OFF Channels Research Articles

Control of retinal information coding by GABAB receptors

The directional selectivity of amacrine and ganglion cells was studied using conventional intracellular recording techniques and drug application in the superfused retina-eyecup preparation of the tiger salamander. Baclofen, a GABAB receptor agonist, enhanced normal directional responses in some directionally selective third-order neurons. In about 30% of the cells that were not normally directional, baclofen induced direction-selective responses. This effect was particularly marked when 2-amino-4-phosphonobutyrate (APB) was used to isolate the OFF pathway. Comparisons of the effects of APB and baclofen on induced directional cells indicate that directional information in the ON and OFF channels is often handled separately and frequently is not aligned. This tends to obscure the observation of directionality as seen from the soma. Application of picrotoxin blocked both normal directional selectivity and baclofen-induced directional selectivity in some cells. Superfusion of picrotoxin and strychnine together blocked directionality in almost all cells. In both normal and induced directionality, the null direction response varied from cell to cell between a small depolarization, no voltage response, or a hyperpolarization. Injection of positive current often revealed "silent" inhibition. Some induced direction-selective cells did not show any evidence of inhibition in the null direction. The similarities in the response to baclofen, the influence of GABA and glycine antagonists, and the characteristics of the null-direction responses suggest that both normal and induced directionality originate from the same sources or mechanisms. Baclofen also induced orientation selectivity, but this was rarely observed.

Dissection of the neuron network in the catfish inner retina. V. Interactions between NA and NB amacrine cells

1. Simultaneous intracellular recordings were made from two neighboring N amacrine cells, one an ON amacrine (NA) cell and the other an OFF amacrine (NB) cell. Extrinsic current was injected into one amacrine cell, and the resulting intracellular responses were recorded from the other amacrine cell. Test signals included 1) a single-frequency sinusoid, 2) a depolarizing or hyperpolarizing pulse, or 3) a white-noise modulated current. In some cell pairs, membrane noise was measured in the dark as well as under a steady background illumination. 2. Current pulses injected into a NA cell evoked a damped oscillation from a NB cell. The first-order kernel derived by cross-correlating the white-noise current injected into a NA cell against the evoked response from a NB cell was a large depolarization followed by a damped oscillation. The frequency of oscillations varied slightly from pair to pair but averaged 35 Hz. 3. Current pulses injected into a NB cell evoked a sign-inverting response (hyperpolarization) of very small amplitude from a NA cell. Similarly, the first-order kernel was a hyperpolarization of very small amplitude. 4. The power spectrum of the membrane noise recorded from NA and NB cells in the dark or during steady illumination often showed a peak at 35 Hz. Such membrane noise synchronizes synergistically among NA cells and among NB cells in the dark. In addition, the membrane fluctuations seen in NA and NB cells in the dark were out of phase. 5. Transmission between NA and NB cells was largely accounted for by a linear component; however, a very small but significant second- and third-order nonlinearity was also generated. 6. These results show that the interactions occurring between amacrine cells of opposite response polarity are much more complex than those between cells of the same response polarity and that the neural circuitry in the inner retina actively controls interactions between ON and OFF channels in the dark as well as in the presence of light stimuli.

Terminal arbors of single ON‐center and OFF‐center X and Y retinal ganglion cell axons within the ferret's lateral geniculate nucleus

