Temporal tuning and nonlinearity of intraretinal pathways in turtle: Effects of temperature,stimulus intensity,and size

Flash responses, amplitude and phase transfer functions, and nonlinearities were measured in turtle retina for pathways with photoreceptor inputs and outputs from horizontal (HC), hyperpolarizing bipolar (HBC), sustained amacrine (AC), and on-off ganglion (GC) cells. Flash responses slowed and attenuated in all cells as temperature decreased. Whitenoise transfer properties of sustained-type cells (HC, HBC, AC) were of low- or bandpass type; highfrequency cut-off (f _c) and phase crossover frequency decreased with temperature. f _c increased as spot diameter was increased. Nonlinearity of these sustained-response pathways (distortion product frequencies in response to a sum-of-sinusoids input probe) increases with intensity and may depend on amplitude saturation limiting. On/off GC synaptic and spike activity increased as spot diameter decreased and intensity increased. Amplitude transfer functions had a low-frequency peak (PSP activity) and monotonically decreasing amplitude vs. frequency shape (spikes and transient PSP activity). Nonlinearity increased with stimulus intensity; it was maximal with 1 mm spot size, less with smaller (500 m) and larger (5 mm) spots. It may depend on the functional equivalent of full-wave rectification (on-off response).This work was supported by NEI grant R01 EY03383     

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.     

Dynamic Characteristics of Retinal Ganglion Cell Responses in Goldfish

A cross-correlation technique has been applied to quantify the dependence of the dynamic characteristics of retinal ganglion cell responses in goldfish on intensity, wavelength, spatial configuration, and spot size. Both theoretical and experimental evidence justify the use of the cross-correlation procedure which allows the completion of rather extensive measurements in a relatively short time. The findings indicate the following. (a) The shape of the amplitude characteristics depends on the energy per unit of time (power) falling within the center of a receptive field rather than on the intensity of the stimulus spot. For spot diameters of up to 1 mm, identical amplitude characteristics can be obtained by interchanging area and intensity. Therefore the receptor processes do not contribute to the change in the amplitude characteristics as a function of the power of the stimulus light. (b) For high frequencies the amplitude characteristics obtained as a function of power join together in a common envelope if plotted on an absolute sensitivity scale. For spontaneous ganglion cells this envelope holds over a range of three log units and the shape is identical for central and peripheral processes. (c) The amplitude characteristics of the central and peripheral processes converging to a ganglion cell are identical, irrespective of the sign (on or off) and the spectral coding of the response. Therefore we have no evidence for interneurons in the goldfish retina unique to the periphery of the receptive field.     

Responses of retinal rods of the frog to light

To study the effect of the intensity, duration, spectral composition, and diameter of the light spot on the amplitude and shape of the response of single rods of the frog retina, potentials were recorded intracellularly. The rods tested could be divided into two groups on the basis of their responses to light spots of different spectral composition: those with maxima of sensitivity at 507 ± 8 nm and 442 ± 8 nm. With an increase in the intensity of light the response amplitude rose gradually and the time for the response to rise to its maximum was shortened. A bright flash temporarily inhibited the sensitivity of the cell to subsequent test flashes. If light spots of larger diameter (1000–1500 µ) were presented a delayed depolarization wave, due to illumination of the distant surroundings of the receptor, was observed in the course of recovery of the photic response; this effect was maximal for stimulation with red light and it was evidently induced by horizontal cell activity. The possible functional role of the depolarizing effect of illumination of the distant surroundings of the receptor is discussed.M. V. Lomonosov Moscow State University. Translated from Neirofiziologiya, Vol. 7, No. 1, pp. 84–92, January–February, 1975.     

Neurons, potassium, and glia in proximal retina of Necturus

Light-evoked K+ flux and intracellular Müller (glial) cell and on/off-neuron responses were recorded from the proximal retina of Necturus in eyecups from which the vitreous was not drained. On/off-responses, probably arising from amacrine cells, showed an initial transient and a sustained component that always exhibited surround antagonism. Müller cell responses were small but otherwise similar to those recorded in eyecups drained of vitreous. The proximal K+ increase and Müller cell responses had identical decay times, and on some occasions the latency and rise time of the K+ increase nearly matched Müller cell responses, indicating that the recorded K+ responses were not always appreciably degraded by electrode "dead space." The spatiotemporal distribution of the K+ increase showed that both diffusion and active reuptake play important roles in K+ clearance. The relationship between on/off-neuron responses and the K+ increase was modelled by assuming that (a) K+ release is positively related to the instantaneous amplitude of the neural response, and (b) K+ accumulating in extracellular space is cleared via mechanisms with approximately exponential time-courses. These two processes were approximated by low-pass filtering the on/off-neuron responses, resulting in modelled responses that match the wave form and time-course of the K+ increase and behave quantitatively like the K+ increase to changes in stimulus intensity and diameter. Thus, on/off-neurons are probably a primary source of the proximal light-evoked K+ increase that depolarizes glial cells to generate the M-wave.     

