Electrical synapses between AII amacrine cells in the retina: Function and modulation

Adaptation enables the visual system to operate across a large range of background light intensities. There is evidence that one component of this adaptation is mediated by modulation of gap junctions functioning as electrical synapses, thereby tuning and functionally optimizing specific retinal microcircuits and pathways. The AII amacrine cell is an interneuron found in most mammalian retinas and plays a crucial role for processing visual signals in starlight, twilight and daylight. AII amacrine cells are connected to each other by gap junctions, potentially serving as a substrate for signal averaging and noise reduction, and there is evidence that the strength of electrical coupling is modulated by the level of background light. Whereas there is extensive knowledge concerning the retinal microcircuits that involve the AII amacrine cell, it is less clear which signaling pathways and intracellular transduction mechanisms are involved in modulating the junctional conductance between electrically coupled AII amacrine cells. Here we review the current state of knowledge, with a focus on the recent evidence that suggests that the modulatory control involves activity-dependent changes in the phosphorylation of the gap junction channels between AII amacrine cells, potentially linked to their intracellular Ca2+ dynamics.acceptedVersio

Dopaminergic Modulation of Gap Junction Permeability Between Amacrine Cells in Mammalian Retina

In mammalian retina, the rod bipolar cells synapse on the AII amacrine cells, which are therefore the third-order neurons in the rod-signal pathway. The AII amacrine cells are connected by gap junctions, both to each other and to fourth-order, On-center cone bipolar cells. They also receive synaptic input from the dopaminergic amacrine cells, and in this study, we investigated whether dopamine modulates the permeability of the gap junctions between AII amacrine cells in the isolated rabbit retina. The small biotinylated tracer Neurobiotin was injected into nuclear yellow-labeled AII cells under direct microscopic control. The extent of tracer coupling to neighboring AII cells, 40-60 min after Neurobiotin injection (0.5 nA for 60 sec), provided a standard measure of the permeability of the homologous gap junctions. Under control conditions, individual All amacrine cells were coupled to 73 +/- 15 neighboring cells, and this was unaffected by changes in pH from 6.6 to 7.8. Exogenous dopamine significantly reduced the tracer coupling at concentrations as low as 10 nM (26 +/- 16 cells), with the eff ect increasing with dopamine concentration up to 10 muM (6 +/- 4 cells). The uncoupling effect of dopamine was both blocked by the selective D1 antagonist SCH-23390 (10 muM) and mimicked by the specific D1 agonist SKF-38393 (500 muM). Moreover, the All amacrine cells were also uncoupled when the retina was incubated in forskolin (60 muM) and isobutylmethylxanthine (200 muM). Taken together, these results indicated that the uncoupling was mediated by a D1-like receptor that stimulates cAMP production. Although the selective D1 antagonist on its own did not increase tracer coupling, suggesting that there was little release of endogenous dopamine in the superfused photo-bleached retina, veratridine-evoked release of endogenous transmitters did uncouple the AII amacrine cells, and this effect was blocked by the specific D1 antagonist

Horizontal cell axon terminals in growing goldfish

In the retina of teleost fish, cone horizontal cell axons penetrate the inner nuclear layer, where they enlarge into fusiform terminal swellings. The present study shows that horizontal cell axon terminals enlarge disproportionately during postembryonic growth of the retina in juvenile and adult goldfish: the relative volume of axon terminals increases almost 20-fold, while the volume of the entire retina increases only about fourfold during a 2-3-yr period. The enlarging axon terminals fill in the gaps created as the numerical density of nuclei in the inner nuclear layer falls. Horizontal cell axon terminals are thought to participate in cone-dominated visual pathways, although their precise role is unclear. The results of this study suggest that a comparison of horizontal cell function in small and large fish might help to resolve this issue.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/28295/1/0000049.pd

Feedback from retinal ganglion cells to the inner retina

Retinal ganglion cells (RGCs) are thought to be strictly postsynaptic within the retina. They carry visual signals from the eye to the brain, but do not make chemical synapses onto other retinal neurons. Nevertheless, they form gap junctions with other RGCs and amacrine cells, providing possibilities for RGC signals to feed back into the inner retina. Here we identified such feedback circuitry in the salamander and mouse retinas. First, using biologically inspired circuit models, we found mutual inhibition among RGCs of the same type. We then experimentally determined that this effect is mediated by gap junctions with amacrine cells. Finally, we found that this negative feedback lowers RGC visual response gain without affecting feature selectivity. The principal neurons of the retina therefore participate in a recurrent circuit much as those in other brain areas, not being a mere collector of retinal signals, but are actively involved in visual computations

Studies on horizontal cells of the carp retina with special reference to temperature and calcium

Carp [Cyprinus carpio) were acclimated to 8±1 C, 16±1.5 C and 26±1 C. Dark adapted retinas were isolated and light induced responses of HI horizontal cells recorded. The dynamic range of these cells was affected by temperature, showing a decrease on heating or cooling from an optimum temperature. The effect of acclimation was to shift this optimum in an adaptive manner. A move from 16 C to 8 C resulted in ~44% acclimation, while a move from 16 C to 26 C resulted in ~67% acclimation. The rates of change of membrane potential and latency of the response also showed adaptive changes on acclimation. Isolated horizontal cells were voltage clamped using the whole cell patch clamp technique. The current-voltage (I-V) relationship of the prominent anomalous rectifier current was displaced by changes in the extracellular potassium concentration and was blocked by Ba(^2+) or Rb(^+). Its amplitude did not appear to be affected by thermal acclimation. A pharmacologically isolated sustained Ca(^2+) current, with an I-V relationship characteristic of an L-type current, also showed no apparent thermal acclimation. The ratiometric calcium indicator Fura-2 was used to measure the intracellular calcium concentration in isolated horizontal cells. The intracellular calcium concentration rose on depolarization of the cells, in an extracellular calcium concentration dependent manner. This increase was blocked by various metal ions with varying sensitivities: La(^3+)>Cd(^2+)>Cu(^2+)>Co≥Ni(^2+). The rate of change of intracellular calcium concentration was increased by increased temperature, but did not appear to be affected by thermal acclimation. Sustained depolarizations (up to 15 minutes) resulted in sustained elevations in intracellular calcium concentration proportional to the degree of depolarization. Possible mechanisms underlying the long and short term effects of temperature on the horizontal cell responses are discussed. The sustained calcium current and the intracellular calcium concentration changes are disscused in terms of the potential roles of this current and the significance of the subsequent intracellular calcium concentration changes

Cover Article Research Articles, Systems/Circuits

Double cones are the most common photoreceptor cell type in most avian retinas, but their precise functions remain a mystery. Among their suggested functions are luminance detection, polarized light detection, and light-dependent, radical-pair-based magnetoreception. To better understand the function of double cones, it will be crucial to know how they are connected to the neural network in the avian retina. Here we use serial sectioning, multi-beam scanning electron microscopy (ssmSEM) to investigate double cone anatomy and connectivity with a particular focus on their contacts to other photoreceptor and bipolar cells in the chicken retina. We found that double cones are highly connected with neighbouring double cones and with other photoreceptor cells through telodendria-to-terminal and telodendria-to-telodendria contacts. We also identified 15 bipolar cell types based on their axonal stratifications, photoreceptor contact pattern, soma position, and dendritic and axonal field mosaics. Thirteen of these 15 bipolar cell types contacted at least one or both members of the double cone. All bipolar cells were bi- or multistratified. We also identified surprising contacts between other cone types and between rods and cones. Our data indicate a much more complex connectivity network in the outer plexiform layer of the avian retina than originally expected