Brisk-transient Ganglion Cells Research Articles

Loss of Sensitivity in an Analog Neural Circuit

A low-contrast spot that activates just one ganglion cell in the retina is detected in the spike train of the cell with about the same sensitivity as it is detected behaviorally. This is consistent with Barlow's proposal that the ganglion cell and later stages of spiking neurons transfer information essentially without loss. Yet, when losses of sensitivity by all preneural factors are accounted for, predicted sensitivity near threshold is considerably greater than behavioral sensitivity, implying that somewhere in the brain information is lost. We hypothesized that the losses occur mainly in the retina, where graded signals are processed by analog circuits that transfer information at high rates and low metabolic cost. To test this, we constructed a model that included all preneural losses for an in vitro mammalian retina, and evaluated the model to predict sensitivity at the cone output. Recording graded responses postsynaptic to the cones (from the type A horizontal cell) and comparing to predicted preneural sensitivity, we found substantial loss of sensitivity (4.2-fold) across the first visual synapse. Recording spike responses from brisk-transient ganglion cells stimulated with the same spot, we found a similar loss (3.5-fold) across the second synapse. The total retinal loss approximated the known overall loss, supporting the hypothesis that from stimulus to perception, most loss near threshold is retinal.

Design of a Neuronal Array

Retinal ganglion cells of a given type overlap their dendritic fields such that every point in space is covered by three to four cells. We investigated what function is served by such extensive overlap. Recording from pairs of ON or OFF brisk-transient ganglion cells at photopic intensities, we confirmed that this overlap causes the Gaussian receptive field centers to be spaced at approximately 2 SDs (sigma). This, together with response nonlinearities and variability, was just sufficient to provide an ideal observer with uniform contrast sensitivity across the retina for both threshold and suprathreshold stimuli. We hypothesized that overlap might maximize the information represented from natural images, thereby optimizing retinal performance for many tasks. Indeed, tested with natural images (which contain statistical correlations), a model ganglion cell array maximized information represented in its population responses with approximately 2sigma spacing, i.e., the overlap observed in the retina. Yet, tested with white noise (which lacks statistical correlations), an array maximized its information by minimizing overlap. In both cases, optimal overlap balanced greater signal-to-noise ratio (from larger receptive fields) against greater redundancy (because of larger receptive field overlap). Thus, dendritic overlap improves vision by taking optimal advantage of the statistical correlations of natural scenes.

Chromatic Properties of Horizontal and Ganglion Cell Responses Follow a Dual Gradient in Cone Opsin Expression

In guinea pig retina, immunostaining reveals a dual gradient of opsins: cones expressing opsin sensitive to medium wavelengths (M) predominate in the upper retina, whereas cones expressing opsin sensitive to shorter wavelengths (S) predominate in the lower retina. Whether these gradients correspond to functional gradients in postreceptoral neurons is essentially unknown. Using monochromatic flashes, we measured the relative weights with which M, S, and rod signals contribute to horizontal cell responses. For a background that produced 4.76 log10 photoisomerizations per rod per second (Rh*/rod/s), mean weights in superior retina were 52% (M), 2% (S), and 46% (rod). Mean weights in inferior retina were 9% (M), 50% (S), and 41% (rod). In superior retina, cone opsin weights agreed quantitatively with relative pigment density estimates from immunostaining. In inferior retina, cone opsin weights agreed qualitatively with relative pigment density estimates, but quantitative comparison was impossible because individual cones coexpress both opsins to varying and unquantifiable degrees. We further characterized the functional gradients in horizontal and brisk-transient ganglion cells using flickering stimuli produced by various mixtures of blue and green primary lights. Cone weights for both cell types resembled those obtained for horizontal cells using monochromatic flashes. Because the brisk-transient ganglion cell is thought to mediate behavioral detection of luminance contrast, our results are consistent with the hypothesis that the dual gradient of cone opsins assists achromatic contrast detection against different spectral backgrounds. In our preparation, rod responses did not completely saturate, even at background light levels typical of outdoor sunlight (5.14 log10 Rh*/rod/s).

Spike generator limits efficiency of information transfer in a retinal ganglion cell.

