Analysis of synaptic inputs to on-off amacrine cells of the carp retina.

To elucidate the synaptic transmission between bipolar cells and amacrine cells, the effect of polarization of a bipolar cell on an amacrine cell was examined by simultaneous intracellular recordings from both cells in the isolated carp retina. When either an ON or OFF bipolar cell was depolarized by an extrinsic current step, an ON-OFF amacrine cell was transiently depolarized at the onset of the current but no sustained polarization during the current was detected. The current hyperpolarizing the OFF bipolar cell also produced the transient depolarization of the amacrine cell at the termination of the current. These responses had a latency of approximately 10 ms. The amplitude of the current-evoked responses changed gradually with current intensity within the range used in these experiments. They were affected by polarization of the amacrine cell membrane; the amplitude of the current-evoked responses as well as the light-evoked responses was increased when the amacrine cell membrane was hyperpolarized, while the amplitude was decreased when the cell was depolarized. These results confirm directly that ON-OFF amacrine cells receive excitatory inputs from both ON and OFF bipolar cells: the ON transient is due to inputs from ON bipolar cells, and the OFF transient to inputs from OFF bipolar cells. The steady polarization of bipolar cells is converted into transient signals during the synaptic process.

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Synaptic microcircuitry of bipolar and amacrine cells with serotonin-like immunoreactivity in the retina of the turtle, Pseudemys scripta elegans

Visual Neuroscience ◽

10.1017/s0952523800004685 ◽

1993 ◽

Vol 10 (3) ◽

pp. 455-471 ◽

Cited By ~ 9

Author(s):

Lawrence B. Hurd ◽

William D. Eldred

Keyword(s):

Bipolar Cell ◽

Amacrine Cell ◽

Plexiform Layer ◽

Amacrine Cells ◽

Bipolar Cells ◽

Outer Plexiform Layer ◽

Inner Plexiform Layer ◽

Synaptic Contacts ◽

Synaptic Inputs ◽

Cell Processes

AbstractAlthough serotonin is thought to be a neurotransmitter in a number of retinal systems, much of the precise synaptic connectivity of serotonergic neurons is unknown. To address this issue, we used an antiserum directed against serotonin to label serotonergic bipolar and amacrine cells in the turtle retina. Light-microscopic analysis of labeled amacrine and bipolar cells indicated that both had bistratified dendritic arborizations primarily in stratum 1 and in strata 4/5 of the inner plexiform layer.Ultrastructural analysis of the neurocircuitry of these cells indicated that the processes of labeled bipolar cells in the outer plexiform layer made basal junction contacts with photoreceptor terminals. Only in rare instances did labeled bipolar cells processes invaginate near photoreceptor ribbon synapses. Processes of labeled bipolar cells received both conventional and small ribbon synaptic contacts in the outer plexiform layer. Bipolar cell processes in stratum 1 of the inner plexiform layer synapsed onto either amacrine/amacrine or amacrine/ganglion cell dyads, and made rare ribbon synaptic contacts onto labeled amacrine cell processes. Synaptic inputs to serotonergic bipolar cells in stratum 1 were from unlabeled bipolar and amacrine cells. Bipolar cell contacts in strata 4/5 were similar to those in stratum 1, but were fewer in number and no bipolar cell inputs were seen.Labeled amacrine cell output in both strata was onto other unlabeled amacrine cells and ganglion cells; but synaptic outputs to unlabeled bipolar cells were only seen in strata 4/5. In both strata 1 and 4/5, synaptic inputs to labeled amacrine cells were from both unlabeled amacrine cells and labeled bipolar cells. The serotonergic amacrine cells had many more synaptic interactions in stratum 1 than in strata 4/5 which supports the role of serotonergic bipolar cells in the OFF pathway of retinal processing. Interactions between serotonergic bipolar and amacrine cells may play an important role in visual processing.

