Complementary roles of two excitatory pathways in retinal directional selectivity

1998 ◽  
Vol 15 (6) ◽  
pp. 1119-1127 ◽  
Author(s):  
NORBERTO M. GRZYWACZ ◽  
DAVID K. MERWINE ◽  
FRANKLIN R. AMTHOR
Keyword(s):  
Ganglion Cells ◽  
Temporal Frequency ◽  
Excitatory Input ◽  
Sinusoidal Grating ◽  
Excitatory Synapses ◽  
Directional Selectivity ◽  
Preferred Direction ◽  
Excitatory Pathways ◽  
Luminance Profile ◽  
The One

The two major excitatory synapses onto ON–OFF directionally selective (DS) ganglion cells of the rabbit retina appear to be nicotinic cholinergic and NMDA glutamatergic. Blockade of either of these synapses with antagonists does not eliminate directional selectivity. This suggests that these synapses may have complementary roles in the computation of the direction of motion. To test this hypothesis, quantitative features of the DS cell excitatory pathways were determined by collecting responses, under nicotinic and/or NMDA blockade, to a sweeping bar, hyperacute apparent motions, or a drifting sinusoidal grating. Sweeping bar responses were reduced, but directional selectivity not eliminated, by blockade of either excitatory path, as previously shown (Cohen & Miller, 1995; Kittila & Massey, 1997). However, residual responses under combined blockades were not statistically significantly DS. NMDA blockade reduced responses more than nicotinic blockade for each protocol, and shifted hyperacute motion thresholds to higher values. This supported the notion that glutamate provides the main excitatory drive to DS cells, that is, the one responsible for contrast sensitivity. In turn, nicotinic, but not NMDA blockade eliminated directional selectivity to a drifting low spatial-frequency sinusoidal grating in these cells. This suggested that acetylcholine (ACh) is the main excitatory input with regards to directional selectivity for some textured stimuli, that is, those with multiple peaks in their spatial luminance profile. Moreover, nicotinic blockade raised the low temporal-frequency cutoff of the grating responses, consistent with the proposal that preferred-direction facilitation, which is temporally sustained, is dependent on the cholinergic input. These different properties of the NMDA and nicotinic pathways are consistent with a recently proposed two-asymmetric-pathways model of directional selectivity.

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.

Effects of Ca2+ channel blockers on directional selectivity of rabbit retinal ganglion cells

1995 ◽  
Vol 74 (1) ◽  
pp. 12-23 ◽  
Author(s):  
R. J. Jensen
Keyword(s):  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Leading Edge ◽  
Channel Blockers ◽  
Directional Selectivity ◽  
Retinal Ganglion ◽  
Null Direction ◽  
Trailing Edge ◽  
Preferred Direction ◽  
Ca2 Channels

1. Extracellular recordings were made from ON-OFF directionally selective ganglion cells in superfused rabbit retinas in order to examine the effects of voltage-activated Ca2+ channel blockers on the response of these ganglion cells to a moving bar of light. 2. Bath application of Cd2+ (67-110 microM) abolished directional selectivity in the ganglion cells. That is, the cells gave nearly equal responses to the leading and trailing edges of a bar of light moved in the preferred and null directions. This effect of Cd2+ was rapidly reversible. 3. Directional selectivity in the ganglion cells was not affected by Ni2+ (120-440 microM), Co2+ (180-690 microM), or the L-type Ca2+ channel blockers nicardipine (7-29 microM) and methoxyverapamil (18-60 microM). These blockers did, however, reduce the responses of the ganglion cells to a bar of light moved in the preferred direction. 4. omega-Conotoxin MVIIC (130 nM-1.9 microM), which potently blocks N-type and Q-type Ca2+ channels, abolished directional selectivity in the ganglion cells. omega-Conotoxin MVIIC not only brought out large leading and trailing edge responses to movement of a bar of light in the null direction, but it also increased the leading and trailing edge responses to movement of the bar of light in the preferred direction. The effect of omega-conotoxin MVIIC was slowly reversible. 5. The N-type Ca2+ channel blocker omega-conotoxin GVIA (1.4-6.3 microM) did not abolish directional selectivity in the ganglion cells. This blocker did, however, bring out some response to the leading edge of a bar of a light moved in the null direction. This effect of omega-conotoxin GVIA appeared to be irreversible. 6. omega-Agatoxin IVA, a potent blocker of P-type Ca2+ channels, when bath applied at low concentrations (66-83 nM), increased the responses to movement of a bar of light in the preferred direction but brought out only small responses to movement of the bar of light in the null direction. At high concentrations (250-280 nM) that reportedly block Q-type Ca2+ channels by > or = 50%, omega-agatoxin IVA nearly abolished directional selectivity. This effect of omega-agatoxin IVA was slowly reversible. 7. These results indicate that omega-conotoxin MVIIC- and omega-agatoxin IVA-sensitive Ca2+ channels (possibly Q-type channels) play an important role in the generation of directional selectivity in rabbit retinal ganglion cells.

