scholarly journals Rapid ‘multi-directed’ cholinergic transmission at central synapses

2020 ◽  
Author(s):  
Santhosh Sethuramanujam ◽  
Akihiro Matsumoto ◽  
J. Michael McIntosh ◽  
Miao Jing ◽  
Yulong Li ◽  
...  
Keyword(s):  
Ganglion Cells ◽  
Amacrine Cells ◽  
Cholinergic Transmission ◽  
Starburst Amacrine Cells ◽  
Local Direction ◽  
The Central Nervous System ◽  
Point To Point ◽  
Central Synapses ◽  
Synaptic Structures ◽  
Synaptic Mechanisms

AbstractAcetylcholine (ACh) is a key neurotransmitter that plays diverse roles in many parts of the central nervous system, including the retina. However, assessing the precise spatiotemporal dynamics of ACh is technically challenging and whether ACh transmits signals via rapid, point-to-point synaptic mechanisms, or broader-scale ‘non-synaptic’ mechanisms has been difficult to ascertain. Here, we examined the properties of cholinergic transmission at individual contacts made between direction-selective starburst amacrine cells and downstream ganglion cells in the retina. Using a combination of electrophysiology, serial block-face electron microscopy, and two-photon ACh imaging, we demonstrate that ACh signaling bears the hallmarks of both non-synaptic and synaptic forms of transmission. ACh co-activates nicotinic ACh receptors located on the intersecting dendrites of pairs of ganglion cells, with equal efficiency (non-synaptic)— and yet retains the ability to generate rapid ‘miniature’ currents (∼1 ms rise times: synaptic). Fast cholinergic signals do not appear to depend on anatomically well-defined synaptic structures. We estimate that ACh spread is limited to ∼1-2 µm from its sites of release, which may help starbursts drive local direction-selective cholinergic responses in ganglion cell dendrites. Together, our results establish the functional architecture for cholinergic signaling at a central synapse and propose a novel motif whereby single presynaptic sites can co-transmit information to multiple neurons on a millisecond timescale.

scholarly journals Rapid multi-directed cholinergic transmission in the central nervous system

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Santhosh Sethuramanujam ◽  
Akihiro Matsumoto ◽  
Geoff deRosenroll ◽  
Benjamin Murphy-Baum ◽  
J Michael McIntosh ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Ganglion Cells ◽  
Release Site ◽  
Amacrine Cells ◽  
Global Scale ◽  
Cholinergic Transmission ◽  
Data Set ◽  
The Central Nervous System ◽  
Synaptic Mechanisms

AbstractIn many parts of the central nervous system, including the retina, it is unclear whether cholinergic transmission is mediated by rapid, point-to-point synaptic mechanisms, or slower, broad-scale ‘non-synaptic’ mechanisms. Here, we characterized the ultrastructural features of cholinergic connections between direction-selective starburst amacrine cells and downstream ganglion cells in an existing serial electron microscopy data set, as well as their functional properties using electrophysiology and two-photon acetylcholine (ACh) imaging. Correlative results demonstrate that a ‘tripartite’ structure facilitates a ‘multi-directed’ form of transmission, in which ACh released from a single vesicle rapidly (~1 ms) co-activates receptors expressed in multiple neurons located within ~1 µm of the release site. Cholinergic signals are direction-selective at a local, but not global scale, and facilitate the transfer of information from starburst to ganglion cell dendrites. These results suggest a distinct operational framework for cholinergic signaling that bears the hallmarks of synaptic and non-synaptic forms of transmission.

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 GABA release selectively regulates synapse development at distinct inputs on direction-selective retinal ganglion cells

2018 ◽  
Vol 115 (51) ◽  
pp. E12083-E12090 ◽  
Author(s):  
Adam Bleckert ◽  
Chi Zhang ◽  
Maxwell H. Turner ◽  
David Koren ◽  
David M. Berson ◽  
...  
Keyword(s):  
Ganglion Cells ◽  
Selective Reduction ◽  
Amacrine Cells ◽  
Gaba Release ◽  
Direction Selectivity ◽  
Inhibitory Synapses ◽  
Retinal Ganglion ◽  
Gabaergic Transmission ◽  
Starburst Amacrine Cells ◽  
Receptor Clusters

