Type 3a and type 3b OFF cone bipolar cells provide for the alternative rod pathway in the mouse retina

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.

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Meclofenamic Acid Blocks Electrical Synapses of Retinal AII Amacrine and on-Cone Bipolar Cells

Journal of Neurophysiology ◽

10.1152/jn.00112.2009 ◽

2009 ◽

Vol 101 (5) ◽

pp. 2339-2347 ◽

Cited By ~ 41

Author(s):

Margaret Lin Veruki ◽

Espen Hartveit

Keyword(s):

Amacrine Cells ◽

Bipolar Cells ◽

Electrical Synapse ◽

Dependent Manner ◽

Electrical Synapses ◽

Meclofenamic Acid ◽

Aii Amacrine Cells ◽

Rod Pathway ◽

Aii Amacrine ◽

Cone Bipolar Cells

Gap junction channels constitute specialized intercellular contacts that can serve as electrical synapses. In the rod pathway of the retina, electrical synapses between AII amacrine cells express connexin 36 (Cx36) and electrical synapses between AII amacrines and on-cone bipolar cells express Cx36 on the amacrine side and Cx36 or Cx45 on the bipolar side. For physiological investigations of the properties and functions of these electrical synapses, it is highly desirable to have access to potent pharmacological blockers with selective and reversible action. Here we use dual whole cell voltage-clamp recordings of pairs of AII amacrine cells and pairs of AII amacrine and on-cone bipolar cells in rat retinal slices to directly measure the junctional conductance ( Gj) between electrically coupled cells and to study the effect of the drug meclofenamic acid (MFA) on Gj. Consistent with previous tracer coupling studies, we found that MFA reversibly blocked the electrical synapse currents in a concentration-dependent manner, with complete block at 100 μM. Whereas MFA evoked a detectable decrease in Gj within minutes of application, the time to complete block of Gj was considerably longer, typically 20–40 min. After washout, Gj recovered to 20–90% of the control level, but the time to maximum recovery was typically >1 h. These results suggest that MFA can be a useful drug to investigate the physiological functions of electrical synapses in the rod pathway, but that the slow kinetics of block and reversal might compromise interpretation of the results and that explicit monitoring of Gj is desirable.

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Type 4 OFF cone bipolar cells of the mouse retina express calsenilin and contact cones as well as rods

The Journal of Comparative Neurology ◽

10.1002/cne.21612 ◽

2007 ◽

Vol 507 (1) ◽

pp. 1087-1101 ◽

Cited By ~ 50

Author(s):

Silke Haverkamp ◽

Dana Specht ◽

Sriparna Majumdar ◽

Nikhat F. Zaidi ◽

Johann Helmut Brandstätter ◽

...

Keyword(s):

Bipolar Cells ◽

Mouse Retina ◽

Cone Bipolar Cells

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Glycinergic synapses in the rod pathway of the rat retina: cone bipolar cells express the alpha 1 subunit of the glycine receptor

Journal of Neuroscience ◽

10.1523/jneurosci.14-08-05131.1994 ◽

1994 ◽

Vol 14 (8) ◽

pp. 5131-5146 ◽

Cited By ~ 142

Author(s):

M Sassoe-Pognetto ◽

H Wassle ◽

U Grunert

Keyword(s):

Glycine Receptor ◽

Bipolar Cells ◽

Rat Retina ◽

Rod Pathway ◽

Cone Bipolar Cells

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Dark-adapted response threshold of OFF ganglion cells is not set by OFF bipolar cells in the mouse retina

Journal of Neurophysiology ◽

10.1152/jn.01202.2011 ◽

2012 ◽

Vol 107 (10) ◽

pp. 2649-2659 ◽

Cited By ~ 27

Author(s):

A. Cyrus Arman ◽

Alapakkam P. Sampath

Keyword(s):

