Characterization of inhibitory postsynaptic currents in rod bipolar cells of the mouse retina

2004 ◽  
Vol 21 (4) ◽  
pp. 645-652 ◽  
Author(s):  
MORITZ J. FRECH ◽  
KURT H. BACKUS
Keyword(s):  
Glutamate Release ◽  
Amacrine Cells ◽  
Bipolar Cells ◽  
Synaptic Activity ◽  
Peak Amplitude ◽  
Mouse Retina ◽  
Decay Kinetics ◽  
Patch Clamp Technique ◽  
Postsynaptic Currents ◽  
Rod Bipolar Cells

The synaptic terminals of mammalian rod bipolar cells are the targets of multiple presynaptic inhibitory inputs arriving from glycinergic and GABAergic amacrine cells. To investigate the contribution of these different inhibitory receptor types, we have applied the patch-clamp technique in acutely isolated slices of the adult mouse retina. By using the whole-cell configuration, we measured and analyzed the spontaneous postsynaptic currents (PSCs) in rod bipolar cells. The spontaneous synaptic activity of rod bipolar cells was very low. However, when amacrine cells were depolarized by AMPA or kainate, the PSC frequency in rod bipolar cells increased significantly. These PSCs comprised several types that could be distinguished by pharmacological and kinetic criteria. Strychnine-sensitive, glycinergic PSCs were characterized by a mean peak amplitude of −43.5 pA and a weighted decay time constant (τw) of 10.9 ms. PSCs that persisted in the presence of strychnine, but were completely inhibited by bicuculline, were mediated by GABAARs. They had a mean peak amplitude of −20.0 pA and a significantly faster τwof 5.8 ms. Few PSCs remained in the presence of strychnine and bicuculline, suggesting that they were mediated by GABACRs. These PSCs were characterized by much smaller amplitudes (−6.2 pA) and a significantly slower decay kinetics (τw= 51.0 ms). We conclude that rod bipolar cells express at least three types of functionally different inhibitory receptors, namely GABAARs, GABACRs, and GlyRs that may ultimately regulate the Ca2+influx into rod bipolar cell terminals, thereby modulating their glutamate release.

Characterization of the Spontaneous Synaptic Activity of Amacrine Cells in the Mouse Retina

2001 ◽  
Vol 86 (4) ◽  
pp. 1632-1643 ◽  
Author(s):  
Moritz J. Frech ◽  
Jorge Pérez-León ◽  
Heinz Wässle ◽  
Kurt H. Backus
Keyword(s):  
Reversal Potential ◽  
Amacrine Cells ◽  
Mean Amplitude ◽  
Synaptic Activity ◽  
Mouse Retina ◽  
Inhibitory Receptors ◽  
Decay Kinetics ◽  
Patch Clamp Technique ◽  
Postsynaptic Currents ◽  
Kinetics Of

Amacrine cells are a heterogeneous class of interneurons that modulate the transfer of the light signals through the retina. In addition to ionotropic glutamate receptors, amacrine cells express two types of inhibitory receptors, GABAA receptors (GABAARs) and glycine receptors (GlyRs). To characterize the functional contribution of these different receptors, spontaneous postsynaptic currents (sPSCs) were recorded with the whole cell configuration of the patch-clamp technique in acutely isolated slices of the adult mouse retina. All amacrine cells investigated ( n = 47) showed spontaneous synaptic activity. In six amacrine cells, spontaneous excitatory postsynaptic currents could be identified by their sensitivity to kynurenic acid. They were characterized by small amplitudes [mean: −13.7 ± 1.5 (SE) pA] and rapid decay kinetics (mean τ: 1.35 ± 0.16 ms). In contrast, the reversal potential of sPSCs characterized by slow decay kinetics (amplitude-weighted time constant, τw, >4 ms) was dependent on the intracellular Cl− concentration ( n = 7), indicating that they were spontaneous inhibitory postsynaptic currents (sIPSCs). In 14 of 34 amacrine cells sIPSCs were blocked by bicuculline (10 μM), indicating that they were mediated by GABAARs. Only four amacrine cells showed glycinergic sIPSCs that were inhibited by strychnine (1 μM). In one amacrine cell, sIPSCs mediated by GABAARs and GlyRs were found simultaneously. GABAergic sIPSCs could be subdivided into one group best fit by a monoexponential decay function and another biexponentially decaying group. The mean amplitude of GABAergic sIPSCs (−42.1 ± 5.8 pA) was not significantly different from that of glycinergic sIPSCs (−28.0 ± 8.5 pA). However, GlyRs (mean T10/90: 2.4 ± 0.08 ms) activated significantly slower than GABAARs (mean T10/90: 1.2 ± 0.03 ms). In addition, the decay kinetics of monoexponentially decaying GABAARs (mean τw: 20.3 ± 0.50), biexponentially decaying GABAARs (mean τw: 30.7 ± 0.95), and GlyRs (mean τw = 25.3 ± 1.94) were significantly different. These differences in the activation and decay kinetics of sIPSCs indicate that amacrine cells of the mouse retina express at least three types of functionally different inhibitory receptors: GlyRs and possibly two subtypes of GABAARs.

