The long-term objectives of these studies are to further our understanding of the biological bases of learning and memory.
The specific aim of this project is to determine the brainstem and cerebellar structures involved in the mechanisms of learning and performing a simple learned reflex. This project relates to health in its potential for improving learning in normal individuals, and in applications of recovery of function in individuals with brain damage. The research design involves training subjects on a simple classical conditioning task. During acquisition, retention and extinction phases of training, both behavior and extracellular multiple unit activity (unit activity) in select brainstem and cerebellar areas are monitored for activity associated with learned and unlearned reflexes: supratrigeminal, interpolaris spinal trigeminal, reticular tegmental and lateral pontine nuclei, cerebellar cortical lobule HVI and interpositus nucleus. In Experiment l, these loci will be temporary lesioned in groups of subjects, who will then be trained, and subsequently tested for retention as normals. The question is whether the subjects can learn without the use of one of these regions. In Experiment 2, subjects will be trained and then temporarily lesioned in interpositus, red nucleus or facial nucleus (different groups) while given extinction training. The question is whether subjects will show the effects of extinction training when they are later tested as normals. The interpositus nucleus is potentially a locus of learning, so in Experiment 3 it will be temporarily inactivated. The question is whether loss of feedback alters the behavior and unit activity for learned and unlearned reflexes are in related brainstem and cerebellar structures. For all experiments, unit activity associated with learning is evaluated by Z- scores and correlations between learned behavior on conditioned stimulus alone test trials. Unit activity associated with reflexive behavior is similarly evaluated on unconditioned stimulus alone test trials and for modulatory effects of the interpositus by evaluating effects of cooling on baseline activity on each trial and evoked stimuli. In Experiment 4 the extent of cooling will be evaluated by 2-deoxyglucose in select subjects from the preceding experiments. These studies specifically evaluate the cerebellar and brainstem hypotheses for their role in learning and memory.
