scholarly journals How do horizontal cells ‘talk’ to cone photoreceptors? Different levels of complexity at the cone-horizontal cell synapse

2017 ◽  
Vol 595 (16) ◽  
pp. 5495-5506 ◽  
Author(s):  
Camille A. Chapot ◽  
Thomas Euler ◽  
Timm Schubert
1998 ◽  
Vol 79 (1) ◽  
pp. 190-196 ◽  
Author(s):  
Lubor Gaal ◽  
Botond Roska ◽  
Serge A. Picaud ◽  
Samuel M. Wu ◽  
Robert Marc ◽  
...  

Gaal, Lubor, Botond Roska, Serge A. Picaud, Samuel M. Wu, Robert Marc, and Frank S. Werblin. Postsynaptic response kinetics are controlled by a glutamate transporter at cone photoreceptors. J. Neurophysiol. 79: 190–196, 1998. We evaluated the role of the sodium/glutamate transporter at the synaptic terminals of cone photoreceptors in controlling postsynaptic response kinetics. The strategy was to measure the changes in horizontal cell response rate induced by blocking transporter uptake in cones with dihydrokainate (DHK). DHK was chosen as the uptake blocker because, as we show through autoradiographic uptake measurements, DHK specifically blocked uptake in cones without affecting uptake in Mueller cells. Horizontal cells depolarized from about −70 to −20 mV as the exogenous glutamate concentration was increased from ∼1 to 40 μM, so horizontal cells can serve as “glutamate electrodes” during the light response. DHK slowed the rate of hyperpolarization of the horizontal cells in a dose-dependent way, but didn't affect the kinetics of the cone responses. At 300 μM DHK, the rate of the horizontal cell hyperpolarization was slowed to only 17 ± 8.5% (mean ± SD) of control. Translating this to changes in glutamate concentration using the slice dose response curve as calibration in Fig. 2 , DHK reduced the rate of removal of glutamate from ∼0.12 to 0.031 μM/s. The voltage dependence of uptake rate in the transporter alone was capable of modulating glutamate concentration: we blocked vesicular released glutamate with bathed 20 mM Mg2+ and then added 30 μM glutamate to the bath to reestablish a physiological glutamate concentration level at the synapse and thereby depolarize the horizontal cells. Under these conditions, a light flash elicited a 17-mV hyperpolarization in the horizontal cells. When we substituted kainate, which is not transported, for glutamate, horizontal cells were depolarized but light did not elicit any response, indicating that the transporter alone was responsible for the removal of glutamate under these conditions. This suggests that the transporter was both voltage dependent and robust enough to modulate glutamate concentration. The transporter must be at least as effective as diffusion in removing glutamate from the synapse because there is only a very small light response once the transporter is blocked. The transporter, via its voltage dependence on cone membrane potential, appears to contribute significantly to the control of postsynaptic response kinetics.[Figure: see text]


2017 ◽  
Author(s):  
Camille A. Chapot ◽  
Christian Behrens ◽  
Luke E. Rogerson ◽  
Tom Baden ◽  
Sinziana Pop ◽  
...  

