scholarly journals Regional Variation of Gap Junctional Connections in the Mammalian Inner Retina

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2396
Author(s):  
Katalin Fusz ◽  
Tamás Kovács-Öller ◽  
Péter Kóbor ◽  
Edina Szabó-Meleg ◽  
Béla Völgyi ◽  
...  
Keyword(s):  
Visual Field ◽  
Electrical Coupling ◽  
Amacrine Cells ◽  
Major Constituent ◽  
Double Labelling ◽  
Electrical Synapses ◽  
Connexin 36 ◽  
Relative Contribution ◽  
Topographical Distribution ◽  
Regional Specialisation

The retinas of many species show regional specialisations that are evident in the differences in the processing of visual input from different parts of the visual field. Regional specialisation is thought to reflect an adaptation to the natural visual environment, optical constraints, and lifestyle of the species. Yet, little is known about regional differences in synaptic circuitry. Here, we were interested in the topographical distribution of connexin-36 (Cx36), the major constituent of electrical synapses in the retina. We compared the retinas of mice, rats, and cats to include species with different patterns of regional specialisations in the analysis. First, we used the density of Prox1-immunoreactive amacrine cells as a marker of any regional specialisation, with higher cell density signifying more central regions. Double-labelling experiments showed that Prox1 is expressed in AII amacrine cells in all three species. Interestingly, large Cx36 plaques were attached to about 8–10% of Prox1-positive amacrine cell somata, suggesting the strong electrical coupling of pairs or small clusters of cell bodies. When analysing the regional changes in the volumetric density of Cx36-immunoreactive plaques, we found a tight correlation with the density of Prox1-expressing amacrine cells in the ON, but not in the OFF sublamina in all three species. The results suggest that the relative contribution of electrical synapses to the ON- and OFF-pathways of the retina changes with retinal location, which may contribute to functional ON/OFF asymmetries across the visual field.

scholarly journals Gap junctional coupling between retinal amacrine and ganglion cells underlies coherent activity integral to global object perception

2017 ◽  
Vol 114 (48) ◽  
pp. E10484-E10493 ◽  
Author(s):  
Kaushambi Roy ◽  
Sandeep Kumar ◽  
Stewart A. Bloomfield
Keyword(s):  
Gap Junctions ◽  
Long Range ◽  
Ganglion Cells ◽  
Electrical Coupling ◽  
Amacrine Cells ◽  
Spatial Separation ◽  
Object Perception ◽  
Mouse Retina ◽  
Genetic Ablation ◽  
Connexin 36

Coherent spike activity occurs between widely separated retinal ganglion cells (RGCs) in response to a large, contiguous object, but not to disjointed objects. Since the large spatial separation between the RGCs precludes common excitatory inputs from bipolar cells, the mechanism underlying this long-range coherence remains unclear. Here, we show that electrical coupling between RGCs and polyaxonal amacrine cells in mouse retina forms the synaptic mechanism responsible for long-range coherent activity in the retina. Pharmacological blockade of gap junctions or genetic ablation of connexin 36 (Cx36) subunits eliminates the long-range correlated spiking between RGCs. Moreover, we find that blockade of gap junctions or ablation of Cx36 significantly reduces the ability of mice to discriminate large, global objects from small, disjointed stimuli. Our results indicate that synchronous activity of RGCs, derived from electrical coupling with amacrine cells, encodes information critical to global object perception.

Action and localization of acetylcholine in the cat retina

1987 ◽  
Vol 58 (5) ◽  
pp. 997-1015 ◽  
Author(s):  
M. Schmidt ◽  
M. F. Humphrey ◽  
H. Wassle
Keyword(s):  
Ganglion Cell ◽  
Amacrine Cells ◽  
Cell Types ◽  
Functional Independence ◽  
Dendritic Morphology ◽  
Immunocytochemical Staining ◽  
Simultaneous Application ◽  
Cat Retina ◽  
Topographical Distribution ◽  
Cholinergic Amacrine Cells

