Descending systems direct development of key spinal motor circuits

The formation of mature spinal motor circuits is dependent on both activity dependent and independent mechanisms during postnatal development. During this time, reorganisation and refinement of spinal sensorimotor circuits occurs as supraspinal projections are integrated. However, specific features of postnatal spinal circuit development remain poorly understood. This study provides the first detailed characterisation of rat spinal sensorimotor circuit development in the presence and absence of descending systems. We show that development of proprioceptive afferent (PA) input to motoneurones (MN) and Renshaw cells (RC) is disrupted by thoracic spinal cord transection (TX) at postnatal day 5 (PN5). PN5TX also lead to malformation of GABApre neuron axo-axonic contacts on Ia afferents and the recurrent inhibitory circuit between MN and RC. Using a novel in situ perfused preparation for studying motor control, we show that malformation of these spinal circuits leads to hyperexcitability of the monosynaptic reflex. Our results demonstrate that removing descending input severely disrupts development of spinal circuits and identifies key mechanisms contributing to motor dysfunction in conditions such as cerebral palsy and spinal cord injury. Significance statement Acquisition of mature behaviour during postnatal development correlates with arrival and maturation of supraspinal projections to the spinal cord. However, we know little about the role descending systems play in maturation of spinal circuits. Here, we characterise postnatal development of key spinal microcircuits in the presence and absence of descending systems. We show that formation of these circuits is abnormal following early (PN5) removal of descending systems, inducing hyperexcitability of the monosynaptic reflex. The study is a detailed characterisation of spinal circuit development elucidating how these mechanisms contribute to motor dysfunction in conditions such as cerebral palsy and spinal cord injury. Understanding these circuits is crucial to develop new and improve current therapeutics in such conditions.