Control of Retinal Sensitivity : III. Lateral Interactions at the Inner Plexiform Layer

Both the "on" and the "on-off" ganglion cells in the mudpuppy retina generate graded responses over a narrow range of log test intensities. Sustained full field or surround backgrounds change the range of center log test intensities that elicits the graded response for both cell types. The on-off, but not the on ganglion cells are further affected by moving or flashing surround backgrounds. These cells are hyperpolarized, threshold is elevated, and the entire graded range of response is elicited by a higher range of log center test intensities. Depolarizing activity is elicited in amacrine cells by moving backgrounds that affect the on-off ganglion cells, but bipolar activity is unaffected. These results suggest that the amacrine cells at the inner plexiform layer mediate a third stage of sensitivity control in the retina, increasing threshold for response to change specifically in the on-off ganglion cells.     

Control of Retinal Sensitivity : I. Light and Dark Adaptation of Vertebrate Rods and Cones

Rods and cones in Necturus respond with graded hyperpolarization to test flashes spanning about 3.5 log units of intensity. Steady background levels hyperpolarize the rods, and the rod responses become progressively smaller as background level is increased. In cones, higher background levels reduce the effectiveness of test flashes, so higher ranges of test intensities are required to elicit the full range of graded responses. When backgrounds are terminated, cones return rapidly, but rods return slowly to the dark potential level. The effects of backgrounds on both rods and cones can be observed at intensities that cause negligible bleaching as determined by retinal densitometry. During dark adaptation, changes are observed in the rods and cones that are similar to those produced by backgrounds. Receptor sensitivities, derived from these results, show that rods saturate, cones obey Weber's law, and sensitization during dark adaptation follows a two-phase time-course.     

The functional organization of the crayfish lamina ganglionaris

The light responses of the second order lamina monopolar neurons were examined in the crayfish compound eye. Single cartridge monopolar neurons (M1-M4) exhibited nonspiking hyperpolarizing light responses; for M1, M3 and M4 the transient 'on' response operated over the same intensity range as the receptor, 3.5 log units. M2 operated in a much narrower intensity range (1.5 log unit). The 'on' responses were associated with a 19% increase in conductance. The hyperpolarizing 'on' response can be reversed at 18 mV below the resting membrane potential. The half-angular sensitivity width of monopolar cells (in partially dark-adapted eyes) is 15 degrees X 8 degrees (horizontal by vertical). Off axis stimuli elicit attenuated hyperpolarizing responses associated with a diminished conductance increase or depolarizing responses associated with a net decrease in conductance. The latter result is consistent with the presynaptic inhibition of a 'back-ground' transmitter release which normally persists in the dark. Lateral inhibition is elicited from the area immediately surrounding the excitatory field, and it is associated with diminished transient responses and an accelerated decay of the response. Inhibitory stimuli decrease the conductance change associated with the hyperpolarizing response. The surround stimuli can also elicit depolarizing 'off' responses with reversal potentials positive to the membrane resting potential. It is concluded that the rapidly repolarizing monopolar cell response is modulated by both pre- and postsynaptic inhibitory mechanisms. A compartment model indicates that signal attenuation along a 500 microns length of monopolar cell axon is 22-34%. Simulation of steady-state signal transmission suggests that passive (decremental) conduction is sufficient to convey 66 to 78% of the monopolar cell signal from lamina to medulla. The current-voltage relation in current clamp is linear over the physiological operating range, and there is no evidence for rectification. Hyperpolarization of single monopolar cells (M1-M4) provides a polysynaptic excitatory signal to the medullary sustaining fibers.     

An analogue model of the luminosity-channel in the vertebrate cone retina

A model of the vertebrate cone retina was tested with physiological stimuli. Results confirm previous findings that, except for photoreceptors, the spatial and temporal properties of simulated retinal elements conform to a linear system. The model is consistent with known physiological correlates. Tonic units detect intensity when the light spot is within the center field, while phasic units detect movement across borders of contrast. There is a dynamic balance between the tonic and phasic channels: the tonic channel is favored by a center field input voltage, while the phasic channel is favored by a surround field input voltage to bipolar cells. The ON discharge of the phasic ganglion cell is developed by the excitatory center field input to the depolarizing-center bipolar cell, which has the shortest delay, while the OFF discharge is the result of the excitatory surround field input voltage to the hyperpolarizing-center bipolar cell, which has the longest delay.     