The lateral geniculate nucleus of the ferret contains not only eye-specific layers, but a further subdivision of layers A and A1 into inner and outer sublaminae that contain, respectively, ON-center and OFF-center cells (Stryker and Zahs, '83). To study how the arbors of single retinal ganglion cell axons correlate with these cellular divisions, we have examined the morphology of physiologically classified retinal axons in the ferret's lateral geniculate nucleus. As in cats, we could classify retinal axons as X or Y on the basis of a number of physiological criteria. X and Y axons have distinct patterns of termination in the lateral geniculate nucleus. Contralateral X axons innervate lamina A and ipsilateral axons lamina A1. X axons are further segregated in these laminae so that ON-center axons terminate in the inner sublamina, and OFF-center axons in the outer sublamina. We did not observe any branches of X axons innervating the medial interlaminar nucleus or the midbrain. Y axons have much larger terminal arbors and exhibit greater variation in their terminations. Generally, within layers A and A1, ON-center Y axons innervate the inner sublamina and OFF-center Y axons innervate the outer sublamina. However, they often innervate both sublaminae, and occasionally have a few boutons in the inappropriate lamina as well. Y axons also terminate in the dorsal C laminae, the interlaminar zones, and the media interlaminar nucleus; branches of these axons course toward the midbrain, presumably to innervate the superior colliculus. Thus, whereas the Y pathway in the ferret is one of high divergence, the X pathway appears to be the substrate for segregated ON and OFF channels through the lateral geniculate nucleus.

Evidence for only depolarizing rod bipolar cells in the primate retina

The mammalian rod bipolar, for which only one class has been identified, has been described as being hyperpolarizing by some investigators and depolarizing by others. We now report the effects of 2-amino-4-phosphonobutyrate (APB), a potent blocker of depolarizing bipolar cells, on visual behavior in the dark-adapted monkey. While in mesopic and photopic conditions only the monkeys' ability to detect incremental stimuli is impaired, under scotopic conditions all light mediated response in the monkey is eliminated. Assuming APB is acting on rod bipolars in the same fashion as it does on cone bipolars, we conclude that the primate rod bipolars all depolarize to light and that the ON and OFF channels are formed by the amacrine cell network.

Neurotransmission in the frog retina: Possible physiological and histological correlations

In the frog retina, extracellular recordings of transient ganglion cells have shown that the inhibitory surround of the receptive field of these cells was mediated by gamma-aminobutyric acid and acetylcholine (through the nicotinic receptors). Histoautoradiographic and immunocytochemical studies for the two respectively have shown that these neurotransmitters can act through horizontal and amacrine cells. The separation of the ON and OFF channels mediated by glutamate at the bipolar cell level may also be obtained by glycine and/or acetylcholine (through muscarinic receptors). Respective histoautoradiographic and immunocytochemical studies indicate that these neurotransmitters act at the amacrine cell level. These data are consistent with the functional separation of spatial and temporal organization of retinal information, with horizontal cells especially responsible for the spatial organization of the ganglion cell responses and amacrine cells involved in both spatial and temporal organization of the responses.

Involvement of ON and OFF retinal channels in the eye and head horizontal optokinetic nystagmus of the frog

The specific role of ON and OFF retinal information channels in the generation of the horizontal optokinetic nystagmus (OKN) of the frog was studied. Coil recordings of monocular eye and head OKN were obtained before and after intravitreal injection of two drugs that block either ON or OFF channels. The intravitreal injection of 2-amino-4-phosphonobutyrate (APB), a glutamate analog that selectively blocks the ON retinal channel, strongly reduced or even cancelled the monocular OKN of the head and of the eye. The intravitreal injection of another glutamate analog, the cis-2,3-piperidine dicarboxylic acid (PDA) that especially blocks the OFF retinal channel, did not affect the gain velocity of the slow phase of both the horizontal monocular head and eye OKN, for low stimulus velocities. Our results suggest that the retinal ON information channel, but not the OFF channel, is involved in the generation of the slow phase of the OKN of the frog, at least at low drum velocities.

