Temporal Modulation of Scotopic Visual Signals by A17 Amacrine Cells in Mammalian Retina In Vivo

2003 ◽  
Vol 89 (4) ◽  
pp. 2159-2166 ◽  
Author(s):  
Cun-Jian Dong ◽  
William A. Hare

We examined function of the feedback pathway from A17 GABAergic amacrine cells to rod bipolar cells (A17 feedback), a critically located inhibitory circuit in the classic rod pathway of the mammalian retina whose role in processing of scotopic visual information is still poorly understood. We show evidence that this A17 feedback has a profound influence on the temporal properties of rod-driven postphotoreceptoral responses (assessed with the scotopic electroretinogram b-wave). Application of a GABAcantagonist prolonged preferentially the decay of the scotopic b-wave. The degree of prolongation increased as the light intensity decreased. Application of selective GABAa antagonists accelerated the kinetics of the scotopic b-wave. This effect was abolished when the GABAc antagonist was coapplied. Selective ablation of A17 cells mimicked the action of the GABAc antagonist. In A17 cell–ablated retinas, the GABAc antagonist was no longer very effective to slow the decay of the scotopic b-wave. Thus the A17 feedback, activated by light stimulation and mediated mainly by the GABAc receptors, makes the scotopic b-wave more transient by accelerating preferentially its decay. The strength of the feedback can be modulated by GABAa receptor–mediated inhibition and by light intensity. Our results also suggest that in the mammalian retina the feedback may be a novel mechanism that contributes postphotoreceptorally to the termination of rod signals, especially those elicited by very dim light stimuli.

2010 ◽  
Vol 103 (1) ◽  
pp. 25-37 ◽  
Author(s):  
Erika D. Eggers ◽  
Peter D. Lukasiewicz

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.


1993 ◽  
Vol 10 (3) ◽  
pp. 511-522 ◽  
Author(s):  
William J. Brunken ◽  
Xiao-Tao Jin

AbstractWe investigated the role of 5HT3 receptors in the mammalian retina using electrophysiological techniques to monitor ganglion cell activity. Activation of 5HT3 receptors with the selective agonist 1-phenylbiguanide (PBG) increased the ON responses of ON-center ganglion cells, while decreasing the OFF responses of OFF-center cells. The application of a selective 5HT3 antagonist had a reciprocal effect, namely it reduced the center response in ON-center cells and concomitantly increased the center responses in OFF-center cells. Since putative serotoninergic amacrine cells in the retina are connected specifically to the rod bipolar cell, these agents most likely affect the rod bipolar terminal. These data, together with previous studies, suggest that both 5HT2 and 5HT3 receptors mediate an excitatory influence which serves to facilitate the output from rod bipolar cells, the former via a phosphatidyl inositol second-messenger system, and the latter via a direction channel.


1990 ◽  
Vol 5 (1) ◽  
pp. 61-66 ◽  
Author(s):  
Heather M. Young ◽  
David I. Vaney

AbstractThis study has shown that the retinae of Prototherian (egg-laying) mammals possess two neuronal types that are present in non-mammalian retinae, but absent or morphologically different in the retinae of Eutherian (placental) mammals. First, endogenous serotonin-like immunoreactivity has been localized in a population of presumptive amacrine cells in the platypus retina, the first such report in a mammalian retina. Second, the protein kinase C-immunoreactive (PKC-IR) bipolar cells in the echidna retina appear similar to the PKC-IR bipolars in the chicken retina, in that their dendrites give rise to a Landolt's club and their axons are multistratified. By contrast, the PKC-IR rod bipolar cells in the rabbit and in the brushtail possum, a Metatherian (marsupial) mammal, have no Landolt's clubs and their axons form terminal lobes in the innermost stratum of the inner plexiform layer.


1997 ◽  
Vol 14 (6) ◽  
pp. 1153-1165 ◽  
Author(s):  
Stewart A. Bloomfield ◽  
Daiyan Xin

AbstractRecent studies have shown that amacrine and ganglion cells in the mammalian retina are extensively coupled as revealed by the intercellular movement of the biotinylated tracers biocytin and Neurobiotin. These demonstrations of tracer coupling suggest that electrical networks formed by proximal neurons (i.e. amacrine and ganglion cells) may underlie the lateral propagation of signals across the inner retina. We studied this question by comparing the receptive-field size, dendritic-field size, and extent of tracer coupling of amacrine and ganglion cells in the dark-adapted, supervised, isolated retina eyecup of the rabbit. Our results indicate that while the center-receptive fields of proximal neurons are approximately 15% larger than their corresponding dendritic diameters, this slight difference can be explained by factors other than electrical coupling such as tissue shrinkage associated with histological processing. However, the extent of tracer coupling of amacrine and ganglion cells was, on average, about twice the size of the corresponding receptive fields. Thus, the receptive field of an individual proximal neuron matched far more closely to its dendritic diameter than to the size of the tracer-coupled network of cells to which it belonged. The exception to this rule was the AII amacrine cells for which center-receptive fields were 2–3 times the size of their dendritic diameters but matched closely to the size of the tracer-coupled arrays. Thus, with the exception of AII cells, our data indicate that tracer coupling between proximal neurons is not associated with an enlargement of their receptive fields. Our results, then, provide no evidence for electrical coupling or, at least, indicate that extensive lateral spread of visual signals does not occur in the proximal mammalian retina.