Intracellular recordings from gecko photoreceptors during light and dark adaptation

Intracellular recordings were obtained from rods in the Gekko gekko retina and the adaptation characteristics of their responses studied during light and dark adaptation. Steady background illumination induced graded and sustained hyperpolarizing potentials and compressed the incremental voltage range of the receptor. Steady backgrounds also shifted the receptor's voltage-intensity curve along the intensity axis, and bright backgrounds lowered the saturation potential of the receptor. Increment thresholds of single receptors followed Weber's law over a range of about 3.5 log units and then saturated. Most of the receptor sensitivity change in light derived from the shift of the voltage-intensity curve, only little from the voltage compression. Treatment of the eyecup with sodium aspartate at concentrations sufficient to eliminate the beta-wave of the electroretinogram (ERG) abolished initial transients in the receptor response, possibly indicating the removal of horizontal cell feedback. Aspartate treatment, however, did not significantly alter the adaptation characteristics of receptor responses, indicating that they derive from processes intrinsic to the receptors. Dark adaptation after a strongly adapting stimulus was similarly associated with temporary elevation of membrane potential, initial lowering of the saturation potential, and shift of the voltage-intensity curve. Under all conditions of adaptation studied, small amplitude responses were linear with light intensity. Further, there was no unique relation between sensitivity and membrane potential suggesting that receptor sensitivity is controlled at least in part by a step of visual transduction preceding the generation of membrane voltage change.     

Weber and noise adaptation in the retina of the toad Bufo marinus

Responses to flashes and steps of light were recorded intracellularly from rods and horizontal cells, and extracellularly from ganglion cells, in toad eyecups which were either dark adapted or exposed to various levels of background light. The average background intensities needed to depress the dark-adapted flash sensitivity by half in the three cell types, determined under identical conditions, were 0.9 Rh*s-1 (rods), 0.8 Rh*s-1 (horizontal cells), and 0.17 Rh*s-1 (ganglion cells), where Rh* denotes one isomerization per rod. Thus, there is a range (approximately 0.7 log units) of weak backgrounds where the sensitivity (response amplitude/Rh*) of rods is not significantly affected, but where that of ganglion cells (1/threshold) is substantially reduced, which implies that the gain of the transmission from rods to the ganglion cell output is decreased. In this range, the ganglion cell threshold rises approximately as the square root of background intensity (i.e. in proportion to the quantal noise from the background), while the maintained rate of discharge stays constant. The threshold response of the cell will then signal light deviations (from a mean level) of constant statistical significance. We propose that this type of ganglion cell desensitization under dim backgrounds is due to a post-receptoral gain control driven by quantal fluctuations, and term it noise adaptation in contrast to the Weber adaptation (desensitization proportional to the mean background intensity) of rods, horizontal cells, and ganglion cells at higher background intensities.     

Adaptive surround modulation in cortical area MT

Visual motion perception relies on two opposing operations: integration and segmentation. Integration overcomes motion ambiguity in the visual image by spatial pooling of motion signals, whereas segmentation identifies differences between adjacent moving objects. For visual motion area MT, previous investigations have reported that stimuli in the receptive field surround, which do not elicit a response when presented alone, can nevertheless modulate responses to stimuli in the receptive field center. The directional tuning of this "surround modulation" has been found to be mainly antagonistic and hence consistent with segmentation. Here, we report that surround modulation in area MT can be either antagonistic or integrative depending upon the visual stimulus. Both types of modulation were delayed relative to response onset. Our results suggest that the dominance of antagonistic modulation in previous MT studies was due to stimulus choice and that segmentation and integration are achieved, in part, via adaptive surround modulation.     

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.     

Stimulation of a Primary Taste Receptor by Salts

A quantitative study was made of the repetitive response of the salt receptor cell of the blowfly taste receptor. The response begins at a high frequency and declines to a steady frequency during brief stimuli. The initial response was found to be a sigmoid function of the log of stimulus intensity over a short range of intensities. It was shown that a theory (Beidler, 1954; for mammalian salt receptors) that relates the magnitude of the steady response to stimulus intensity applies to this receptor. From the theory, it was calculated that the relative free energy change of the reaction between salt and receptor site was in the range 0 to -1 kcal/mole; and, therefore, the reaction probably involves weak physical forces. Evidence is given that the salt-combining sites of the receptor are anionic and strongly acidic and that consequently the cation of a salt largely dominates stimulation. Preliminary evidence suggests that the receptor has a high degree of specificity toward salts, being stimulated primarily by monovalent inorganic cations.     

