A novel in vitro preparation that takes advantage of the turtle's unusual resistance to anoxia has been developed to explore mechanisms of the central representation of motor programs. This preparation preserves the cerebellorubral circuit which is comprised of synaptic connections between the cerebellum, red nucleus and reticular formation. Bursts of activity recorded in the red nucleus in behaving monkeys, cats and turtles correlate closely with parameters of movement such as velocity and appear to represent simple motor programs. Burst discharges can also be elicited in the in vitro preparation. The goals of the proposed experiments are to examine the cellular and circuit mechanisms that contribute to the generation of burst discharges in the red nucleus, and by analogy, to motor program generation. Extracellular and intracellular recordings of red nucleus neurons in combination with ion substitution and application of activity-dependent dye will be performed to study the relative contributions of recurrent excitation and intrinsic membrane properties in the production of burst discharges. Mechanisms must also be present to modify movement commands so that they are adaptive to the environment. Mechanisms that might be used to adjust red nucleus motor output could include neurotransmitters or neuromodulators, such as GABA or serotonin. Studies of the fine control of burst discharges will be examined with extracellular recordings and iontophoresis of neurotransmitters and their antagonists. These studies of the cellular and circuit bases of synaptic integration underlying activity in the red nucleus will provide new data required to better understand the contribution of cerebellorubral synaptic pathways to adaptive motor control and to movement disorders, particularly Parkinson's disease.
