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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