The stimulus control of biting inAplysia

Summary A number of different parameters of the biting response ofAplysia californica were examined while varying either the strength of excitatory stimuli that elicit biting, or the strength of inhibitory stimuli that suppress biting and produce satiation. Response amplitude, response latency and the interresponse interval of repetitive responses were the parameters investigated. In individual animals as well as in the mean data, all parameters of the biting response were found to be affected in a graded manner when the concentration of seaweed extract was varied, and when animals were fed to different levels of satiation. Feeding animals with non-nutritive bulk produced graded effects similar to those seen when animals were fed with seaweed. These results indicate that the biting response is modulated in a graded manner by external stimuli which elicit the response, as well as by internal stimuli which produce satiation.We would like to thank L. Eli Bronner for assistance in collecting the data, S. Hauser and K. Hilten for assistance with the illustrations, and T. Carew, V. Castellucci, and E. Kandel for comments on earlier drafts of this paper. This research was supported by NINCDS grant NS 12492, by P.H.S. Predoctoral Training Grant to the Department of Physiology, New York University Medical School, 71176-234, and by Sloan Foundation 360-3070-2772.     

A model of anuran retina relating interneurons to ganglion cell responses

A model is presented which accounts for many characteristic response properties used to classify anuran ganglion cell types while being consistent with data concerning interneurons. In the model color is ignored and input stimuli are assumed to be only black and white at high contrast. We show that accurate ganglion cell responses are obtained even with simplified receptors and horizontal cells: Receptors are modeled as responding with a step change, while horizontal cells respond only to global changes in intensity brought about by full field illumination changes. A hyperpolarizing and depolarizing bipolar cell are generated y subtracting local receptor and horizontal potentials. Two transient amacrine cells (On and Off) are generated using a high-pass filter like mechanism with a thresholded output which responds to positive going changes in the corresponding bipolar cell potentials. The model shows how a selective combination of bipolar and amacrine channels can account for many of the response properties used to classify the anuran ganglion cell types (class-0 through 4) and makes several experimental predictions.     

Comparative Studies on Dark Adaptation in the Compound Eyes of Nocturnal and Diurnal Lepidoptera

A comparative analysis has been carried out of the time course and range of dark adaptation in the compound eyes of some common butterflies and noctuid moths (Lepidoptera). The change in sensitivity of the eye during dark adaptation was determined by measurements of the intensity of illumination necessary to elicit an electrical response of a given magnitude of the eye. It was found that the curve for dark adaptation in the diurnal species was smooth. The range of adaptive change varied in different species but usually did not cover more than 1 to 1.5 log units. In the nocturnal species the dark adaptation was found to proceed in two phases. The first phase was usually completed in less than 10 minutes and covered a range of 1 to 1.5 log units. The second phase was more prolonged and covered a range of 2 to 3 log units. In some of the experiments on nocturnal species the second phase failed to appear. Measurements of the size of the response at different intensities showed that the intensity/amplitude relationship was the same in the light-adapted eye as in the dark-adapted eye. In the nocturnal insects the response of the eye in the light-adapted condition was about 20 per cent of that in the dark-adapted eye, while in diurnal insects it was about 60 per cent.     

Light-induced changes of sensitivity in Limulus ventral photoreceptors

The responses of Limulus ventral photoreceptors to brief test flashes and to longer adapting lights were measured under voltage clamp conditions. When the cell was dark adapted, there was a range of energy of the test flashes over which the peak amplitude of the responses (light-induced currents) was directly proportional to the flash energy. This was also true when test flashes were superposed on adapting stimuli but the proportionality constant (termed peak currently/photon) was reduced. The peak current/photon was attenuated more by brighter adapting stimuli than by less bright adapting stimuli. The peak current/photon is a measure of the sensitivity of the conductance-increase mechanism underlying the light response of the photo-receptor. The response elicited by an adapting stimulus had a large initial transient which declined to a smaller plateau. The peak current/photon decreased sharply during the declining phase of the transient and was relatively stable during the plateau. This indicates that the onset of light adaptation is delayed with respect to the onset of the response to the adapting stimulus. If the adaptational state just before the onset of each of a series of adapting stimuli was constant, the amplitude of the transient was a nearly linear function of intensity. When the total intensity was rapidly doubled (or halved) during a plateau response, the total current approximately doubled (or halved). We argue that the transition from transient to plateau, light-elicited changes of threshold, and the nonlinear function relating the plateau response to stimulus intensity all reflect changes of the responsiveness of the conductance-increase mechanism.     

