scholarly journals Activation of the Tonic GABAC Receptor Current in Retinal Bipolar Cell Terminals by Nonvesicular GABA Release

2009 ◽  
Vol 102 (2) ◽  
pp. 691-699 ◽  
Author(s):  
S. M. Jones ◽  
M. J. Palmer
Keyword(s):  
Bipolar Cell ◽  
Ganglion Cells ◽  
Gaba Release ◽  
Visual Signal ◽  
Inhibitory Input ◽  
Axon Terminals ◽  
Gaba Transporters ◽  
Concanamycin A ◽  
Vesicular Release ◽  
Tonic Current

Within the second synaptic layer of the retina, bipolar cell (BC) output to ganglion cells is regulated by inhibitory input to BC axon terminals. GABAA receptors (GABAARs) mediate rapid synaptic currents in BC terminals, whereas GABAC receptors (GABACRs) mediate slow evoked currents and a tonic current, which is strongly regulated by GAT-1 GABA transporters. We have used voltage-clamp recordings from BC terminals in goldfish retinal slices to determine the source of GABA for activation of these currents. Inhibition of vesicular release with concanamycin A or tetanus toxin significantly inhibited GABAAR inhibitory postsynaptic currents and glutamate-evoked GABAAR and GABACR currents but did not reduce the tonic GABACR current, which was also not dependent on extracellular Ca2+. The tonic current was strongly potentiated by inhibition of GABA transaminase, under both normal and Ca2+-free conditions, and was activated by exogenous taurine; however inhibition of taurine transport had little effect. The tonic current was unaffected by GAT-2/3 inhibition and was potentiated by GAT-1 inhibition even in the absence of vesicular release, indicating that it is unlikely to be evoked by reversal of GABA transporters or by ambient GABA. In addition, GABA release does not appear to occur via hemichannels or P2X7 receptors. BC terminals therefore exhibit two forms of GABACR-mediated inhibition, activated by vesicular and by nonvesicular GABA release, which are likely to have distinct functions in visual signal processing. The tonic GABACR current in BC terminals exhibits similar properties to tonic GABAAR and glutamate receptor currents in the brain.

The Transmembrane Sodium Gradient Influences Ambient GABA Concentration by Altering the Equilibrium of GABA Transporters

2006 ◽  
Vol 96 (5) ◽  
pp. 2425-2436 ◽  
Author(s):  
Yuanming Wu ◽  
Wengang Wang ◽  
George B. Richerson
Keyword(s):  
Hippocampal Slices ◽  
Gaba Release ◽  
Synaptic Cleft ◽  
Tonic Inhibition ◽  
Multiple Sources ◽  
Sodium Removal ◽  
Gaba Transporters ◽  
Sodium Gradient ◽  
Ambient Gaba ◽  
Tonic Current

Tonic inhibition is widely believed to be caused solely by “spillover” of GABA that escapes the synaptic cleft and activates extrasynaptic GABAA receptors. However, an exclusively vesicular source is not consistent with the observation that tonic inhibition can still occur after blocking vesicular release. Here, we made patch-clamp recordings from neurons in rat hippocampal cultures and measured the tonic current that was blocked by bicuculline or gabazine. During perforated patch recordings, the tonic GABA current was decreased by the GAT1 antagonist SKF-89976a. Zero calcium solution did not change the amount of tonic current, despite a large reduction in vesicular GABA release. Perturbations that would be expected to alter the transmembrane sodium gradient influenced the tonic current. For example, in zero calcium Ringer, TTX (which can decrease cytosolic [Na+]) reduced tonic current, whereas veratridine (which can increase cytosolic [Na+]) increased tonic current. Likewise, removal of extracellular sodium led to a large increase in tonic current. The increases in tonic current induced by veratridine and sodium removal were completely blocked by SKF89976a. When these experiments were repeated in hippocampal slices, similar results were obtained except that a GAT1- and GAT3-independent nonvesicular source(s) of GABA was found to contribute to the tonic current. We conclude that multiple sources can contribute to ambient GABA, including spillover and GAT1 reversal. The source of GABA release may be conceptually less important in determining the amount of tonic inhibition than the factors that control the equilibrium of GABA transporters.