Synaptic inhibition controls a neuron’s output via functionally distinct inputs at two subcellular compartments, the cell body and the dendrites. It is unclear whether the assembly of these distinct inhibitory inputs can be regulated independently by neurotransmission. In the mammalian retina, γ-aminobutyric acid (GABA) release from starburst amacrine cells (SACs) onto the dendrites of on–off direction-selective ganglion cells (ooDSGCs) is essential for directionally selective responses. We found that ooDSGCs also receive GABAergic input on their somata from other amacrine cells (ACs), including ACs containing the vasoactive intestinal peptide (VIP). When net GABAergic transmission is reduced, somatic, but not dendritic, GABAA receptor clusters on the ooDSGC increased in number and size. Correlative fluorescence imaging and serial electron microscopy revealed that these enlarged somatic receptor clusters are localized to synapses. By contrast, selectively blocking vesicular GABA release from either SACs or VIP ACs did not alter dendritic or somatic receptor distributions on the ooDSGCs, showing that neither SAC nor VIP AC GABA release alone is required for the development of inhibitory synapses in ooDSGCs. Furthermore, a reduction in net GABAergic transmission, but not a selective reduction from SACs, increased excitatory drive onto ooDSGCs. This increased excitation may drive a homeostatic increase in ooDSGC somatic GABAA receptors. Differential regulation of GABAA receptors on the ooDSGC’s soma and dendrites could facilitate homeostatic control of the ooDSGC’s output while enabling the assembly of the GABAergic connectivity underlying direction selectivity to be indifferent to altered transmission.

scholarly journals Formation of retinal direction-selective circuitry initiated by starburst amacrine cell homotypic contact

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Thomas A Ray ◽  
Suva Roy ◽  
Christopher Kozlowski ◽  
Jingjing Wang ◽  
Jon Cafaro ◽  
...  
Keyword(s):  
Synapse Formation ◽  
Ganglion Cells ◽  
Plexiform Layer ◽  
Surface Protein ◽  
Amacrine Cells ◽  
Direction Selectivity ◽  
Mouse Retina ◽  
Inner Plexiform Layer ◽  
Starburst Amacrine Cells ◽  
Developing Neurons

A common strategy by which developing neurons locate their synaptic partners is through projections to circuit-specific neuropil sublayers. Once established, sublayers serve as a substrate for selective synapse formation, but how sublayers arise during neurodevelopment remains unknown. Here, we identify the earliest events that initiate formation of the direction-selective circuit in the inner plexiform layer of mouse retina. We demonstrate that radially migrating newborn starburst amacrine cells establish homotypic contacts on arrival at the inner retina. These contacts, mediated by the cell-surface protein MEGF10, trigger neuropil innervation resulting in generation of two sublayers comprising starburst-cell dendrites. This dendritic scaffold then recruits projections from circuit partners. Abolishing MEGF10-mediated contacts profoundly delays and ultimately disrupts sublayer formation, leading to broader direction tuning and weaker direction-selectivity in retinal ganglion cells. Our findings reveal a mechanism by which differentiating neurons transition from migratory to mature morphology, and highlight this mechanism’s importance in forming circuit-specific sublayers.

Neural architecture of the “transient” ON directionally selective (class IIb1) ganglion cells in rabbit retina, partly co-stratified with starburst amacrine cells

2016 ◽  
Vol 33 ◽  
Author(s):  
EDWARD V. FAMIGLIETTI
Keyword(s):  
T Cells ◽  
Ganglion Cell ◽  
Ganglion Cells ◽  
Amacrine Cells ◽  
Dendritic Morphology ◽  
Inner Plexiform Layer ◽  
Rabbit Retina ◽  
Branching Pattern ◽  
Stimulus Velocity ◽  
Starburst Amacrine Cells

AbstractRecent physiological studies coupled with intracellular staining have subdivided ON directionally selective (DS) ganglion cells of rabbit retina into two types. One exhibits more “transient” and more “brisk” responses (ON DS-t), and the other has more “sustained’ and more “sluggish” responses (ON DS-s), although both represent the same three preferred directions and show preference for low stimulus velocity, as reported in previous studies of ON DS ganglion cells in rabbit retina. ON DS-s cells have the morphology of ganglion cells previously shown to project to the medial terminal nucleus (MTN) of the accessory optic system, and the MTN-projecting, class IVus1 cells have been well-characterized previously in terms of their dendritic morphology, branching pattern, and stratification. ON DS-t ganglion cells have a distinctly different morphology and exhibit heterotypic coupling to amacrine cells, including axon-bearing amacrine cells, with accompanying synchronous firing, while ON DS-s cells are not coupled. The present study shows that ON DS-t cells are morphologically identical to the previously well-characterized, “orphan” class IIb1 ganglion cell, previously regarded as a member of the “brisk-concentric” category of ganglion cells. Its branching pattern, quantitatively analyzed, is similar to that of the morphological counterparts of X and Y cells, and very different from that of the ON DS-s ganglion cell. Close analysis of the dendritic stratification of class IIb1 ganglion cells together with fiducial cells indicates that they differ from that of the ON DS-s cells. In agreement with one of the three previous studies, class IIb1/ON DS-t cells, unlike class IVus1/ON DS-s ganglion cells, in the main do not co-stratify with starburst amacrine cells. As the present study shows, however, portions of their dendrites do deviate from the main substratum, coming within range of starburst boutons. Parsimony favors DS input from starburst amacrine cells both to ON DS-s and to ON DS-t ganglion cells, given the similarity of their DS responses, but further studies will be required to substantiate the origin of the DS responses of ON DS-t cells. Previously reported OFF DS responses in ON DS-t cells, unmasked by pharmacological agents, and mediated by gap junctions with amacrine cells, suggests an unusual trans-sublaminar organization of directional selectivity in the inner plexiform layer, connecting sublamina a and sublamina b.

