The spectral sensitivities of rods and cones in macaque and human retinas were determined by recording the membrane current from single outer segments. In the macaque retina, the wavelengths of maximum sensitivity were at about 430, 530, and 561 nm for the blue, green, and red cones, respectively, and at 491 nm for the rods. The shapes of the spectra of the three cones were similar when plotted on a log wavenumber scale; the rod spectrum was slightly broader. Spectral sensitivities of the red and green cones from a human retina were virtually identical to those of macaque cones. For comparison with human psychophysical measurements, the rod and cone spectra were adjusted to give the sensitivities expected for light incident on the cornea of the human eye. These functions satisfactorily predicted the scotopic and photopic luminosity functions as well as results from human color-matching experiments. The adjusted spectra of the red and green cones also agreed well with the π-mechanisms of Stiles (1953, 1959).

The response to spatially focal flicker is enhanced by dim, spatially diffuse, rod-stimulating backgrounds. This effect is called suppressive rod-cone interaction (SRCI) as it reflects a tonic, suppressive influence of dark-adapted rods upon cone pathways which is removed by selective rod-light adaptation. SRCI is observed in amphibian retina with intracellular recordings from most cone-driven cells including the cones themselves, and is most obvious using stimuli flickering at frequencies too rapid for rods to follow. SRCI is blocked by glutamate analogs which selectively block the photic response of horizontal cells (HCs). In the presence of these agents, flicker responses from bipolar cells and cones are enhanced to levels normally seen only with selective rod-light adaptation. In the HCs themselves, SRCI is similarly blocked by lead chloride which blocks rod-, but not cone-related activity.

In amphibian and cat HCs and in human observers, SRCI is limited by a space constant of very similar value (between 100 and 150 μm). We suggest that SRCI in all three species is mediated by HCs: in amphibians, SRCI must at least partially reflect rod-modulation of HC feedback onto cones.

In order to elucidate the role of putative indoleaminergic amacrine cells in visual processing, we have employed pharmacological agents specific for the two classes of serotonin receptor, 5-HT2 and 5-HT1, which have been identified in both the retina and brain. Perfusion of the rabbit retina with 5-HT2 selective antagonists decreases the ON-excitation of all classes of ganglion cell as well as the spontaneous activity of these cells. The effect on OFF-responses depends on the cell type: OFF-excitation of center-surround brisk and sluggish cells is increased or not affected by these drugs, but OFF excitation of ON/OFF direction selective cells is reduced. No disruption of the trigger features of direction selective or orientation selective cells was discovered, suggesting that indoleaminergic amacrine cells do not play a role in the generation of the complex properties of these cells.

5-HT1 receptors are heterogeneous and classified as a, b, or c subtypes. Since no selective antagonists are available for these sites, we have employed specific agonists. The most specific of these are for the 5-HT1A receptor. Perfusion with these agonists had physiological effects similar to those with perfusion of 5-HT2 antagonists. Thus, we have suggested that these two classes of serotonin receptors mediate opponent processes in the neural pathway. Since indoleaminergic cells make reciprocal synaptic connections with rod bipolar cell terminals, which are depolarizing in the rabbit retina, we hypothesize that 5-HT2 receptors facilitate the synaptic transmission from the depolarizing rod bipolar cell thus facilitating ON-excitation in the retinal network while 5-HT1A receptors mediate an inhibitory process. Similar self-opponent processing appears to take place in the hypothalamic and hippocampal serotonergic systems as well as in the dopaminergic retinal system. Thus, it is likely that this organization is a general feature of monoamine signal transmission in the central nervous system.

In 1827, plant biologist Robert Brown discovered what is known as Brownian motion, a class of chaos. Formal derivative of Brownian motion is Gaussian white-noise. In 1938, Norbert Wiener proposed to use the Gaussian white-noise as an input probe to identify a system by a series of orthogonal functionals known as the Wiener G-functionals.

White-noise analysis is uniquely suited for studying the response dynamics of retinal neurons because (1) white-noise light stimulus is a modulation around a mean luminance, as are the natural photic inputs, and it is a highly efficient input; and (2) the analysis defines the response dynamics and can be extended to spike trains, the final output of the retina. Demonstrated here are typical examples and results from applications of white-noise analysis to a visual system.