scholarly journals Rapid regulation of tonic GABA currents in cultured rat hippocampal neurons

2013 ◽  
Vol 109 (3) ◽  
pp. 803-812 ◽  
Author(s):  
Christopher B. Ransom ◽  
Wucheng Tao ◽  
Yuanming Wu ◽  
William J. Spain ◽  
George B. Richerson
Keyword(s):  
Hippocampal Neurons ◽  
Brain Slices ◽  
Reversal Potential ◽  
Gaba Release ◽  
Tonic Inhibition ◽  
Concanamycin A ◽  
Voltage Dependent ◽  
Tonic Current ◽  
Induced Changes ◽  
Time Frames

Subacute and chronic changes in tonic GABAergic inhibition occur in human and experimental epilepsy. Less is known about how tonic inhibition is modulated over shorter time frames (seconds). We measured endogenous tonic GABA currents from cultured rat hippocampal neurons to evaluate how they are affected by 1) transient increases in extracellular GABA concentration ([GABA]), 2) transient postsynaptic depolarization, and 3) depolarization of presynaptic cells. Transient increases in [GABA] (1 μM) reduced tonic currents; this reduction resulted from GABA-induced shifts in the reversal potential for GABA currents ( EGABA). Transient depolarization of postsynaptic neurons reversed the effects of exogenous GABA and potentiated tonic currents. The voltage-dependent potentiation of tonic GABA currents was independent of EGABA shifts and represented postdepolarization potentiation (PDP), an intrinsic GABAA receptor property (Ransom CB, Wu Y, Richerson GB. J Neurosci 30: 7672–7684, 2010). Inhibition of vesicular GABA release with concanamycin A (ConA) did not affect tonic currents. In ConA-treated cells, transient application of 12 mM K+ to depolarize presynaptic neurons and glia produced a persistent increase in tonic current amplitude. The K+-induced increase in tonic current was reversibly inhibited by SKF89976a (40 μM), indicating that this was caused by nonvesicular GABA release from GABA transporter type 1 (GAT1). Nonvesicular GABA release due to GAT1 reversal also occurred in acute hippocampal brain slices. Our results indicate that tonic GABA currents are rapidly regulated by GABA-induced changes in intracellular Cl− concentration, PDP of extrasynaptic GABAA receptors, and nonvesicular GABA release. These mechanisms may influence tonic inhibition during seizures when neurons are robustly depolarized and extracellular GABA and K+ concentrations are elevated.

Roles of aspartate and glutamate in synaptic transmission in rabbit retina. II. Inner plexiform layer

1985 ◽  
Vol 53 (3) ◽  
pp. 714-725 ◽  
Author(s):  
S. A. Bloomfield ◽  
J. E. Dowling
Keyword(s):  
Membrane Potential ◽  
Bipolar Cell ◽  
Ganglion Cells ◽  
Plexiform Layer ◽  
Bipolar Cells ◽  
Inner Plexiform Layer ◽  
Retinal Neurons ◽  
Inner Retina ◽  
Axon Terminals ◽  
Cell Responses