Spontaneous Oscillatory Activity of Starburst Amacrine Cells in the Mouse Retina

2005 ◽  
Vol 94 (3) ◽  
pp. 1770-1780 ◽  
Author(s):  
Jerome Petit-Jacques ◽  
Béla Völgyi ◽  
Bernardo Rudy ◽  
Stewart Bloomfield
Keyword(s):  
Feedback Inhibition ◽  
Glutamate Release ◽  
Amacrine Cells ◽  
Bipolar Cells ◽  
Kainate Receptors ◽  
Oscillatory Activity ◽  
Mouse Retina ◽  
Inner Plexiform Layer ◽  
Experimental Conditions ◽  
Starburst Amacrine Cells

Using patch-clamp techniques, we investigated the characteristics of the spontaneous oscillatory activity displayed by starburst amacrine cells in the mouse retina. At a holding potential of –70 mV, oscillations appeared as spontaneous, rhythmic inward currents with a frequency of ∼3.5 Hz and an average maximal amplitude of ∼120 pA. Application of TEA, a potassium channel blocker, increased the amplitude of oscillatory currents by >70% but reduced their frequency by ∼17%. The TEA effects did not appear to result from direct actions on starburst cells, but rather a modulation of their synaptic inputs. Oscillatory currents were inhibited by 6-cyano-7-nitroquinoxalene-2,3-dione (CNQX), an antagonist of AMPA/kainate receptors, indicating that they were dependent on a periodic glutamatergic input likely from presynaptic bipolar cells. The oscillations were also inhibited by the calcium channel blockers cadmium and nifedipine, suggesting that the glutamate release was calcium dependent. Application of AP4, an agonist of mGluR6 receptors on on-center bipolar cells, blocked the oscillatory currents in starburst cells. However, application of TEA overcame the AP4 blockade, suggesting that the periodic glutamate release from bipolar cells is intrinsic to the inner plexiform layer in that, under experimental conditions, it can occur independent of photoreceptor input. The GABA receptor antagonists picrotoxin and bicuculline enhanced the amplitude of oscillations in starburst cells prestimulated with TEA. Our results suggest that this enhancement was due to a reduction of a GABAergic feedback inhibition from amacrine cells to bipolar cells and the resultant increased glutamate release. Finally, we found that some ganglion cells and other types of amacrine cell also displayed rhythmic activity, suggesting that oscillatory behavior is expressed by a number of inner retinal neurons.

Unique functional properties of the APB sensitive and insensitive rod pathways signaling light decrements in mouse retinal ganglion cells

2006 ◽  
Vol 23 (1) ◽  
pp. 127-135 ◽  
Author(s):  
GUO-YONG WANG
Keyword(s):  
Functional Properties ◽  
Ganglion Cells ◽  
Amacrine Cells ◽  
Bipolar Cells ◽  
Mouse Retina ◽  
Clear Cut ◽  
Types Of Information ◽  
Rod Bipolar Cells ◽  
Rod Pathway ◽  
Cone Bipolar Cells

