Spinal cord development

CIRCUIT FORMATION AND MOTOR MATURATION

Neurons operate within neural circuits. These circuits ensure proper transmission and integration of neural activity. However, these circuits are not completely set-up during embryonic development, or even after birth. There is still a great deal of refinement in neural circuits involved in movement, which explains why babies at birth do not arrive with a fully formed set of movements. As babies develop and learn to control their muscles to make movements in more skillful ways, their neural circuits are further refined through changes in intrinsic properties of individual neurons, birth and death of neurons, and changes in synaptic connectivity. We wish to study exactly how the maturation of motor control occurs through specific mechanisms that refine neural circuits in developing nervous systems. We have identified circuits within the spinal cord of either mouse or zebrafish that are ideal to answer this question.

dI3 interneurons
One circuit of interest in the mouse is centered on a population of spinal neurons named dI3 interneurons (dI3 INs). DI3 INs integrate sensory information related to touch (mechanoreception) and state of muscle activity (proprioception) and in turn, they shape the activity of motor circuits within the spinal cord.

DI3 INs form circuits that in newborns, control the palmar grasp reflex, a reflex where the paw closes when the skin of the palm is stroked by an object. We have shown that these circuits become crucial for properly controlling hand grasp. This suggests that the palmar grasp reflex is the precursor to controlling hand grasp. Hand grasp would develop as the brain learns to use the spinal circuits formed by dI3 INs. Our lab is studying the changes in connectivity of dI3 INs that allow their role to transition from mediating a reflex to willful control of hand grasping.

Spinal swimming networks
Developing zebrafish undergo a rapid transition in swimming movements in the days following fertilization. Electrophysiological, optical, and optogenetic techniques developed in zebrafish make this species an ideal model to study motor maturation during development.

Current work in the lab is showing how spinal circuits dedicated to the control of swimming undergo fundamental changes in the way that the rhythm of tail beats during swimming are generated.

SPINAL CORD PATTERNING

The development of embryos requires proper body patterning along various axes (e.g. head to toe, front to back). Improper development along these axes has important consequences (imagine the face being placed at the back of the head). The nervous system has a precise structure and even simpler areas such as the cylinder-like spinal cord require proper patterning on the rostrocaudal (head-to-toe) and the dorsoventral (back-to-front) axes. The dorsal half of the spinal cord is dedicated to processing of sensory information whereas the ventral half is associated with the control of movements. Incomplete development of the dorsal spinal cord has been shown to lead to deficits with sensory processing. Disrupted development of the ventral half has resulted in deficits in movements. Therefore, understanding the patterning of the spinal cord is important for understanding how the spinal cord functions properly.

In collaboration with Dr. Marie-Andree Akimenko (University of Ottawa), our lab is studying the transcriptional programs that establish proper patterning of the spinal cord of zebrafish. Using a number of transgenic strains in combination with molecular techniques such as immunohistochemistry and in-situ hybridization, our lab is determining genes involved in spinal cord patterning and their transcriptional regulation.