A Key Role of Starburst Amacrine Cells in Originating Retinal Directional Selectivity and Optokinetic Eye Movement

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.

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Pharmacology of Directionally Selective Ganglion Cells in the Rabbit Retina

Journal of Neurophysiology ◽

10.1152/jn.1997.77.2.675 ◽

1997 ◽

Vol 77 (2) ◽

pp. 675-689 ◽

Cited By ~ 122

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.

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Realistic retinal modeling unravels the differential role of excitation and inhibition to starburst amacrine cells in direction selectivity

PLoS Computational Biology ◽

10.1371/journal.pcbi.1009754 ◽

2021 ◽

Vol 17 (12) ◽

pp. e1009754

Author(s):

Elishai Ezra-Tsur ◽

Oren Amsalem ◽

Lea Ankri ◽

Pritish Patil ◽

Idan Segev ◽

...

Keyword(s):

Genetic Algorithm ◽

Amacrine Cells ◽

Direction Selectivity ◽

Neuronal Morphology ◽

Data Driven ◽

Biophysical Properties ◽

Retinal Stimulation ◽

Starburst Amacrine Cells ◽

Experimental Findings

Retinal direction-selectivity originates in starburst amacrine cells (SACs), which display a centrifugal preference, responding with greater depolarization to a stimulus expanding from soma to dendrites than to a collapsing stimulus. Various mechanisms were hypothesized to underlie SAC centrifugal preference, but dissociating them is experimentally challenging and the mechanisms remain debatable. To address this issue, we developed the Retinal Stimulation Modeling Environment (RSME), a multifaceted data-driven retinal model that encompasses detailed neuronal morphology and biophysical properties, retina-tailored connectivity scheme and visual input. Using a genetic algorithm, we demonstrated that spatiotemporally diverse excitatory inputs–sustained in the proximal and transient in the distal processes–are sufficient to generate experimentally validated centrifugal preference in a single SAC. Reversing these input kinetics did not produce any centrifugal-preferring SAC. We then explored the contribution of SAC-SAC inhibitory connections in establishing the centrifugal preference. SAC inhibitory network enhanced the centrifugal preference, but failed to generate it in its absence. Embedding a direction selective ganglion cell (DSGC) in a SAC network showed that the known SAC-DSGC asymmetric connectivity by itself produces direction selectivity. Still, this selectivity is sharpened in a centrifugal-preferring SAC network. Finally, we use RSME to demonstrate the contribution of SAC-SAC inhibitory connections in mediating direction selectivity and recapitulate recent experimental findings. Thus, using RSME, we obtained a mechanistic understanding of SACs’ centrifugal preference and its contribution to direction selectivity.

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Presynaptic SNAP-25 regulates retinal waves and retinogeniculate projection via phosphorylation

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1812169116 ◽

2019 ◽

Vol 116 (8) ◽

pp. 3262-3267 ◽

Cited By ~ 1

Author(s):

Yu-Tien Hsiao ◽

Wen-Chi Shu ◽

Pin-Chun Chen ◽

Hui-Ju Yang ◽

Hsin-Yo Chen ◽

...

Keyword(s):

Ganglion Cells ◽

Amacrine Cells ◽

Calcium Transients ◽

Retinal Ganglion ◽

Retinal Waves ◽

Starburst Amacrine Cells ◽

Retinogeniculate Projection ◽

Wave Properties

Patterned spontaneous activity periodically displays in developing retinas termed retinal waves, essential for visual circuit refinement. In neonatal rodents, retinal waves initiate in starburst amacrine cells (SACs), propagating across retinal ganglion cells (RGCs), further through visual centers. Although these waves are shown temporally synchronized with transiently high PKA activity, the downstream PKA target important for regulating the transmission from SACs remains unidentified. A t-SNARE, synaptosome-associated protein of 25 kDa (SNAP-25/SN25), serves as a PKA substrate, implying a potential role of SN25 in regulating retinal development. Here, we examined whether SN25 in SACs could regulate wave properties and retinogeniculate projection during development. In developing SACs, overexpression of wild-type SN25b, but not the PKA-phosphodeficient mutant (SN25b-T138A), decreased the frequency and spatial correlation of wave-associated calcium transients. Overexpressing SN25b, but not SN25b-T138A, in SACs dampened spontaneous, wave-associated, postsynaptic currents in RGCs and decreased the SAC release upon augmenting the cAMP-PKA signaling. These results suggest that SN25b overexpression may inhibit the strength of transmission from SACs via PKA-mediated phosphorylation at T138. Moreover, knockdown of endogenous SN25b increased the frequency of wave-associated calcium transients, supporting the role of SN25 in restraining wave periodicity. Finally, the eye-specific segregation of retinogeniculate projection was impaired by in vivo overexpression of SN25b, but not SN25b-T138A, in SACs. These results suggest that SN25 in developing SACs dampens the spatiotemporal properties of retinal waves and limits visual circuit refinement by phosphorylation at T138. Therefore, SN25 in SACs plays a profound role in regulating visual circuit refinement.

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The role of starburst amacrine cells in visual signal processing

Visual Neuroscience ◽

10.1017/s0952523811000393 ◽

2012 ◽

Vol 29 (1) ◽

pp. 73-81 ◽

Cited By ~ 46

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.