Intracellular recordings were obtained from amacrine and ganglion cells in the superfused, isolated retina-eyecup of the rabbit. The putative neurotransmitters aspartate, glutamate, and several of their analogues were added to the superfusate while the membrane potential and light-responsiveness of the retinal neurons were monitored. Both L-aspartate and L-glutamate displayed excitatory actions on the activity of the vast majority of amacrine and ganglion cells studied. However, these agents occasionally appeared to inhibit the responses of the inner retinal neurons by producing hyperpolarization of the membrane potential and blockage of the light-evoked responses. In either case, the effects of aspartate and glutamate were indistinguishable. The glutamate analogues kainate and quisqualate produced strong excitatory effects on the responses of amacrine and ganglion cells at concentrations some 200-fold less than those needed to obtain similar effects with aspartate or glutamate. The aspartate analogue, n-methyl DL-aspartate (NMDLA), also produced strong excitatory effects but was approximately three times less potent than kainate or quisqualate. On one occasion, we encountered a ganglion cell that was depolarized by kainate, but hyperpolarized by NMDLA. The glutamate antagonist alpha-methyl glutamate and the aspartate antagonist alpha-amino adipate effectively blocked the responses of amacrine and ganglion cells. However, on any one cell, one antagonist was always clearly more potent than the other. We examined the actions of the glutamate analogue 2-amino-4-phosphonobutyrate (APB) on the responses of inner retinal neurons and found that it selectively abolished all "on" activity in the inner retina. Together with our finding that APB selectively abolishes on-bipolar cell responses (see Ref. 6), these data support the hypothesis that on-bipolar cells subserve the "on" activity of amacrine and ganglion cells. Our data suggest that aspartate and glutamate are excitatory transmitters in the inner retina, possibly being released from bipolar cell axon terminals in the inner plexiform layer.

scholarly journals The role of starburst amacrine cells in visual signal processing

2012 ◽  
Vol 29 (1) ◽  
pp. 73-81 ◽  
Author(s):  
W.R. TAYLOR ◽  
R.G. SMITH
Keyword(s):  
Ganglion Cells ◽  
Cholinergic Neurons ◽  
Amacrine Cells ◽  
Gaba Release ◽  
Reciprocal Inhibition ◽  
Visual Signal ◽  
Cholinergic Transmission ◽  
Mammalian Retina ◽  
Starburst Amacrine Cells

AbstractStarburst amacrine cells (SBACs) within the adult mammalian retina provide the critical inhibition that underlies the receptive field properties of direction-selective ganglion cells (DSGCs). The SBACs generate direction-selective output of GABA that differentially inhibits the DSGCs. We review the biophysical mechanisms that produce directional GABA release from SBACs and test a network model that predicts the effects of reciprocal inhibition between adjacent SBACs. The results of the model simulations suggest that reciprocal inhibitory connections between closely spaced SBACs should be spatially selective, while connections between more widely spaced cells could be indiscriminate. SBACs were initially identified as cholinergic neurons and were subsequently shown to contain release both acetylcholine and GABA. While the role of the GABAergic transmission is well established, the role of the cholinergic transmission remains unclear.

scholarly journals Different Combinations of GABAA and GABAC Receptors Confer Distinct Temporal Properties to Retinal Synaptic Responses

1998 ◽  
Vol 79 (6) ◽  
pp. 3157-3167 ◽  
Author(s):  
Peter D. Lukasiewicz ◽  
Colleen R. Shields
Keyword(s):  
Bipolar Cell ◽  
Ganglion Cells ◽  
Amacrine Cells ◽  
Bipolar Cells ◽  
Inhibitory Input ◽  
Synaptic Currents ◽  
Temporal Properties ◽  
Receptor Component ◽  
Time Courses ◽  
Synaptic Responses

