The goal of this project is to understand the generation and transmission of electrical signals in the neurons of the retina. Two different approaches to this goal will be pursued. First, the mechanisms of neurotransmitter release from synaptic terminals of tineal neurons will be studies. this is a fundamental aspect of all neuronal communication. Chemical neurotransmitter is released from synaptic terminals via calcium triggered exocytosis of synaptic vesicles, and this fundamental process will be studied by monitoring the changes in membrane surface area accompanying vesicle fusion in single synaptic terminals. In addition, the mechanisms of membrane retrieval (endocytosis) after vesicle fusion will also be examined. Because neurotransmitter releasers controlled by presynaptic calcium influx, experiments will also be conducted to determine the mechanisms controlling internal calcium in synaptic terminals, including uptake, extrusion, and buffering mechanisms on the one hand, and calcium entry on the other. Second, voltage-dependent sodium channels of the retina will be examined, from both physiological and molecular biological viewpoints. voltage dependent sodium channels are responsible for the generation of sodium action potential, the ubiquitous long distance electrical signal of the nervous system. In the retina, however, some classes of neuron express voltage dependent sodium channels, while other do not. In addition, there are multiple subtypes of sodium-channel gene, expressed differentially in different parts of the nervous system, including in the retina. Experiments will be conducted to examine the molecular regulation of this differential sodium-channel expression in retinal cells. Transcription factor(s) and the genetic regulatory elements with which they interact will be identified, and the regulation of channel expression by growth factors will also be studied. These two lines of research will provide information about basic aspects of retinal signal processing and about genetic mechanisms that control neuronal phenotype in the retina. The results will also be of general significance for neuronal function in other parts of the nervous system outside the retina.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY003821-18
Application #
2710839
Study Section
Visual Sciences C Study Section (VISC)
Project Start
1981-08-01
Project End
2002-07-31
Budget Start
1998-08-01
Budget End
1999-07-31
Support Year
18
Fiscal Year
1998
Total Cost
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
Vaithianathan, Thirumalini; Henry, Diane; Akmentin, Wendy et al. (2016) Nanoscale dynamics of synaptic vesicle trafficking and fusion at the presynaptic active zone. Elife 5:
Vaithianathan, Thirumalini; Henry, Diane; Akmentin, Wendy et al. (2015) Functional roles of complexin in neurotransmitter release at ribbon synapses of mouse retinal bipolar neurons. J Neurosci 35:4065-70
Vaithianathan, Thirumalini; Matthews, Gary (2014) Visualizing synaptic vesicle turnover and pool refilling driven by calcium nanodomains at presynaptic active zones of ribbon synapses. Proc Natl Acad Sci U S A 111:8655-60
Vaithianathan, Thirumalini; Akmentin, Wendy; Henry, Diane et al. (2013) The ribbon-associated protein C-terminal-binding protein 1 is not essential for the structure and function of retinal ribbon synapses. Mol Vis 19:917-26
Vaithianathan, Thirumalini; Zanazzi, George; Henry, Diane et al. (2013) Stabilization of spontaneous neurotransmitter release at ribbon synapses by ribbon-specific subtypes of complexin. J Neurosci 33:8216-26
Vega, Ana V; Avila, Guillermo; Matthews, Gary (2013) Interaction between the transcriptional corepressor Sin3B and voltage-gated sodium channels modulates functional channel expression. Sci Rep 3:2809
Snellman, Josefin; Mehta, Bhupesh; Babai, Norbert et al. (2011) Acute destruction of the synaptic ribbon reveals a role for the ribbon in vesicle priming. Nat Neurosci 14:1135-41
Hunanyan, Arsen S; Alessi, Valentina; Patel, Samik et al. (2011) Alterations of action potentials and the localization of Nav1.6 sodium channels in spared axons after hemisection injury of the spinal cord in adult rats. J Neurophysiol 105:1033-44
Zanazzi, George; Matthews, Gary (2010) Enrichment and differential targeting of complexins 3 and 4 in ribbon-containing sensory neurons during zebrafish development. Neural Dev 5:24
Matthews, Gary; Fuchs, Paul (2010) The diverse roles of ribbon synapses in sensory neurotransmission. Nat Rev Neurosci 11:812-22

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