title: Pharmacological modulation of on and off ganglion cells in the cat retina.
abstract: We studied the effects of 2-amino-4-phosphonobutyric acid and 2-amino-4-phosphonovaleric acid, which are antagonists to excitatory amino acids, on brisk-sustained(X) and brisk-transient(Y) ganglion cells in the cat retina. The ganglion cells were recorded extracellularly with a multibarreled electrode in the intact eye in vivo and drugs were applied iontophoretically. We found contrasting effects of 2-amino-4-phosphonobutyric acid and 2-amino-4-phosphonovaleric acid on ON- and OFF-centre cells irrespective of the brisk-sustained(X)/brisk-transient(Y) dichotomy. The maintained discharge and the light response of ON-centre cells decreased during 2-amino-4-phosphonobutyric acid and 2-amino-4-phosphonovaleric acid application, whereas the maintained discharge of OFF-centre cells increased. The light response of OFF-centre cells was not significantly affected. 2-Amino-4-phosphonovaleric acid was generally less potent than 2-amino-4-phosphonobutyric acid. It was shown in the mudpuppy retina [Slaughter and Miller (1981) Science, N.Y. 211, 182-185; Slaughter and Miller (1981) Invest. ophthal. Vis. Sci. 20, 44] that 2-amino-4-phosphonobutyric and 2-amino-4-phosphonovaleric acid selectively block the response of ON-bipolar cells. Assuming that these drugs act on the same synaptic sites in the cat retina, one expects a block of ON-centre ganglion cells. Moreover, the drug response of OFF-centre ganglion cells is then consistent with Sterling's hypothesis [Sterling (1983) A. Rev. Neurosci. 6, 149-185] that OFF-ganglion cells receive a direct inhibitory input from ON-bipolars. For some period 19 out of 108 cells responded to 2-amino-4-phosphonobutyric acid and 2-amino-4-phosphonovaleric acid in an opposite way to that described above: ON-centre cells increased and OFF-centre cells decreased their maintained discharge. It is proposed that this "reverse response" may be mediated by autoreceptors to excitatory amino acids or due to different receptor sites triggering antagonistic response mechanisms.
mesh_terms: D015763:2-Amino-5-phosphonovalerate; D000613:Aminobutyrates / Q000494:pharmacology*; D000818:Animals; D002415:Cats; D007478:Iontophoresis; D012160:Retina / Q000187:drug effects*; D012165:Retinal Ganglion Cells / Q000187:drug effects*; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000613:Aminobutyrates; D015763:2-Amino-5-phosphonovalerate; C012729:2-amino-4-phosphonobutyric acid; D014633:Valine