scholarly journals Antagonistic center-surround mechanisms for direction selectivity in the retina

2019 ◽  
Author(s):  
Lea Ankri ◽  
Elishai Ezra-Tsur ◽  
Shir R. Maimon ◽  
Nathali Kaushansky ◽  
Michal Rivlin-Etzion
Keyword(s):  
Receptive Field ◽  
Sensory Processing ◽  
Ganglion Cells ◽  
Amacrine Cells ◽  
Direction Selectivity ◽  
Repetitive Stimulation ◽  
Spatiotemporal Model ◽  
Starburst Amacrine Cells ◽  
Modeling Data

SummaryA key feature in sensory processing is center-surround receptive field antagonism. Retinal direction-selectivity (DS) relies on asymmetric inhibition from starburst amacrine cells (SAC) to direction selective ganglion cells (DSGC). SAC exhibit antagonistic center-surround, depolarizing to light increments and decrements in their center and surround, respectively, but the role of this property in DS remains elusive. We found that a repetitive stimulation exhausts SAC center and enhances its surround and used it to distinguish center-from surround-mediated responses. Center, but not surround stimulation, induced direction-selective responses in SAC, as predicted by an elementary spatiotemporal model. Nevertheless, both SAC center and surround elicited direction-selective responses in DSGCs, but to opposite directions. Physiological and morphology-based modeling data show that the opposed responses resulted from inverted DSGC’s excitatory-inhibitory temporal balance, indicating that SAC response time rules DS. Our findings reveal antagonistic center-surround mechanisms for DS, and demonstrate how context-dependent center-surround reorganization enables flexible computations.

scholarly journals Receptoral Mechanisms for Fast Cholinergic Transmission in Direction-Selective Retinal Circuitry

2020 ◽  
Vol 14 ◽  
Author(s):  
Joseph Pottackal ◽  
Joshua H. Singer ◽  
Jonathan B. Demb
Keyword(s):  
Synaptic Transmission ◽  
Amacrine Cells ◽  
Direction Selectivity ◽  
Gabaergic Inhibition ◽  
Temporal Difference ◽  
Cholinergic Transmission ◽  
Null Direction ◽  
Gabaergic Transmission ◽  
Temporal Properties ◽  
Synaptic Mechanisms

Direction selectivity represents an elementary sensory computation that can be related to underlying synaptic mechanisms. In mammalian retina, direction-selective ganglion cells (DSGCs) respond strongly to visual motion in a “preferred” direction and weakly to motion in the opposite, “null” direction. The DS mechanism depends on starburst amacrine cells (SACs), which provide null direction-tuned GABAergic inhibition and untuned cholinergic excitation to DSGCs. GABAergic inhibition depends on conventional synaptic transmission, whereas cholinergic excitation apparently depends on paracrine (i.e., non-synaptic) transmission. Despite its paracrine mode of transmission, cholinergic excitation is more transient than GABAergic inhibition, yielding a temporal difference that contributes essentially to the DS computation. To isolate synaptic mechanisms that generate the distinct temporal properties of cholinergic and GABAergic transmission from SACs to DSGCs, we optogenetically stimulated SACs while recording postsynaptic currents (PSCs) from DSGCs in mouse retina. Direct recordings from channelrhodopsin-2-expressing (ChR2+) SACs during quasi-white noise (WN) (0-30 Hz) photostimulation demonstrated precise, graded optogenetic control of SAC membrane current and potential. Linear systems analysis of ChR2-evoked PSCs recorded in DSGCs revealed cholinergic transmission to be faster than GABAergic transmission. A deconvolution-based analysis showed that distinct postsynaptic receptor kinetics fully account for the temporal difference between cholinergic and GABAergic transmission. Furthermore, GABAA receptor blockade prolonged cholinergic transmission, identifying a new functional role for GABAergic inhibition of SACs. Thus, fast cholinergic transmission from SACs to DSGCs arises from at least two distinct mechanisms, yielding temporal properties consistent with conventional synapses despite its paracrine nature.

