4.6 Article

Dopamine differentially affects retinal circuits to shape the retinal code

Journal

JOURNAL OF PHYSIOLOGY-LONDON
Volume 601, Issue 7, Pages 1265-1286

Publisher

WILEY
DOI: 10.1113/JP284215

Keywords

apomorphine; centre-surround receptive field; dopamine; multielectrode array; retina; retinal ganglion cells; transient Off-alpha RGC

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Dopamine has subtype-specific effects on retinal ganglion cells (RGCs) in the mouse retina. The non-selective dopamine receptor agonist apomorphine can either increase or decrease RGCs' surround strength depending on their subtype. D-1- and D-2-like receptor blockers have opposite effects on RGC subtypes, with D-2-R blocker reducing surround antagonism and D-1-R blocker leading to surround activation.
Dopamine has long been reported to enhance antagonistic surrounds of retinal ganglion cells (RGCs). Yet, the retina contains many different RGC subtypes and the effects of dopamine can be subtype-specific. Using multielectrode array (MEA) recordings we investigated how dopamine shapes the receptive fields of RGCs in the mouse retina. We found that the non-selective dopamine receptor agonist apomorphine can either increase or decrease RGCs' surround strength, depending on their subtype. We then used two-photon targeted patch-clamp to target a specific RGC subtype, the transient-Off-alpha RGC. In line with our MEA recordings, apomorphine did not increase the antagonistic surround of transient-Off-alpha RGCs but enhanced their responses to Off stimuli in the centre receptive field. Both D-1- and D-2-like family receptor (D-1-R and D-2-R) blockers had the opposite effect and reduced centre-mediated responses, but differently affected transient-Off-alpha RGC's surround. While D-2-R blocker reduced surround antagonism, D-1-R blocker led to surround activation, revealing On responses to large stimuli. Using voltage-clamp recordings we separated excitatory inputs from Off cone bipolar cells and inhibitory inputs from the primary rod pathway. In control conditions, cone inputs displayed strong surround antagonism, while inputs from the primary rod pathway showed no surround. Yet, the surround activation in the D-1-R blockade originated from the primary rod pathway. Our findings demonstrate that dopamine differentially affects RGC subtypes via distinct pathways, suggesting that dopamine has a more complex role in shaping the retinal code than previously reported

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