Response Properties of a Newly Identified Tristratified Narrow Field Amacrine Cell in the Mouse Retina

Amacrine cells were targeted for whole cell recording using two-photon fluorescence microscopy in a transgenic mouse line in which the promoter for dopamine receptor 2 drove expression of green fluorescent protein in a narrow field tristratified amacrine cell (TNAC) that had not been studied previously. Light evoked a multiphasic response that was the sum of hyperpolarizing and depolarization synaptic inputs consistent with distinct dendritic ramifications in the off and on sublamina of the inner plexiform layer. The amplitude and waveform of the response, which consisted of an initial brief hyperpolarization at light onset followed by recovery to a plateau potential close to dark resting potential and a hyperpolarizing response at the light offset varied little over an intensity range from 0.4 to ~10^6 Rh*/rod/s. This suggests that the cell functions as a differentiator that generates an output signal (a transient reduction in inhibitory input to downstream retina neurons) that is proportional to the derivative of light input independent of its intensity. The underlying circuitry appears to consist of rod and cone driven on and off bipolar cells that provide direct excitatory input to the cell as well as to GABAergic amacrine cells that are synaptically coupled to TNAC. Canonical reagents that blocked excitatory (glutamatergic) and inhibitory (GABA and glycine) synaptic transmission had effects on responses to scotopic stimuli consistent with the rod driven component of the proposed circuit. However, responses evoked by photopic stimuli were paradoxical and could not be interpreted on the basis of conventional thinking about the neuropharmacology of synaptic interactions in the retina.     

Contrast gain, signal-to-noise ratio, and linearity in light-adapted blowfly photoreceptors

Response properties of short-type (R1-6) photoreceptors of the blowfly (Calliphora vicina) were investigated with intracellular recordings using repeated sequences of pseudorandomly modulated light contrast stimuli at adapting backgrounds covering 5 log intensity units. The resulting voltage responses were used to determine the effects of adaptational regulation on signal-to-noise ratios (SNR), signal induced noise, contrast gain, linearity and the dead time in phototransduction. In light adaptation the SNR of the photoreceptors improved more than 100-fold due to (a) increased photoreceptor voltage responses to a contrast stimulus and (b) reduction of voltage noise at high intensity backgrounds. In the frequency domain the SNR was attenuated in low frequencies with an increase in the middle and high frequency ranges. A pseudorandom contrast stimulus by itself did not produce any additional noise. The contrast gain of the photoreceptor frequency responses increased with mean illumination and the gain was best fitted with a model consisting of two second order and one double pole of first order. The coherence function (a normalized measure of linearity and SNR) of the frequency responses demonstrated that the photoreceptors responded linearly (from 1 to 150 Hz) to the contrast stimuli even under fairly dim conditions. The theoretically derived and the recorded phase functions were used to calculate phototransduction dead time, which decreased in light adaptation from approximately 5-2.5 ms. This analysis suggests that the ability of fly photoreceptors to maintain linear performance under dynamic stimulation conditions results from the high early gain followed by delayed compressive feed-back mechanisms.     

Synaptic inputs to the ganglion cells in the tiger salamander retina

The postsynaptic potentials (PSPs) that form the ganglion cell light response were isolated by polarizing the cell membrane with extrinsic currents while stimulating at either the center or surround of the cell's receptive field. The time-course and receptive field properties of the PSPs were correlated with those of the bipolar and amacrine cells. The tiger salamander retina contains four main types of ganglion cell: "on" center, "off" center, "on-off", and a "hybrid" cell that responds transiently to center, but sustainedly, to surround illumination. The results lead to these inferences. The on-ganglion cell receives excitatory synpatic input from the on bipolars and that synapse is "silent" in the dark. The off-ganglion cell receives excitatory synaptic input from the off bipolars with this synapse tonically active in the dark. The on-off and hybrid ganglion cells receive a transient excitatory input with narrow receptive field, not simply correlated with the activity of any presynaptic cell. All cell types receive a broad field transient inhibitory input, which apparently originates in the transient amacrine cells. Thus, most, but not all, ganglion cell responses can be explained in terms of synaptic inputs from bipolar and amacrine cells, integrated at the ganglion cell membrane.     

