A multidisciplinary approach involving intracellular recording and dye injection, optic nerve backfilling and postembed light and electron microscopic immunocytochemistry will be employed to study the synaptic organization of identified neurons in the retinas of goldfish and tiger salamander. 1) The relative proportion and spatial distribution of inhibitory and excitory inputs on the dendrites of ON, OFF and ON-OFF cells is not known. Amacrine cells and ganglion cells will be recorded, classified as to their response to light, injected with HRP and processed for EM to determine their synaptic organization with respect to the inhibitory transmitter, GABA and glycine and excitatory transmitters, ACh and glutamine. Also, we plan to develop a retinal slice preparation in goldfish to combine transmitter pharmacology, dye injection and EM analysis of identified ganglion cells. 2) Determine the distribution of GABA receptors (monoclonal antibody against GABA/A/benzodazepine receptor complex) in the retina of goldfish and other vertebrate species and compare this distribution with ohter GABAergic markers. This mAB labels photoreceptor terminals in nonmammals, and analysis will provide information about sites of feedback transmission from horizontal cells to photoreceptors. 3) Determine the organization of synaptic terminals of mixed rod/cone bipolar cells in goldfish. Electrophysiological evidence suggest that ON (mb-type) and OFF (ma-type) differ on the basis of direct vs indirect GABAergic input. There is little known about other synaptic inputs or about the output targets of these large bipolar cells. 4) Determine if Na-K ATPase staining in the goldfish IPL is correlated with whether the transmitter at a synapase is excititory or inhibitory. This study could provide an independent means to predict the ionic conductance gated at a given synapase (i.e., sodium vs potassium or chloride). Also, test my hypothesis that the Na-K ATPase is involved in the dopamine-mediated inhibition of transmitter GABA release from goldfish horizontal cells. This study would provide a mechanism for the control of transmitter release that does not involve calcium-dependent vesicular exocytosis. These studies will provide detailed transmitter connectivity of physiologically identified retinal neurons. The transmitters under study are sufficiently conserved across species that these data should lead to a general understanding of the role of these transmitters in visual encoding.

National Institute of Health (NIH)
National Eye Institute (NEI)
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Visual Sciences B Study Section (VISB)
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State University New York Stony Brook
Schools of Arts and Sciences
Stony Brook
United States
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Klooster, Jan; Yazulla, Stephen; Kamermans, Maarten (2009) Ultrastructural analysis of the glutamatergic system in the outer plexiform layer of zebrafish retina. J Chem Neuroanat 37:254-65
Yazulla, Stephen (2008) Endocannabinoids in the retina: from marijuana to neuroprotection. Prog Retin Eye Res 27:501-26
Zimov, Sarah; Yazulla, Stephen (2008) Novel processes invaginate the pre-synaptic terminal of retinal bipolar cells. Cell Tissue Res 333:1-16
Zimov, Sarah; Yazulla, Stephen (2007) Vanilloid receptor 1 (TRPV1/VR1) co-localizes with fatty acid amide hydrolase (FAAH) in retinal amacrine cells. Vis Neurosci 24:581-91
Fan, Shih-Fang; Yazulla, Stephen (2007) Retrograde endocannabinoid inhibition of goldfish retinal cones is mediated by 2-arachidonoyl glycerol. Vis Neurosci 24:257-67
Hull, Court; Studholme, Keith; Yazulla, Stephen et al. (2006) Diurnal changes in exocytosis and the number of synaptic ribbons at active zones of an ON-type bipolar cell terminal. J Neurophysiol 96:2025-33
Struik, Mieke L; Yazulla, Stephen; Kamermans, Maarten (2006) Cannabinoid agonist WIN 55212-2 speeds up the cone response to light offset in goldfish retina. Vis Neurosci 23:285-93
Glaser, Sherrye T; Deutsch, Dale G; Studholme, Keith M et al. (2005) Endocannabinoids in the intact retina: 3 H-anandamide uptake, fatty acid amide hydrolase immunoreactivity and hydrolysis of anandamide. Vis Neurosci 22:693-705
Fan, Shih-Fang; Yazulla, Stephen (2005) Reciprocal inhibition of voltage-gated potassium currents (I K(V)) by activation of cannabinoid CB1 and dopamine D1 receptors in ON bipolar cells of goldfish retina. Vis Neurosci 22:55-63
Fan, Shih-Fang; Yazulla, Stephen (2004) Inhibitory interaction of cannabinoid CB1 receptor and dopamine D2 receptor agonists on voltage-gated currents of goldfish cones. Vis Neurosci 21:69-77

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