Light decrements are mediated by two distinct groups of rod pathways in the dark-adapted retina that can be differentiated on the basis of their sensitivity to the glutamate agonist DL-2-amino-phosphonobutyric (APB). By means of the APB sensitive pathway, rods transmit light decrementsviarod bipolar cells to AII amacrine cells, then to Off cone bipolar cells, which in turn innervate the dendrites of Off ganglion cells. APB hyperpolarizes rod bipolar cells, thus blocking this rod pathway. With APB insensitive pathways, rods either directly synapse onto Off cone bipolar cells, or rods pass light decrement signal to cones by gap junctions. In the present study, whole-cell patch-clamp recordings were made from ganglion cells in the dark-adapted mouse retina to investigate the functional properties of APB sensitive and insensitive rod pathways. The results revealed several clear-cut differences between the APB sensitive and APB insensitive rod pathways. The latency of Off responses to a flashing spot of light was significantly shorter for the APB insensitive pathways than those for the APB sensitive pathway. Moreover, Off responses of the APB insensitive pathways were found to be capable of following substantially higher stimulus frequencies. Nitric oxide was found to selectively block Off responses in the APB sensitive rod pathway. Collectively, these results provide evidence that the APB sensitive and insensitive rod pathways can convey different types of information signaling light decrements in the dark-adapted retina.

scholarly journals Cross-synaptic synchrony and transmission of signal and noise across the mouse retina

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
William N Grimes ◽  
Mrinalini Hoon ◽  
Kevin L Briggman ◽  
Rachel O Wong ◽  
Fred Rieke
Keyword(s):  
Single Neuron ◽  
Amacrine Cells ◽  
Light Level ◽  
Bipolar Cells ◽  
Mouse Retina ◽  
Anatomical Connectivity ◽  
Physiological Conditions ◽  
Synaptic Noise ◽  
Mammalian Retina ◽  
Rod Bipolar Cells

Cross-synaptic synchrony—correlations in transmitter release across output synapses of a single neuron—is a key determinant of how signal and noise traverse neural circuits. The anatomical connectivity between rod bipolar and A17 amacrine cells in the mammalian retina, specifically that neighboring A17s often receive input from many of the same rod bipolar cells, provides a rare technical opportunity to measure cross-synaptic synchrony under physiological conditions. This approach reveals that synchronization of rod bipolar cell synapses is near perfect in the dark and decreases with increasing light level. Strong synaptic synchronization in the dark minimizes intrinsic synaptic noise and allows rod bipolar cells to faithfully transmit upstream signal and noise to downstream neurons. Desynchronization in steady light lowers the sensitivity of the rod bipolar output to upstream voltage fluctuations. This work reveals how cross-synaptic synchrony shapes retinal responses to physiological light inputs and, more generally, signaling in complex neural networks.

scholarly journals Different types of retinal inhibition have distinct neurotransmitter release properties

2015 ◽  
Vol 113 (7) ◽  
pp. 2078-2090 ◽  
Author(s):  
Johnnie M. Moore-Dotson ◽  
Justin S. Klein ◽  
Reece E. Mazade ◽  
Erika D. Eggers
Keyword(s):  
Bipolar Cell ◽  
Neurotransmitter Release ◽  
Amacrine Cell ◽  
Glutamate Release ◽  
Amacrine Cells ◽  
Gaba Release ◽  
Bipolar Cells ◽  
Glycine Release ◽  
Presynaptic Mechanisms ◽  
Rod Bipolar Cells