1. Retinal ganglion cells were recorded extracellularly in the intact eye of anesthetized adult cats. The effects of acetylcholine (ACh), the muscarinic antagonist scopolamine (Sco), the nicotinic antagonist dihydro-beta-erythroidine (DBE), and the acetylcholinesterase inhibitor physostigmine (Phy) on maintained and light-evoked ganglion cell discharge was examined using iontophoresis techniques. 2. A monoclonal antibody directed against the ACh synthesizing enzyme choline acetyltransferase (ChAT) was used to label cholinergic cells in retinal wholemounts. The topographical distribution of these cells was studied. 3. Intracellular filling with the fluorescent dye lucifer yellow (LY) was performed to identify the dendritic morphology of putative cholinergic neurons. 4. ACh increased and Sco decreased neuronal activity of all brisk ganglion cell types under all stimulus conditions tested in this study. The action of ACh was abolished during simultaneous application of Sco. 5. DBE raised the firing rate of ON-center brisk cells and decreased activity of OFF-center brisk cells. Again there was no difference under different stimulus conditions. During DBE application the ACh action on OFF-center cells was completely blocked. The ACh action on ON-center cells was diminished. 6. Phy prolonged and enhanced ACh action on all ganglion cell types. During simultaneous stimulation of the receptive-field center and the surround, Phy caused an activity shift in favor of the center response. 7. Immunocytochemical staining revealed two populations of amacrine cells, one in the inner nuclear layer, and the other in the ganglion cell layer. Their total density increased from 250 cells/mm2 in the periphery to 2,700 cells/mm2 in the central area. Analysis of the distribution pattern indicated a functional independence of the two subpopulations. 8. The dendritic morphology of putative cholinergic amacrine cells in the cat retina resembled that of rabbit and rat "starburst" amacrines, which are known to be cholinergic. 9. The possible function of cholinergic amacrine cells in the cat retina is discussed in view of the present findings and compared with results from other mammalian species.

The retinal ganglion cell distribution and the representation of the visual field in area 17 of the owl monkey, Aotus trivirgatus

1993 ◽  
Vol 10 (5) ◽  
pp. 887-897 ◽  
Author(s):  
L. C. L. Silveira ◽  
V. H. Perry ◽  
E. S. Yamada
Keyword(s):  
Visual Cortex ◽  
Visual Field ◽  
Ganglion Cell ◽  
Cell Density ◽  
Ganglion Cells ◽  
Amacrine Cells ◽  
Temporal Region ◽  
Cell Distribution ◽  
Area 17 ◽  
Displaced Amacrine Cells

AbstractThe distribution of ganglion cells and displaced amacrine cells was determined in whole-mounted Aotus retinae. In contrast to diurnal simians, Aotus has only a rudimentary fovea. Ganglion cell density decreases towards the periphery at approximately the same rate along all meridians, but is 1.2–1.8 times higher in the nasal periphery when compared to temporal region at the same eccentricities. The total number of ganglion cells varied from 421,500 to 508,700. Ganglion cell density peaked at 15,000/mm2 at 0.25 mm dorsal to the fovea. The displaced amacrine cells have a shallow density gradient, their peak density in the central region is about 1500–2000/mm2 and their total number varied from 315,900 to 482,800. Comparison between ganglion cell density and areal cortical magnification factor for the primary visual cortex, area 17, shows that there is not a simple proportional representation of the ganglion cell distribution. There is an overrepresentation of the central 10 deg of the visual field in the visual cortex. The present results for Aotus and the results of a similar analysis of data from other primates indicate that the overrepresentation of the central visual field is a general feature of the visual system of primates.

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

2009 ◽  
Vol 101 (5) ◽  
pp. 2339-2347 ◽  
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.

scholarly journals A high-density narrow-field inhibitory retinal interneuron with direct coupling to Müller glia

2020 ◽  
Author(s):  
William N Grimes ◽  
Didem Göz Aytürk ◽  
Mrinalini Hoon ◽  
Takeshi Yoshimatsu ◽  
Clare Gamlin ◽  
...  
Keyword(s):  
Gap Junctions ◽  
Glial Cells ◽  
Amacrine Cell ◽  
Electrical Coupling ◽  
Amacrine Cells ◽  
Muller Glia ◽  
Müller Glia ◽  
Cell Type ◽  
Mammalian Retina ◽  
Ganglion Neurons