Inhibitory mechanisms within the receptive fields of X-and Y-type retinal ganglion cells of the cat (author's transl)]

Two-stages of the inhibitory mechanisms were assumed within the on-center receptive field (RF) of the cat's retinal ganglion cell on the basis of the following two experiments: 1) Effect of background intensity upon the magnitude of the response to the RF-centered spot of stimulus, and 2) the time course of the inhibitory effect when the additional spot of light is presented in the same RF center region. The first stage is an inhibitory feed-back from horizontal cell to the photoreceptor. Both X-and Y-fields have this feed-back route. By this gain control machanisms, the ganglion cell will respond to the intensity ratio of the spot to the backgound. The second stage of inhibitory mechanism in X-field is the feed-back from sustained amacrine cell to the bipolar cell. Above two stages of feed-back mechanism in X-field explain the strong maintained suppressive effect produced by the additional spot of light. On the other hand, the Y-type ganglion cell will recive the inhibitory input via feed-forward path from trannsient amacrine cell. This explains the transient on- and of f-suppressive effects     

Modulation of synaptic transfer between retinal cones and horizontal cells by spatial contrast

We studied the influence of steady annular light on the kinetics and sensitivity of horizontal cell (HC) responses to modulation of the intensity of small concentric spots in the turtle retina. As shown by previous investigators, when the intensity of the annulus was equal to the mean spot intensity, spot response kinetics were the same as those for the modulation of spatially uniform light. Turning off the annulus attenuated dramatically high-frequency flicker sensitivity and enhanced somewhat low-frequency sensitivity. This phenomenon reflects a modulation of synaptic transfer between cones and second-order neurons that is mediated by cones, and it will be referred to as cone-mediated surround enhancement (CMSE). Our main results are as follows: (a) The change in test-spot response sensitivity and kinetics upon dimming a steady surrounding annulus is a consequence of the change in spatial contrast rather than change in overall light level. (b) Introduction of moderate contrast between the mean spot intensity and steady surrounding light intensity causes a marked change in spot response kinetics. (c) The dependence of spot response kinetics on surrounding light can be described by a phenomenological model in which the steady state gain and the time constant of one or two single-stage, low-pass filters increase with decreasing annular light intensity (d) The effect of surrounding light on spot responses of a given HC is not determined by change in the steady component of the membrane potential of that cell. (e) Light outside the receptive field of an HC can affect that cell's spot response kinetics. (f) In an expanding annulus experiment, the distance over which steady annular light affects spot response kinetics varies among HCs and can be quite different even between two cells with closely matched receptive field sizes. (g) The degree of CMSE is correlated with HC receptive field size. This correlation suggests that part of the enhancement mechanism is located in the HC. Taken together, our results suggest the involvement of the inner retina in CMSE.     

Effect of stimulus intensity on unit responses in the cat frontal cortex

Unit activity of the frontal cortex during changes in stimulus intensity in the near-threshold range (15–16 dB above the threshold for the combined evoked potential) was investigated by an extracellular recording method in acute experiments on cats anesthetized with chloralose (70 mg/kg). Comparative analysis of unit responses in specific (SI) and nonspecific projection areas revealed basically similar changes in pattern during an increase in stimulus intensity: A decrease in the latent period, an increase in the total frequency and the phasic character of the discharge, and an increase in the probability of response. However, a relatively stable latent period and probability of response were observed in specific projection neurons for a stimulus intensity of 3–5 threshold units, whereas for the nonspecific projection neurons it was observed for a stimulus intensity of 10–15 threshold units. All sensory projections in the frontal cortex are formed by two inputs: short-latency low-threshold and long-latency high-threshold. Analysis of modality-dependent differences in the threshold of sensitivity and the latent period of response of the polysensory neurons suggests that stimuli of different modalities converge directly on cortical neurons.A. A. Zhdanov Leningrad State University. Translated from Neirofiziologiya, Vol. 8, No. 6, pp. 606–612, November–December, 1976.     

