Inhibition of adult rat retinal ganglion cells by D1-type dopamine receptor activation.
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 I(h). Consistent with the reduced rate of spike rise, dopamine reduced voltage-gated Na(+) current (I(Na)) amplitude, and tetrodotoxin, at doses that reduced I(Na) as moderately as dopamine, also inhibited spiking. These results provide the first direct evidence that D(1)-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.
Hayashida
Yuki
Y
Department of Neurobiology, University of California, Davis, California 95616, USA.
Rodríguez
Carolina Varela
CV
Ogata
Genki
G
Partida
Gloria J
GJ
Oi
Hanako
H
Stradleigh
Tyler W
TW
Lee
Sherwin C
SC
Colado
Anselmo Felipe
AF
Ishida
Andrew T
AT
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000378:metabolism; D003911:Dextrans; D004298:Dopamine / Q000378:metabolism*; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D005260:Female; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D056347:Neuroanatomical Tract-Tracing Techniques; D056325:Neuronal Tract-Tracers; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D051381:Rats; D020318:Rats, Long-Evans; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000378:metabolism*; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D014785:Vision, Ocular / Q000187:drug effects / Q000502:physiology
D003911:Dextrans; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D056325:Neuronal Tract-Tracers; D017447:Receptors, Dopamine D1; D015222:Sodium Channels; D000242:Cyclic AMP; D004298:Dopamine