Dopaminergic Modulation of Signal Processing in a Subset of Retinal Bipolar Cells

Abstract

The retina and the olfactory bulb are the gateways to the visual and olfactory systems, respectively, similarly using neural networks to initiate sensory signal processing. Sensory receptors receive signals that are transmitted to neural networks before projecting to primary cortices. These networks filter sensory signals based on their unique features and adjust their sensitivities by gain control systems. Interestingly, dopamine modulates sensory signal transduction in both systems. In the retina, dopamine adjusts the retinal network for daylight conditions ("light adaptation"). In the olfactory system, dopamine mediates lateral inhibition between the glomeruli, resulting in odorant signal decorrelation and discrimination. While dopamine is essential for signal discrimination in the olfactory system, it is not understood whether dopamine has similar roles in visual signal processing in the retina. To elucidate dopaminergic effects on visual processing, we conducted patch-clamp recording from second-order retinal bipolar cells, which exhibit multiple types that can convey different temporal features of light. We recorded excitatory postsynaptic potentials (EPSPs) evoked by various frequencies of sinusoidal light in the absence and presence of a dopamine receptor 1 (D 1 R) agonist or antagonist. Application of a D 1 R agonist, SKF-38393, shifted the peak temporal responses toward higher frequencies in a subset of bipolar cells. In contrast, a D 1 R antagonist, SCH-23390, reversed the effects of SKF on these types of bipolar cells. To examine the mechanism of dopaminergic modulation, we recorded voltage-gated currents, hyperpolarizationactivated cyclic nucleotide-gated (HCN) channels, and low-voltage activated (LVA) Ca 2+ channels. SKF modulated HCN and LVA currents, suggesting that these channels are the target of D 1 R signaling to modulate visual signaling in these bipolar cells. Taken together, we found that dopamine modulates the temporal tuning of a subset of retinal bipolar cells. Consequently, we determined that dopamine plays a role in visual signal processing, which is similar to its role in signal decorrelation in the olfactory bulb.

Dopamine-Mediated Circadian and Light/Dark-Adaptive Modulation of Chemical and Electrical Synapses in the Outer Retina

“…Recent work has suggested that D 1 Rs are expressed by most mouse cBCs, but not by all cBC subtypes (Farshi et al, 2016 ) and that D 1 R effects may be cBC subtype-specific (Hellmer et al, 2020 ). These results raise the interesting possibility that one important effect of D 1 Rs is to decorrelate the activity of different cBC subtypes, implying that ganglion cell subtypes and their post-synaptic targets through the visual system (Caldwell and Daw, 1978 ; Mangel et al, 1983 ; Troy and Shou, 2002 ; Wienbar and Schwartz, 2017 ) may be differentially affected as well.…”

Activation of oxytocin receptors in mouse GABAergic amacrine cells modulates retinal dopaminergic signaling

“…S7B). Retinal DA is reported to modulate the activity of bipolar cells and ERG b-wave amplitude via DA receptors, especially the D1 receptor [ 50 – 53 ]. To establish the involvement of DA signaling, DA D1 receptor antagonist—SCH23390—was intraperitoneally injected ~ 30 min before oxytocin application, and the effect of oxytocin-induced b-wave amplitude reduction disappeared (Fig.…”

“…DA D1 and D2 receptors are differently expressed in the retina, with D1 receptors expressed in a broad range of retinal neurons, whereas D2 receptors are mainly in photoreceptors and DA neurons [ 55 , 71 ]. Activating D1 receptors will increase the activity of GABA(A) receptors on dendrites of ON bipolar cells and also suppress voltage-gated calcium currents in some bipolar cells, which leads to a strong inhibition of the activity of bipolar cells and the reduction of ERG b-wave amplitude [ 52 , 53 ]. Previous studies also reported that the application of exogenous DA and its agonist decreased the amplitude of the b-wave in the mammalian retina [ 51 , 72 ].…”

Is there any correlation between alpha-synuclein levels in tears and retinal layer thickness in Parkinson's disease?

“…43,46,47 Dopamine is a retina neurotransmitter that regulates neural activity and integrates visual information. 48,49 The nuclei of dopaminergic cells are situated predominantly in the inner layers close to ganglion cells. Excessive glutamate synthesis, neuronal death, and cellular dysregulation may result from a dopamine deficit.…”