh1-lineage neurons in the thoracolumbar spinal cord respond to electrical activity. Using in vitro acute spinal cord slices and whole-cell patch clamp, we characterized the passive and active electrical properties of CC and thoracolumbar Atoh1-lineage neurons. We find that most CC neurons increase their action potential firing frequency linearly upon increased current injection up to high frequencies likely due to a hyperpolarization-activated current (Ih). In contrast, most Atoh1-lineage neurons do not have an Ih current and therefore, their firing frequency fades with increasing current injection. Interestingly, although Atoh1-lineage neurons are classically subdivided into a contralaterally-projecting Medial and ipsilaterally-projecting Lateral population, we find no obvious electrophysiological signatures that could distinguish these spatially distinct populations. Finally, we set out to determine the organization of the inputs to CC and Atoh1-lineage neurons. In a hemisected spinal cord preparation, while recording from neurons in the lower thoracic to upper lumbar segments, we find that CC neurons receive low threshold inputs (proprioceptive or low threshold mechanoreceptor) from lumbar 2 to 4 dorsal roots, while Atoh1-lineage Medial neurons do not. This raises the possibility that Atoh1-lineage Medial neurons receive proprioceptive inputs from more local dorsal roots. Altogether, we find that CC and Atoh1-lineage neurons have distinct membrane properties and sensory input organization even though they are both reported to receive proprioceptive information and are in close proximity in lamina V-VII of the thoracolumbar spinal cord.