Scott A. Nawy

---

Mechanisms of synaptic transmission in the retina

The primary interest of the lab is an understanding of information processing in the retina at the level of individual synapses. Emphasis is on the molecular mechanisms by which synaptic information is modified by short and long-term changes in the visual scene.

One current project is the synapse between photoreceptors and an interneuron called the On bipolar cell, a critically important synapse in vision because all visual information flows through it. Our lab has shown that the On bipolar cell expresses a metabotropic glutamate receptor (mGluR6) that is coupled indirectly to the synaptic channel by a GTP-binding protein. Binding of glutamate to the postsynaptic receptor activates the G-protein and closes the synaptic channel. We have recently discovered that an enzyme called cGMP-dependent kinase reduces the efficacy of glutamate: The same concentration of glutamate closes fewer channels when this kinase is activated. This is important because it means that when this kinase is turned on, responses to dim light will be amplified. On the other hand, when kinase activity is low, sensitivity will be reduced, provide a wider operating range in brighter light. One future goal of this project is to identify those proteins in the bipolar cell enzymatic pathway that are targets of phosphorylation. Another goal is to determine how the levels of ambient light detected by the retina control the amount of phosphorylation.

A new project in the lab is a collaboration with Dr. Reed Carroll on the role of activity in the regulation of glutamate receptor trafficking at synapses of the inner retina. We are using cultured retinal cells as our primary model system so that we can directly visualize the movement of glutamate receptors into and out of the synaptic membrane. What we have found is that in pure cultures of inhibitory interneurons called amacrine cells, glutamate receptors are present, and move in and out of the membrane quite rapidly, perhaps in such of the excitatory input that is absent in these cultures. However, when amacrine cell cultures are "doped" with excitatory cells, turnover of receptors slows down in amacrine cells that receive synaptic input from these excitatory cells. Interestingly, glutamate receptors in amacrine cells that do not receive excitatory synaptic input, or in cells where input is pharmacologically blocked, continue to rapidly turnover. Our hypothesis is that synaptic activity converts glutamate receptor turnover from a dynamic to a stable state. We are currently working to identify this molecular switch.

 

Nawy, S. (2000) Regulation of the On bipolar cell mGluR6 pathway by Ca2+. J Neurosci. 20

Snellman, J. and Nawy, S. (2002) Regulation of the Retinal Bipolar Cell mGluR6 Pathway by Calcineurin. J. Neurophysiol. 88, 1088-1096.

Xia, Y. and Nawy, S. (2003) The Gap Junction Blockers Carbenoxolone and 18(beta)-Glycyrrhetinic Acid Antagonize Cone-Driven Light Responses in the Mouse Retina. Vis. Neurosci. 20, 429-435.

Nawy, S. (2004) Desensitization of the mGluR6 transduction current in Tiger Salamander On bipolar cells. J. Physiol. 558, 137-146.

Snellman, J. and Nawy, S. (2004) cGMP-dependent kinase regulates postsynaptic sensitivity of the mouse On bipolar cell. J. Neurosci. [in press].

 

---