The autonomous spinal networks that generate movements in vertebrates are referred to as central pattern generators (CPGs). The principal neurons in the locomotor circuitry include ipsilateral rhythmogenic interneurons, (rhythm generators), commissural interneurons that coordinate the rhythms between the left-right sides of the spinal cord (rhythm coordinators) and motoneurons. The integrated activity of these neuronal populations produces rhythmic excitation of motoneurons during hindlimb movements in walking vertebrates. The primary challenge in studying the cellular and synaptic mechanisms underlying rhythm generation in the locomotor circuitry is the identification of interneuronal populations that comprised integral components of rhythm-generating and rhythm-coordinating networks. To overcome some of the technical difficulties identifying locomotor-related interneurons in the isolated spinal cord, transgenic mice have been used with the intention of characterizing interneuronal populations based on their unique gene expression. Recent studies have documented that ventral neurons can be divided into five domains of specific genes that represent physiologically distinct neuronal populations with defined functions in motor behavior. .Such genes have been widely used to express the reporter gene green fluorescent protein (GFP), giving rise to visually identified neurons that can be targeted for repeated electrophysiological, morphological and immunohistochemical studies. In this proposal two lines of GFP positive transgenic mice will be used to study the mechanisms of rhythm generation in ipsilateral excitatory interneurons expressing the HB9 protein, and inhibitory commissural interneurons that synthesize the enzyme GAD67. The objectives of this proposal are: (1) to test the hypothesis that the Hb9 and GAD67 interneurons are integrated in rhythm-generating and rhythm- coordinating networks, respectively and (2) to test the hypothesis that different synaptic and cellular mechanisms underlie rhythm generation in these interneurons that perform different functions in the locomotor circuitry. Understanding the mechanisms that modulate the patterns of locomotion rhythms in functionally identified interneurons in the isolated spinal cord that is disconnected from descending voluntary control, will provide important insight into possible therapeutic strategies of activating undamaged neurons in rhythm generating networks of patients with spinal cord injuries.
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