AbstractAmacrine cells are interneurons comprising the most diverse cell type in the mammalian retina. They help encode visual features such as edges or directed motion by mediating excitatory and inhibitory interactions between input (i.e. bipolar) and output (i.e. ganglion) neurons in the inner plexiform layer (IPL). Like other brain regions, the retina also contains glial cells that contribute to neurotransmitter uptake, neurovascular control and metabolic regulation. Here, we report that a previously poorly characterized, but relatively abundant, inhibitory amacrine cell type in the mouse retina is coupled directly to Müller glia. Electron microscopic reconstructions of this amacrine type revealed extensive associations with Müller glia, whose processes often completely ensheathe the neurites of this amacrine cell type. Microinjections of small tracer molecules into the somas of these amacrine cells led to selective labelling of nearby Müller glia, leading us to suggest the name “Müller glia-coupled amacrine cell” or MAC. Our electrophysiological data also indicate that MACs release glycine at conventional chemical synapses with amacrine, bipolar and retinal ganglion cells (RGCs), and viral transsynaptic tracing showed connections to several known RGC types. Visually-evoked responses revealed a strong preference for light increments; these “ON” responses were primarily mediated by excitatory chemical synaptic input and direct electrical coupling to other cells. This initial characterization of the MAC provides the first evidence for neuron-glia coupling in the mammalian retina and identifies the MAC as a potential link between inhibitory processing and glial function.Significance StatementGap junctions between pairs of neurons or glial cells are commonly found throughout the nervous system, and play a myriad of roles including electrical coupling and metabolic exchange. In contrast, gap junctions between neurons and glia cells are rare and poorly understood. Here we report the first evidence for neuron-glia coupling in the mammalian retina, specifically between an abundant (but previously unstudied) inhibitory interneuron and Müller glia.

scholarly journals Tubulin-Dependent Transport of Connexin-36 Potentiates the Size and Strength of Electrical Synapses

Cells ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 1146 ◽  
Author(s):  
Brown ◽  
del Corsso ◽  
Zoidl ◽  
Donaldson ◽  
Spray ◽  
...  
Keyword(s):  
Protein Transport ◽  
Mutational Analysis ◽  
Binding Motif ◽  
Dependent Manner ◽  
Electrical Synapses ◽  
Binding Motifs ◽  
Connexin 36 ◽  
Dependent Transport ◽  
Carboxy Terminal

Connexin-36 (Cx36) electrical synapses strengthen transmission in a calcium/calmodulin (CaM)/calmodulin-dependent kinase II (CaMKII)-dependent manner similar to a mechanism whereby the N-methyl-D-aspartate (NMDA) receptor subunit NR2B facilitates chemical transmission. Since NR2B–microtubule interactions recruit receptors to the cell membrane during plasticity, we hypothesized an analogous modality for Cx36. We determined that Cx36 binding to tubulin at the carboxy-terminal domain was distinct from Cx43 and NR2B by binding a motif overlapping with the CaM and CaMKII binding motifs. Dual patch-clamp recordings demonstrated that pharmacological interference of the cytoskeleton and deleting the binding motif at the Cx36 carboxyl-terminal (CT) reversibly abolished Cx36 plasticity. Mechanistic details of trafficking to the gap-junction plaque (GJP) were probed pharmacologically and through mutational analysis, all of which affected GJP size and formation between cell pairs. Lys279, Ile280, and Lys281 positions were particularly critical. This study demonstrates that tubulin-dependent transport of Cx36 potentiates synaptic strength by delivering channels to GJPs, reinforcing the role of protein transport at chemical and electrical synapses to fine-tune communication between neurons.

scholarly journals Response to coincident inputs in electrically coupled primary afferents is heterogeneous and is enhanced by H-current (IH) modulation

2019 ◽  
Vol 122 (1) ◽  
pp. 151-175
Author(s):  
Federico Davoine ◽  
Sebastian Curti
Keyword(s):  
Neuronal Excitability ◽  
Signal To Noise Ratio ◽  
Electrical Coupling ◽  
Primary Afferents ◽  
Coincidence Detection ◽  
Mammalian Brain ◽  
Electrical Transmission ◽  
Electrical Synapses ◽  
Electrophysiological Properties ◽  
Cationic Current

