Inhibition of adult rat retinal ganglion cells by D1-type dopamine receptor activation

Yuki Hayashida, Carolina Varela Rodríguez, Genki Ogata, Gloria J. Partida, Hanako Oi, Tyler W. Stradleigh, Sherwin C. Lee, Anselmo Felipe Colado, Andrew Ishida

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

The spike output of neural pathways can be regulated by modulating output neuron excitability and/or their synaptic inputs. Dopaminergic interneurons synapse onto cells that route signals to mammalian retinal ganglion cells, but it is unknown whether dopamine can activate receptors in these ganglion cells and, if it does, how this affects their excitability. Here, we show D 1a receptor-like immunoreactivity in ganglion cells identified in adult rats by retrogradely transported dextran, and that dopamine, D 1-type receptor agonists, and cAMP analogs inhibit spiking in ganglion cells dissociated from adult rats. These ligands curtailed repetitive spiking during constant current injections and reduced the number and rate of rise of spikes elicited by fluctuating current injections without significantly altering the timing of the remaining spikes. Consistent with mediation by D 1-type receptors, SCH-23390 [R-(+)-7-chloro-8-hydroxy-3-methyl-1- phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine] reversed the effects of dopamine on spikes. Contrary to a recent report, spike inhibition by dopamine was not precluded by blocking Ih. Consistent with the reduced rate of spike rise, dopamine reduced voltage-gated Na+ current (INa) amplitude, and tetrodotoxin, at doses that reduced INa as moderately as dopamine, also inhibited spiking. These results provide the first direct evidence that D1-type dopamine receptor activation can alter mammalian retinal ganglion cell excitability and demonstrate that dopamine can modulate spikes in these cells by a mechanism different from the presynaptic and postsynaptic means proposed by previous studies. To our knowledge, our results also provide the first evidence that dopamine receptor activation can reduce excitability without altering the temporal precision of spike firing.

Original languageEnglish (US)
Pages (from-to)15001-15016
Number of pages16
JournalJournal of Neuroscience
Volume29
Issue number47
DOIs
StatePublished - Nov 25 2009

ASJC Scopus subject areas

  • Neuroscience(all)

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    Hayashida, Y., Rodríguez, C. V., Ogata, G., Partida, G. J., Oi, H., Stradleigh, T. W., Lee, S. C., Colado, A. F., & Ishida, A. (2009). Inhibition of adult rat retinal ganglion cells by D1-type dopamine receptor activation. Journal of Neuroscience, 29(47), 15001-15016. https://doi.org/10.1523/JNEUROSCI.3827-09.2009