SummaryThe mouse retina contains a single type of horizontal cell, a GABAergic interneuron that samples from all cone photoreceptors within reach and modulates their glutamatergic output via parallel feedback mechanisms. Because horizontal cells form an electrically-coupled network, they have been implicated in global signal processing, such as large scale contrast enhancement. Recently, it has been proposed that horizontal cells can also act locally at the level of individual cone photoreceptors. To test this possibility physiologically, we used two-photon microscopy to record light stimulus-evoked Ca2+signals in cone axon terminals and horizontal cell dendrites as well as glutamate release in the outer plexiform layer. By selectively stimulating the two mouse cone opsins with green and UV light, we assessed whether signals from individual cones remain “isolated” within horizontal cell dendritic tips, or whether they spread across the dendritic arbour. Consistent with the mouse‘s opsin expression gradient, we found that the Ca2+signals recorded from dendrites of dorsal horizontal cells were dominated by M- and those of ventral horizontal cells by S-opsin activation. The signals measured in neighbouring horizontal cell dendritic tips varied markedly in their chromatic preference, arguing against global processing. Rather, our experimental data and results from biophysically realistic modelling support the idea that horizontal cells can process cone input locally, extending the “classical” view of horizontal cells function. Pharmacologically removing horizontal cells from the circuitry reduced the sensitivity of the cone signal to low frequencies, suggesting that local horizontal cell feedback shapes the temporal properties of cone output.HighlightsLight-evoked Ca2+signals in horizontal cell dendrites reflect opsin gradientChromatic preferences in neighbouring dendritic tips vary markedlyMouse horizontal cells process cone photoreceptor input locallyLocal horizontal cell feedback shapes the temporal properties of cone outputeTOC BlurbChapot et al. show that local light responses in mouse horizontal cell dendrites inherit properties, including chromatic preference, from the presynaptic cone photoreceptor, suggesting that their dendrites can provide “private” feedback to cones, for instance, to shape the temporal filtering properties of the cone synapse.


2000 ◽  
Vol 84 (3) ◽  
pp. 1256-1265 ◽  
Author(s):  
D. A. Kraaij ◽  
H. Spekreijse ◽  
M. Kamermans

Under constant light-adapted conditions, vision seems to be rather linear. However, the processes underlying the synaptic transmission between cones and second-order neurons (bipolar cells and horizontal cells) are highly nonlinear. In this paper, the gain-characteristics of the transmission from cones to horizontal cells and from horizontal cells to cones are determined with and without negative feedback from horizontal cells to cones. It is shown that 1) the gain-characteristic from cones to horizontal cells is strongly nonlinear without feedback from horizontal cells, 2) the gain-characteristic between cones and horizontal cells becomes linear when feedback is active, and 3) horizontal cells feed back to cones via a linear mechanism. In a quantitative analysis, it will be shown that negative feedback linearizes the synaptic transmission between cones and horizontal cells. The physiological consequences are discussed.


1989 ◽  
Vol 93 (4) ◽  
pp. 681-694 ◽  
Author(s):  
M Kamermans ◽  
B W van Dijk ◽  
H Spekreijse ◽  
R C Zweypfenning

The spatial and color coding of the monophasic horizontal cells were studied in light- and dark-adapted retinae. Slit displacement experiments revealed differences in integration area for the different cone inputs of the monophasic horizontal cells. The integration area measured with a 670-nm stimulus was larger than that measured with a 570-nm stimulus. Experiments in which the diameter of the test spot was varied, however, revealed at high stimulus intensities a larger summation area for 520-nm stimuli than for 670-nm stimuli. The reverse was found for low stimulus intensities. To investigate whether these differences were due to interaction between the various cone inputs to the monophasic horizontal cell, adaptation experiments were performed. It was found that the various cone inputs were not independent. Finally, some mechanisms for the spatial and color coding will be discussed.


