The representation and processing of temporal information is an essential component of many cognitive tasks, including the comprehension of spoken language. Patients with cerebellar lesions display problems with both understanding and generating language, and research on human subjects indicates that this cerebellar linguistic deficit may be largely due to a problem in timing. Nonetheless, despite a potential key role for the cerebellum in processing of time, little is known about how cerebellar neurons actually represent and transform temporal information. We propose to develop a novel experimental approach to examine the neural mechanisms of temporal information processing at the microcircuit level. Our goal is to test longstanding hypotheses of the representation of temporal information by the cerebellum, and to derive general principles of temporal processing that will inform understanding of human language comprehension. We will combine two-photon fluorescence microscopy, the delivery of simple auditory stimuli comprising tones and pauses, and an in vivo mouse preparation to examine temporal processing in cerebellar granule cells, the most common but least studied neuron in the brain. Because cerebellar microcircuitry is highly conserved across cerebellar subregions and vertebrate species, our studies in mouse will provide information that is directly relevant to an understanding of human cerebellar function. For over a century, it's been known that cerebellum is important for movement: cerebellar lesions from strokes, genetic mutations, and injuries all can cause ataxia, dysmetria, dysarthria, and tremor, impairing the lives of millions of people worldwide. Patients with many of these symptoms also have impaired timing sensation, including problems with speech and sound perception, arenas where less is known and whose therapy has been less evaluated. Knowledge of the role of the cerebellum in analyzing temporal processing of sound would open up new horizons into the analysis and production of speech. ? ?
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