While the organization of the constituent interneurons in the central pattern generator (CPG) controlling swimming in non-limbed animals is known in great detail, little is known about the cellular organization of CPGs controlling walking in limbed mammals. This application proposes to identify and characterize a key feature of the mammalian locomotor network, namely the CPG-circuits involved in left/right alternation. Commissural interneurons or CINs that project axons to the opposite site of the cord are by necessity included in this circuit. These interneurons will be the focus of this investigation because their specific projection pattern and their well-defined role in locomotion makes CPG-CINs uniquely identifiable. The scientific goals of this project will be obtained using in vitro preparations of early postnatal rats and a range of unique approaches, which we have been developed specifically for this project. The proposed work will provide a comprehensive anatomical and electrophysiological characterization of locomotor related CINs and their connectivity. There are six specific aims: 1) anatomical identification of subpopulations of CINs; 2) determination of activity patterns of CINs and their phase relations to the locomotor pattern; 3) electrophysiological identification of projections from CINs to contralateral motoneurons; 4) electrophysiological identification of projections from CINs to last order interneurons in the pathway to contralateral motoneurons; 5) determination of projections between CINs on opposite sides of the spinal cord; 6) characterization of transmitter-modulated bursting properties of CINs. Such information will represent one of the first characterizations of the role of a neuronal population in the production of behavior by the mammalian spinal cord. By comparing these results with work performed in non-mammalian vertebrates the work also specifically will assess whether new organizational principles emerged for the construction of vertebrate CPGs as the behavioral task changed from non-limbed swimming to limbed walking. Because CPG function is localized to the spinal cord and is critical for spinal control of walking, the planned work is of strong relevance to the ongoing effort to re-establish locomotor function in patients with spinal cord injury.
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