The quality of the signal a retinal ganglion cell transmits to the brain is important for preception because it sets the minimum detectable stimulus. The ganglion cell converts graded potentials into a spike train with a selective filter but in the process adds noise. To explore how efficiently information is transferred to spikes, we measured contrast detection threshold and increment threshold from graded potential and spike responses of brisk-transient ganglion cells. Intracellular responses to a spot flashed over the receptive field center of the cell were recorded in an intact mammalian retina maintained in vitro at 37 degrees C. Thresholds were measured in a single-interval forced-choice procedure with an ideal observer. The graded potential gave a detection threshold of 1.5% contrast, whereas spikes gave 3.8%. The graded potential also gave increment thresholds approximately twofold lower and carried approximately 60% more gray levels. Increment threshold "dipped" below the detection threshold at a low contrast (<5%) but increased rapidly at higher contrasts. The magnitude of the "dipper" for both graded potential and spikes could be predicted from a threshold nonlinearity in the responses. Depolarization of the cell by current injection reduced the detection threshold for spikes but also reduced the range of contrasts they can transmit. This suggests that contrast sensitivity and dynamic range are related in an essential trade-off.

Matching neural morphology to molecular expression: single cell injection following immunostaining.

To match a neuron's morphology with its expression of a particular protein, it is useful to first identify the cell by immunostaining and then inject it with fluorescent dye. Such targeted injection cannot be performed with a hydrophilic dye (such as Lucifer yellow) because the neuron, once rendered porous to antibodies, does not retain it. But a lipophilic dye (such as DiI) injected iontophoretically into the soma forms a crystal and is thereby trapped. From this intracellular depot dye diffuses into the cell membrane to reveal the detailed morphology. We have used this strategy to identify the morphology of a GABAergic retinal bipolar cell and several types of GABAergic amacrine cell. In addition, we demonstrate probable connections from a narrow-field, GABAergic amacrine cell to the OFF brisk-transient ganglion cell. Finally, we show that the strategy works in the cortical slice, showing a layer IV cell immunostained for parvalbumin to be a "nest basket cell".

Contrast threshold of a brisk-transient ganglion cell in vitro.

We measured the contrast threshold for mammalian brisk-transient ganglion cells in vitro. Spikes were recorded extracellularly in the intact retina (guinea pig) in response to a spot with sharp onset, flashed for 100 ms over the receptive field center. Probability density functions were constructed from spike responses to stimulus contrasts that bracketed threshold. Then an "ideal observer" (IO) compared additional trials to these probability distributions and decided, using a single-interval, two-alternative forced-choice procedure, which contrasts had most likely been presented. From these decisions we constructed neurometric functions that yielded the threshold contrast by linear interpolation. Based on the number of spikes in a response, the IO detected contrasts as low as 1% [4.2 +/- 0.4% (SE); n = 35]; based on the temporal pattern of spikes, the IO detected contrasts as low as 0.8% (2.8 +/- 0.2%). Contrast increments above a very low "basal contrast" were discriminated with greater sensitivity than they were detected against the background. Performance was optimal near 37 degrees C and declined with a Q(10) of about 2, similar to that of retinal metabolism. By the method used by previous in vivo studies of brisk-transient cells, our most sensitive cells had similar thresholds. The in vitro measurements thus provide an important benchmark for comparing sensitivity of neurons upstream (cone and bipolar cell) and downstream to assess efficiency of retinal and central circuits.

Orientation bias of brisk-transient y-cells of the cat retina for drifting and alternating gratings.

Brisk-transient ganglion cells of the cat's retina were examined for orientation bias using two different stimuli: drifting gratings and alternating gratings, both of fixed contrast (50%) and fixed temporal frequency (2 Hz). Some cells were strongly biassed for both stimuli, some were not biassed for either while still others were strongly biassed for only one or other stimulus. The preferred orientations for the two types of grating tended to be the same, on average, but substantial differences were not uncommon. A systematic preference for radially-oriented gratings was evident when the stimulus was drifting but there was an additional preference for tangentially-oriented gratings when the stimulus was alternating. Orientation bias for drifting gratings often extended over a broad range of spatial frequencies and was maximum near the resolution limit. For alternating gratings, bias was evident only at the highest spatial frequencies. Results indicate that the arrangement of receptive field components responsible for linear and nonlinear kinds of behaviour may sometimes possess different axes of symmetry.