Effect of ON pathway blockade on directional selectivity in the rabbit retina

1995 ◽  
Vol 73 (2) ◽  
pp. 703-712 ◽  
Author(s):  
C. A. Kittila ◽  
S. C. Massey
Keyword(s):  
Ganglion Cells ◽  
Aminobutyric Acid ◽  
Directional Selectivity ◽  
Rabbit Retina ◽  
Gamma Aminobutyric Acid ◽  
Channel Blockade ◽  
Moving Stimuli ◽  
Preferred Direction ◽  
Gabaa Antagonist ◽  
Dependent Mechanism

1. In this report we describe extracellular recordings made from directionally selective (DS) ganglion cells in the rabbit retina during perfusion with 2-amino-4-phosphonobutyric acid (APB) to block ON channels through the retina. 2. Application of 100 microM APB selectively and reversibly abolished the responses of ON ganglion cells in the rabbit retina. In addition, 100 microM APB completely and reversibly blocked ON component responses of ON-OFF DS ganglion cells to both stationary and moving stimuli. These results are consistent with the idea that APB blocks ON pathways through the retina. 3. Under ON pathway blockade with APB, OFF component responses of ON-OFF DS ganglion cells remained DS. DS OFF responses retained the same preferred direction as the pre-APB ON-OFF responses and could be driven using either normal or reversed contrast stimuli. 4. Extracellular responses of ON DS ganglion cells were completely blocked by APB. Under APB, these cells showed no response to stationary or moving stimuli. 5. Application of the gamma-aminobutyric acid-A (GABAA) antagonist 2-(3-Carboxypropyl)-3-amino-6-(4-methoxyphenyl)pyridazinium bromide (SR95531) reversibly abolished directional selectivity of ON DS and ON-OFF DS ganglion cells in the rabbit retina. This finding is consistent with previous data for picrotoxin. 6. Application of SR95531 during ON channel blockade by APB caused OFF component responses of ON-OFF DS ganglion cells to lose their directional selectivity. Under these conditions, OFF responses to movement in the preferred and null directions became virtually identical. 7. These results indicate that simultaneous ON and OFF layer input is not required to generate directional responses in ON-OFF DS ganglion cells. In addition, it appears that a GABAA-dependent mechanism for directional selectivity may operate independently in the two separate dendritic layers of the ON-OFF DS ganglion cell.

Directionally selective motion detection in the sustaining fibers of the crayfish optic nerve: linear and nonlinear mechanisms

1995 ◽  
Vol 74 (1) ◽  
pp. 142-152 ◽  
Author(s):  
R. M. Glantz ◽  
C. Wyatt ◽  
H. Mahncke
Keyword(s):  
Temporal Frequency ◽  
Band Pass Filter ◽  
Directional Selectivity ◽  
Directional Response ◽  
Pass Filter ◽  
Modulation Response ◽  
Functional Connections ◽  
Preferred Direction ◽  
Band Pass ◽  
The Mean

