Spinal circuitry underlying crossed reflex

Abstract

Sensory information is used to generate various behaviour including protective and corrective reflexes. Following perturbation in one leg, motor activity can be elicited in the contralateral side of the body known as a crossed reflex. It has been shown that neuronal pathways underlying crossed reflexes involve commissural interneurons with cell bodies located in the Rexed Lamina VIII as described in cats. The existence of analogous crossed reflexes has been shown in rodents. However, we have no insights into the organization of these crossed reflex pathways and their function in awake animals. Utilizing the mouse model, my Ph.D. work has focused on: 1) Understanding how sensory information (cutaneous and/or proprioceptive) is transferred to the contralateral spinal cord, and which muscles are being targeted by these pathways, and 2) investigating the spinal circuitry underlying crossed reflex. First, I reveal that in WT mice, crossed reflexes include an excitatory and inhibitory component which are modulated during locomotion depending on the activity of the muscle prior to the stimulation. Furthermore, the origin of the crossed reflex stimulation results in mostly similar outputs with slight differences. Notably, the existence of a long latency crossed reflex responses when the common peroneal nerve is stimulated, but not when the tibial or sural nerves are stimulated. To study the role of commissural interneurons, involve in the transmission of sensory afferent information, I used genetically engineered mice with manipulated (killed or silenced) V0 and V3 commissural interneurons respectively. Crossed reflexes between V0kill and WT mice were mostly similar with a stronger inhibitory component observed in V0kill mice. Meanwhile, V3off mice exhibit a non-significant decrease in the excitatory response and significant disruption in the inhibitory crossed reflex responses. As V3 interneurons represent a mostly excitatory interneuronal population, I investigated the role of a deep dorsal horn interneuron (dPVs) in crossed reflex. In dPVablat mice, crossed inhibitory reflex occurrence remained similar to control, suggesting that dPVs interneurons are not involved in inhibitory crossed reflex pathways. Taken together, my thesis provides the first framework to draw a spinal circuitry for the transmission of sensory afferent information in the spinal cord.