Dopaminergic modulation of ganglion-cell photoreceptors in rat

Matthew Van Hook, Kwoon Y. Wong, David M. Berson

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

A novel class of photoreceptors, the intrinsically photosensitive retinal ganglion cells (ipRGCs), express the photopigment melanopsin and drive non-image-forming responses to light such as circadian photoentrainment, the pupillary light reflex and suppression of nocturnal melatonin production in the pineal. Because dendrites from one subclass of these cells - the M1-type ipRGCs - make presumptive synaptic contacts at sites of dopamine release from dopaminergic amacrine cells, they are prime targets for modulation by dopamine, a neuromodulator implicated in retinal circadian rhythms and light adaptation. In patch-clamp recordings from ipRGCs in intact rat retinas, dopamine attenuated the melanopsin-based photocurrent. We confirmed that this was the result of direct action on ipRGCs by replicating the effect in dissociated ipRGCs that were isolated from influences of other retinal neurons. In these recordings, the D1-family dopamine receptor agonist SKF38393 attenuated the photocurrent, caused a modest depolarization, and reduced the input resistance of ipRGCs. The D2-family agonist quinpirole had no effect on the photocurrent. Single-cell reverse-transcriptase polymerase chain reaction revealed that the majority of ipRGCs tested expressed drd1a, the gene coding for the D1a dopamine receptor. This finding was supported by immunohistochemical localization of D1a receptor protein in melanopsin-expressing ganglion cells. Finally, the adenylate cyclase activator forskolin, applied in combination with the phosphodiesterase inhibitor IBMX (isobutylmethylxanthine), mimicked the effects of SKF38393 on the ipRGC photocurrent, membrane potential and input resistance, consistent with a D1-receptor signaling pathway. These data suggest that dopamine, acting via D1-family receptors, alters the responses of ipRGCs and thus of non-image-forming vision.

Original languageEnglish (US)
Pages (from-to)507-518
Number of pages12
JournalEuropean Journal of Neuroscience
Volume35
Issue number3-4
DOIs
StatePublished - Feb 1 2012

Fingerprint

Photoreceptor Cells
Retinal Ganglion Cells
Ganglia
Dopamine
2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine
Pupillary Reflex
Ocular Adaptation
Quinpirole
Retinal Neurons
Amacrine Cells
Light
Phosphodiesterase Inhibitors
Dopamine Agonists
Dopamine Receptors
Colforsin
Melatonin
Dendrites
Circadian Rhythm
Reverse Transcriptase Polymerase Chain Reaction
Adenylyl Cyclases

Keywords

  • Cyclic AMP (cAMP)
  • D1 receptor
  • Intrinsically photosensitive retinal ganglion cells (ipRGCs)
  • Melanopsin
  • Retina

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Dopaminergic modulation of ganglion-cell photoreceptors in rat. / Van Hook, Matthew; Wong, Kwoon Y.; Berson, David M.

In: European Journal of Neuroscience, Vol. 35, No. 3-4, 01.02.2012, p. 507-518.

Research output: Contribution to journalArticle

Van Hook, Matthew ; Wong, Kwoon Y. ; Berson, David M. / Dopaminergic modulation of ganglion-cell photoreceptors in rat. In: European Journal of Neuroscience. 2012 ; Vol. 35, No. 3-4. pp. 507-518.
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