1. Directional selectivity of crayfish sustaining fibers was examined with drifting sine wave gratings and with intracellular and extracellular recordings. Directionality was measured for variations in stimulus contrast, spatial frequency, and temporal frequency. 2. Sustaining fibers exhibit directional selectivity in the magnitude of the compound postsynaptic potential (PSP), the impulse frequency modulation response, and the mean firing rate. The mean synaptic potential is insensitive to direction. The directionality of the mean impulse rate appears to arise by rectification in the voltage-to-impulse transduction. 3. The preferred directions of three identified sustaining fibers are similar to those of head-down optomotor neurons to which these sustaining fibers project. 4. The modulatory response, elicited by gratings drifting in the preferred direction, increased linearly with contrast until saturation (typically at a contrast of 0.5), where maximum directional selectivity obtains. 5. The magnitude of the directional response is a band-pass function of spatial and temporal frequency and exhibits reversal of directionality (i.e., aliasing) at high spatial and temporal frequencies. The results imply a spatial sampling interval of 4.5 degrees and a temperature-dependent inhibitory delay of 40-90 ms. The PSP modulation response shares several features with that of neighboring tangential (Tan1) neurons. 6. A qualitative model is proposed for the transformation of a phase-sensitive, linear directional response to a phase-insensitive and nonlinear time-averaged response, based on the functional connections from Tan1 neurons to sustaining fibers to optomotor neurons. The model includes a threshold rectification, a synaptic band-pass filter, and differences in temporal phase among converging modulatory signals.

Non-monotonic contrast behavior in directionally selective ganglion cells and evidence for its dependence on their GABAergic input

1998 ◽  
Vol 15 (6) ◽  
pp. 1129-1136 ◽  
Author(s):  
DAVID K. MERWINE ◽  
NORBERTO M. GRZYWACZ ◽  
DARREL S. TJEPKES ◽  
FRANKLIN R. AMTHOR
Keyword(s):  
Gaba Receptors ◽  
Direct Evidence ◽  
Ganglion Cells ◽  
Directional Selectivity ◽  
Gabaergic Inhibition ◽  
Rabbit Retina ◽  
Null Direction ◽  
Preferred Direction ◽  
Nmda Glutamate Receptors ◽  
First Time

We serendipitously discovered that the preferred-direction responses of ON–OFF directionally selective (DS) ganglion cells in the rabbit retina fall as a function of contrast when the contrast of a moving bar exceeds about 100%. Null-direction responses did not fall for contrasts up to 400%. Because the non-monotonic (rise-then-fall) behavior as a function of contrast occurred only for preferred-direction responses, it must depend on the mechanism of directional selectivity. It became thus of interest to investigate how this non-monotonicity depends on the major synapses involved in directional selectivity. Blockades of nicotinic acetylcholine (ACh) and NMDA glutamate receptors reduced responses without eliminating preferred-response non-monotonicity. Blocking GABAergic inhibition, however, did eliminate non-monotonicity. These results pose a difficult puzzle, since in the accompanying paper (Grzywacz et al., 1998), we showed that residual responses under combined nicotinic and NMDA blockades are not statistically significantly directionally selective. How is it possible that null-direction GABAergic inhibition affects non-nicotinic-non-NMDA residual responses without generating directional selectivity? This may happen if there exists an asymmetric GABAergic input to distal dendrites of the DS cell while the excitatory, non-nicotinic-non-NMDA input is to proximal dendrites. In support of this hypothesis, bath-applied GABA reduces responses to exogenous ACh under synaptic block, providing for the first time in the rabbit's retina, direct evidence of GABA receptors on DS cells.

Is the input to a GABAergic or cholinergic synapse the sole asymmetry in rabbit's retinal directional selectivity?

1997 ◽  
Vol 14 (1) ◽  
pp. 39-54 ◽  
Author(s):  
Norberto M. Grzywacz ◽  
John S. Tootle ◽  
Franklin R. Amthor
Keyword(s):  
Ganglion Cells ◽  
Cholinergic Receptors ◽  
Cholinergic Antagonists ◽  
Directional Selectivity ◽  
Spike Generation ◽  
Cholinergic Synapse ◽  
Inhibition Model ◽  
Preferred Direction ◽  
Cholinergic Pathway ◽  
Alternate Model

