Mark Schnitzer
Stanford University

In vivo microendoscopy and computational modeling studies of mammalian brain circuits

Tuesday 21st of March 2006 at 12:30pm
Beach Room - 3105 Tolman

I will describe two biophysical approaches to the study of mammalian learning and memory that my lab is pursuing. First, we are developing fluorescence microendoscopy, an emerging optical modality providing cellular level imaging in deep brain tissues that have been inaccessible to in vivo microscopy. One- and two-photon fluorescence microendoscopy based on minimally invasive micro-lenses (350-1000 micron diameter) offer micron-scale resolution and have enabled visualization of neurons and blood cells in deep areas of the live mammalian brain. We have recently developed a chronic mouse preparation that has enabled in vivo microendoscopy imaging of fluorescent CA1 hippocampal pyramidal cells over several months after an initial surgery. We have also built a compact (3.9 gram) two-photon fluorescence microendoscope that is intended for brain imaging in freely moving mice. Second, we are performing computational studies of cerebellum-dependent motor learning, including classical conditioning of motor reflexes and adaptation of the vestibulo-ocular reflex (VOR), to address basic questions about how cerebellar brain circuits process timed stimuli and produce well-timed motor outputs. The leading theoretical framework invokes a long-term depression (LTD) of cerebellar parallel fiber to Purkinje cell synapses as a mechanism underlying learning. This does not account for several temporal aspects of motor behavior, and assumes GABAergic projections from Purkinje cells to deep cerebellar nuclei (DCN) neurons are purely inhibitory in effect. However, it is well established that hyperpolarization of DCN neurons commonly leads to subsequent depolarization due to rebound conductances. We have developed a theory of learning based on such rebound excitation, which makes testable predictions and provides a consistent account of previously unexplained aspects of classical conditioning and VOR adaptation during acquisition and expression phases of learning.

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