Response to the length of moving visual stimuli of the brisk classes of ganglion cells in the cat retina.

Response histograms were collected for brisk-sustained and brisk-transient ganglion cells in the cat retina as narrow bars were moved backwards and forwards across their receptive fields. When a bar of fixed length was moved across the centre of the receptive field with contrast proportional to velocity, a constant response was obtained as long as the centre of the receptive field was crossed within the summation time. However, if the length of the bar was such that it extended beyond the centre, then there was a small but steady increase in surround antagonism for an increase in velocity. The same response was produced by a brief whole-field flash as by an extended bar moving across the receptive field at high velocity if both stimulus conditions delivered the same energy uniformly across the receptive field. With brisk-sustained cells it was observed, for small bar lengths, that bar length and contrast could be exchanged to give a constant response, even when there was considerable non-linearity in the over-all stimulus-response relationship. Thus conditions that resulted in constant stimulus flux produced a constant response. This property was seen at both high and low velocities for the majority of brisk-sustained units. The stimulus-response relationship had a greater range of linearity at high velocities than at low velocities. From similar experiments with brisk-transient cells it was observed that bar length and contrast could only be exchanged to give a constant response at high velocities. At low velocities there was considerable non-linearity: there appeared to be saturation of the response from local regions and it was necessary to extend the bar outside such a region to obtain an increase in response. At lower velocities, despite the changes seen in length-response curves under different conditions of contrast and velocity, the degree of surround antagonism remained constant for a given cell. Further, both brisk-sustained and brisk-transient cells showed the same degree of surround antagonism.

Visual Resolution and Receptive Field Size: Examination of Two Kinds of Cat Retinal Ganglion Cell

Intraocular recordings from brisk-sustained and brisk-transient ganglion cells in the cat's retina revealed a systematic increase in center size and decrease in spatial cut-off frequency with increasing distance from the area centralis. At any one eccentricity sizes of the centers of sustained and transient cells did not overlap, and the variation in cut-off frequency for each class was constrained to about one-half octave.

Properties of rarely encountered types of ganglion cells in the cat's retina and an overall classification.

1. In a reference sample of 960 cat retinal ganglion cells, seventy-three had receptive fields departing from the concentric centre-surround pattern.2. Five classes were distinguished among the subset: local edge detectors, direction-selective cells, colour-coded cells, uniformity detectors, edge inhibitory off-centre cells.3. Local edge detectors (forty-five) possessed a radially symmetrical pattern of responses to both centrifugal and centripetal movements of both black and white small targets, an on-off receptive field with a silent inhibitory surround and a low or zero maintained discharge. Their operation could be interpreted as the detection of a contrasting border confined to a small region of the visual field.4. With direction-selective units (eleven) it was possible to find an axis through the receptive field along which sharply different responses could be obtained for opposite directions of movement of small black or white targets.5. Colour units (six) were mostly of the single opponent type having excitatory input from blue-sensitive cones and inhibitory input from long wave-length cones. Both inputs coexisted at the centre of the field and either could be spatially more extensive than the other. One example changed over to rod input under scotopic conditions, another did not.6. Uniformity detectors (five) had a brisk maintained discharge which was reduced or abolished temporarily by all forms of visual stimulation.7. Edge inhibitory off-centre units (three) behaved like uniformity detectors for small targets and fine gratings but like off-centre on-surround units for large targets. Their receptive fields consisted of three concentric regions: a small sized, central edge inhibitory region; a larger zone of off-responsiveness; and an outlying annulus of on-responsiveness.8. It is argued that the above physiological types belong to the morphologically heterogeneous class of cells called gamma cells. The argument is based on similarity in the sizes of receptive fields and dendritic trees and on evidence that the axons are thinner than those of the brisk-sustained and brisk-transient ganglion cells.9. The physiological classification of cat retinal ganglion cells developed in this paper and the preceding one is summarized in a Table.10. It now appears that cat and rabbit possess a qualitatively similar complement of receptive field types among their ganglion cells; the differences reside in the quantitative expression of the various classes.