Dataset Information

Dopamine Regulation of GABAA Receptors Contributes to Light/Dark Modulation of the ON-Cone Bipolar Cell Receptive Field Surround in the Retina.

ABSTRACT: Cone bipolar cells are interneurons that receive synaptic input from cone photoreceptor cells and provide the output of the first synaptic layer of the retina. These cells exhibit center-surround receptive fields, a prototype of lateral inhibition between neighboring sensory cells in which stimulation of the receptive field center excites the cell whereas stimulation of the surrounding region laterally inhibits the cell. This fundamental sensory coding mechanism facilitates spatial discrimination and detection of stimulus edges. However, although it is well established that the receptive field surround is strongest when ambient or background illumination is most intense, e.g., at midday, and that the surround is minimal following maintained darkness, the synaptic mechanisms that produce and modulate the surround have not been resolved. Using electrical recording of bipolar cells under experimental conditions in which the cells exhibited surround light responses, and light and electron microscopic immunocytochemistry, we show in the rabbit retina that bright-light-induced activation of dopamine D1 receptors located on ON-center cone bipolar cell dendrites increases the expression and activity of GABAA receptors on the dendrites of the cells and that surround light responses depend on endogenous GABAA receptor activation. We also show that maintained darkness and D1 receptor blockade following maintained illumination and D1 receptor activation result in minimal GABAA receptor expression and activity and greatly diminished surrounds. Modulation of the D1/GABAA receptor signaling pathway of ON-cBC dendrites by the ambient light level facilitates detection of spatial details on bright days and large dim objects on moonless nights.

SUBMITTER: Chaffiol A

PROVIDER: S-EPMC5595654 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Dopamine Regulation of GABA<sub>A</sub> Receptors Contributes to Light/Dark Modulation of the ON-Cone Bipolar Cell Receptive Field Surround in the Retina.

Chaffiol Antoine A Ishii Masaaki M Cao Yu Y Mangel Stuart C SC

Current biology : CB 20170824 17

Cone bipolar cells are interneurons that receive synaptic input from cone photoreceptor cells and provide the output of the first synaptic layer of the retina. These cells exhibit center-surround receptive fields, a prototype of lateral inhibition between neighboring sensory cells in which stimulation of the receptive field center excites the cell whereas stimulation of the surrounding region laterally inhibits the cell. This fundamental sensory coding mechanism facilitates spatial discriminatio ...[more]

PMID: 28844643

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Project description:We previously reported strikingly normal morphologies and functional connectivities of regenerated retinal bipolar neurons (BPs) in zebrafish retinas sampled 60 days after a ouabain-mediated lesion of inner retinal neurons (60 DPI) (McGinn et al., 2018). Here we report early steps in the birth of BPs and formation of their dendritic trees and axonal arbors during regeneration. Adult zebrafish were subjected to ouabain-mediated lesion that destroys inner retinal neurons but spares photoreceptors and Müller glia, and were sampled at 13, 17, and 21 DPI, a timeframe over which plexiform layers reemerge. We show that this timeframe corresponds to reemergence of two populations of BPs (PKCα+ and nyx::mYFP+). Sequential BrdU, EdU incorporation reveals that similar fractions of PKCα+ BPs and HuC/D+ amacrine/ganglion cells are regenerated concurrently, suggesting that the sequence of neuronal production during retinal regeneration does not strictly match that observed during embryonic development. Further, accumulation of regenerated BPs appears protracted, at least through 21 DPI. The existence of isolated, nyx::mYFP+ BPs allowed examination of cytological detail through confocal microscopy, image tracing, morphometric analyses, identification of cone synaptic contacts, and rendering/visualization. Apically-projecting neurites (=dendrites) of regenerated BPs sampled at 13, 17, and 21 DPI are either truncated, or display smaller dendritic trees when compared to controls. In cases where BP dendrites reach the outer plexiform layer (OPL), numbers of dendritic tips are similar to those of controls at all sampling times. Further, by 13-17 DPI, BPs with dendritic tips reaching the outer nuclear layer (ONL) show patterns of photoreceptor connections that are statistically indistinguishable from controls, while those sampled at 21 DPI slightly favor contacts with double cone synaptic terminals over those of blue-sensitive cones. These findings suggest that once regenerated BP dendrites reach the OPL, normal photoreceptor connectomes are established, albeit with some plasticity. Through 17 DPI, some basally-projecting neurites (=axons) of regenerated nyx::mYFP+ BPs traverse long distances, branch into inappropriate layers, or appear to abruptly terminate. These findings suggest that, after a tissue-disrupting lesion, regeneration of inner retinal neurons is a dynamic process that includes ongoing genesis of new neurons and changes in BP morphology.

Project description:The influence of the mammalian retinal circadian clock on retinal physiology and function is widely recognized, yet the cellular elements and neural regulation of retinal circadian pacemaking remain unclear due to the challenge of long-term culture of adult mammalian retina and the lack of an ideal experimental measure of the retinal circadian clock. In the current study, we developed a protocol for long-term culture of intact mouse retinas, which allows retinal circadian rhythms to be monitored in real time as luminescence rhythms from a PERIOD2::LUCIFERASE (PER2::LUC) clock gene reporter. With this in vitro assay, we studied the characteristics and location within the retina of circadian PER2::LUC rhythms, the influence of major retinal neurotransmitters, and the resetting of the retinal circadian clock by light. Retinal PER2::LUC rhythms were routinely measured from whole-mount retinal explants for 10 d and for up to 30 d. Imaging of vertical retinal slices demonstrated that the rhythmic luminescence signals were concentrated in the inner nuclear layer. Interruption of cell communication via the major neurotransmitter systems of photoreceptors and ganglion cells (melatonin and glutamate) and the inner nuclear layer (dopamine, acetylcholine, GABA, glycine, and glutamate) did not disrupt generation of retinal circadian PER2::LUC rhythms, nor did interruption of intercellular communication through sodium-dependent action potentials or connexin 36 (cx36)-containing gap junctions, indicating that PER2::LUC rhythms generation in the inner nuclear layer is likely cell autonomous. However, dopamine, acting through D1 receptors, and GABA, acting through membrane hyperpolarization and casein kinase, set the phase and amplitude of retinal PER2::LUC rhythms, respectively. Light pulses reset the phase of the in vitro retinal oscillator and dopamine D1 receptor antagonists attenuated these phase shifts. Thus, dopamine and GABA act at the molecular level of PER proteins to play key roles in the organization of the retinal circadian clock.

Dataset Information

Dopamine Regulation of GABAA Receptors Contributes to Light/Dark Modulation of the ON-Cone Bipolar Cell Receptive Field Surround in the Retina.

Publications

Dopamine Regulation of GABA<sub>A</sub> Receptors Contributes to Light/Dark Modulation of the ON-Cone Bipolar Cell Receptive Field Surround in the Retina.

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