The long-term objective of the proposed research is to understand the contribution of motoneuron discharge properties to long-lasting changes in motor function. Of particular interest is adaptation in firing frequency during sustained repetitive discharge which has been implicated as a contributor to motor fatigue, a significant component of movement control. The two phases of adaptation, early and late, are thought to result from the activity of different membrane conductances. These conductances have not been identified. In this application, there are two specific aims. The first specific aim is to extend pilot studies of hypoglossal motoneuron repetitive discharge by including a more detailed analysis of the role of specific ionic conductances in generating adaptation. Adaptation will be studied in hypoglossal motoneurons of an in vitro rat brainstem slice preparation. The motoneurons will be stimulated intracellularly with constant current pulses of suprathreshold intensity in order to produce 60 second trains of sustained repetitive discharge. The membrane conductances that will be studied with electrophysiologic and pharmacologic manipulations are the Na+-K+ pump, the voltage sensitive Na+ and K+ channels, and the Ca++ mediated K+ channels. Attempts will be made to identify changes in these conductances associated with both early and late adaptation. The second specific aim is to determine if changes in motor fatigue properties are correlated with changes in motoneuron adaptation. The rat model of tardive dyskinesia (TD) will be established as a model for chronic increases in tongue movement. The representation of different muscle fiber types will be compared in the tongue of normal and TD rats to determine whether a change in motor fatigue properties has occurred. Motoneuron discharge will be examined in the same animals for changes in the character of adaptation by the techniques used for the first specific aim. These data will be used to determine if the changes in muscle fiber type are accompanied by changes in motoneuron adaptation. Alterations in specific membrane conductances that relate to the changes in adaptation will also be examined in the motoneurons of these TD animals using electrophysiologic and pharmacologic interventions. The results of the projects for these specific aims are expected to further our understanding of motoneuron discharge patterns and the functional significance of motoneuron adaptation in movement.
