Much of the circuitry for producing locomotion is contained entirely within the lumbar spinal cord. However for normal motor function, it is essential that individual motoneuron pools become selectively connected with appropriate muscles and with specific populations of cord interneurons during development or regeneration following injury. The goal of the proposed research is to understand how individual chick and mouse motoneuron pools are specified, how they become incorporated into functional cord circuits, and the role that early spontaneous patterned activity plays in these processes. Early physiological differences between flexor and extensor motoneurons, and fast and slow, will be determined in isolated cells and in the intact circuit by patch clamp recordings of motoneurons identified by prior back labeling an E4-5 chick and E11-12 mouse cords. The contribution of intrinsic membrane properties and interneuron connectivity to pool specific bursting patterns will be determined. It will also be determined if alterations in the LIM gene code, which alter peripheral motor axon trajectories, alter the central connectivity. In vitro assays will probe the molecular basis of pool selective fasciculation and directed axonal growth, and a number of genes which have been found to be differentially expressed in early motor pools will be further characterized. The role of spontaneous electrical activity in these processes will be tested in the chick by blocking it in ovo with the GABA agonist muscimol. A better understanding of the cellular and molecular basis of how lumbar spinal cord circuits form should aid in developing strategies to either retrain cord circuits or improve the proper reconnection of descending input after spinal cord injury.
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