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Interneuron Circuits Tune Inhibition in Retinal Bipolar Cells

Journal of Neurophysiology ◽

10.1152/jn.00458.2009 ◽

2010 ◽

Vol 103 (1) ◽

pp. 25-37 ◽

Cited By ~ 45

Author(s):

Erika D. Eggers ◽

Peter D. Lukasiewicz

Keyword(s):

Ganglion Cell ◽

Bipolar Cell ◽

Amacrine Cell ◽

Ganglion Cells ◽

Feedback Inhibition ◽

Amacrine Cells ◽

Bipolar Cells ◽

Light Stimuli ◽

Cell Inhibition ◽

Cell Networks

While connections between inhibitory interneurons are common circuit elements, it has been difficult to define their signal processing roles because of the inability to activate these circuits using natural stimuli. We overcame this limitation by studying connections between inhibitory amacrine cells in the retina. These interneurons form spatially extensive inhibitory networks that shape signaling between bipolar cell relay neurons to ganglion cell output neurons. We investigated how amacrine cell networks modulate these retinal signals by selectively activating the networks with spatially defined light stimuli. The roles of amacrine cell networks were assessed by recording their inhibitory synaptic outputs in bipolar cells that suppress bipolar cell output to ganglion cells. When the amacrine cell network was activated by large light stimuli, the inhibitory connections between amacrine cells unexpectedly depressed bipolar cell inhibition. Bipolar cell inhibition elicited by smaller light stimuli or electrically activated feedback inhibition was not suppressed because these stimuli did not activate the connections between amacrine cells. Thus the activation of amacrine cell circuits with large light stimuli can shape the spatial sensitivity of the retina by limiting the spatial extent of bipolar cell inhibition. Because inner retinal inhibition contributes to ganglion cell surround inhibition, in part, by controlling input from bipolar cells, these connections may refine the spatial properties of the retinal output. This functional role of interneuron connections may be repeated throughout the CNS.

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Heterocellular coupling between amacrine cell and ganglion cells

10.1101/328815 ◽

2018 ◽

Author(s):

Robert E. Marc ◽

Crystal Sigulinsky ◽

Rebecca L. Pfeiffer ◽

Daniel Emrich ◽

James R. Anderson ◽

...

Keyword(s):

Gap Junctions ◽

Ganglion Cell ◽

Bipolar Cell ◽

Amacrine Cell ◽

Ganglion Cells ◽

Plexiform Layer ◽

Amacrine Cells ◽

Bipolar Cells ◽

Inner Plexiform Layer ◽

Tem Analysis

AbstractAll superclasses of retinal neurons display some form of electrical coupling including the key neurons of the inner plexiform layer: bipolar cells (BCs), amacrine or axonal cells (ACs) and ganglion cells (GCs). However, coupling varies extensively by class. For example, mammalian rod bipolar cells form no gap junctions at all, while all cone bipolar cells form class-specific coupling arrays, many of them homocellular in-superclass arrays. Ganglion cells are unique in that classes with coupling predominantly form heterocellular cross-class arrays of ganglion cell::amacrine cell (GC::AC) coupling in the mammalian retina. Ganglion cells are the least frequent superclass in the inner plexiform layer and GC::AC gap junctions are sparsely arrayed amidst massive cohorts of AC::AC, bipolar cell BC::BC, and AC::BC gap junctions. Many of these gap junctions and most ganglion cell gap junctions are suboptical, complicating analysis of specific ganglion cells. High resolution 2 nm TEM analysis of rabbit retinal connectome RC1 allows quantitative GC::AC coupling maps of identified ganglion cells. Ganglion cells classes apparently avoid direct cross-class homocellular coupling altogether even though they have opportunities via direct membrane touches, while transient OFF alpha ganglion cells and transient ON directionally selective (DS) ganglion cells are strongly coupled to distinct amacrine / axonal cell cohorts.A key feature of coupled ganglion cells is intercellular metabolite flux. Most GC::AC coupling involves GABAergic cells (γ+ amacrine cells), which results in significant GABA flux into ganglion cells. Surveying GABA coupling signatures in the ganglion cell layer across species suggests that the majority of vertebrate retinas engage in GC::AC coupling.Multi-hop synaptic queries of the entire RC1 connectome clearly profiles the coupled amacrine and axonal cells. Photic drive polarities and source bipolar cell class selec-tivities are tightly matched across coupled cells. OFF alpha ganglion cells are coupled to OFF γ+ amacrine cells and transient ON DS ganglion cells are coupled to ON γ+ amacrine cells including a large interstitial axonal cell (IAC). Synaptic tabulations show close matches between the classes of bipolar cells sampled by the coupled amacrine and ganglion cells. Further, both ON and OFF coupling ganglion networks show a common theme: synaptic asymmetry whereby the coupled γ+ neurons are also presynaptic to ganglion cell dendrites from different classes of ganglion cells outside the coupled set. In effect, these heterocellular coupling patterns enable an excited ganglion cell to directly inhibit nearby ganglion cells of different classes. Similarly, coupled γ+ amacrine cells engaged in feedback networks can leverage the additional gain of bipolar cell synapses in shaping the signaling of a spectrum of downstream targets based on their own selective coupling with ganglion cells.

