Gain control is a salient feature of information processing throughout the visual system. Heeger (1991, 1992) described a mechanism that could underpin gain control in primary visual cortex (V1). According to this model, a neuron's response is normalized by dividing its output by the sum of a population of neurons, which are selective for orientations covering a broad range. Gain control in this scheme is manifested as a change in the semisaturation constant (contrast gain) of a V1 neuron. Here we examine how flanking and annular gratings of the same or orthogonal orientation to that preferred by a neuron presented beyond the receptive field modulate gain in V1 neurons in anesthetized marmosets (Callithrix jacchus). To characterize how gain was modulated by surround stimuli, the Michaelis–Menten equation was fitted to response versus contrast functions obtained under each stimulus condition. The modulation of gain by surround stimuli was modelled best as a divisive reduction in response gain. Response gain varied with the orientation of surround stimuli, but was reduced most when the orientation of a large annular grating beyond the classical receptive field matched the preferred orientation of neurons. The strength of surround suppression did not vary significantly with retinal eccentricity or laminar distribution. In the marmoset, as in macaques (Angelucci et al., 2002a, b), gain control over the sort of distances reported here (up to 10 deg) may be mediated by feedback from extrastriate areas.

Although there are many glutamate receptors in the retina, 2-amino-4-phosphonobutyrate (L-AP4) is an agonist that acts selectively at metabotropic glutamate receptors (mGluR6) of ON bipolar cells. We explored the properties of agonists that activate this receptor. The effects of various glutamate analogs on the b-wave of the electroretinogram (ERG) were used as a measure of their activity. Conformational comparisons among agonists suggest that ligands in an extended conformation preferentially bind to the ON bipolar synaptic receptor. But this property is insufficient to explain the selectivity of mGluR6 because some inactive glutamate analogs could also match this extended conformation. Comparative molecular field analysis (CoMFA) was used to compare the electrostatic and steric potentials of agonists with their action at the ON bipolar synapse. Steric potentials beneath a plane defined by the three putative binding sites plays a key role in determining agonist activity. The CoMFA model was used to predict the activity of glutamate analogs and correlations between predicted and measured activity support the model.

Limulus photoreceptors utilize the phosphoinositide pathway to generate light-induced single photon events (quantum bumps) that sum to form the depolarizing receptor potential. The protein kinase C (PKC) activator, (−)-indolactam V (ILV) rapidly desensitizes the light response in Limulus ventral nerve photoreceptors. Within 10 min of extracellular application, 100 nM (−)-ILV caused a decrease in the mean amplitude of quantum bumps to 38% of control values. PKC activation by (−)-ILV also causes photosensitive membrane disorganization and endocytosis. To investigate whether this precedes desensitization of the electrical response, we fixed cells after 10-min incubation with 25 μM (−)-ILV, a concentration sufficient to cause a 1000-fold desensitization of the receptor potential. The photosensitive microvilli of these photoreceptors remained narrow, densely packed, and well organized. Increasing the incubation time to 60 min did, however, induce disorganization and swelling of the microvilli and endocytosis of the photosensitive membrane, as previously reported. Measurement of membrane capacitance did not indicate a significant reduction in membrane area accompanying desensitization by (−)-ILV. PKC-induced reduction in light sensitivity therefore precedes the detection of ultrastructural changes in the rhabdomeral membrane and is not due to a net loss of membrane.

A fast-scanning dichroic microspectrophotometer was used to trace products of rhodopsin photolysis (metarhodopsins I/II/III and later) in structurally intact amphibian rod outer segments (ROSs) and metabolically active rods. The instrument allows the recording of absorbance spectra with a time resolution better than 1 s, and to discriminate between products with similar absorbance spectra that differ with respect to the orientation of their chromophore in the photoreceptor membrane. We demonstrate that metarhodopsin III is in a pH-reversible equilibrium with metarhodopsin II and that the metarhodopsin III chromophore is orientated with respect to the membrane plane even more strictly than the 11-cis retinal in “dark” rhodopsin. This indicates that all-trans retinal in metarhodopsin III is still attached to its native binding site on opsin. The kinetic scheme of the decay of metarhodopsins is presented in which metarhodopsin III lies in a shunt pathway from metarhodopsin II to retinal. Formation of metarhodopsin III was detected at bleaches as low as ≈ 3%, contrary to previous reports that it is not formed at below 10% bleaches. Another product that is spectrally similar to metarhodopsin III, termed P440, appears at later stages of photolysis as the result of the decay of metarhodopsin II and metarhodopsin III. The chromophoric group in P440 is orientated preferentially across the disk membrane. The final product(s) in isolated ROS, where the reduction of retinal to retinol is blocked, consists of a mixture of a free retinal and retinal possibly attached to different binding sites in the membrane. In metabolically active rods the later products are quickly converted to retinol. We conclude that metarhodopsin III represents a specific conformational state of metarhodopsin where the chromophoric binding site is still occupied by all-trans retinal. Hence, the formation and decay of metarhodopsin III may be limiting for the rate of rhodopsin regeneration and photoreceptor dark adaptation.

