The Journal of Neurophysiology Vol. 77 No. 2 February 1997, pp. 675-689
Copyright ©1997 The American Physiological Society

Pharmacology of Directionally Selective Ganglion Cells in the Rabbit Retina

Christopher A. Kittila and Stephen C. Massey

Department of Ophthalmology and Visual Science, University of Texas Medical School, Houston, Texas 77030

Kittila, Christopher A. and Stephen C. Massey. Pharmacology of directionally selective ganglion cells in the rabbit retina. J. Neurophysiol. 77: 675-689, 1997. In this report we describe extracellular recordings made from ON and ON-OFF directionally selective (DS) ganglion cells in the rabbit retina during perfusion with agonists and antagonists to acetylcholine (ACh), glutamate, and -aminobutyric acid (GABA). Nicotinic ACh agonists strongly excited DS ganglion cell in a dose-dependent manner. Dose-response curves showed a wide range of potencies, with (±)-exo-2-(6-chloro-3pyridinyl)-7-azabicyclo[2.2.1] heptane dihydrochloride (epibatidine)  nicotine > 1,1-dimethyl-4-phenylpiperazinium iodide = carbachol. In addition, the mixed cholinergic agonist carbachol produced a small excitation, mediated by muscarinic receptors, that could be blocked by atropine. The specific nicotinic antagonists hexamethonium bromide (100 µM), dihydro--erythroidine (50 µM), mecamylamine (50 µM), and tubocurarine (50 µM) blocked the responses to nicotinic agonists. In addition, nicotinic antagonists reduced the light-driven input to DS ganglion cells by ~50%. However, attenuated responses were still DS. We deduce that cholinergic input is not required for directional selectivity. These experiments reveal the importance of bipolar cell input mediated by glutamate. N-methyl-D-aspartic acid (NMDA) excited DS ganglion cells, but NMDA antagonists did not abolish directional selectivity. However, a combined cholinergic and NMDA blockade reduced the responses of DS ganglion cells by >90%. This indicates that most of the noncholinergic excitatory input appears to be mediated by NMDA receptors, with a small residual made upb y    - a m i n o - 3 - h y d r o x y - 5 - m e t h y l - 4 - i s o x a z o l e p r o p i o n i c   a c i d(AMPA)/kainate (KA) receptors. Responses to AMPA and KA were highly variable and often evoked a mixture of excitation and inhibition due to the release of ACh and GABA. Under cholinergic blockade AMPA/KA elicited a strong GABA-mediated inhibition in DS ganglion cells. AMPA/KA antagonists, such as 2,3-dihydroxy-6-nitro-7-sulfamoylbenzo(F)quinoxaline dione and GYKI-53655, promoted null responses and abolished directional selectivity due to the blockade of GABA release. We conclude that GABA release, mediated by non-NMDA glutamate receptors, is an essential part of the mechanism of directional selectivity. The source of the GABA is unknown, but may arise from starburst amacrine cells.

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