||Professor of Neurobiology, Department of Molecular & Cell Biology
Member, Helen Wills Neuroscience Institute
The Effect of Neural Activity on the Assembly of Neural Circuits
We are interested in the mechanisms that guide the assembly of visual circuits during development. We use a combination of conventional and two-photon imaging, electrophysiology and transgenic approaches to address two major questions. First, we study how immature retinal circuits generate retinal waves — a term used to describe highly patterned spontaneous activity in the immature retina — and what role this activity plays in the development of the visual system. Second, we study the development of the circuits that mediate direction selectivity in the retina.
Cellular mechanisms underlying retinal waves:
There are several examples throughout the developing vertebrate nervous system, including the retina, spinal cord, hippocampus and neocortex, where immature neural circuits generate activity patterns that are distinct from the functioning adult circuitry. It has been proposed that these transitional circuits provide the “test patterns” necessary for normal development of the adult nervous system. In my laboratory, we study the cellular mechanisms that underlie the reliable generation of retinal waves.
Development of direction selectivity
How are circuits wired up during development to perform specific computations? We address this question in the retina, which is comprised of multiple circuits that encode different features of the visual scene, culminating in the roughly 15 different types of retinal ganglion cells. Direction-selective ganglion cells (DSGCs) respond strongly to an image moving in the preferred direction and weakly to an image moving in the opposite, or null direction. In the mammalian retina, the directional preference of an On-Off DSGC is caused by asymmetric inhibitory inputs: movement in the null direction causes strong inhibition that effectively shunts light-evoked excitatory inputs. The mechanisms that guide the emergence of directional circuits in the retina are unknown. Direction selective responses are detected at the age of the earliest visual responses, indicating that the retinal circuitry mediating direction selectivity emerge prior to normal visual experience. Hence, direction-selective circuits emerge at a time during development when the retina itself is undergoing a remarkable transformation from intrinsically generated retinal waves to visually evoked responses. We use a several several recently developed transgenic mouse models that express GFP in different subtypes of DSGCs, to determine the mechanisms that underlie the development of the two essential features of direction-selective circuits – the maturation of null-side specific inhibition and DSGC mosaics.
Visit Lab Page for the full list of published works.