Development of neurochemical separation of ON and OFF channels at retinal ganglion cells

Anatomical and physiological segregation of neurons into ON (brightening detector) and OFF (darkening detector) channels in the retina and subsequent visual system ensure the high sensitivity required for contrast detection and spatial discrimination. This segregation is finest at the visual axis. Neurochemically, ON and OFF ganglion cells at the visual axis seem to be distinguished by different inhibitory transmitters but not excitatory transmitters. Microiontophoretic studies of inhibitory transmitters on the retinal ganglion cells in kittens and adult cats suggest that this neurochemical distinction is poor in immature ganglion cells at the visual axis. Initially both ON and OFF cells seem to be supplied by GABAergic, glycinergic, and catecholaminergic amacrine cells, but in adults, ON cells remain supplied only by GABAergic amacrines, while OFF cells are supplied by glycinergic amacrines. Postnatal elimination of multiple inputs and strengthening of the appropriate inputs, as seen in the central nervous system, also seem to occur at the retinal neurotransmitter synapses during development.

Development of cytochrome oxidase staining in the retina and lateral geniculate nucleus: a possible correlate of ON- and OFF-center channel maturation

A histochemical stain for cytochrome oxidase (CO) activity was used to examine the maturation of a neurochemical correlate of ON and OFF channels in the retina and dorsal lateral geniculate nucleus (LGN) of the tree shrew. In the adult tree shrew, the CO staining pattern can be used as a histochemical marker of segregated ON- and OFF-center channels in the retina, LGN, and striate cortex. Our previous studies have shown that the retina is immature and the LGN unlaminated at birth. In the present study, we show that the laminar development of CO reactivity emerges during the first postnatal week in the LGN, while the maturation of CO staining in the presumed ON and OFF sublaminae of the retinal inner plexiform layer develops slowly, well after the appearance of differential laminar CO staining in the LGN.

Functions of the ON and OFF channels of the visual system.

In the mammalian eye, the ON-centre and OFF-centre retinal ganglion cells form two major pathways projecting to central visual structures from the retina. These two pathways originate at the bipolar cell level: one class of bipolar cells becomes hyperpolarized in response to light, as do all photoreceptor cells, and the other class becomes depolarized on exposure to light, thereby inverting the receptor signal. It has recently become possible to examine the functional role of the ON-pathway in vision by selectively blocking it at the bipolar cell level using the glutamate neurotransmitter analogue 2-amino-4-phosphonobutyrate (APB)1. APB application to monkey, cat and rabbit retinas abolishes ON responses in retinal ganglion cells, the lateral geniculate nucleus and the visual cortex but has no effect on the centre-surround antagonism of OFF cells or the orientation and direction selectivities in the cortex2-5. These and related findings6-11 suggest that the ON and OFF pathways remain largely separate through the lateral geniculate nucleus and that in the cortex, contrary to some hypotheses, they are not directly involved in mechanisms giving rise to orientation and direction selectivities. We have examined the roles of the ON and OFF channels in vision in rhesus monkeys trained to do visual detection and discrimination tasks. We report here that the ON channel is reversibly blocked by injection of APB into the vitreous. Detection of light increment but not of light decrement is severely impaired, and there is a pronounced loss in contrast sensitivity. The perception of shape, colour, flicker, movement and stereo images is only mildly impaired, but longer times are required for their discrimination. Our results suggest that two reasons that the mammalian visual system has both ON and OFF channels is to yield equal sensitivity and rapid information transfer for both incremental and decremental light stimuli and to facilitate high contrast sensitivity.

Identification of a distinct synaptic glutamate receptor on horizontal cells in mudpuppy retina.

The separation of ON and OFF channels and the development of an antagonistic surround occur at the first synapse in the vertebrate retina. This functional differentiation is mediated by the action of the photoreceptor neurotransmitter on the ON bipolar, OFF bipolar and horizontal cells, respectively. Glutamate mimics the action of the photoreceptor transmitter on all second-order neurones in fish, amphibian and mammalian retinas. The diversity of cellular responses produced by one neurotransmitter raises the possibility of multiple postsynaptic receptor-ionophore complexes. We reported previously that one glutamate analogue, 2-amino-4-phosphonobutyrate, reveals that the ON bipolar synaptic receptor is pharmacologically different from those of other second-order neurones. The results presented here demonstrate that another glutamate analogue, D-O-phosphoserine, selectively antagonizes the synaptic responses of horizontal cells. Taken together, these findings indicate that there are three glutamate-like receptor subtypes in the outer retina and suggest a correlation between receptor subtype and the physiological properties of second-order neurones.

