Department of Neuromuscular Diseases, University College London, London, United Kingdom
Sophie Skarlatou
Max Delbruck Center for Molecular Medicine, Berlin, Germany
Bianca K Barriga
Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, United States; Biological Sciences Graduate Program, University of California, San Diego, San Diego, United States
B Anne Bannatyne
Institute of Neuroscience and Psychology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom
Gardave Singh Bhumbra
Department of Neuroscience Physiology and Pharmacology, University College London, London, United Kingdom
Joshua D Foster
Department of Neuroscience Physiology and Pharmacology, University College London, London, United Kingdom
Jeffrey D Moore
Howard Hughes Medical Institute and Department of Molecular and Cellular Biology, Center for Brain Science, Harvard University, Cambridge, United States
Camille Lancelin
Department of Neuromuscular Diseases, University College London, London, United Kingdom
Amanda M Pocratsky
Department of Neuromuscular Diseases, University College London, London, United Kingdom
Mustafa Görkem Özyurt
Department of Neuromuscular Diseases, University College London, London, United Kingdom
Calvin Chad Smith
Department of Neuromuscular Diseases, University College London, London, United Kingdom
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.