The goals of this study are to elucidate the operation of the interneuronal networks that coordinate muscle activity on the two sides of the body. We plan, in particular, to investigate how the activity of spinal interneurons with axons that cross the midline (commissural interneurons) is integrated with the activity of other spinal neurons. This information is essential for understanding the functional roles of these interneurons in behaviour. Our previous work has identified two distinct subpopulations of commissural interneurons with different patterns of peripheral and descending inputs, both of which include excitatory and inhibitory neurons that are premotor to contralateral motoneurons. As a continuation of this work we plan (A) to characterize the two subpopulations of commissural interneurons in terms of neurochemistry (including neurotransmitter and monoamine receptor phenotype), pharmacology (including monoaminergic and GABAergic modulation of their activity) and morphology, in addition to their electrophysiological properties in vivo, (B) to examine which spinal neurons provide input to these interneurons and (C) which neurons they target other than contralateral motoneurons. To this end, the expertise and facilities in our three research groups in Goteborg, Sweden and in Glasgow and Cambridge in the UK will be used to apply these different synergistic experimental approaches. This combination of approaches is not being used by any other group, and will provide a full profile of each functional class of interneuron, enabling the neuronal networks formed by commissural, interneurons to be pieced together, modeled and examined during behaviour. Insights provided by the study will be important for the refinement and introduction of new therapeutic strategies for CNS repair, and also for the interpretation of results of molecular/genetic and in vitro studies of spinal functions. ? ?
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