Transient adaptation and sensitization in the retina of Necturus

Responses to repetitive stimulation were monitored at several retinal levels in the eyecup of the mudpuppy Necturus maculosus. When alternating sequences of low-intensity small and large spots were presented, two effects were found, which could be localized to the proximal retina: (a) response decrement (RD), in which, after the first small spot response, subsequent small spot responses are decreased in amplitude and (b) transient response enhancement (TRE), in which the first small spot response after a large spot sequence is larger than preceding or subsequent small spot responses. RD and TRE are absent or weak in sustained on or off responses (horizontal and bipolar cells, and ON and OFF ganglion cell post-stimulus time histograms (PSTH) but are particularly well developed in the on/off responses of the proximal retina (proximal negative response, M-wave, PSTHs of ON/OFF ganglion cells, and intracellular responses from on/off neurons and Muller cells). RD and TRE appear to arise from a stimulus-evoked slow depolarization in on/off neurons that interacts with the amplitude of succeeding responses. We conclude that RD and TRE are a form of neural adaptation that is largely specific to the on/off channels of the proximal retina.     

Analysis of synaptic inputs to on-off amacrine cells of the carp retina

To elucidate the synaptic transmission between bipolar cells and amacrine cells, the effect of polarization of a bipolar cell on an amacrine cell was examined by simultaneous intracellular recordings from both cells in the isolated carp retina. When either an ON or OFF bipolar cell was depolarized by an extrinsic current step, an ON-OFF amacrine cell was transiently depolarized at the onset of the current but no sustained polarization during the current was detected. The current hyperpolarizing the OFF bipolar cell also produced the transient depolarization of the amacrine cell at the termination of the current. These responses had a latency of approximately 10 ms. The amplitude of the current-evoked responses changed gradually with current intensity within the range used in these experiments. They were affected by polarization of the amacrine cell membrane; the amplitude of the current-evoked responses as well as the light-evoked responses was increased when the amacrine cell membrane was hyperpolarized, while the amplitude was decreased when the cell was depolarized. These results confirm directly that ON-OFF amacrine cells receive excitatory inputs from both ON and OFF bipolar cells: the ON transient is due to inputs from ON bipolar cells, and the OFF transient to inputs from OFF bipolar cells. The steady polarization of bipolar cells is converted into transient signals during the synaptic process.     

Dynamics of turtle horizontal cell response

The small- and large-field (cone) horizontal cells produce similar dynamic responses to a stimulus whose mean luminance is modulated by a white-noise signal. Nonlinear components increase with an increase in the mean luminance and may produce a mean square error (MSE) of up to 15%. Increases in the mean luminance of the field stimulus bring about three major changes: the incremental sensitivity defined by the amplitude of the kernels decreases in a Weber-Fechner fashion; the waveforms of the kernels are transformed from monophasic (integrating) to biphasic (differentiating); the peak response time of the kernels becomes shorter and the cells respond to much higher-frequency inputs. The dynamics of the horizontal cell response also depend on the area of the retina stimulated. Smaller spots of light produce monophasic kernels of a longer peak response time. The presence of a steady background produces three major changes in the spot kernels: the kernel's amplitude becomes larger (incremental sensitivity increases); the peak response times become shorter; the waveform of the kernels changes in a fashion similar to that observed with an increase in the mean luminance of the field stimulus. A similar enhancement in the incremental sensitivity by a steady background has also been observed in catfish, which shows that this phenomenon is a common feature of the horizontal cells in the lower vertebrate retina.     

Application of transretinal current stimulation for the study of bipolar-amacrine transmission

Transretinal current flowing from the receptor side to the vitreous side depolarizes the axon terminals of retinal cells and facilitates the release of transmitter. Such current elicited a depolarizing response in off-center bipolar cells and a hyperpolarizing response in on-center bipolar cells. It also elicited a response of relatively complex waveform in amacrine cells. The responses elicited in bipolar cells were suppressed in the presence of 5-10 mM glutamate in the perfusing Ringer solution, while the responses of amacrine cells persisted, although their waveform changed to a simple one that showed monotonic depolarization irrespective of the type of amacrine cell and were accompanied by a decrease in the membrane resistance. The results indicate excitatory synaptic transmission from bipolar cells to amacrine cells. Since the response elicited by current in ON-OFF cells was almost identical to those elicited in ON or OFF amacrine cells, the transient nature of their light response cannot be due to their membrane properties. ON-OFF cells responded to transretinal current flowing in the opposite direction with a small hyperpolarization accompanied by a resistance increase. The hyperpolarizing response was suppressed by the addition of GABA in glutamate Ringer solution. The results suggest an activation by the current of GABA-ergic feedback pathways from amacrine cells to bipolar cells.     

