MAR 20, 2014 02:00 PM PDT

Disinhibition Drives Rapid Movement and Associative Motor Memory Formation in the Cerebellum

Presented At Neuroscience
  • Investigator, LA BioMed & Assistant Professor of Neurology, UCLA
      Dr. Paul J. Mathews received his bachelors degree from the University of Oregon where he studied invertebrate behavioral plasticity in the lab of Dr. Nathan Tublitz. He received his Ph.D. in neuroscience from the University of Texas at Austin under the mentorship of Dr. Nace Golding. Dr. Mathews work focused on understanding how the biophysical properties of specific voltage-gated ion channels in an auditory brainstem nuclei contribute to their capacity to make sub-millisecond computations necessary for low frequency sound localization. For the past several years Dr. Mathews has been working at UCLA under the mentorship of Dr. Tom Otis where he is currently working to uncover the cerebellar circuit mechanisms that underlie motor learning and memory. To do this Dr. Mathews is utilizing a multifaceted approach that includes both in vitro and in vivo electrophysiology, optogenetics, advanced optics, histology, and behavioral manipulations to make links between cerebellar circuit activity and motor output in rodent models. He is currently on the job market looking for a tenured track assistant professor position.


    Motor coordination relies on accurate predictions that specify how the body should move in particular sensorimotor contexts. Although such predictions are thought to be stored as associative motor memories in the cerebellum, the circuit mechanisms by which they form and are acted upon remain unclear. Correlates of such memories, typically reductions in the firing rate of Purkinje neurons in advance of a learned movement, have been observed in the firing patterns of cerebellar Purkinje neurons. Given that Purkinje neurons powerfully inhibit deep cerebellar nuclei neurons, and that some deep cerebellar nuclei neurons project directly to motor nuclei like the red nucleus, pauses in spontaneous Purkinje neuron firing have the potential to drive motor output. However, it is unclear whether reductions in Purkinje neuron firing alone are sufficient to drive movement, and if so whether their ability to drive movement depends upon prior learning. To examine these questions we have utilized an approach to selectively manipulate Purkinje neuron firing activity in an awake, behaving animal while simultaneously monitoring cellular activity or motor movement. Together, the results I will present indicate movements driven by Purkinje neuron pauses are influenced by whether or not learning has occurred, and support the hypothesis that during learning Purkinje neuron activity instructs memory-related changes in the deep cerebellar nucleus.

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