1996 ◽  
Vol 76 (3) ◽  
pp. 2005-2019 ◽  
Author(s):  
W. A. Hare ◽  
W. G. Owen

1. It is widely believed that signals contributing to the receptive field surrounds of retinal bipolar cells pass from horizontal cells to bipolar cells via GABAergic synapses. To test this notion, we applied gamma-aminobutyric acid (GABA) agonists and antagonists to isolated, perfused retinas of the salamander Ambystoma tigrinum while recording intracellularly from bipolar cells, horizontal cells, and photoreceptors. 2. As we previously reported, administration of the GABA analogue D-aminovaleric acid in concert with picrotoxin did not block horizontal cell responses or the center responses of bipolar cells but blocked the surround responses of both on-center and off-center bipolar cells. 3. Surround responses were not blocked by the GABA, antagonists picrotoxin or bicuculline, the GABAB agonist baclofen or the GABAB antagonist phaclofen, and the GABAC antagonists picrotoxin or cis-4-aminocrotonic acid. Combinations of these drugs were similarly ineffective. 4. GABA itself activated a powerful GABA uptake mechanism in horizontal cells for which nipecotic acid is a competitive agonist. It also activated, both in horizontal cells and bipolar cells, large GABAA conductances that shunted light responses but that could be blocked by picrotoxin or bicuculline. 5. GABA, administered together with picrotoxin to block the shunting effect of GABAA activation, did not eliminate bipolar cell surround responses at concentrations sufficient to saturate the known types of GABA receptors. 6. Surround responses were not blocked by glycine or its antagonist strychnine, or by combinations of drugs designed to eliminate GABAergic and glycinergic pathways simultaneously. 7. Although we cannot fully discount the involvement of a novel GABAergic synapse, the simplest explanation of our findings is that the primary pathway mediating the bipolar cell's surround is neither GABAergic nor glycinergic.


1996 ◽  
Vol 76 (4) ◽  
pp. 2307-2315 ◽  
Author(s):  
D. G. McMahon ◽  
L. V. Ponomareva

1. In the retina, as in other regions of the vertebrate central nervous system, glutamate receptors mediate excitatory chemical synaptic transmission and are a critical site for the regulation of cellular communication. In this study, retinal horizontal cells from the hybrid less were dissociated in cell culture, voltage clamped by the whole cell recording technique, and the currents evoked by application of excitatory amino acids recorded. 2. Responses to glutamate and its agonist kainate were reduced by approximately 50% in the presence of the nitric oxide (NO) donors sodium nitroprusside and S-nitroso-N-acetylpenicillamine. The effect of these compounds was blocked by the NO scavenger hemoglobin. 3. This effect of NO donors on kainate currents could be mimicked by the application of a membrane permeable guanosine 3',5'-cyclic monophosphate (cGMP) analogue, 8-Br-cGMP. The NO effect was also blocked by application of the guanylate cyclase inhibitor LY-83583, and by a protein kinase G inhibitor peptide. 4. In H1-type horizontal cells, stimulation of endogenous nitric oxide synthase with L-arginine reduced kainate responses, whereas application of D-arginine had no effect. 5. This receptor modulation mechanism may act in concert with other pre- and postsynaptic mechanisms to modify horizontal cell synaptic function according to the adaptational state of the retina and also may protect horizontal cells from glutamate excitotoxicity.


1997 ◽  
Vol 14 (2) ◽  
pp. 207-212 ◽  
Author(s):  
Keith M. Studholme ◽  
Stephen Yazulla

AbstractThere are four types of horizontal cell in the goldfish retina, three cone- and one rod-type. The neurotransmitter of only one type, the H1 (cone) horizontal cell, has been identified as GABA. 3H-adenosine uptake was examined as a possible marker for the other classes of horizontal cell. Isolated goldfish retinae were incubated in 3H-adenosine (10–40 μCi) in HEPES-buffered saline for 30 min, then fixed, embedded in plastic, and processed for light-microscopic autoradiography (ARG). For double-label immuno/ARG studies, l-μm-thick sections were processed for GABA postembed immunocytochemistry, then for ARG. 3H-adenosine uptake was localized to cone photoreceptors, presumed precursor cells in the proximal outer nuclear layer, and to a single, continuous row of horizontal cell bodies in the inner nuclear layer. No uptake was localized to the region of horizontal cell axon terminals. 3H-adenosine uptake did not colocalize with GABA-IR in H1 horizontal cells, but it did colocalize with adenosine deaminase immunoreactivity. It is concluded that 3H-adenosine uptake selectively labels rod horizontal cells in the goldfish retina based on position and staining pattern, which are similar to rod horizontal cells stained by Golgi or HRP injection methods. The use of 3H-adenosine uptake may provide a useful tool to study other properties of rod horizontal cells (i.e. development) as well as provide clues as to the transmitter used by these interneurons.


