scholarly journals Horizontal slices of mouse retina expose horizontal cells and their properties (Commentary on Feigenspan & Babai)

2015 ◽  
Vol 42 (9) ◽  
pp. 2613-2614
Author(s):  
Wallace B. Thoreson
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.


2004 ◽  
Vol 92 (5) ◽  
pp. 2789-2801 ◽  
Author(s):  
Andreas Feigenspan ◽  
Reto Weiler

GABA-induced currents have been characterized in isolated horizontal cells from lower vertebrates but not in mammalian horizontal cells. Therefore horizontal cells were isolated after enzymatical and mechanical dissociation of the adult mouse retina and visually identified. We recorded from horizontal cell bodies using the whole cell and outside-out configuration of the patch-clamp technique. Extracellular application of GABA induced inward currents carried by chloride ions. GABA-evoked currents were completely and reversibly blocked by the competitive GABAA receptor antagonist bicuculline (IC50 = 1.7 μM), indicating expression of GABAA but not GABAC receptors. Their affinity for GABA was moderate (EC50 = 30 μM), and the Hill coefficient was 1.3, corresponding to two GABA binding sites. GABA responses were partially reduced by picrotoxin with differential effects on peak and steady-state current values. Zinc blocked the GABA response with an IC50 value of 7.3 μM in a noncompetitive manner. Furthermore, GABA receptors of horizontal cells were modulated by extracellular application of diazepam, zolpidem, methyl 6,7-dimethoxy-4-ethyl-β-carboxylate, pentobarbital, and alphaxalone, thus showing typical pharmacological properties of CNS GABAA receptors. GABA-evoked single-channel currents were characterized by a main conductance state of 29.8 pS and two subconductance states (20.2 and 10.8 pS, respectively). Kinetic analysis of single-channel events within bursts revealed similar mean open and closed times for the main conductance and the 20.2-pS subconductance state, resulting in open probabilities of 44.6 and 42.7%, respectively. The ratio of open to closed times, however, was significantly different for the 10.8-pS subconductance state with an open probability of 57.2%.


Development ◽  
2007 ◽  
Vol 134 (6) ◽  
pp. 1151-1160 ◽  
Author(s):  
H. Nakhai ◽  
S. Sel ◽  
J. Favor ◽  
L. Mendoza-Torres ◽  
F. Paulsen ◽  
...  

2016 ◽  
Vol 116 (2) ◽  
pp. 686-697 ◽  
Author(s):  
Xue Liu ◽  
James C. R. Grove ◽  
Arlene A. Hirano ◽  
Nicholas C. Brecha ◽  
Steven Barnes

Horizontal cells form the first laterally interacting network of inhibitory interneurons in the retina. Dopamine released onto horizontal cells under photic and circadian control modulates horizontal cell function. Using isolated, identified horizontal cells from a connexin-57-iCre × ROSA26-tdTomato transgenic mouse line, we investigated dopaminergic modulation of calcium channel currents ( ICa) with whole cell patch-clamp techniques. Dopamine (10 μM) blocked 27% of steady-state ICa, an action blunted to 9% in the presence of the L-type Ca channel blocker verapamil (50 μM). The dopamine type 1 receptor (D1R) agonist SKF38393 (20 μM) inhibited ICa by 24%. The D1R antagonist SCH23390 (20 μM) reduced dopamine and SKF38393 inhibition. Dopamine slowed ICa activation, blocking ICa by 38% early in a voltage step. Enhanced early inhibition of ICa was eliminated by applying voltage prepulses to +120 mV for 100 ms, increasing ICa by 31% and 11% for early and steady-state currents, respectively. Voltage-dependent facilitation of ICa and block of dopamine inhibition after preincubation with a Gβγ-blocking peptide suggested involvement of Gβγ proteins in the D1R-mediated modulation. When the G protein activator guanosine 5′- O-(3-thiotriphosphate) (GTPγS) was added intracellularly, ICa was smaller and showed the same slowed kinetics seen during D1R activation. With GTPγS in the pipette, additional block of ICa by dopamine was only 6%. Strong depolarizing voltage prepulses restored the GTPγS-reduced early ICa amplitude by 36% and steady-state ICa amplitude by 3%. These results suggest that dopaminergic inhibition of ICa via D1Rs is primarily mediated through the action of Gβγ proteins in horizontal cells.


