Physiological effects of chronic and acute application of N-methyl- d-aspartate and 5-amino-phosphonovaleric acid to the optic tectum of Rana pipiens frogs

Abstract

Visually elicited activity contributes to the formation of orderly connections in the optic tectum of frogs. Glutamate receptors of the N-methyl- d-aspartate class participate in this process. Blocking those receptors interferes with activity-dependent refinement of maps in normal frogs and of ocular dominance bands in surgically produced animals with three eyes. Chronic application of N-methyl- d-aspartate sharpens the bands. The possibility that 5-amino-phosphonovaleric acid depresses tectal responsiveness was motivation for studying the effects of 5-amino-phosphonovaleric acid and N-methyl- d-aspartate applied both chronically and acutely. We evaluated tectal responsiveness to visual input by presenting flashes of light to one eye and recording responses in the ipsilateral tectal lobe. This method reveals the output of the tectal cells contralateral to the stimulated eye. These cells project via the nucleus isthmi to the opposite tectal lobe. We also mapped the receptive field dimensions of the crossed isthmotectal axons. Our results show that acute topical application of 500 μM or 1 mM N-methyl- d-aspartate dramatically increases spontaneous activity, while 100 μM N-methyl- d-aspartate causes little change. Chronic treatment with N-methyl- d-aspartate at a low dose (estimated to be in the micromolar range) shown to influence retinotectal mapping, reduces response latencies but produces no statistically significant changes in tectal cell firing rates or receptive field size. Acute application of 5-amino-phosphonovaleric acid produces complex results: 10 μM produces no changes in firing, 100 μM 5-amino-phosphonovaleric acid decreases firing, and doses of 500−100 μM increase the firing. Chronic micromolar 5-amino-phosphono-valeric acid, at doses capable of blocking activity-dependent refinement of retinotectal maps, decreases spontaneous firing and the latency of visually evoked bursts but otherwise produces no notable changes in tectal cell responses. Our data support the hypothesis that chronic treatment with N-methyl- d-aspartate and 5-amino-phos-phonovaleric acid influence retinotectal development by affecting the N-methyl- d-aspartate receptor specifically and not by causing overall changes in tectal activity.