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Synaptic inputs from identified bipolar and amacrine cells to a sparsely branched ganglion cell in rabbit retina

Visual Neuroscience ◽

10.1017/s0952523819000014 ◽

2019 ◽

Vol 36 ◽

Cited By ~ 4

Author(s):

Andrea S. Bordt ◽

Diego Perez ◽

Luke Tseng ◽

Weiley Sunny Liu ◽

Jay Neitz ◽

...

Keyword(s):

Ganglion Cell ◽

Retinal Ganglion Cells ◽

Amacrine Cell ◽

Ganglion Cells ◽

Amacrine Cells ◽

Bipolar Cells ◽

Rabbit Retina ◽

Retinal Ganglion ◽

Synaptic Inputs ◽

Class Iv

AbstractThere are more than 30 distinct types of mammalian retinal ganglion cells, each sensitive to different features of the visual environment. In rabbit retina, they can be grouped into four classes according to their morphology and stratification of their dendrites in the inner plexiform layer (IPL). The goal of this study was to describe the synaptic inputs to one type of Class IV ganglion cell, the third member of the sparsely branched Class IV cells (SB3). One cell of this type was partially reconstructed in a retinal connectome developed using automated transmission electron microscopy (ATEM). It had slender, relatively straight dendrites that ramify in the sublamina a of the IPL. The dendrites of the SB3 cell were always postsynaptic in the IPL, supporting its identity as a ganglion cell. It received 29% of its input from bipolar cells, a value in the middle of the range for rabbit retinal ganglion cells studied previously. The SB3 cell typically received only one synapse per bipolar cell from multiple types of presumed OFF bipolar cells; reciprocal synapses from amacrine cells at the dyad synapses were infrequent. In a few instances, the bipolar cells presynaptic to the SB3 ganglion cell also provided input to an amacrine cell presynaptic to the ganglion cell. There was apparently no crossover inhibition from narrow-field ON amacrine cells. Most of the amacrine cell inputs were from axons and dendrites of GABAergic amacrine cells, likely providing inhibitory input from outside the classical receptive field.

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Stratification of alpha ganglion cells and ON/OFF directionally selective ganglion cells in the rabbit retina

Visual Neuroscience ◽

10.1017/s0952523805224148 ◽

2005 ◽

Vol 22 (4) ◽

pp. 535-549 ◽

Cited By ~ 17

Author(s):

JIAN ZHANG ◽

WEI LI ◽

HIDEO HOSHI ◽

STEPHEN L. MILLS ◽

STEPHEN C. MASSEY

Keyword(s):

Bipolar Cell ◽

Amacrine Cell ◽

Ganglion Cells ◽

Amacrine Cells ◽

Bipolar Cells ◽

Confocal Imaging ◽

Rabbit Retina ◽

Firing Rates ◽

Starburst Amacrine Cells ◽

Cholinergic Sensitivity

The correlation between cholinergic sensitivity and the level of stratification for ganglion cells was examined in the rabbit retina. As examples, we have used ON or OFF α ganglion cells and ON/OFF directionally selective (DS) ganglion cells. Nicotine, a cholinergic agonist, depolarized ON/OFF DS ganglion cells and greatly enhanced their firing rates but it had modest excitatory effects on ON or OFF α ganglion cells. As previously reported, we conclude that DS ganglion cells are the most sensitive to cholinergic drugs. Confocal imaging showed that ON/OFF DS ganglion cells ramify precisely at the level of the cholinergic amacrine cell dendrites, and co-fasciculate with the cholinergic matrix of starburst amacrine cells. However, neither ON or OFF α ganglion cells have more than a chance association with the cholinergic matrix. Z-axis reconstruction showed that OFF α ganglion cells stratify just below the cholinergic band in sublamina a while ON α ganglion cells stratify just below cholinergic b. The latter is at the same level as the terminals of calbindin bipolar cells. Thus, the calbindin bipolar cell appears to be a prime candidate to provide the bipolar cell input to ON α ganglion cells in the rabbit retina. We conclude that the precise level of stratification is correlated with the strength of cholinergic input. Alpha ganglion cells receive a weak cholinergic input and they are narrowly stratified just below the cholinergic bands.