The temporal structure of transient ON/OFF ganglion cell responses and its relation to intra-retinal processing

A subpopulation of transient ON/OFF ganglion cells in the turtle retina transmits changes in stimulus intensity as series of distinct spike events. The temporal structure of these event sequences depends systematically on the stimulus and thus carries information about the preceding intensity change. To study the spike events' intra-retinal origins, we performed extracellular ganglion cell recordings and simultaneous intracellular recordings from horizontal and amacrine cells. Based on these data, we developed a computational retina model, reproducing spike event patterns with realistic intensity dependence under various experimental conditions. The model's main features are negative feedback from sustained amacrine onto bipolar cells, and a two-step cascade of ganglion cell suppression via a slow and a fast transient amacrine cell. Pharmacologically blocking glycinergic transmission results in disappearance of the spike event sequence, an effect predicted by the model if a single connection, namely suppression of the fast by the slow transient amacrine cell, is weakened. We suggest that the slow transient amacrine cell is glycinergic, whereas the other types release GABA. Thus, the interplay of amacrine cell mediated inhibition is likely to induce distinct temporal structure in ganglion cell responses, forming the basis for a temporal code. Action Editor: Jonathan D. Victor     

Investigation of electrical responses recorded from the fenestra cochleae in cats

Electrical responses of the fenestra cochleae to stimulation by clicks of different intensity, polarity, and frequency, were studied in anesthetized cats. The absolute values of amplitude and latent period of the neural component of the response reflect the physiological state of the auditory nerve. Besides ordinary potentials characterized by peaks N1 and N2, specific responses were observed when clicks with an intensity of 85 dB or "rarefaction" clicks were used. Dependence of the amplitude of these responses on the intensity of acoustic stimuli of different polarity was investigated during a change in the rhythm of the stimulation; the effect of different rhythms of stimulation on the gradient of the curve reflecting this relationship was examined. The possible mechanisms of the effect of stimulus frequency are discussed.Scientific-Research Institute of Otolaryngology, Ministry of Health of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 11, No. 2, pp. 151–157, March–April, 1979.     

Structure of receptive fields of cat pulvinar neurons sensitive to photic stimulation

Receptive fields of 262 pulvinar neurons were studied. Receptive fields of 142 of these neurons were studied in detail with the aid of a stationary spot of light, flashing in different parts of the receptive field. Depending on responses to presentation of the stationary stimulus the neurons were divided into six groups. The first group included neurons with on—off responses to photic stimulation (44 of 142), the second group neurons with off responses only (42 of 142). In cells of the third group (19 of 142) an on response only was recorded in all structures of the receptive field tested. Neurons of the fourth group (eight of 142) had a receptive field of similar structure to that of the simple receptive fields of neurons in cortical area 17. The fifth group (10 of 142) included neurons with a receptive field of concentric structure, the sixth (19 of 142) consisted of neurons with receptive fields with multiple discharge centers. The structure of the receptive field of these neurons was mosaic, with an irregular distribution of exciting and "silent" zones. The mean response latency of the pulvinar neurons was 40–70 msec. Responses of neurons with shorter (20 msec) and longer (130–160 msec) latent periods also were recorded.L. A. Orbeli Institute of Physiology, Academy of Sciences of the Armenian SSR, Erevan. Translated from Neirofiziologiya, Vol. 11, No. 1, pp. 3–10, January–February, 1979.     

Electrophysiological evidence for push-pull interactions in the inner retina of turtle

The responses of the inner retinal neurons of turtle to light spots of sizes were studied in an attempt to reveal characteristics that may reflect possible interactions of the neural circuits underlying the center and surround responses. For the ON-OFF cells, the responses were also analyzed to observe whether interference or augmentation of these responses occur. The intracellular recordings revealed several such interactions, observed either in the form of altered spike activity or as changes in the transiency of the light responses. The ON-responding amacrine cell presented in this study became more sustained, while for the ON-OFF amacrine cells larger light spots tended to make the responses more transient and both the ON and OFF components became more pronounced. The spiking activity of the OFF-type ganglion cell shifted in relation to the light stimulus and the number of spikes observed upon presentation of larger spots increased. We suggest that the surround circuits activated by increasing light spots may substantially influence and reorganize not only the overall center-surround balance, but also the center response of the cells. Although it cannot be excluded that intrinsic membrane properties also influence these processes to some extent, it is more likely that lateral inhibition and disinhibitory mechanisms play the leading role in this process.     