2021 ◽  
Vol 15 ◽  
Author(s):  
Lena Nemitz ◽  
Karin Dedek ◽  
Ulrike Janssen-Bienhold

The first synapse of the visual pathway is formed by photoreceptors, horizontal cells and bipolar cells. While ON bipolar cells invaginate into the photoreceptor terminal and form synaptic triads together with invaginating horizontal cell processes, OFF bipolar cells make flat contacts at the base of the terminal. When horizontal cells are ablated during retina development, no invaginating synapses are formed in rod photoreceptors. However, how cone photoreceptors and their synaptic connections with bipolar cells react to this insult, is unclear so far. To answer this question, we specifically ablated horizontal cells from the developing mouse retina. Following ablation around postnatal day 4 (P4)/P5, cones initially exhibited a normal morphology and formed flat contacts with OFF bipolar cells, but only few invaginating contacts with ON bipolar cells. From P15 on, synaptic remodeling became obvious with clustering of cone terminals and mislocalized cone somata in the OPL. Adult cones (P56) finally displayed highly branched axons with numerous terminals which contained ribbons and vesicular glutamate transporters. Furthermore, type 3a, 3b, and 4 OFF bipolar cell dendrites sprouted into the outer nuclear layer and even expressed glutamate receptors at the base of newly formed cone terminals. These results indicate that cones may be able to form new synapses with OFF bipolar cells in adult mice. In contrast, cone terminals lost their invaginating contacts with ON bipolar cells, highlighting the importance of horizontal cells for synapse maintenance. Taken together, our data demonstrate that early postnatal horizontal cell ablation leads to differential remodeling in the cone pathway: whereas synapses between cones and ON bipolar cells were lost, new putative synapses were established between cones and OFF bipolar cells. These results suggest that synapse formation and maintenance are regulated very differently between flat and invaginating contacts at cone terminals.


2004 ◽  
Vol 19 (10) ◽  
pp. 2633-2640 ◽  
Author(s):  
Sonja Hombach ◽  
Ulrike Janssen-Bienhold ◽  
Goran Sohl ◽  
Timm Schubert ◽  
Heinrich Bussow ◽  
...  

2003 ◽  
Vol 20 (4) ◽  
pp. 429-435 ◽  
Author(s):  
YINGQIU XIA ◽  
SCOTT NAWY

Gap junctions are widely expressed throughout the retina, and play an important role in the processing of visual information. It has been proposed that horizontal cells express unpaired gap junctions, or hemichannels, in their dendrites, and that current flowing through hemichannels reduces transmembrane voltage at cone terminals, promoting the opening of Ca2+ channels near sites of transmitter release. This model predicts that pharmacological block of gap junctions should reduce the Ca2+ current at the equivalent cone voltage, thereby decreasing the postsynaptic light response. To test this prediction, and estimate the relative magnitude of this effect on third-order cells, we recorded light responses in mouse ganglion cells under photopic conditions and applied two gap junction antagonists, carbenoxolone and the structurally related 18β-glycyrrhetinic acid (GA). Both carbenoxolone and GA decreased the size of the light response to about 30% of control. Cells that were physiologically identified as ON, OFF, or ON/OFF were equally affected by carbenoxolone/GA. These gap junction blockers did not interfere with gamma-aminobutyric acid (GABA) or glutamate receptors, as they did not affect responses to direct activation of these receptors. Under control conditions, spots larger than 200 μm in diameter activated ganglion cell receptive-field surrounds. Comparing responses to small and large spots before and during carbenoxolone treatment, we found that carbenoxolone did not preferentially inhibit surround antagonism at the ganglion cell level, but instead scaled the responses to all spot sizes. Our results extend the findings of studies in lower vertebrates which showed that light responses in horizontal cells are decreased by carbenoxolone treatment, and support the idea that hemichannels in the outer retina, most likely on horizontal cells, constitute important gates that are critical for allowing light responses to move forward into the retinal circuit. Furthermore, it suggests that ganglion cell surrounds are generated in the inner retina.


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