Motor control systems in the spinal cord of embryos

Neurological Disorders And Stroke

Investigators

Linked publications & trials

Abstract

The primary objective of this work is to elucidate the cellular and synaptic mechanisms responsible for the genesis of rhythmic activity by the spinal cord. Experiments are performed on isolated preparations of the chick and mouse spinal cords maintained in vitro. We use electrophysiological, optical and anatomical methods to analyze the function and properties of the spinal networks. Recently we have formulated a qualitative model to account for the genesis of rhythmic activity by developing spinal networks. This model is derived from our observation that network activity and synaptic transmission are depressed after a spontaneous episode of rhythmic bursting. The depression arises, in part, because of a decrease in the responsiveness of postsynaptic GABA receptors due to ionic redistribution during an prolonged activity. Experiments are currently in progress to establish if this mechanism contributes to the genesis of synchronized bursting in the disinhibited mouse spinal cord. In isolated neonatal mice cords it has been possible to activate locomotor-like activity using dorsal root stimulation or bath-applied drugs. Using optical methods, we have recently identified a rostrocaudal wave of activity that accompanies each cycle of locomotor-like discharge. The mechanism of this wave is unknown, but we hypothesize that it may play an important role in the intersegmental coordination of locomotion. We have also developed a new method based on electroporation to load calcium-sensitive dyes into neurons. We are applying this technique to the mouse spinal cord in combination with 2-photon microscopy to identify neurons involved in locomotion. Finally we are continuing studies on the recurrent connections between motoneurons and Renshaw cells in the mouse spinal cord. We have found evidence that ventral root stimulation results in an unexpected monosynaptic glutamatergic response in Renshaw cells. Experiments are in progress to establish if glutamate is released from the central terminals of motoneurons.