AbstractWe examined contrast, direction of motion, and concentration dependencies of the effects of GABAergic and cholinergic antagonists, and anticholinesterases on responses to movement of On—Off directionally selective (DS) ganglion cells of the rabbit's retina. The drugs tested were curare and hexamethonium bromide (cholinergic antagonists), physostigmine (anticholinesterase), and picrotoxin (GABAergic antagonist). They all reduced the cells' directional selectivity, while maintaining their preferred-null axis. However, cholinergic antagonists did not block directional selectivity completely even at saturating concentrations. The failure to eliminate directional selectivity was probably not due to an incomplete blockade of cholinergic receptors. In a extension of a Masland and Ames (1976) experiment, saturating concentrations of antagonists blocked the effects of exogenous acetylcholine or nicotine applied during synaptic blockade. Consequently, a noncholinergic pathway may be sufficient to account for at least some directional selectivity. This putative pathway interacts with the cholinergic pathway before spike generation, since physostigmine eliminated directional selectivity at contrasts lower than those saturating responses. This elimination apparently resulted from cholinergic-induced saturation, since reduction of contrast restored directional selectivity. Under picrotoxin, directional selectivity was lost in 33% of the cells regardless of contrast. However, 47% maintained their preferred direction despite saturating concentrations of picrotoxin, and 20% reversed the preferred and null directions. Therefore, models based solely on a GABAergic implementation of Barlow and Levick's asymmetric-inhibition model or solely on a cholinergic implementation of asymmetric-excitation models are not complete models of directional selectivity in the rabbit. We propose an alternate model for this retinal property.

Effects of the destruction of starburst-cholinergic amacrine cells by the toxin AF64A on rabbit retinal directional selectivity

2002 ◽  
Vol 19 (4) ◽  
pp. 495-509 ◽  
Author(s):  
FRANKLIN R. AMTHOR ◽  
KENT T. KEYSER ◽  
NINA A. DMITRIEVA
Keyword(s):  
Ganglion Cell ◽  
Ganglion Cells ◽  
Lucifer Yellow ◽  
Amacrine Cells ◽  
Fluorescent Dye ◽  
Choline Uptake ◽  
Directional Selectivity ◽  
Irreversible Inhibitor ◽  
Preferred Direction ◽  
Cholinergic Amacrine Cells

The effects of intraocular injections of ethylcholine mustard aziridinium ion (AF64A), an irreversible inhibitor of choline uptake, on the rabbit retina were assessed electrophysiologically, pharmacologically, anatomically, and behaviorally. Survival times from 1 day to 30 days were investigated. After 24 h, the shortest time tested, the directional selectivity of On–Off responding ganglion cells having the characteristic morphology of On–Off directionally selective directionally selective (DS) ganglion cells, as revealed by intracellular dye injection, was significantly reduced, both by an apparent decrease of preferred direction responses and an increase in responses to null-direction movement. No toxin-mediated changes in the dendritic trees of these cells were noted. Cells in AF64A-affected retinas having the DS morphology did not respond significantly to GABAergic or cholinergic agents such as picrotoxin and eserine, but did respond to nicotine. Recordings from a small random sample of other ganglion cell classes in the same retinas yielded no obvious changes in response properties. The direct effects on starburst (cholinergic) amacrine cells, which were identified by intraocular injection of the fluorescent dye DAPI with the AF64A, were investigated by intracellular injections of Lucifer yellow, and by immunohistochemical staining with antibodies to choline acetyltransferase (ChAT). Although starburst amacrine cell somas survived the AF64A treatment for at least several days, the dendrites could not be visualized by fluorescent dye injection in affected retinas due to dye leakage of the injected fluorescent dye from either the soma or proximal dendritic region. ChAT staining revealed a sequence in which ChAT-positive cells were undetectable first in the inner nuclear layer, and then in the ganglion cell layer. Cholinergic amacrine cells in the central retina were also affected before those in the periphery. The electrophysiological changes observed typically preceded the loss of ChAT activity. Behavioral tests for optokinetic nystagmus responses also revealed a lack of such responses in the affected eyes.