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Retinal Direction Selectivity: Role of Starburst Amacrine Cells

10.1007/springerreference_118652 ◽

2012 ◽

Keyword(s):

Amacrine Cells ◽

Direction Selectivity ◽

Starburst Amacrine Cells

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The Role Of Eye Movement Desensitization And Reprocessing (EMDR) In The Interdisciplinary Treatment Of Low Sexual Desire Women

PsycEXTRA Dataset ◽

10.1037/e322352004-140 ◽

2002 ◽

Author(s):

Sara Mize

Keyword(s):

Eye Movement ◽

Sexual Desire ◽

Interdisciplinary Treatment ◽

Low Sexual Desire

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Role of Primate Cerebellar Hemisphere in Voluntary Eye Movement Control Revealed by Lesion Effects

Journal of Neurophysiology ◽

10.1152/jn.90440.2008 ◽

2009 ◽

Vol 101 (2) ◽

pp. 934-947 ◽

Cited By ~ 35

Author(s):

Masafumi Ohki ◽

Hiromasa Kitazawa ◽

Takahito Hiramatsu ◽

Kimitake Kaga ◽

Taiko Kitamura ◽

...

Keyword(s):

Eye Movements ◽

Eye Movement ◽

Smooth Pursuit ◽

Movement Control ◽

Cerebellar Hemisphere ◽

Target Velocity ◽

Eye Movement Control ◽

Pursuit Eye Movements ◽

Catch Up

The anatomical connection between the frontal eye field and the cerebellar hemispheric lobule VII (H-VII) suggests a potential role of the hemisphere in voluntary eye movement control. To reveal the involvement of the hemisphere in smooth pursuit and saccade control, we made a unilateral lesion around H-VII and examined its effects in three Macaca fuscata that were trained to pursue visually a small target. To the step (3°)-ramp (5–20°/s) target motion, the monkeys usually showed an initial pursuit eye movement at a latency of 80–140 ms and a small catch-up saccade at 140–220 ms that was followed by a postsaccadic pursuit eye movement that roughly matched the ramp target velocity. After unilateral cerebellar hemispheric lesioning, the initial pursuit eye movements were impaired, and the velocities of the postsaccadic pursuit eye movements decreased. The onsets of 5° visually guided saccades to the stationary target were delayed, and their amplitudes showed a tendency of increased trial-to-trial variability but never became hypo- or hypermetric. Similar tendencies were observed in the onsets and amplitudes of catch-up saccades. The adaptation of open-loop smooth pursuit velocity, tested by a step increase in target velocity for a brief period, was impaired. These lesion effects were recognized in all directions, particularly in the ipsiversive direction. A recovery was observed at 4 wk postlesion for some of these lesion effects. These results suggest that the cerebellar hemispheric region around lobule VII is involved in the control of smooth pursuit and saccadic eye movements.

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Réponses évoquées par les mouvements oculaires d'exploration (réponse lambda): Rôle des afférences intervenant à divers moments du processus oculo-moteur

Perception ◽

10.1068/p010167 ◽

1972 ◽

Vol 1 (2) ◽

pp. 167-175 ◽

Cited By ~ 4

Author(s):

Nicole Lesèvre ◽

A Rémond

Keyword(s):

Eye Movements ◽

Eye Movement ◽

Visual Effects ◽

Experimental Conditions ◽

Initial Portion ◽

Vertical Movements ◽

Black Field ◽

Fixation Points ◽

Lambda Response

Experiments are reported the aim of which was to elucidate the cause of each of the components of the lambda response, and particularly to evaluate the role of ‘on’ and ‘off’ visual effects which appear at various times during the oculomotor process and also the possible influence of non-visual mechanisms. Eight subjects with normal sight were studied under the following conditions: (i) horizontal eye movements of 12° were guided by fixation points placed on a dimly-lit uniform black field of 20°; a checkerboard of 6° aperture was placed in this field so as to be integrated into the oculomotor process at different times—at the beginning, during and at the end of the eye movement; (ii) successive horizontal eye movements of 3°, 7° and 11° scanned a checkerboard of 20°, each square of which had a 40′ aperture; (iii) the checkerboard was moved with an amplitude and period similar to those of the eye movements in (ii), but this time with gaze fixed. Horizontal and vertical movements of both eyes were recorded with an EOG. An EEG of the parieto-occipital regions was obtained using eight linked bipolar derivations in line on two montages, median longitudinal and right-left transverse. The EEG and EOG data were digitalized and a numerical programme of waveform recognition was used to identify the beginning of the saccade which triggers the averaging out of the EEG before (100 ms) and after (500 ms) the eye movement. A discussion of the results, taking into account the latency of the different components and their reinforcements or inhibition depending on experimental conditions, suggests that the two initial components of lambda response (including the initial portion of the classical lambda wave) might be due to visual effects (‘off effect’) that arise at the start of the movement or slightly before it at the time that the saccadic suppression begins. The later components could be attributed to visual effects brought into play towards the end of the movement (‘on effect’), when perception becomes normal again. It is, however, difficult to explain some of the results related to the amplitude of lambda components without bringing in a mechanism of non-visual origin (corollary discharge).

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