Description of Research Expertise

RESEARCH INTERESTS
Retinal processing with focus on chemical architecture and principles of signal processing. Recently- Alzheimer

RESEARCH TECHNIQUES
Electrophysiology; immunocytochemistry; electroretinogram; dye injection; electron microscopy; molecular biology; yeast two hybrid systems; computer simulation; live two photon imaging.

RESEARCH SUMMARY
General Description: The retina provides an excellent model system for signal processing because the input (visual image) is well defined, the output (ganglion cell responses) has been thoroughly studied, and circuits of parallel pathways from photoreceptor to ganglion cells were described better than any other neural system. To reliably transfer the signal from photoreceptor to ganglion cells through these pathways under a large range of luminances the retina employs gain control and noise removal mechanisms. Gain is adjusted by GABAergic and glycinergic feedback circuits in the outer and inner plexiform layers. These circuits tune photoreceptor, bipolar and ganglion cells' responses by averaging and feeding back ambient light information. A major focus of the lab was the pathway of the ON bipolar cells and their signaling cascade. The ON bipolar cells express the metabotropic glutamate receptor mGluR6. This receptor activates Go, and this eventually closes the nonspecific TRPM1 cation channel. We studied the events that occur downstream of Go and how they are modulated. Whether Go activates directly the channel, or through a second messenger is important because the manner of activation determines the gain and the adaptation of these cells. In particular, both mGluR6 and Go are present in both rod and cone bipolar cells, but the two classes have different function (slow for night vision vs. fast for day vision), and one expects the cascade to differ in order to match and optimize the function. Another aspect of our studies is to figure out how the whole complex of the cascade is trafficked to the dendritic tip, and how a lack of a certain element destabilizes the complex and the synapse. Knowledge of this cascade is essential for understanding and treating night blindness. Another project concerns cone bipolar cell types; there exist about 5 types that are thought to conduct different temporal bandwidth. Nothing is known about their precise light properties and how they achieve their differences. We study this by calcium imaging of ON bipolar cells. Such understanding will shed light on day light vision and retinal diseases. I am recently engaged in applying the knowledge we acquired to therapeutic methods for structural and functional protection of retinal circuits. Furthermore, in collaboration with a biochemist who studies mitochondria function and dysfunction, I am researching new approaches to mitigate Alzheimer and Parkinson disease progression. The key in these studies is using small molecules (such as VBIT) that interfere with the mitochondrial processes that leads to cell death. Specifically, when the mitochondria senses abnormal changes, the channel VDAC1, which is important in transferring metabolites in and out of the mitochondria, get oligomerized and creates a large channel that allows cytochrome C to leave the mitochondria and activate caspases that then kill the cells. The VBIT molecules prevent the formation of the large channel.