Lukasiewicz, Peter D. and Colleen R. Shields. Different combinations of GABAA and GABAC receptors confer distinct temporal properties to retinal synaptic responses. J. Neurophysiol. 79:3157–3167, 1998. This study addresses how γ-aminobutyric acid-A(GABAA) and GABAC receptors confer distinct temporal properties to neuronal synaptic responses. The retina is a model system for the study of postsynaptic contributions to synaptic responses because GABAergic amacrine cells synapse onto neurons, which have different combinations of GABAA and GABAC receptors. It is not known, however, how GABAA versus GABAC receptors influence the time course of retinal synaptic responses or what proportion of inhibitory input is mediated by each receptor type. We examined the time courses of synaptic responses mediated by GABA receptors in ganglion and bipolar cells by recording currents evoked by activating amacrine cells with a stimulating electrode in the salamander retinal slice. The pharmacologically isolated, GABAergic synaptic currents were long-lasting in bipolar cells and relatively brief in ganglion cells. The receptors that mediated these temporally distinct synaptic responses exhibited different pharmacological properties. In ganglion cells, GABAergic synaptic currents were abolished by the GABAA receptor antagonists bicuculline or SR95531. In bipolar cells, the GABAC receptor antagonist 3-aminopropyl[methyl]phosphonic acid (3-APMPA) largely blocked GABAergic synaptic responses; the remaining response was blocked by bicuculline or SR95531. The GABAA receptor component of the bipolar cell response was relatively brief compared with the GABAC receptor component. Puffing GABA onto ganglion cell dendrites or bipolar cell terminals yielded similar pharmacological and kinetic results, indicating that transmitter release differences did not determine the response time courses. Moreover, the GABAC receptors on bipolar cells may be different from those reported in rat or fish retina because imidazole-4-acetic acid (I4AA), which acts as an antagonist in these preparations, acts as an agonist in salamander. Our data show that the prolonged synaptic responses in bipolar cells were mediated predominantly by GABAC receptors, whereas transient synaptic responses in ganglion cells were mediated by GABAA receptors.

scholarly journals Synapse-specific direction selectivity in retinal bipolar cell axon terminals

2020 ◽  
Author(s):  
Akihiro Matsumoto ◽  
Weaam Agbariah ◽  
Stella Solveig Nolte ◽  
Rawan Andrawos ◽  
Hadara Levi ◽  
...  
Keyword(s):  
Bipolar Cell ◽  
Ganglion Cells ◽  
Visual Pathway ◽  
Direction Selectivity ◽  
Image Motion ◽  
Gabaergic Inhibition ◽  
Axon Terminals ◽  
Two Photon ◽  
Synaptic Release ◽  
Specific Direction

AbstractThe ability to encode the direction of image motion is fundamental to our sense of vision. Direction selectivity along the four cardinal directions is thought to originate in direction-selective ganglion cells (DSGCs), due to directionally-tuned GABAergic suppression by starburst cells. Here, by utilizing two-photon glutamate imaging to measure synaptic release, we reveal that direction selectivity along all four directions arises earlier than expected, at bipolar cell outputs. Thus, DSGCs receive directionally-aligned glutamatergic inputs from bipolar cell boutons. We further show that this bouton-specific tuning relies on cholinergic excitation and GABAergic inhibition from starburst cells. In this way, starburst cells are able to refine directional tuning in the excitatory visual pathway by modulating the activity of DSGC dendrites and their axonal inputs using two different neurotransmitters.

Organization of the primate retina: Light microscopy, with an appendix: A second type of midget bipolar cell in the primate retina

1969 ◽  
Vol 255 (799) ◽  
pp. 109-184 ◽  
Keyword(s):  
Ganglion Cell ◽  
Bipolar Cell ◽  
Ganglion Cells ◽  
Horizontal Cell ◽  
Light And Electron Microscopy ◽  
Plexiform Layer ◽  
Amacrine Cells ◽  
Cell Types ◽  
Inner Plexiform Layer ◽  
Axon Terminals

The structure of the human, but mainly of the rhesus monkey, retina as examined by Golgi-staining techniques is described and interpreted on evidence from both light and electron microscopy. One type of rod bipolar cell and two types of cone bipolar cell are recognized. The rod bipolar is exclusively connected to rods. The midget bipolar is postsynaptic to only one cone but each cone is also presynaptic to a diffuse cone (flat) bipolar. Such flat bipolar cells are in synaptic relationship with about seven cones. No other bipolar cell types have been found. The brush bipolar of Polyak is interpreted as probably a distorted rod bipolar, while Polyak’s centrifugal bipolar is a misinterpretation of the morphology of diffuse amacrine cells. When presumptive centrifugal bipolars were observed they appeared to be a developmental stage of amacrine cells. In the outer plexiform layer two types of horizontal cell have been defined. Each type of horizontal cell has a single axon and two kinds of horizontal cell axon terminals are recognized. In the inner plexiform layer there are two main classes of amacrine cells: the stratified amacrines and the diffuse amacrines. Each class of amacrine has a wide variety of shapes. Polyak’s midget ganglion cell is confirmed and his five other kinds of ganglion cell are classified into diffuse and stratified ganglion cells according to the level at which their dendrites branch within the inner plexiform layer. A fuller summary is given by the diagram and in the legend of figure 98, p. 174. A new type of midget bipolar is described in the Appendix (p. 177).