Neurotransmitter release varies between neurons due to differences in presynaptic mechanisms such as Ca2+ sensitivity and timing. Retinal rod bipolar cells respond to brief dim illumination with prolonged glutamate release that is tuned by the differential release of GABA and glycine from amacrine cells in the inner retina. To test if differences among types of GABA and glycine release are due to inherent amacrine cell release properties, we directly activated amacrine cell neurotransmitter release by electrical stimulation. We found that the timing of electrically evoked inhibitory currents was inherently slow and that the timecourse of inhibition from slowest to fastest was GABAC receptors > glycine receptors > GABAA receptors. Deconvolution analysis showed that the distinct timing was due to differences in prolonged GABA and glycine release from amacrine cells. The timecourses of slow glycine release and GABA release onto GABAC receptors were reduced by Ca2+ buffering with EGTA-AM and BAPTA-AM, but faster GABA release on GABAA receptors was not, suggesting that release onto GABAA receptors is tightly coupled to Ca2+. The differential timing of GABA release was detected from spiking amacrine cells and not nonspiking A17 amacrine cells that form a reciprocal synapse with rod bipolar cells. Our results indicate that release from amacrine cells is inherently asynchronous and that the source of nonreciprocal rod bipolar cell inhibition differs between GABA receptors. The slow, differential timecourse of inhibition may be a mechanism to match the prolonged rod bipolar cell glutamate release and provide a way to temporally tune information across retinal pathways.

Postsynaptic calcium feedback between rods and rod bipolar cells in the mouse retina

2004 ◽  
Vol 21 (6) ◽  
pp. 913-924 ◽  
Author(s):  
AMY BERNTSON ◽  
ROBERT G. SMITH ◽  
W. ROWLAND TAYLOR
Keyword(s):  
Intracellular Calcium ◽  
Time Constant ◽  
Time Course ◽  
Dynamic Range ◽  
Amacrine Cells ◽  
Bipolar Cells ◽  
Mouse Retina ◽  
Inward Current ◽  
Rod Bipolar Cells ◽  
In Cells

Light-evoked currents were recorded from rod bipolar cells in a dark-adapted mouse retinal slice preparation. Low-intensity light steps evoked a sustained inward current. Saturating light steps evoked an inward current with an initial peak that inactivated, with a time constant of about 60–70 ms, to a steady plateau level that was maintained for the duration of the step. The inactivation was strongest at hyperpolarized potentials, and absent at positive potentials. Inactivation was mediated by an increase in the intracellular calcium concentration, as it was abolished in cells dialyzed with 10 mM BAPTA, but was present in cells dialyzed with 1 mM EGTA. Moreover, responses to brief flashes of light were broader in the presence of intracellular BAPTA indicating that the calcium feedback actively shapes the time course of the light responses. Recovery from inactivation observed for paired-pulse stimuli occurred with a time constant of about 375 ms. Calcium feedback could act to increase the dynamic range of the bipolar cells, and to reduce variability in the amplitude and duration of the single-photon signal. This may be important for nonlinear processing at downstream sites of convergence from rod bipolar cells to AII amacrine cells. A model in which intracellular calcium rapidly binds to the light-gated channel and reduces the conductance can account for the results.

Modulation by Zn2+ of GABA responses in bipolar cells of the mouse retina

2000 ◽  
Vol 17 (2) ◽  
pp. 273-281 ◽  
Author(s):  
M. KANEDA ◽  
B. ANDRÁSFALVY ◽  
A. KANEKO
Keyword(s):  
Axon Terminal ◽  
Inhibitory Action ◽  
Phosphinic Acid ◽  
Amacrine Cells ◽  
Bipolar Cells ◽  
Mouse Retina ◽  
Induced Responses ◽  
Inhibitory Interaction ◽  
Cell Recording ◽  
Recording Conditions

The localization of endogenous Zn2+ in the mouse retina was examined histochemically and the inhibitory action of Zn2+ on GABA-induced responses was studied in bipolar cells isolated from the mouse retina. Accumulation of endogenous Zn2+ was detected in photoreceptors, bipolar, and/or amacrine cells by either the bromopyridylazo-diethylaminophenol method or the dithizone method. Under whole-cell recording conditions, GABA induced a Cl− current in isolated bipolar cells. The current consisted of two components. The first component was inhibited completely by application of 100 μM bicuculline, suggesting that this is a GABAA-receptor mediated current. The second component was inhibited completely by 100 μM 3-aminopropyl-(methyl)-phosphinic acid, suggesting that this is a GABAC-receptor mediated current. GABAC receptors were present at a higher density on the axon terminal than on dendrites. Zn2+ inhibited both GABAA and GABAC receptors. GABAC receptors were more susceptible to Zn2+; the IC50 for the GABAA receptor was 67.4 μM and that for the GABAC receptor was 1.9 μM. These results suggest that Zn2+ modulates the inhibitory interaction between amacrine and bipolar cells, particularly that mediated by the GABAC receptor.

