The question of where and how memories are stored is one of the major interests in the field of neuroscience. Among the different brain structures investigated for localization of memory formation, such as hippocampus and amygdala, the cerebellum has been widely accepted as serving the neural basis for classical eyeblink conditioning. A growing body of evidence suggests that both cerebellar cortex and deep nuclei contribute to learning and memory of eyeblink conditioning. In this study, the role of the mammalian cerebellum was extensively examined in a novel mice model system with Purkinje cell deficiency. Glucose-regulated protein (GRP, 78kDa) conditional knockout mice demonstrated impaired learning with aberrant timing and amplitude of the conditioned response, and the interpositus nucleus was found to be crucial for expression of conditioned response. In addition, the molecular mechanism of cerebellar learning was investigated using immediate-early gene protein detection in the rat cerebellum following a single training session of eyeblink conditioning. c-Fos protein, a regulatory transcription factor, was detected in the Purkinje cells of the rat cerebellum perfused 1 hour after the onset of training. Activity-regulated cytoskeletal-associated protein (Arc) was significantly increased in the cerebellar cortex when compared to naive or pseudoconditioned animals. Also, Stargazin expression was increased following training, which reinforces the notion that Stargazin is required for synaptic plasticity and learning and memory. Together, these studies extend previous findings of the role of cerebellum and the molecular dynamics underlying the establishment of memory trace in the mammalian cerebellum.
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