2006 ◽  
Vol 96 (1) ◽  
pp. 471-477 ◽  
Author(s):  
Thomas A. Münch ◽  
Frank S. Werblin

Starburst amacrine cells in the mammalian retina respond asymmetrically to movement along their dendrites; centrifugal movement elicits stronger responses in each dendrite than centripetal movement. It has been suggested that the asymmetrical response can be attributed to intrinsic properties of the processes themselves. But starburst cells are known to release and have receptors for both GABA and acetylcholine. We tested whether interactions within the starburst cell network can contribute to their directional response properties. In a computational model of interacting starburst amacrine cells, we simulated the response of individual dendrites to moving light stimuli. By setting the model parameters for “synaptic connection strength” ( cs) to positive or negative values, overlapping starburst dendrites could either excite or inhibit each other. For some values of cs, we observed a very robust inward/outward asymmetry of the starburst dendrites consistent with the reported physiological findings. This is the case, for example, if a starburst cell receives inhibition from other starburst cells located in its surround. For other values of cs, individual dendrites can respond best either to inward movement or respond symmetrically. A properly wired network of starburst cells can therefore account for the experimentally observed asymmetry of their response to movement, independent of any internal biophysical or biochemical properties of starburst cell dendrites.


Development ◽  
1997 ◽  
Vol 124 (5) ◽  
pp. 1055-1067 ◽  
Author(s):  
Z.D. Ezzeddine ◽  
X. Yang ◽  
T. DeChiara ◽  
G. Yancopoulos ◽  
C.L. Cepko

Lineage analyses of vertebrate retinae have led to the suggestions that cell fate decisions are made during or after the terminal cell division and that extrinsic factors can influence fate choices. The evidence for a role of extrinsic factors is strongest for development of rodent rod photoreceptors ('rods'). In an effort to identify molecules that may regulate rod development, a number of known factors were assayed in vitro. Ciliary neurotrophic factor (CNTF) was found to have a range of effects on retinal cells. Addition of CNTF to postnatal rat retinal explants resulted in a dramatic reduction in the number of differentiating rods. Conversly, the number of cells expressing markers of bipolar cell differentiation was increased to a level not normally seen in vivo or in vitro. In addition, a small increase in the percentage of cells expressing either a marker of amacrine cells or a marker of Muller glia was noted. It was determined that many of the cells that would normally differentiate into rods were the cells that differentiated as bipolar cells in the presence of CNTF. Prospective rod photoreceptors could make this change even when they were postmitotic, indicating that at least a subset of cells fated to be rods were not committed to this fate at the time they were born. These findings highlight the distinction between cell fate and commitment. Resistance to the effect of CNTF on rod differentiation occurred at about the time that a cell began to express opsin. The time of commitment to terminal rod differentiation may thus coincide with the initiation of opsin expression. In agreement with the hypothesis that CNTF plays a role in rod differentiation in vivo, a greater percentage of cells were observed differentiating as rod photoreceptors in mouse retinal explants lacking a functional CNTF receptor, relative to wild-type littermates.


2000 ◽  
Vol 83 (4) ◽  
pp. 1817-1829 ◽  
Author(s):  
Thomas Euler ◽  
Richard H. Masland

We recorded light-evoked responses from rod and cone bipolar cells using patch-clamp techniques in a slice preparation of the rat retina. Rod bipolar cells responded to light with a sustained depolarization (on response) followed at light offset by a slight hyperpolarization. on and off cone bipolar cells were encountered, both with diverse temporal properties. The responses of rod bipolar cells were composed primarily of two components, a nonspecific cation current and a chloride current. The chloride current was reduced greatly in axotomized cells and could be suppressed by coapplication of the GABAA antagonist bicuculline and the GABAC antagonist (1,2,5,6-tetrahydropyridine-4-yl)methylphosphinic acid. This suggests that it largely reflects feedback from GABAergic amacrine cells. The response latency of intact rod bipolar cells was shorter than that of the axotomized cells, and the sensitivity curve covered more than twice the dynamic range. Application of the GABA receptor antagonists partially mimicked the effects of axotomy. These findings suggest that functional properties of the axon terminal system—notably synaptic feedback from amacrine cells—play an important role in defining the response properties of mammalian bipolar cells.