Ganglion Cells ◽

Amacrine Cells ◽

Bipolar Cells ◽

Response Threshold ◽

Mouse Retina ◽

Signal Flow ◽

Visual Threshold ◽

Aii Amacrine Cells ◽

Aii Amacrine ◽

Cone Bipolar Cells

The nervous system frequently integrates parallel streams of information to encode a broad range of stimulus strengths. In mammalian retina it is generally believed that signals generated by rod and cone photoreceptors converge onto cone bipolar cells prior to reaching the retinal output, the ganglion cells. Near absolute visual threshold a specialized mammalian retinal circuit, the rod bipolar pathway, pools signals from many rods and converges on depolarizing (AII) amacrine cells. However, whether subsequent signal flow to OFF ganglion cells requires OFF cone bipolar cells near visual threshold remains unclear. Glycinergic synapses between AII amacrine cells and OFF cone bipolar cells are believed to relay subsequently rod-driven signals to OFF ganglion cells. However, AII amacrine cells also make glycinergic synapses directly with OFF ganglion cells. To determine the route for signal flow near visual threshold, we measured the effect of the glycine receptor antagonist strychnine on response threshold in fully dark-adapted retinal cells. As shown previously, we found that response threshold for OFF ganglion cells was elevated by strychnine. Surprisingly, strychnine did not elevate response threshold in any subclass of OFF cone bipolar cell. Instead, in every OFF cone bipolar subclass strychnine suppressed tonic glycinergic inhibition without altering response threshold. Consistent with this lack of influence of strychnine, we found that the dominant input to OFF cone bipolar cells in darkness was excitatory and the response threshold of the excitatory input varied by subclass. Thus, in the dark-adapted mouse retina, the high absolute sensitivity of OFF ganglion cells cannot be explained by signal transmission through OFF cone bipolar cells.

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Modulation of Excitatory Synaptic Transmission by GABAC Receptor-Mediated Feedback in the Mouse Inner Retina

Journal of Neurophysiology ◽

10.1152/jn.2001.86.5.2285 ◽

2001 ◽

Vol 86 (5) ◽

pp. 2285-2298 ◽

Cited By ~ 36

Author(s):

Ko Matsui ◽

Jun Hasegawa ◽

Masao Tachibana

Keyword(s):

Nmda Receptors ◽

Time Course ◽

Feedback Inhibition ◽

Plexiform Layer ◽

Amacrine Cells ◽

Bipolar Cells ◽

Mouse Retina ◽

Receptor Subtypes ◽

Inner Plexiform Layer ◽

Cone Bipolar Cells

In many vertebrate CNS synapses, the neurotransmitter glutamate activates postsynaptic non- N-methyl-d-aspartate (NMDA) and NMDA receptors. Since their biophysical properties are quite different, the time course of excitatory postsynaptic currents (EPSCs) depends largely on the relative contribution of their activation. To investigate whether the activation of the two receptor subtypes is affected by the synaptic interaction in the inner plexiform layer (IPL) of the mouse retina, we analyzed the properties of the light-evoked responses ofon-cone bipolar cells and on-transient amacrine cells in a retinal slice preparation. on-transient amacrine cells were whole cell voltage-clamped, and the glutamatergic synaptic input from bipolar cells was isolated by a cocktail of pharmacological agents (bicuculline, strychnine, curare, and atropine). Direct puff application of NMDA revealed the presence of functional NMDA receptors. However, the light-evoked EPSC was not significantly affected byd(−)-2-amino-5-phosphonopentanoic acid (d-AP5), but suppressed by 2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide (NBQX) or 1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine hydrochloride (GYKI 52466). These results indicate that the light-evoked EPSC is mediated mainly by AMPA receptors under this condition. Since bipolar cells have GABACreceptors at their terminals, it has been suggested that bipolar cells receive feedback inhibition from amacrine cells. Application of (1,2,5,6-tetrahydropyridin-4-yl)methylphosphinic acid (TPMPA), a specific blocker of GABAC receptors, suppressed both the GABA-induced current and the light-evoked feedback inhibition observed in on-cone bipolar cells and enhanced the light-evoked EPSC of on-transient amacrine cells. In the presence of TPMPA, the light-evoked EPSC of amacrine cells was composed of AMPA and NMDA receptor-mediated components. Our results suggest that photoresponses of on-transient amacrine cells in the mouse retina are modified by the activation of presynaptic GABAC receptors, which may control the extent of glutamate spillover.