The role of NMDA channels in rabbit retinal directional selectivity

2000 ◽  
Vol 17 (2) ◽  
pp. 291-302 ◽  
Author(s):  
DARREL S. TJEPKES ◽  
FRANKLIN R. AMTHOR
Keyword(s):  
Ganglion Cells ◽  
Amacrine Cells ◽  
Directional Selectivity ◽  
Free Medium ◽  
Null Direction ◽  
Preferred Direction ◽  
Dendritic Membrane ◽  
Release Of Acetylcholine ◽  
Nmda Channels ◽  
Free Media

It has been previously demonstrated that the majority of the glutamatergic input to directionally selective (DS) ganglion cells in the rabbit retina is mediated by NMDA receptors. To examine whether NMDA channels have any role in directional selectivity, we eliminated magnesium from the superfusion medium to prevent the magnesium block of the channels at hyperpolarized membrane potentials. During superfusion in magnesium-free media, the response to null-direction motion increased to the level of the response to preferred-direction motion. This effect was specifically mediated by NMDA channels because subsequent blocking of the NMDA channels with AP7 restored directional selectivity. We also tested whether the increase in the null-direction response in magnesium-free medium was due to an increased release of acetylcholine from the cholinergic amacrine cells, rather than an effect on the DS ganglion cells themselves, by blocking acetylcholine transmission with d-tubocurarine during superfusion with the magnesium-free medium. During zero-magnesium superfusion, d-tubocurarine reduced both the preferred- and null-direction responses of DS ganglion cells but did not restore directional selectivity. These findings suggest that null-direction motion normally causes portions of the dendritic membrane of the directionally selective ganglion cell to be maintained at a sufficiently negative potential that the NMDA channels are blocked by magnesium ions. This result is discussed in terms of several models for the mechanisms of directional selectivity.

Is the input to a GABAergic synapse the sole asymmetry in turtle's retinal directional selectivity?

1996 ◽  
Vol 13 (3) ◽  
pp. 423-439 ◽  
Author(s):  
Randall D. Smith ◽  
Norberto M. Grzywacz ◽  
Lyle J. Borg-Graham
Keyword(s):  
Ganglion Cells ◽  
Visual Stimuli ◽  
Directional Selectivity ◽  
Null Direction ◽  
Gabaergic Synapse ◽  
Inhibitory Neurotransmitter ◽  
Alternative Models ◽  
Inhibition Model ◽  
Preferred Direction

AbstractWe examined the effects of picrotoxin and pentylenetetrazol (PTZ) on the responses to motions of ON-OFF directionally selective (DS) ganglion cells of the turtle's retina. These drugs are antagonists of the inhibitory neurotransmitter GABA. For continuous motions, picrotoxin markedly reduced the overall directionality of the cells. In 21% of the cells, directional selectivity was lost regardless of speed and contrast. However, other cells maintained their preferred direction despite saturating concentrations of picrotoxin. And in most cells, loss, maintenance, or even reversal of preferred and null directions could occur as speed and contrast were modulated. In 50% of the cells, reversal of preferred and null directions occurred at some condition of visual stimuli. However, picrotoxin did not tend to alter the preferred-null axis for directional selectivity. For apparent motions, picrotoxin made motion facilitation, which normally occurs exclusively in preferred-direction responses, to become erratic and often occur during null-direction motions. Finally, PTZ had effects similar to picrotoxin but with less potency. The results in this paper indicated that models of directional selectivity based solely on a GABAergic implementation of Barlow and Levick's asymmetric-inhibition model do not apply to the turtle retina. Alternative models may comprise multiple directional mechanisms and/or a symmetric inhibitory one, but not asymmetric facilitation.

scholarly journals Dependence of center radius on temporal frequency for the receptive fields of X retinal ganglion cells of cat.

1989 ◽  
Vol 94 (6) ◽  
pp. 987-995 ◽  
Author(s):  
J B Troy ◽  
C Enroth-Cugell
Keyword(s):  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Signal To Noise Ratio ◽  
Temporal Frequency ◽  
Receptive Fields ◽  
Retinal Ganglion ◽  
Spatial Expansion ◽  
Neuronal Membranes ◽  
Inductive Elements ◽  
X Cells

We examined the dependence of the center radius of X cells on temporal frequency and found that at temporal frequencies above 40 Hz the radius increases in a monotonic fashion, reaching a size approximately 30% larger at 70 Hz. This kind of spatial expansion has been predicted with cable models of receptive fields where inductive elements are included in modeling the neuronal membranes. Hence, the expansion of the center radius is clearly important for modeling X cell receptive fields. On the other hand, we feel that it might be of only minor functional significance, since the responsivity of X cells is attenuated at these high temporal frequencies and the signal-to-noise ratio is considerably worse than at low and midrange temporal frequencies.

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