scholarly journals The Effect of PKCα on the Light Response of Rod Bipolar Cells in the Mouse Retina

2015 ◽  
Vol 56 (8) ◽  
pp. 4961 ◽  
Author(s):  
Wei-Hong Xiong ◽  
Ji-Jie Pang ◽  
Mark E. Pennesi ◽  
Robert M. Duvoisin ◽  
Samuel M. Wu ◽  
...  
Keyword(s):  
Light Response ◽  
Bipolar Cells ◽  
Mouse Retina ◽  
Rod Bipolar Cells

Membrane currents evoked by ionotropic glutamate receptor agonists in rod bipolar cells in the rat retinal slice preparation

1996 ◽  
Vol 76 (1) ◽  
pp. 401-422 ◽  
Author(s):  
E. Hartveit
Keyword(s):  
Nmda Receptor ◽  
Plexiform Layer ◽  
Amacrine Cells ◽  
Bipolar Cells ◽  
Inner Plexiform Layer ◽  
Receptor Agonists ◽  
Long Latency ◽  
Glutamate Receptor Agonists ◽  
Conductance Increase ◽  
Rod Bipolar Cells

1. With the use of the whole cell voltage-clamp technique, I have recorded the current responses to ionotropic glutamate receptor agonists of rod bipolar cells in vertical slices of rat retina. Rod bipolar cells constitute a single population of cells and were visualized by infrared differential interference contrast video microscopy. They were targeted by the position of their cell bodies in the inner nuclear layer and, after recording, were visualized in their entirety by labeling with the fluorescent dye Lucifer yellow, which was included in the recording pipette. To study current-voltage relationships of evoked currents, voltage-gated potassium currents were blocked by including Cs+ and tetraethylammonium+ in the recording pipette. 2. Pressure application of the non-N-methyl-D-aspartate (non-NMDA) receptor agonists kainate and (S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) from puffer pipettes evoked a long-latency conductance increase selective for chloride ions. When the intracellular chloride concentration was increased, the reversal potential changed, corresponding to the change in equilibrium potential for chloride. The response was evoked in the presence of 5 mM Co2+ and nominally O mM Ca2+ in the extracellular solution, presumably blocking all external Ca2(+)-dependent release of neurotransmitter. 3. The long latency of kainate-evoked currents in bipolar cells contrasted with the short-latency currents evoked by gamma-aminobutyric acid (GABA) and glycine in rod bipolar cells and by kainate in amacrine cells. 4. Application of NMDA evoked no response in rod bipolar cells. 5. Coapplication of AMPA with cyclothiazide, a blocker of agonist-evoked desensitization of AMPA receptors, enhanced the conductance increase compared with application of AMPA alone. Coapplication of the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione blocked the response to kainate and AMPA, indicating that the response was mediated by conventional ionotropic glutamate receptors. 6. The conductance increase evoked by non-NMDA receptor agonists could not be blocked by a combination of 100 microM picrotoxin and 10 microM strychnine. Application of the GABAC receptor antagonist 3-aminopropyl (methyl)phosphinic acid (3-APMPA) strongly reduced the response, and coapplication of 500 microM 3-APMPA and 100 microM picrotoxin completely blocked the response. These results suggested that the conductance increase evoked by non-NMDA receptor agonists was mediated by release of GABA and activation of GABAC receptors, and most likely also GABAA receptors, on rod bipolar cells. 7. Kainate responses like those described above could not be evoked in bipolar cells in which the axon had been cut somewhere along its passage to the inner plexiform layer during the slicing procedure. This suggests that the response was dependent on the integrity of the axon terminal in the inner plexiform layer, known to receive GABAergic synaptic input from amacrine cells. 8. The results indicate that ionotropic glutamate receptors are not involved in mediating synaptic input from photoreceptors to rod bipolar cells and that an unconventional mechanism of GABA release from amacrine cells might operate in the inner plexiform layer.

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