Frequency Characteristics of Retinal Neurons in the Carp

Frequency characteristics of various retinal neurons in the carp were studied using sinusoidally modulated light as an input. They were affected by both intensity and pattern of illumination. In the horizontal cells, in which the effect of light intensity was studied most extensively, an increase in the light intensity brought about a decrease of the gain, which was more marked at lower frequencies, resulting in a shift of cutoff frequency towards higher frequencies and in a slight low frequency attenuation. A decrease in the area illuminated had an effect similar to a decrease in the light intensity. In the receptor, the low frequency attenuation was not apparent even at high light intensities. The adaptation process in receptors was not sufficient to explain the low frequency attenuation in the horizontal cells, and a possible contribution of negative feedback from horizontal cells to receptors was suggested. In the bipolar cell, the lateral interaction played an important role. An increase in an area resulted in the suppression of the response at low frequencies where the phases of the center and the surround responses were opposed, but in the augmentation near 5 Hz where the two responses were in phase. In amacrine cells, a low frequency attenuation and a phase advance at low frequencies were very prominent, and were considered to be due mainly to a process designated here as the neural adaptation.     

Dynamics of turtle cones

The response dynamics of turtle photoreceptors (cones) were studied by the cross-correlation method using a white-noise-modulated light stimulus. Incremental responses were characterized by the kernels. White-noise-evoked responses with a peak-to-peak excursion of greater than 5 mV were linear, with mean square errors of approximately 8%, a degree of linearity comparable to the horizontal cell responses. Both a spot (0.17 mm diam) and a large field of light produced almost identical kernels. The amplitudes of receptor kernels obtained at various mean irradiances fitted approximately the Weber-Fechner relationship and the mean levels controlled both the amplitude and the response dynamics; kernels were slow and monophasic at low mean irradiance and were fast and biphasic at high mean irradiance. This is a parametric change and is a piecewise linearization. Horizontal cell kernels evoked by the small spot of light were monophasic and slower than the receptor kernels produced by the same stimulus. Larger spots of light or a steady annular illumination transformed the slow horizontal cell kernel into a fast kernel similar to those of the receptors. The slowing down of the kernel waveform was modeled by a simple low-pass circuit and the presumed feedback from horizontal cells onto cones did not appear to play a major role.     

Dynamic characteristics of the receptive field of L-cells for monochromatic lights

We applied the Wiener theory to analyse receptive field responses of L-cells in the carp and studied some dynamic properties of the receptive field of L-cells for monochromatic light stimuli. The L-cells were stimulated by each monochromatic light modulated in white-noise fashion. They responded almost linearly to all the monochromatic light stimuli. The impulse responses of the L-cells became larger in amplitude and faster in latency, peak response time, and repolarising phase as a spot of monochromatic light was enlarged. The L-cells seem to respond like a lowpass filter and the cutoff frequency of their gain characteristics increases with the enlargement of the monochromatic light spot. The relation between shift of cutoff frequency and spot diameter was monotonic increasing for each monochromatic light.     

Sensory interaction in the snailHelix lucorum

The activity of hair cells of statocysts inHelix lucorum was investigated by means of intra- and extracellular recording, applying appropriate stimulation of the organs of balance, optic photoreceptors, and the chemoreceptors of the optic tentacle bulb. Mechanical stimulation of the statocysts evoked a firing reaction in the hair cells as a result of generator potentials occurring at the receptors. The amplitude of generator potentials was proportional to the intensity of the reaction. Stimulating the optic photoreceptors by switching on a light produced a spike response in the hair cells with a short latency of 0.3–2 sec. The latent period of this response was inversely proportional to the intensity of the light. Appropriate stimulation of the chemoreceptors of the optic tentacle bulb caused a faint spike response with a long latent period of 20–40 sec in the hair cells. Illumination and stimulation of the chemoreceptors produced an inhibitory response in the form of bursts of IPSP in 2 out of more than 50 hair cells.Institute of Higher Nervous Activity and Neurophysiology, Academy of Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 18, No. 1, pp. 17–26, January–February, 1986.