Bipolar cells in the mudpuppy retina use an excitatory amino acid neurotransmitter.

The bipolar cells of the vertebrate retina are the principal neuronal elements which transmit photoreceptor activity from the outer to the inner retina. An important function of the bipolars is to segregate photoreceptor input into independent ON and OFF channels which are subserved, respectively, by the depolarizing and hyperpolarizing bipolar subtypes. Ultrastructural and physiological observations suggest that chemical neurotransmission is the predominant means of bipolar input to the inner retina. Both ON and OFF bipolars apparently release excitatory transmitters. Histological studies with cytotoxic agents and physiological studies indicate that third-order neurones have excitatory amino acid receptors. In ON-OFF amacrine and ganglion cells, which receive input from both bipolars, ON and OFF excitation have a similar ionic basis, suggesting that the same transmitter may be released by both types of bipolars. We have now found that (+/-)cis-2,3-piperidine dicarboxylic acid (PDA), a new excitatory amino acid antagonist, blocks bipolar input to the inner retina and thus suggests that an excitatory amino acid is a bipolar cell transmitter.

Laminar organization of receptive-field properties in lateral geniculate nucleus of bush baby (Galago crassicaudatus).

Laminar organization of receptive-field properties in lateral geniculate nucleus of bush baby (Galago crassicaudatus).T T Norton, and V A CasagrandeT T Norton, and V A CasagrandePublished Online:01 Apr 1982https://doi.org/10.1152/jn.1982.47.4.715MoreSectionsPDF (5 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited ByBinocular response modulation in the lateral geniculate nucleus9 March 2018 | Journal of Comparative Neurology, Vol. 118The functional asymmetry of ON and OFF channels in the perception of contrastYaoguang Jiang, Gopathy Purushothaman, and Vivien A. Casagrande17 November 2015 | Journal of Neurophysiology, Vol. 114, No. 5Perceptual decision related activity in the lateral geniculate nucleusYaoguang Jiang, Dmitry Yampolsky, Gopathy Purushothaman, and Vivien A. Casagrande24 July 2015 | Journal of Neurophysiology, Vol. 114, No. 1Visual Spatial Summation in Macaque Geniculocortical AfferentsMichael P. Sceniak, Soumya Chatterjee, and Edward M. Callaway1 December 2006 | Journal of Neurophysiology, Vol. 96, No. 6Temporal modulation sensitivity of tree shrew retinal ganglion cells18 November 2003 | Visual Neuroscience, Vol. 20, No. 04Spatial properties of koniocellular cells in the lateral geniculate nucleus of the marmoset Callithrix jacchus5 August 2004 | The Journal of Physiology, Vol. 533, No. 2A comparison of koniocellular, magnocellular and parvocellular receptive field properties in the lateral geniculate nucleus of the owl monkey ( Aotus trivirgatus )5 August 2004 | The Journal of Physiology, Vol. 531, No. 1Visual physiology of the lateral geniculate nucleus in two species of New World monkey: Saimiri sciureus and Aotus trivirgatis13 August 2004 | The Journal of Physiology, Vol. 523, No. 3Temporal contrast sensitivity in the lateral geniculate nucleus of a New World monkey, the marmoset Callithrix jacchus8 September 2004 | The Journal of Physiology, Vol. 517, No. 3Temporal aspects of neural coding in the retina and lateral geniculate9 July 2009 | Network: Computation in Neural Systems, Vol. 10, No. 4Segregation of Receptive Field Properties in the Lateral Geniculate Nucleus of a New-World Monkey, the Marmoset Callithrix jacchusAndrew J. R. White, Heath D. Wilder, Ann K. Goodchild, Ann Jervie Sefton, and Paul R. Martin1 October 1998 | Journal of Neurophysiology, Vol. 80, No. 4Functional Organization of Owl Monkey Lateral Geniculate Nucleus and Visual CortexLawrence P. O'Keefe, Jonathan B. Levitt, Daniel C. Kiper, Robert M. Shapley, and J. Anthony Movshon1 August 1998 | Journal of Neurophysiology, Vol. 80, No. 2Visual Field Representation in Striate and Prestriate Cortices of a Prosimian Primate (Galago garnetti)Marcello G. P. Rosa, Vivien A. Casagrande, Todd Preuss, and Jon H. Kaas1 June 1997 | Journal of Neurophysiology, Vol. 77, No. 6Laminar organization of acetylcholinesterase and cytochrome oxidase in the lateral geniculate nucleus of prosimiansNeuroscience, Vol. 54, No. 4The ON and OFF channels of the visual systemTrends in Neurosciences, Vol. 15, No. 3Effect of light deprivation upon the morphology of axon terminals in the dorsal lateral geniculate nucleus of mouse: an electron microscopical study using serial sectionsNeuroscience Research, Vol. 4, No. 4Visual resolution and sensitivity in a nocturnal primate (galago) measured with visual evoked potentialsVision Research, Vol. 27, No. 6Laminar distribution of tectal, parabigeminal and pretectal inputs to the primate dorsal lateral geniculate nucleus: Connectional studies in Galago crassicaudatusBrain Research, Vol. 366, No. 1-2W-like response properties of interlaminar zone cells in the lateral geniculate nucleus of a primate (Galago crassicaudatus)Brain Research, Vol. 362, No. 2The central visual systemVision Research, Vol. 26, No. 9Morphology of geniculo-striate afferents in a prosimian primateBrain Research, Vol. 270, No. 1 More from this issue > Volume 47Issue 4April 1982Pages 715-41 https://doi.org/10.1152/jn.1982.47.4.715PubMed6279794History Published online 1 April 1982 Published in print 1 April 1982 Metrics