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Light adaptation alters the source of inhibition to the mouse retinal OFF pathway

Journal of Neurophysiology ◽

10.1152/jn.00384.2013 ◽

2013 ◽

Vol 110 (9) ◽

pp. 2113-2128 ◽

Cited By ~ 13

Author(s):

Reece E. Mazade ◽

Erika D. Eggers

Keyword(s):

Bipolar Cell ◽

Light Adaptation ◽

Amacrine Cell ◽

Bipolar Cells ◽

Gabaergic Inhibition ◽

Light Sensing ◽

Wide Range ◽

Rod Pathway ◽

Aii Amacrine ◽

Cone Bipolar Cells

Sensory systems must avoid saturation to encode a wide range of stimulus intensities. One way the retina accomplishes this is by using both dim-light-sensing rod and bright-light-sensing cone photoreceptor circuits. OFF cone bipolar cells are a key point in this process, as they receive both excitatory input from cones and inhibitory input from AII amacrine cells via the rod pathway. However, in addition to AII amacrine cell input, other inhibitory inputs from cone pathways also modulate OFF cone bipolar cell light signals. It is unknown how these inhibitory inputs to OFF cone bipolar cells change when switching between rod and cone pathways or whether all OFF cone bipolar cells receive rod pathway input. We found that one group of OFF cone bipolar cells (types 1, 2, and 4) receive rod-mediated inhibitory inputs that likely come from the rod-AII amacrine cell pathway, while another group of OFF cone bipolar cells (type 3) do not. In both cases, dark-adapted rod-dominant light responses showed a significant contribution of glycinergic inhibition, which decreased with light adaptation and was, surprisingly, compensated by an increase in GABAergic inhibition. As GABAergic input has distinct timing and spatial spread from glycinergic input, a shift from glycinergic to GABAergic inhibition could significantly alter OFF cone bipolar cell signaling to downstream OFF ganglion cells. Larger GABAergic input could reflect an adjustment of OFF bipolar cell spatial inhibition, which may be one mechanism that contributes to retinal spatial sensitivity in the light.

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The unitary event amplitude of mouse retinal on-cone bipolar cells

Visual Neuroscience ◽

10.1017/s0952523803206040 ◽

2003 ◽

Vol 20 (6) ◽

pp. 621-626 ◽

Cited By ~ 16

Author(s):

AMY BERNTSON ◽

W. ROWLAND TAYLOR

Keyword(s):

Transmitter Release ◽

Bipolar Cell ◽

Bright Light ◽

Bipolar Cells ◽

Mouse Retina ◽

Integration Time ◽

Synaptic Current ◽

Postsynaptic Response ◽

Flash Response ◽

Cone Bipolar Cells

Light-evoked synaptic currents were recorded from on-cone bipolar cells in the mouse retina. Fluctuations in the synaptic current observed during maintained light steps were analyzed in order to estimate the amplitude of the underlying unitary event. The maximal synaptic current variance was 5-fold larger than the maximum expected from fluctuations in the number of active postsynaptic channels. Due to uncertainty in the contribution from channel variance, we calculated a range of values for the unitary event amplitude. The observed variance could be accounted for if 30–39 synaptic sites randomly generated unitary events with a waveform identical to the flash-response, and an amplitude of −3.1 to −2.4 pA. The amplitude is consistent with gating about five mGluR6 channels. The shape of the variance–mean relation suggests that in bright light transmitter release approaches zero, while in darkness transmitter release saturates the postsynaptic response. Thus the on-cone bipolar cell synapse is operating over its entire possible range. If it is assumed that the postsynaptic response saturates when one unitary event occurs per integration time, then a lower bound for the unitary event rate is 18 events/s/synaptic site. If the unitary event is generated by a single synaptic vesicle, the results suggest the total vesicle cycling rate available for encoding the on-cone bipolar cell signal is about 540–700 s−1.

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