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

Abstract

Proprioception, the sense of limb and body position, is required to produce accurate and precise movements. Proprioceptive sensory neurons transmit muscle length and tension information to the spinal cord. The function of excitatory neurons in the intermediate spinal cord, which receive this proprioceptive information, remains poorly understood. Using genetic labeling strategies and patch clamp techniques in acute spinal cord preparations in mice, we set out to uncover how two sets of spinal neurons, Clarke's column (CC) and Atoh1-lineage neurons, respond to electrical activity and how their inputs are organized. Both sets of neurons are located in close proximity in lamina V-VII of the thoracolumbar spinal cord and have been described to receive proprioceptive signals. We find that a majority of CC neurons have a tonic firing-type and express a distinctive hyperpolarization-activated current (I_h). Atoh1-lineage neurons, which cluster into two spatially distinct populations, are mostly a fading firing-type and display similar electrophysiological properties to each other, possibly due to their common developmental lineage. Finally, we find that CC neurons respond to stimulation of lumbar dorsal roots, consistent with prior knowledge that CC neurons receive hindlimb proprioceptive information. In contrast, using a combination of electrical stimulation, optogenetic stimulation, and transsynaptic rabies virus tracing, we found that Atoh1-lineage neurons receive heterogeneous, predominantly local thoracic inputs that include Parvalbumin-lineage sensory afferents and local interneuron presynaptic inputs. Altogether, we find that CC and Atoh1-lineage neurons have distinct membrane properties and sensory input organization, representing different subcircuit modes of proprioceptive information processing.

Significance Statement How excitatory spinal cord neurons in the intermediate spinal cord integrate and relay proprioceptive sensory information is not well understood. Our investigation focuses on two sets of spinal neurons that receive proprioceptive information, but whose electrophysiological response properties have not been previously described. We characterize both their passive and active electrophysiological properties in addition to their input connectivity. We identify unique electrophysiological signatures of each population as well as features of their input organization. We find that a hyperpolarization-activated current distinguishes Clarke's column neurons and that Atoh1-lineage neurons receive predominantly local inputs. These experiments lay the foundation for future endeavors aimed at understanding the mechanisms by which proprioceptive information is integrated and relayed through these neurons.