2-amino-4-phosphonobutyric acid: a new pharmacological tool for retina research.

Information processing in the vertebrate retina occurs in two separate channels known as ON and OFF channels. When intracellular electrophysiological recordings were obtained from the perfused retina-eyecup preparation of the mud-puppy (Necturus maculosus), the addition of 2-amino-4-phosphonobutyric acid to the bathing medium blocked all responses in the ON channel but left intact the OFF responses including OFF ganglion cell discharge. 2-Amino-4-phosphonobutyric acid blocks the light response of the ON bipolar cell by mimicking the endogenous photoreceptor transmitter.

Neuronal basis of a sensory analyser, the acridid movement detector system. III. Control of response amplitude by tonic lateral inhibition.

1. The Lobular Giant Movement Detector neurone (LGMD) of Schistocerca responds with spikes when small areas of the visual field change in luminance. Previous work has shown that changes of +/- 1 log 10 unit are enough to produce maximal ON and OFF responses. 2. Using a 5 degree test area, it is shown that the number of spikes generated by such a stimulus depends on the luminance of the surrounding area. When the surround is dark, the response is maximal; when it is brightly lit, the response is minimal. Intermediate intensities produce intermediate values of response. A X 2 change in response is produced by about 3 log 10 units change in surround intensity. 3. A bright annulus, with diameters of 10-5 degrees and 25-8 degrees, inhibits both ON and OFF responses when concentric with the 5 degree test area, but not when it is 30 degrees eccentric to the test area. The inhibitory effect shows no decrease after 4 min. 4. These results are interpreted to indicate a tonic lateral inhibitory network, sited peripherally in the optic lobe prior to the divergence of the separate ON and OFF channels found in the projection from the medulla to the LGMD. It is probably identical with that described for the lamina by previous workers.

Response of units in striate cortex of squirrel monkeys to visual and electrical stimuli.

