Cerebellar Neural Networks and Eyeblink Conditioning

描述：（改编自申请人的摘要）：的长期目标

DESCRIPTION: (Adapted from applicant's abstract): The long-term objective of this research is to advance our understanding of how the cerebellum is involved in encoding classical eyeblink conditioning, a simple, associative, motor learning procedure. Data collected to date have provided strong evidence that populations of neurons in specific regions of the cerebellar cortex and the interpositus nucleus receive convergent input concerning the stimuli used in eyeblink conditioning and change their firing patterns in a manner that is responsible for the acquisition and performance of the learned CR. While the neural network involved in encoding classical eyeblink conditioning has been worked out, there is much less known about how portions of this network interact during learning. The specific objectives of the research proposed here are to use brain recording, lesion and stimulation methods to study relationships between learning-related activity in the cerebellar cortex and learning-related activity in the interpositus nucleus. Four experiments are proposed. First, the interpositus nucleus will be either permanently lesioned with kainic acid or temporarily activated by muscimol and activity in the cerebellar cortex (lobule HVI and the anterior lobe) will be studied during acquisition and performance of eyeblink conditioning. Second, the cerebellar cortex will be either lesioned or inactivated and conditioning related activity in the interpositus nucleus will be examined. Third, double-labeling, tract-tracing techniques will be used to study the pattern of projections between cerebellar cortical areas and the deep cerebellar nuclei. Lastly, stimulation and recording techniques will be used to evaluate whether or not a "rebound from cortical inhibition" mechanism may play a role in promoting neural plasticity associated with conditioning. When completed, this research should provide important new data concerning how cerebellar neural networks are involved in motor learning procedures, and, more generally how neural systems interact to promote behavioral change. This systems-level understanding of how the brain operates during learning is crucial for the development of new treatments and therapies for a variety of pathologies that produce learning and memory deficits, including developmental influences, degenerative diseases and neural injury.