The experiments which are proposed in this application are designed to capitalize on the foundation of knowledge that we have developed relating to age-determined changes in the basic membrane and synaptic properties of motoneurons in old cats. Two interrelated studies will be carried out in cats at 1-3 (adult controls), 6-8, 10-12, and 14-16 years of age. The first study entails an examination of the functional consequences of the changes in motoneuron properties that we have described in the acute, anesthetized cat preparation. This study will involve a determination of the fashion in which age- related changes in the basic membrane and synaptic properties of motoneurons actually affect the modulation of their activity in chronic, unanesthetized, normally respiring cats during states of sleep and wakefulness. The second study entails a determination of the fashion in which motoneurons in aged cats react to the insult of axotomy during states of sleep and wakefulness. We will also examine the extent to which axotomy in adult cats induces changes that occur naturally in motoneurons in old age. Finally, we will explore the extent to which the axotomized motoneuron may serve as a model for age-determined changes in motoneurons and their synaptic control. These data will (a) establish the functional consequences of the effects of age on motoneurons and (b) demonstrate the extent to which axotomized motoneurons can serve as a model for certain aspects of the aging process as it affects motoneurons. If normal aged changes parallel those present in axotomized motoneurons, other groups of investigators that do not have the resources to obtain or maintain old cats will be able to utilize this model to help understand specific effects of motoneuron aging in a readily available, relatively inexpensive, easily standardized preparation.
Showing the most recent 10 out of 37 publications