Response of units in striate cortex of squirrel monkeys to visual and electrical stimuli.J R Bartlett, and R W Doty SrJ R Bartlett, and R W Doty SrPublished Online:01 Jul 1974https://doi.org/10.1152/jn.1974.37.4.621MoreSectionsPDF (4 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited ByLuminance potentiates human visuocortical responsesLouis N. Vinke and Sam Ling28 January 2020 | Journal of Neurophysiology, Vol. 123, No. 2Cone and melanopsin contributions to human brightness estimation30 January 2018 | Journal of the Optical Society of America A, Vol. 35, No. 4Neurons in primary visual cortex represent distribution of luminance21 September 2016 | Physiological Reports, Vol. 4, No. 18Visual Prosthesis1 January 2008 | Perception, Vol. 37, No. 10V1 Response Timing and Surface Filling-InXin Huang, and Michael A. Paradiso1 July 2008 | Journal of Neurophysiology, Vol. 100, No. 1Psychophysics of Electrical Stimulation of Striate Cortex in MacaquesJohn R. Bartlett✠, Edgar A. DeYoe, Robert W. Doty, Barry B. Lee, Jeffrey D. Lewine, Nubio Negrão, and William H. Overman1 November 2005 | Journal of Neurophysiology, Vol. 94, No. 5Peaked Encoding of Relative Luminance in Macaque Areas V1 and V2Xinmiao Peng, and David C. Van Essen1 March 2005 | Journal of Neurophysiology, Vol. 93, No. 3Functional Organization of the Cat Visual Cortex in Relation to the Representation of a Uniform SurfaceToshiki Tani, Isao Yokoi, Minami Ito, Shigeru Tanaka, and Hidehiko Komatsu1 February 2003 | Journal of Neurophysiology, Vol. 89, No. 2Neural Representation of the Luminance and Brightness of a Uniform Surface in the Macaque Primary Visual CortexMasaharu Kinoshita, and Hidehiko Komatsu1 November 2001 | Journal of Neurophysiology, Vol. 86, No. 5Functional magnetic resonance imaging (FMRI) of the human brainJournal of Neuroscience Methods, Vol. 54, No. 2An analysis of the VEP to luminance modulation and of its nonlinearityVision Research, Vol. 32, No. 8The ON and OFF channels of the visual systemTrends in Neurosciences, Vol. 15, No. 3Brightness perception and filling-inVision Research, Vol. 31, No. 7-8Transcranial Doppler ultrasonographic assessment of intermittent light stimulation at different frequencies.Stroke, Vol. 21, No. 12Color and brightness fade-out in the ganzfeld is wavelength dependentVision Research, Vol. 29, No. 10Intensity coding and luxotonic activity in the ground squirrel lateral geniculate nucleusVision Research, Vol. 27, No. 12Lamina-specific differences of visual latencies following photic stimulation in the cat striate cortexBrain Research, Vol. 385, No. 2Occipital and inferotemporal responses to visual signals in the monkeyExperimental Neurology, Vol. 90, No. 2Encoding of visual information: correlation of EEG response to intracellular responseBrain Research, Vol. 244, No. 1Two-dimensional spectral analysis of cortical receptive field profilesVision Research, Vol. 20, No. 10Sensory Interaction: Vision is Modulated by Hearing25 June 2016 | Perception, Vol. 5, No. 4Brightness sensation in a ganzfeldVision Research, Vol. 16, No. 11Spatial and chromatic properties of neurons subserving foveal and parafoveal vision in rhesus monkeyBrain Research, Vol. 100, No. 1 More from this issue > Volume 37Issue 4July 1974Pages 621-41 https://doi.org/10.1152/jn.1974.37.4.621PubMed4209701History Published online 1 July 1974 Published in print 1 July 1974 Metrics

Discharge patterns and functional organization of mammalian retina.

Discharge patterns and functional organization of mammalian retina.