Electrical synapses represent a widespread modality of interneuronal communication in the mammalian brain. These contacts, by lowering the effectiveness of random or temporally uncorrelated inputs, endow circuits of coupled neurons with the ability to selectively respond to simultaneous depolarizations. This mechanism may support coincidence detection, a property involved in sensory perception, organization of motor outputs, and improvement signal-to-noise ratio. While the role of electrical coupling is well established, little is known about the contribution of the cellular excitability and its modulations to the susceptibility of groups of neurons to coincident inputs. Here, we obtained dual whole cell patch-clamp recordings of pairs of mesencephalic trigeminal (MesV) neurons in brainstem slices from rats to evaluate coincidence detection and its determinants. MesV neurons are primary afferents involved in the organization of orofacial behaviors whose cell bodies are electrically coupled mainly in pairs through soma-somatic gap junctions. We found that coincidence detection is highly heterogeneous across the population of coupled neurons. Furthermore, combined electrophysiological and modeling approaches reveal that this heterogeneity arises from the diversity of MesV neuron intrinsic excitability. Consistently, increasing these cells’ excitability by upregulating the hyperpolarization-activated cationic current ( IH) triggered by cGMP results in a dramatic enhancement of the susceptibility of coupled neurons to coincident inputs. In conclusion, the ability of coupled neurons to detect coincident inputs is critically shaped by their intrinsic electrophysiological properties, emphasizing the relevance of neuronal excitability for the many functional operations supported by electrical transmission in mammals. NEW & NOTEWORTHY We show that the susceptibility of pairs of coupled mesencephalic trigeminal (MesV) neurons to coincident inputs is highly heterogenous and depends on the interaction between electrical coupling and neuronal excitability. Additionally, upregulating the hyperpolarization-activated cationic current ( IH) by cGMP results in a dramatic increase of this susceptibility. The IH and electrical synapses have been shown to coexist in many neuronal populations, suggesting that modulation of this conductance could represent a common strategy to regulate circuit operation supported by electrical coupling.

Electrical Synapses Between AII Amacrine Cells: Dynamic Range and Functional Consequences of Variation in Junctional Conductance

2008 ◽  
Vol 100 (6) ◽  
pp. 3305-3322 ◽  
Author(s):  
Margaret Lin Veruki ◽  
Leif Oltedal ◽  
Espen Hartveit
Keyword(s):  
Dynamic Range ◽  
Amacrine Cells ◽  
Electrical Synapses ◽  
Pass Filter ◽  
Low Pass Filter ◽  
Junctional Conductance ◽  
Coupled Cells ◽  
Functional Consequences ◽  
Aii Amacrine Cells ◽  
Aii Amacrine

AII amacrine cells form a network of electrically coupled interneurons in the mammalian retina and tracer coupling studies suggest that the junctional conductance ( Gj) can be modulated. However, the dynamic range of Gj and the functional consequences of varying Gj over the dynamic range are unknown. Here we use whole cell recordings from pairs of coupled AII amacrine cells in rat retinal slices to provide direct evidence for physiological modulation of Gj, appearing as a time-dependent increase from about 500 pS to a maximum of about 3,000 pS after 30–90 min of recording. The increase occurred in recordings with low- but not high-resistance pipettes, suggesting that it was related to intracellular washout and perturbation of a modulatory system. Computer simulations of a network of electrically coupled cells verified that our recordings were able to detect and quantify changes in Gj over a large range. Dynamic-clamp electrophysiology, with insertion of electrical synapses between AII amacrine cells, allowed us to finely and reversibly control Gj within the same range observed for physiologically coupled cells and to examine the quantitative relationship between Gj and steady-state coupling coefficient, synchronization of subthreshold membrane potential fluctuations, synchronization and transmission of action potentials, and low-pass filter characteristics. The range of Gj values over which signal transmission was modulated depended strongly on the specific functional parameter examined, with the largest range observed for action potential transmission and synchronization, suggesting that the full range of Gj values observed during spontaneous run-up of coupling could represent a physiologically relevant dynamic range.

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