Network Function In The Developing Spinal Cord Of The Ch

Neurological Disorders And Stroke

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Abstract

The primary objective of this work is to elucidate the cellular and synaptic mechanisms responsible for the genesis of rhythmic activity in 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 developing 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 recent observation that network activity and synaptic transmission are depressed after a spontaneous episode. The depression arises, in part, because of a decrease in the responsiveness of postsynaptic glutamate and GABA receptors due to ionic redistribution during an episode. 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 intersegmental coordination of locomotion. We are presently investigating the importance of intersegmental axons in mediating the wave. In parallel with the physiological experiments, we have been examining the development of transmitter phenotype from E12 to the adult. We have found that GABA-immunoreactive spinal interneurons are present transiently in the ventral spinal cord as has been found in the rat and the chick. These fate of these neurons is unknown but we have proposed that they undergo a transmitter switch from GABA to glycine.