Synaptic transmission at N-methyl-D-aspartate receptors in the proximal retina of the mudpuppy

Abstract

The effects of excitatory amino acid analogues and antagonists on retinal ganglion cells were studied using intracellular recording in the superfused mudpuppy eyecup preparation. Aspartate, glutamate, quisqualate (QA), kainate (KA) and N-methylaspartate (NMA) caused depolarization and decreased input resistance in all classes of ganglion cells. The order of sensitivity was QA greater than or equal to KA greater than NMA greater than aspartate greater than or equal to glutamate. All of these agonists were effective when transmitter release was blocked with 4 mM-Co2+ or Mn2+, indicating that they acted at receptor sites on the ganglion cells. At a concentration of 250 microM, 2-amino-5-phosphonovalerate (APV) blocked the responses of all ganglion cells to NMA, but not to QA or KA, indicating that NMA acts at different receptor sites from QA or KA. Responses to bath-applied aspartate and glutamate were reduced slightly or not at all in the presence of APV, indicating that they were acting mainly at non-NMDA (N-methyl-D-aspartate) receptors. In all ganglion cells 250 microM-APV strongly suppressed the sustained responses driven by the 'on'-pathway but not those driven by the 'off'-pathway. In most on-off ganglion cells the transient excitatory responses at 'light on' and 'light off' were not reduced by 500 microM-APV. APV-resistant transient excitatory responses were also present in some on-centre ganglion cells. APV did not block the transient inhibitory responses in any class of ganglion cells. At concentrations which blocked the sustained responses of ganglion cells, APV did not affect the sustained responses of bipolar cells, indicating that it acted at sites which were post-synaptic to bipolar cells. The simplest interpretation of these results is that the transmitter released by depolarizing bipolar cells acts at NMDA receptors on sustained depolarizing amacrine and ganglion cells. It may act at non-NMDA receptors at synapses which produce transient excitatory responses, but this could not be proved. The transmitter released by hyperpolarizing bipolar cells does not appear to act at NMDA receptors on any post-synaptic cells.