2020 ◽  
Vol 37 ◽  
Author(s):  
Erika D. Eggers ◽  
Teresia A. Carreon

Abstract Diabetic retinopathy is now well understood as a neurovascular disease. Significant deficits early in diabetes are found in the inner retina that consists of bipolar cells that receive inputs from rod and cone photoreceptors, ganglion cells that receive inputs from bipolar cells, and amacrine cells that modulate these connections. These functional deficits can be measured in vivo in diabetic humans and animal models using the electroretinogram (ERG) and behavioral visual testing. Early effects of diabetes on both the human and animal model ERGs are changes to the oscillatory potentials that suggest dysfunctional communication between amacrine cells and bipolar cells as well as ERG measures that suggest ganglion cell dysfunction. These are coupled with changes in contrast sensitivity that suggest inner retinal changes. Mechanistic in vitro neuronal studies have suggested that these inner retinal changes are due to decreased inhibition in the retina, potentially due to decreased gamma aminobutyric acid (GABA) release, increased glutamate release, and increased excitation of retinal ganglion cells. Inner retinal deficits in dopamine levels have also been observed that can be reversed to limit inner retinal damage. Inner retinal targets present a promising new avenue for therapies for early-stage diabetic eye disease.


1995 ◽  
Vol 12 (2) ◽  
pp. 345-358 ◽  
Author(s):  
J.H. Brandstätter ◽  
U. Greferath ◽  
T. Euler ◽  
H. Wässle

AbstractDirection-selective (DS) ganglion cells of the mammalian retina have their dendrites in the inner plexiform layer (IPL) confined to two narrow strata. The same strata are also occupied by the dendrites of cholinergic amacrine cells which are probably presynaptic to the DS ganglion cells. GABA is known to play a crucial role in creating DS responses. We examined the types of GABAA receptors expressed by the cholinergic amacrine cells and also those expressed by their presynaptic and postsynaptic neurons, by applying immunocytochemical markers to vertical sections of rat retinas. Double-labelling experiments with antibodies against choline acetyltransferase (ChAT) and specific antibodies against different GABAA receptor subunits were performed. Cholinergic amacrine cells seem to express an unusual combination of GABAA receptor subunits consisting of α2-, β1-, β2/3-, γ2-, and δ-subunits. Bipolar cells, which could provide synaptic input to the DS circuitry, were stained with antibodies against the glutamate transporter GLT-1. The axon terminals of these bipolar cells are narrowly stratified in close proximity to the dendritic plexus of displaced cholinergic amacrine cells. The retinal distribution of synaptoporin, a synaptic vesicle associated protein, was studied. Strong reduction of immunolabelling was observed in the two cholinergic strata. The anatomical findings are discussed in the context of models of the DS circuitry of the mammalian retina.


2014 ◽  
Vol 112 (8) ◽  
pp. 1950-1962 ◽  
Author(s):  
Minggang Chen ◽  
Seunghoon Lee ◽  
Silvia J. H. Park ◽  
Loren L. Looger ◽  
Z. Jimmy Zhou

Retinal bipolar cells (BCs) transmit visual signals in parallel channels from the outer to the inner retina, where they provide glutamatergic inputs to specific networks of amacrine and ganglion cells. Intricate network computation at BC axon terminals has been proposed as a mechanism for complex network computation, such as direction selectivity, but direct knowledge of the receptive field property and the synaptic connectivity of the axon terminals of various BC types is required in order to understand the role of axonal computation by BCs. The present study tested the essential assumptions of the presynaptic model of direction selectivity at axon terminals of three functionally distinct BC types that ramify in the direction-selective strata of the mouse retina. Results from two-photon Ca2+ imaging, optogenetic stimulation, and dual patch-clamp recording demonstrated that 1) CB5 cells do not receive fast GABAergic synaptic feedback from starburst amacrine cells (SACs); 2) light-evoked and spontaneous Ca2+ responses are well coordinated among various local regions of CB5 axon terminals; 3) CB5 axon terminals are not directionally selective; 4) CB5 cells consist of two novel functional subtypes with distinct receptive field structures; 5) CB7 cells provide direct excitatory synaptic inputs to, but receive no direct GABAergic synaptic feedback from, SACs; and 6) CB7 axon terminals are not directionally selective, either. These findings help to simplify models of direction selectivity by ruling out complex computation at BC terminals. They also show that CB5 comprises two functional subclasses of BCs.


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