): The goal of this project is to understand the molecular mechanisms of neurotransmitter responses in retinal bipolar neurons, with a focus on the roles of cyclic nucleotide-gated (CNG) channels. Visual signals from the photoreceptors are funneled to the rest of the brain exclusively through bipolar neurons, which therefore occupy a central position in retinal information processing. The separation of visual information into the ON pathway (in which cells depolarize in response to light) and the OFF pathway (in which cells hyperpolarize in response to light) occurs in bipolar neurons, at the first synapse in the visual system. The proposed research project will explore the cellular mechanisms that generate the ON pathway at the synapse between photoreceptor cells and ON bipolar neurons. At this synapse, glutamate released from the photoreceptor hyperpolarizes ON bipolar cells by activating a transduction cascade culminating in closure of cation channels. These cation channels may be members of the family of CNG channels, which open when cyclic GMP binds directly to the intracellular portion of the channel. A combination of electrical recording and fluorescence imaging techniques will be used to establish the role of CNG channels and cyclic GMP in the glutamate response of ON bipolar cells. Other potential roles of CNG channels will also be explored, such as modulation of neurotransmitter release in the synaptic terminal of the bipolar cell. Molecular biological techniques will be used to identify and characterize the CNG channel subtypes expressed in bipolar neurons. From amino acid sequences derived from complementary DNA encoding CNG channel subtypes, selective antibodies will be produced that can be used to localize the channel subtypes in isolated cells and retinal tissue. Biophysical characterization of CNG channel subtypes found in bipolar neurons will be carried out both in bipolar neurons and in cells transfected with full-length complementary DNA encoding a specific channel subtype. The proposed experiments will provide new information about the synaptic responses of an important class of retinal neurons and will specify physiological roles for specific types of CNG channels expressed in these neurons. Because cyclic nucleotide-gated channels are found in a variety of cell types throughout the nervous system, the results of the proposed project will also have general implications for cellular communication in the other parts of the brain.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY013251-02
Application #
6498368
Study Section
Visual Sciences C Study Section (VISC)
Program Officer
Mariani, Andrew P
Project Start
2001-02-01
Project End
2006-01-31
Budget Start
2002-02-01
Budget End
2003-01-31
Support Year
2
Fiscal Year
2002
Total Cost
$301,000
Indirect Cost
Name
State University New York Stony Brook
Department
Other Basic Sciences
Type
Schools of Arts and Sciences
DUNS #
804878247
City
Stony Brook
State
NY
Country
United States
Zip Code
11794
Tetreault, Michelle L; Henry, Diane; Horrigan, Diana M et al. (2006) Characterization of a novel cyclic nucleotide-gated channel from zebrafish brain. Biochem Biophys Res Commun 348:441-9
Henry, Diane; Burke, Stephanie; Shishido, Emiko et al. (2003) Retinal bipolar neurons express the cyclic nucleotide-gated channel of cone photoreceptors. J Neurophysiol 89:754-61