scholarly journals Synaptic input to an ON parasol ganglion cell in the macaque retina: A serial section analysis

2002 ◽  
Vol 19 (3) ◽  
pp. 299-305 ◽  
Author(s):  
DAVID W. MARSHAK ◽  
ELIZABETH S. YAMADA ◽  
ANDREA S. BORDT ◽  
WENDY C. PERRYMAN
Keyword(s):  
Ganglion Cell ◽  
Bipolar Cell ◽  
Amacrine Cell ◽  
Ganglion Cells ◽  
Plexiform Layer ◽  
Amacrine Cells ◽  
Bipolar Cells ◽  
Inhibitory Input ◽  
Inner Plexiform Layer ◽  
Cell Processes

A labeled ON parasol ganglion cell from a macaque retina was analyzed in serial, ultrathin sections. It received 13% of its input from diffuse bipolar cells. These directed a large proportion of their output to amacrine cells but received a relatively small proportion of their amacrine cell input via feedback synapses. In these respects, they were similar to the DB3 bipolar cells that make synapses onto OFF parasol cells. Bipolar cell axons that contacted the ON parasol cell in stratum 4 of the inner plexiform layer always made synapses onto the dendrite, and therefore, the number of bipolar cell synapses onto these ganglion cells could be estimated reliably by light microscopy in the future. Amacrine cells provided the majority of inputs to the ON parasol cell. Only a few of the presynaptic amacrine cell processes received inputs from the same bipolar cells as the parasol cells, and most of the presynaptic amacrine cell processes did not receive any inputs at all within the series. These findings suggest that most of the inhibitory input to the ON parasol cell originates from other areas of the retina. Amacrine cells presynaptic to the parasol ganglion cell interacted very infrequently with other neurons in the circuit, and therefore, they would be expected to act independently, for the most part.

scholarly journals Inhibitory input to the direction-selective ganglion cell is saturated at low contrast

2015 ◽  
Vol 114 (2) ◽  
pp. 927-941 ◽  
Author(s):  
Mikhail Y. Lipin ◽  
W. Rowland Taylor ◽  
Robert G. Smith
Keyword(s):  
Spike Train ◽  
Ganglion Cells ◽  
Signal To Noise Ratio ◽  
Temporal Correlation ◽  
Gaba Release ◽  
Inhibitory Input ◽  
Low Contrast ◽  
Preferred Direction ◽  
Wide Range ◽  
Starburst Amacrine Cell

Direction-selective ganglion cells (DSGCs) respond selectively to motion toward a “preferred” direction, but much less to motion toward the opposite “null” direction. Directional signals in the DSGC depend on GABAergic inhibition and are observed over a wide range of speeds, which precludes motion detection based on a fixed temporal correlation. A voltage-clamp analysis, using narrow bar stimuli similar in width to the receptive field center, demonstrated that inhibition to DSGCs saturates rapidly above a threshold contrast. However, for wide bar stimuli that activate both the center and surround, inhibition depends more linearly on contrast. Excitation for both wide and narrow bars was also more linear. We propose that positive feedback, likely within the starburst amacrine cell or its network, produces steep saturation of inhibition at relatively low contrast. This mechanism renders GABA release essentially contrast and speed invariant, which enhances directional signals for small objects and thereby increases the signal-to-noise ratio for direction-selective signals in the spike train over a wide range of stimulus conditions. The steep saturation of inhibition confers to a neuron immunity to noise in its spike train, because when inhibition is strong no spikes are initiated.

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