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Rod signals are routed through specific Off cone bipolar cells in primate retina

10.1101/2020.05.17.100982 ◽

2020 ◽

Author(s):

Amanda J. McLaughlin ◽

Kumiko A. Percival ◽

Jacqueline Gayet-Primo ◽

Teresa Puthussery

Keyword(s):

Bipolar Cell ◽

Amacrine Cell ◽

Amacrine Cells ◽

Cell Types ◽

Bipolar Cells ◽

Visual Signals ◽

Night Time ◽

Pass Through ◽

Aii Amacrine ◽

Cone Bipolar Cells

AbstractAdapting between scotopic and photopic illumination involves switching the routing of retinal signals between rod and cone-dominated circuits. In the daytime, cone signals pass through parallel On and Off cone bipolar cells, that are sensitive to increments and decrements in luminance, respectively. At night, rod signals are routed into these cone-pathways via a key glycinergic interneuron, the AII amacrine cell (AII-AC). In primates, it is not known whether AII-ACs contact all Off-bipolar cell types indiscriminately, or whether their outputs are biased towards specific Off-bipolar cell types. Here, we show that the rod-driven glycinergic output of AII-ACs is strongly biased towards a subset of macaque Off-cone bipolar cells. The Off-bipolar types that receive this glycinergic input have sustained physiological properties and include the Off-midget bipolar cells, which provide excitatory input to the Off-midget ganglion cells (parvocellular pathway). The kinetics of the glycinergic events are consistent with the involvement of the α1 glycine receptor subunit. Taken together with results in mouse retina, our findings point towards a conserved motif whereby rod signals are preferentially routed into sustained Off signaling pathways.Significance StatementVisual signals pass through different retinal neurons depending on the prevailing level of illumination. Under night-time light levels, signals from rods pass through the AII amacrine cell, an inhibitory interneuron that routes rod signals into On and Off bipolar cells to detect increments and decrements in light intensity, respectively. Here, we show in primate retina that the output of AII amacrine cells is strongly biased towards specific Off bipolar cell types, which suggests that rod signals reach the brain via specific neural channels. Our results further our understanding of how visual signals are routed through visual circuits during night-time vision.

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Different types of retinal inhibition have distinct neurotransmitter release properties

Journal of Neurophysiology ◽

10.1152/jn.00447.2014 ◽

2015 ◽

Vol 113 (7) ◽

pp. 2078-2090 ◽

Cited By ~ 6

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.

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Synaptic circuitry of neuropeptide-containing amacrine cells in the retina of the cane toad, Bufo marinus

Visual Neuroscience ◽

10.1017/s0952523800009470 ◽

1995 ◽

Vol 12 (5) ◽

pp. 919-927 ◽

Cited By ~ 9

Author(s):

Bao-Song Zhu ◽

Ian Gibbins

Keyword(s):

Ganglion Cell ◽

Bipolar Cell ◽

Amacrine Cell ◽

Plexiform Layer ◽

Amacrine Cells ◽

Bufo Marinus ◽

Inner Plexiform Layer ◽

Cane Toad ◽

Synaptic Inputs ◽

Cell Processes

AbstractSynaptic connections of amacrine cells with substance P-like or neuropeptide Y-like immunoreactivity (SP-LI or NPY-LI) in the retina of the cane toad, Bufo marinus, were investigated using ultrastructural immunocytochemistry. The perikarya of SP-LI or NPY-LI amacrine cells were located in the innermost row of the inner nuclear layer. The synapses associated with SP-LI amacrine cells were distributed mainly in sublaminae 3 and 4 with about 10% in sublamina 1 of the inner plexiform layer. The synapses formed by NPY-LI amacrine cells were found in sublaminae 1, 2, and 4 with approximately equal frequency. Of a total of 175 SP-LI profiles, 56% were in presynaptic positions and 44% in postsynaptic positions. The synaptic inputs to SP-LI profiles predominantly derived from other unlabeled amacrine cell dendrites, and to a lesser extent, from bipolar cell terminals. The majority of synaptic outputs from SP-LI amacrine cell dendrites were directed onto unlabeled amacrine cell processes. The SP-LI profiles also made synapses onto bipolar cell terminals and formed synapses onto presumed ganglion cell dendrites. Of a total of 200 NPY-LI profiles, 48% were in presynaptic positions and 52% in postsynaptic positions. The profiles of NPY-LI amacrine cells mainly received their synaptic inputs from other unlabeled amacrine cell processes, and to a lesser extent, from bipolar cell terminals. The majority of NPY-LI amacrine cell profiles gave their synaptic outputs onto unlabeled amacrine cell dendrites, and others formed synapses onto presumed ganglion cell processes. These results suggest that these two populations of neuropeptide-containing amacrine cells in the Bufo retina are involved in different synaptic circuits.

