Spinal premotor interneurons controlling antagonistic muscles are spatially intermingled.

Elaborate behaviours are produced by tightly controlled flexor-extensor motor neuron activation patterns. Motor neurons are regulated by a network of interneurons within the spinal cord, but the computational processes involved in motor control are not fully understood. The neuroanatomical arrangement of motor and premotor neurons into topographic patterns related to their controlled muscles is thought to facilitate how information is processed by spinal circuits. Rabies retrograde monosynaptic tracing has been used to label premotor interneurons innervating specific motor neuron pools, with previous studies reporting topographic mediolateral positional biases in flexor and extensor premotor interneurons. To more precisely define how premotor interneurons contacting specific motor pools are organized, we used multiple complementary viral-tracing approaches in mice to minimize systematic biases associated with each method. Contrary to expectations, we found that premotor interneurons contacting motor pools controlling flexion and extension of the ankle are highly intermingled rather than segregated into specific domains like motor neurons. Thus, premotor spinal neurons controlling different muscles process motor instructions in the absence of clear spatial patterns among the flexor-extensor circuit components.
Competing Interests: RR, SS, BB, BB, GB, JF, JM, CL, AP, MÖ, AT, DM, SP, NZ, MB No competing interests declared, CS is currently an employee of Sania therapeutics. His work is not related to that reported in this manuscript, AM is a co-founder of Sania Therapeutics. His work is not related to that reported in this manuscript. AM has founders stock in Sania Therapeutics, Ltd, RB has a grant from Medical Research Council, is a a co-founder of the parent company, Sania Therapeutics, Ltd. Work not related to that reported in this manuscript. RB is as an Associate Editor for Journal of Neurophysiology, has a patent (18 July, 2020, Priority patent GB 2010981.5; published 20 Jan, 2022, WO/2022/013396 "Gene therapy for neuromuscular and neuromotor disorders") unrelated to this manuscript and is an unpaid Trustee for Stoke Mandeville Spinal Research, International Spinal Research Trust and Scientific Advisory Board, Brain Research UK. RB has founders stock in Sania Therapeutics, Ltd
(© 2022, Ronzano, Skarlatou, Barriga et al.)