1991 ◽  
Vol 66 (6) ◽  
pp. 1993-2001 ◽  
Author(s):  
S. Borges ◽  
M. Wilson

1. The effects of glycine on horizontal cells have been examined by microelectrode recording from superfused retinas isolated from the salamander. 2. Low concentrations of glycine (less than 50 microM) hyperpolarized horizontal cells and increased the magnitude of their light responses. Millimolar concentrations produced the opposite effect of depolarizing these cells and reducing their light response amplitudes. 3. In the presence of Co2+ and Mg2+ at concentrations sufficient to suppress the light response, millimolar glycine still exerted a depolarizing effect on horizontal cells, implying that this effect was largely a direct one on horizontal cell membranes. 4. Although both the rod and the cone contributions to horizontal cell light responses were reduced by millimolar glycine, rod input was reduced more, suggesting that millimolar glycine may also exert a presynaptic effect. 5. Strychnine (10 microns) antagonized the effects of millimolar glycine and, in the absence of exogenously applied glycine, caused horizontal cells to hyperpolarize and their light responses to increase in amplitude. This result implies that, in darkness, glycine is tonically released onto horizontal cells and maintains them in a state of partial depolarization. 6. The low-concentration effect of glycine was accompanied by an increased membrane resistance and receptive field size but no change in the balance of rod and cone input. 7. Low concentrations of glycine were often seen to cause a speeding of light responses, whereas high concentrations sometimes caused a slowing of response kinetics. Response kinetics were found to correlate with horizontal cell dark membrane potential so that, positive to -30 mV, depolarization slowed responses whereas kinetics at more negative values were largely independent of voltage.


1990 ◽  
Vol 64 (1) ◽  
pp. 248-261 ◽  
Author(s):  
R. L. Winslow ◽  
S. Ma

1. We have previously presented a model of horizontal-cell soma isolated from fish retina. The model consists of a synaptic conductance representing input from photoreceptors in parallel with voltage-dependent membrane currents. Membrane-current models are based on I-V curves measured in isolated fish horizontal cells. Bifurcation theory was used to analyze model properties. The major findings of this study were 1) the inward Ca2+ current must be inactivated to account for horizontal-cell resting potentials and hyperpolarizing responses to light stimuli in a background of dark, and 2) the synaptic conductance controls the bifurcation structure of the model, with bistable behavior occurring at small and monostable behavior occurring at larger values of the synaptic conductance. The synaptic conductance at the point of transition from bistable to monostable behavior corresponds to the activation of as few as 100 synaptic channels. Thus tonic synaptic input from photoreceptors and inactivation of the inward Ca2+ current act to “linearize” responses of isolated horizontal-cell models. 2. The model described in this paper extends these analyses to large networks of horizontal cells in which each cell is coupled resistively to its nearest neighbors and is modeled with the use of the full complement of nonlinear membrane currents. Network responses to arbitrary patterns of conductance change (simulating inputs from photoreceptors), current-, or voltage-clamp stimuli are computed using the Newton iteration. The Newton descent direction is computed using either conjugate gradient (CG) or preconditioned CG algorithms. 3. An analysis of network stability properties is performed. Network I-V curves are computed by voltage-clamping the center node and computing the current required to maintain the clamp voltage. Computations are performed on networks of model cells in which the Ca2+ current is fully activated and the synaptic conductance is zero, thus making each cell as nonlinear as possible. Coupling conductance values slightly greater than 100 pS provide a current shunt sufficient to prevent the generation of Ca2+ action potentials in the network. This coupling conductance corresponds to the conductance of as few as two gap-junction channels and is more than two orders of magnitude less than the coupling known to exist between pairs of cultured horizontal cells.(ABSTRACT TRUNCATED AT 400 WORDS)


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