Pharmacology of Directionally Selective Ganglion Cells in the Rabbit Retina

1997 ◽  
Vol 77 (2) ◽  
pp. 675-689 ◽  
Author(s):  
Christopher A. Kittila ◽  
Stephen C. Massey
Keyword(s):  
Ganglion Cells ◽  
Amacrine Cells ◽  
Gaba Release ◽  
Excitatory Input ◽  
Directional Selectivity ◽  
Dependent Manner ◽  
Rabbit Retina ◽  
Response Curves ◽  
Wide Range ◽  
Starburst Amacrine Cells

Kittila, Christopher A. and Stephen C. Massey. Pharmacology of directionally selective ganglion cells in the rabbit retina. J. Neurophysiol. 77: 675–689, 1997. In this report we describe extracellular recordings made from on and on-off directionally selective (DS) ganglion cells in the rabbit retina during perfusion with agonists and antagonists to acetylcholine (ACh), glutamate, and γ-aminobutyric acid (GABA). Nicotinic ACh agonists strongly excited DS ganglion cell in a dose-dependent manner. Dose-response curves showed a wide range of potencies, with (±)-exo-2-(6-chloro-3pyridinyl)-7-azabicyclo[2.2.1] heptane dihydrochloride (epibatidine) ≫ nicotine > 1,1-dimethyl-4-phenylpiperazinium iodide = carbachol. In addition, the mixed cholinergic agonist carbachol produced a small excitation, mediated by muscarinic receptors, that could be blocked by atropine. The specific nicotinic antagonists hexamethonium bromide (100 μM), dihydro-β-erythroidine (50 μM), mecamylamine (50 μM), and tubocurarine (50 μM) blocked the responses to nicotinic agonists. In addition, nicotinic antagonists reduced the light-driven input to DS ganglion cells by ∼50%. However, attenuated responses were still DS. We deduce that cholinergic input is not required for directional selectivity. These experiments reveal the importance of bipolar cell input mediated by glutamate. N-methyl-d-aspartic acid (NMDA) excited DS ganglion cells, but NMDA antagonists did not abolish directional selectivity. However, a combined cholinergic and NMDA blockade reduced the responses of DS ganglion cells by >90%. This indicates that most of the noncholinergic excitatory input appears to be mediated by NMDA receptors, with a small residual made upb y  α - a m i n o - 3 - h y d r o x y - 5 - m e t h y l - 4 - i s o x a z o l e p r o p i o n i c  a c i d(AMPA)/kainate (KA) receptors. Responses to AMPA and KA were highly variable and often evoked a mixture of excitation and inhibition due to the release of ACh and GABA. Under cholinergic blockade AMPA/KA elicited a strong GABA-mediated inhibition in DS ganglion cells. AMPA/KA antagonists, such as 2,3-dihydroxy-6-nitro-7-sulfamoylbenzo(F)quinoxaline dione and GYKI-53655, promoted null responses and abolished directional selectivity due to the blockade of GABA release. We conclude that GABA release, mediated by non-NMDA glutamate receptors, is an essential part of the mechanism of directional selectivity. The source of the GABA is unknown, but may arise from starburst amacrine cells.

Melanopsin and calbindin immunoreactivity in the inner retina of humans and marmosets

2019 ◽  
Vol 36 ◽  
Author(s):  
Ashleigh J. Chandra ◽  
Sammy C.S. Lee ◽  
Ulrike Grünert
Keyword(s):  
Ganglion Cell ◽  
Calcium Binding ◽  
Ganglion Cell Layer ◽  
Ganglion Cells ◽  
Cell Layer ◽  
Amacrine Cells ◽  
Bipolar Cells ◽  
Human Retina ◽  
Immunohistochemical Markers ◽  
Starburst Amacrine Cells

Abstract In primate retina, the calcium-binding protein calbindin is expressed by a variety of neurons including cones, bipolar cells, and amacrine cells but it is not known which type(s) of cell express calbindin in the ganglion cell layer. The present study aimed to identify calbindin-positive cell type(s) in the amacrine and ganglion cell layer of human and marmoset retina using immunohistochemical markers for ganglion cells (RBPMS and melanopsin) and cholinergic amacrine (ChAT) cells. Intracellular injections following immunolabeling was used to reveal the morphology of calbindin-positive cells. In human retina, calbindin-labeled cells in the ganglion cell layer were identified as inner and outer stratifying melanopsin-expressing ganglion cells, and ON ChAT (starburst amacrine) cells. In marmoset, calbindin immunoreactivity in the ganglion cell layer was absent from ganglion cells but present in ON ChAT cells. In the inner nuclear layer of human retina, calbindin was found in melanopsin-expressing displaced ganglion cells and in at least two populations of amacrine cells including about a quarter of the OFF ChAT cells. In marmoset, a very low proportion of OFF ChAT cells was calbindin-positive. These results suggest that in both species there may be two types of OFF ChAT cells. Consistent with previous studies, the ratio of ON to OFF ChAT cells was about 70 to 30 in human and 30 to 70 in marmoset. Our results show that there are species-related differences between different primates with respect to the expression of calbindin.

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