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Glutamate antagonists that block hyperpolarizing bipolar cells increase the release of dopamine from turtle retina

Visual Neuroscience ◽

10.1017/s0952523800010683 ◽

1992 ◽

Vol 9 (3-4) ◽

pp. 271-278 ◽

Cited By ~ 16

Author(s):

Stuart D. Critz ◽

Robert E. Marc

Keyword(s):

Bipolar Cell ◽

Dopamine Release ◽

Amacrine Cell ◽

Amacrine Cells ◽

High Specificity ◽

Bipolar Cells ◽

Release Process ◽

Gabaergic Synapse ◽

Glutamate Antagonists ◽

Dose Dependent

AbstractSome neurochemical features of the neuronal circuitry regulating dopamine release were examined in the retina of the turtle, Pseudemys scripta elegans. Glutamate antagonists that block hyperpolarizing bipolar cells, such as 2,3 piperidine dicarboxylic acid (PDA), produced dose-dependent dopamine release. In contrast, the glutamate agonist 2-amino-4-phosphonobutyric acid (APB), which blocks depolarizing bipolar cell responses with high specificity, had no effect on the release of dopamine. The γ-aminobutyric acid (GABA) antagonist, bicuculline, also produced potent dose-dependent release of dopamine. The release of dopamine produced by PDA was blocked by exogenous GABA and muscimol, suggesting that the PDA-mediated release process was polysynaptic and involved a GABAergic synapse interposed between the bipolar and dopaminergic amacrine cells. The only other agents that produced dopamine release were chloride-free media and high extracellular K+; in particular, kainic acid and glutamate itself were ineffective. These results suggest that the primary neuronal chain mediating dopamine release in the turtle retina is: cone → hyperpolarizing bipolar cell → GABAergic amacrine cell → dopaminergic amacrine cell.

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Slow changes in Ca2+ cause prolonged release from GABAergic retinal amacrine cells

Journal of Neurophysiology ◽

10.1152/jn.00913.2012 ◽

2013 ◽

Vol 110 (3) ◽

pp. 709-719 ◽

Cited By ~ 5

Author(s):

Erika D. Eggers ◽

Justin S. Klein ◽

Johnnie M. Moore-Dotson

Keyword(s):

Bipolar Cell ◽

Neurotransmitter Release ◽

Time Course ◽

Amacrine Cell ◽

Glutamate Release ◽

Amacrine Cells ◽

Bipolar Cells ◽

Prolonged Release ◽

Deconvolution Analysis ◽

Presynaptic Mechanisms

The timing of neurotransmitter release from neurons can be modulated by many presynaptic mechanisms. The retina uses synaptic ribbons to mediate slow graded glutamate release from bipolar cells that carry photoreceptor inputs. However, many inhibitory amacrine cells, which modulate bipolar cell output, spike and do not have ribbons for graded release. Despite this, slow glutamate release from bipolar cells is modulated by slow GABAergic inputs that shorten the output of bipolar cells, changing the timing of visual signaling. The time course of light-evoked inhibition is slow due to a combination of receptor properties and prolonged neurotransmitter release. However, the light-evoked release of GABA requires activation of neurons upstream from the amacrine cells, so it is possible that prolonged release is due to slow amacrine cell activation, rather than slow inherent release properties of the amacrine cells. To test this idea, we directly activated primarily action potential-dependent amacrine cell inputs to bipolar cells with electrical stimulation. We found that the decay of GABAC receptor-mediated electrically evoked inhibitory currents was significantly longer than would be predicted by GABAC receptor kinetics, and GABA release, estimated by deconvolution analysis, was inherently slow. Release became more transient after increasing slow Ca2+ buffering or blocking prolonged L-type Ca2+ channels and Ca2+ release from intracellular stores. Our results suggest that GABAergic amacrine cells have a prolonged buildup of Ca2+ in their terminals that causes slow, asynchronous release. This could be a mechanism of matching the time course of amacrine cell inhibition to bipolar cell glutamate release.

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