Dopamine differentially affects retinal circuits to shape the retinal code.

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 used two-photon targeted patch-clamp to target a specific RGC subtype, the transient-Off-αRGC. In line with our MEA recordings, apomorphine did not increase the antagonistic surround of transient-Off-αRGCs 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-αRGC'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. KEY POINTS: Receptive fields of retinal ganglion cells (RGCs) have a center-surround organisation and previous work has shown that this organisation can be modulated by dopamine in a light-intensity dependent manner. Dopamine is thought to enhance RGCs' antagonistic surround, but a detailed understanding of how different RGC subtypes are affected is missing. Using a multielectrode array recordings, clustering analysis and pharmacological manipulations, we found that dopamine can either enhance or weaken antagonistic surrounds, and also change response kinetics, of RGCs in a subtype-specific manner. We performed targeted patch-clamp recordings of one RGC subtype, the transient-Off-αRGC, and identified the underlying circuits via which dopamine shapes its receptive field. Our findings demonstrate that dopamine acts in a subtype-specific manner and can have complex effects, which has implications for other retinal computations that rely on receptive field structure. Abstract figure legend This study focusses on the receptive field organisation of retinal ganglion cells (RGCs), the output neurons of the retina (left). RGCs display a center-surround receptive field organization. Here, we asked how the neuromodulator dopamine, which is released by the dopaminergic amacrine cell, alters RGCs' receptive field organization. We performed large-scale multi-electrode array recordings of RGCs while presenting visual stimuli in control condition and in the presence of the dopamine receptor agonist apomorphine. After clustering RGCs into functional subtype, we identified subtypes whose receptive field organization is affected by apomorphine, and found that effects were subtype-specific. We then performed targeted patch clamp recordings of an RGC subtype that was affected, the transient Off-αRGC, for a detailed characterization of how dopamine shapes its receptive field. This article is protected by copyright. All rights reserved.