Ionic mechanisms underlying the responses of off-center bipolar cells in the carp retina. I. Studies on responses evoked by light

Off-center bipolar cells show hyperpolarizing responses to spot illumination in the receptive field center and depolarization responses to an annulus in the surround. To understand the ionic mechanisms underlying these responses, we examined the current-voltage relationship of these bipolar cells, input resistance changes during their light-evoked responses, and the reversal potentials of these responses. Off-center bipolar cells generally showed inward rectification when they were hyperpolarized and outward rectification when they were strongly depolarized. The membrane potential at which the I-V relationship deviated from linearity varied in individual cells. Hyperpolarizing center responses were generally accompanied by a resistance increase, irrespective of signal inputs either from red- sensitive cones or from rods, and the response polarities reversed at greater than +50 mV. Depolarizing surround responses were accompanied by a resistance decrease with a reversal potential at about +28 mV (one case). From the above observations, it is suggested that the center responses are generated by a decrease in sodium conductance (gNa) and the surround response is generated by an increase in gNa.     

Magnitude of increase in retinal cGMP metabolic flux determined by 18O incorporation into nucleotide alpha-phosphoryls corresponds with intensity of photic stimulation

The property of cyclic nucleotide phosphodiesterases to catalyze 3'-P--O bond cleavage and the insertion of a single nonexchangeable atom of 18O from [18O]water into the phosphoryl of the 5'-nucleotide product has been utilized as a means for measuring the hydrolytic flux of cGMP and cAMP in isolated dark-adapted intact rabbit retinas. Without illumination 18O labeling of guanine nucleotide (GTP and GDP) alpha-phosphoryls proceeds linearly for at least 80 s at a rate of 3.3 nmol of 18O/s.g of retina (wet weight). This rate is estimated to be approximately 8 times greater in the rod outer segment layer where over 90% of retinal cGMP metabolic components reside. Photic stimulation during a 20-s incubation was provided by intermittent flashes of light representing 800 ms of total illumination. Light stimuli over a range of intensities of greater than 3 log units commencing with a minimally detectable intensity produce graded increments in the rate of 18O incorporation into guanine nucleotide alpha-phosphoryls to a maximum increase of 5-fold. On the basis of only the 800-ms period of illumination this maximum increase is 125-fold. Steady state levels of retinal cGMP are not altered appreciably over this greater than 3 log range of light intensities but a light stimulus exceeding this intensity range causes an approximate 50% decrease in retinal cGMP concentration and a relative decline in the maximal rate of 18O labeling of guanine nucleotide alpha-phosphoryls. No light-related increases were detected in 18O incorporation into adenine nucleotide alpha-phosphoryls nor the gamma-phosphoryls of GTP or ATP or Pi. These observations indicate that light stimuli over greater than 3 log of light intensity produce incremental increases in cGMP metabolic flux that result from comparable increases in the rates of both cGMP generation and cGMP hydrolysis. It is postulated that increases in cGMP metabolic flux rather than changes in cGMP steady state levels are integral to phototransduction by a mechanism that involves the coupling of cGMP synthesis and/or hydrolysis to either the release of calcium from disc membranes or the inhibition of Na+ conductance by the photoreceptor membrane. This is suggested to occur by an energy-linked process and/or the generation of protons.     

Ionic mechanisms of two types of on-center bipolar cells in the carp retina. II. The responses to annular illumination

On-center bipolar cells in the dark-adapted carp retina were divided into four types (A, B, C, and D) on the basis of response wave forms, spectral response properties, and electrical membrane properties. Type A and B cells responded to a spot of light with a transient depolarization followed by a plateau, whereas the response of type C and D cells were approximately rectangular in shape. The center and surround responses of type A cells had maximum spectral response of approximately 525 nm in the lower mesopic range; the polarity of both responses was reversed at positive membrane potentials as the membrane was depolarized by extrinsic current. The center and surround responses of type D cells had a maximum spectral response of approximately 625 nm in the mesopic or photopic range; the polarity of both responses was reversed at membrane potentials that were more negative than those at the dark level. The results suggest that the center and surround responses mediated by rods are generated by changes in sodium conductance, but in opposite ways; whereas those mediated by red cones are generated by changes in potassium and/or chloride conductances. In type B and C cells, which probably receive inputs from both rods and/or green cones as well as red cones, the center responses were composed of the two ionic mechanisms described above. The surround responses of many type B and C cells were dominated by only one ionic mechanism with a negative reversal potential, but in some type B cells the surround responses were resulted from two ionic mechanisms similar to those of the center responses.