Bipolar cells make reciprocal synapses with amacrine cells in the inner plexiform layer; both feedforward connections and feedback connections are present. The physiological properties of the feedback synapse have not been well described. Since some amacrine cells are thought to be GABAergic, we examined bipolar cells for feedback input from γ-aminobtyric acid (GABA)ergic amacrine cells. Solitary bipolar cells were dissociated enzymatically from the goldfish retina. Cells were voltage clamped with a patch pipette and their GABA sensitivity was examined. GABA evoked responses in all bipolar cells with a large axon terminal, which were identified to be the rod dominant ON type, and in some bipolar cells with a small axon terminal. The highest GABA sensitivity was located at the axon terminal. The least effective dose was as low as 100 nM. A small insignificant response of high threshold was evoked when GABA was applied to the dendrite and soma. GABA increased the Cl conductance and caused membrane hyperpolarization. The bipolar cells had the GABAA receptor coupled with a benzodiazepine receptor. The GABA-evoked response was not susceptible to Co ions, which suppressed the GABA-induced responses in turtle cones by 50% at 5 fiM concentration. Incomplete desensitization was observed, suggesting that the GABAergic pathway seems capable of transmitting signals tonically. The present results strongly indicate that the rod-dominant ON-type bipolar cells and some bipolar cells with a small axon terminal receive negative feedback inputs from GABAergic amacrine cells.

We have investigated responses in proximal retina of the cat that contribute to two kinds of electroretinogram (ERG) recordings: (1) the pattern ERG, a light-adapted response and (2) the threshold and near threshold ERG, a dark-adapted response (Sieving et al., 1986a, 1986b; Sieving & Steinberg, 1985). In intraretinal, extracellular recordings, two negative-going responses were identified that are maximal around the inner plexiform layer, and distinct from PII, which is maximal in distal retina: under light-adapted conditions, a spatially tuned response at light onset and light offset, the “M-wave” (previously described in cold-blooded animals by Karwoski & Proenza (1977, 1980)), and under dark-adapted conditions, the scotopic threshold response, or “STR,” a response at light onset. The results under dark-adapted conditions are examined in more detail here.

The STR is a very sensitive response whose threshold is 1.5–2.0 log units below that of the dc-component of PII and therefore well below the threshold of the a-, b-, and c-waves. It saturates about 2.4 log units below rod saturation. The STR contributes a negative-going potential to the dark-adapted ERG that is dominant near threshold; while PII (dc-component and b-wave) contributes a positive-going potential that is dominant at higher intensities (Sieving et al., 1986b). Investigation of the mechanism of the proximal retinal responses that contribute to the ERG supports a K+-Müller cell hypothesis of their origin.

The neural circuitry underlying movement detection was inferred from studies of amacrine cells under whole-cell patch clamp in retinal slices. Cells were identified by Lucifer yellow staining. Synaptic inputs were driven by “puffing“ transmitter substances at the dendrites of presynaptic cells. Spatial sensitivity profiles for amacrine cells were measured by puffing transmitter substances along the lateral spread of their processes. Synaptic pathways were separated and identified with appropriate pre- and postsynaptic pharmacological blocking agents.

Two distinct amacrine cell types were found: one with narrow spread of processes that sustained excitatory synaptic current, the other with very wide spread of processes that transient excitatory synaptic currents. The transient currents found only in the wide-field amacrine cell were formed presynaptically at GABAB receptors. They could be blocked with baclofen, a GABAB agonist, and their time course was extended by AVA, a GABAB antagonist. Baclofen and AVA had no direct affect upon the wide-field amacrine cell, but picrotoxin blocked a separate, direct GABA input to this cell.

The narrow-field amacrine cell was shown to be GABAergic by counterstaining with anti-GABA antiserum after it was filled with Lucifer yellow. Its narrow, spatial profile and sustained synaptic input are properties that closely match those of the GABAergic antagonistic signal that forms transient activity (described above), suggesting that the narrow-field amacrine cell itself is the source of the GABAergic interaction mediating transient activity in the inner plexiform layer (IPL). Other work has shown a GABAB sensitivity at some bipolar terminals, suggesting a population of bipolars as the probable site of interaction mediating transient action.

The results suggest that two local populations of amacrine cell types (sustained and transient) interact with the two populations of bipolar cell types (transient forming and nontransient forming). These interactions underlie the formation of the change-detecting subunits. We suggest that local populations of these subunits converge to form the receptive fields of movement-detecting ganglion cells.