In the nob mouse, a mutation in nyctalopin results in a loss of signal transmission from photoreceptors to depolarizing bipolar cells (DBCs). We used immunohistochemical techniques to assess the expression pattern of proteins found at either the photoreceptor terminal or bipolar cell dendrites within the outer plexiform layer. We labeled normal and nob retinas with antibodies against mGluR6, PKC, G0α, bassoon, PSD-95, the α1F subunit of voltage-gated calcium channels, trkB, and dystrophin. All labeling patterns in nob and normal retinas were comparable to those previously reported in mouse retina. Our results indicate that the absence of nyctalopin does not disrupt the expression pattern of other proteins known to be required for synaptic transmission.

Retinal ganglion cells (RGCs) usually increase their dendritic field area with postnatal retinal growth. The mechanisms that regulate the postnatal shape of dendritic arbors in the growing retina are not well understood. Quantitative studies suffer from the difficulty of labeling specific subpopulations of RGCs selectively including their dendritic processes. In this study, we labeled displaced retinal ganglion cells (DGC) that are known to project to the accessory optic system (AOS) in juvenile and adult chameleons by retrograde transport of dextran amines. The complete population of DGCs was quantitatively screened for the effects of postnatal retinal growth on cell morphology, dendritic field coverage, and dendritic arbor size. The adult eye contained 2000 DGCs/retina. This number was already present at birth. The smaller size of the hatchling eye (approximately 1/3 of the adult size) led to higher densities of DGCs. The greatest accumulation of juvenile DGCs (two-fold higher compared to the adult) was found in the periphery of the retina where the greatest surface expansion was observed. DGC dendritic field areas were adjusted proportionally to this expansion in order to maintain a constant dendritic coverage. The increase of dendritic fields was mediated by two putative passive mechanisms: First, an elongation of individual dendrites similar to previous reports of postnatal RGC development in the retina of goldfish and chicks. Second, and more prominent, we observed that neighboring dendrites were pulled apart from each other. This resulted in a looser spacing of the initially tightly packed dendrites of each dendritic arbor. This dispersal of dendrites over a larger area was, due to its passive nature, proportional to the increase of the retinal surface and preserved a constant dendritic coverage irrespective of the animal's age and eye size.

Inhibitory synaptic transmission via GABA and glycine receptors plays a crucial role in shaping the excitatory response of neurons in the retina. Whole-cell recordings were obtained from ganglion cells in the intact rabbit eyecup preparation to correlate GABA- and glycine-activated currents with the presence of their specific receptors on morphologically identified α ganglion cells. Alpha ganglion cells were chosen based upon their large somata when viewing the retinal surface, and responses to light and dark spots were used to identify OFF-alpha ganglion cells. Light responses were abolished by superfusion of Ringer's containing cobalt to synaptically isolate the cell by blocking all Ca2+-mediated transmitter release. Pressure pulses of GABA and glycine were delivered to an area that encompassed the dendritic field while receptor antagonists were applied through superfusion to characterize the direct inhibition onto the ganglion cell. Physiological results indicated that OFF-α cells did not have any GABAC receptor-activated currents, but did express currents mediated by ionotropic GABAA receptors and metabotropic GABAB receptors that were blocked by their specific antagonists bicuculline and CGP55845, respectively. The amplitudes of strychnine-sensitive glycine-activated currents were always larger than the currents elicited by GABA. Confocal optical sections of physiologically identified, sulforhodamine B-stained cells displayed the localization of glycine and GABAA receptor subunit labeling dispersed over the stained dendrites.

The electroretinogram (ERG) of the cone system provides a useful noninvasive measure of the activity of the cone pathway. Despite a wide application of the cone ERG in the study of rodent models of human hereditary retinal disease, the cellular origins of the rat cone ERG have not been well defined. Here, we address this issue using a pharmacological approach that has been used previously to derive ERG response components. Agents that impair synaptic transmission at well-defined retinal loci were dissolved in saline and injected into the vitreous of adult Sprague-Dawley rats anesthetized with ketamine/xylazine, and cone ERGs were recorded approximately 2 h later. Analysis of the resulting waveforms indicated that the rat cone ERG includes a relatively small-amplitude component of negative polarity that is derived from the activity of cone photoreceptors, and perhaps retinal glial (Müller) cells. The cone depolarizing bipolar cell pathway contributes a positive potential of large amplitude to the rat cone ERG. In comparison, the contribution of hyperpolarizing bipolar cells is of negative polarity and of much smaller amplitude. The inner retina contributes a negative wave upon which higher frequency oscillations are superimposed. These results provide a foundation for interpreting changes in the waveform of the rat cone ERG that may be observed following genetic alteration or other experimental treatment.

Microspectrophotometry indicates the presence of at least three cone visual pigments in two Australian marsupials, the fat-tailed dunnart (Sminthopsis crassicaudata) and honey possum (Tarsipes rostratus). Here we have examined the distribution of cone types using antisera, JH455 and JH492, that recognize short-wavelength-sensitive (SWS) and medium-to-long-wavelength-sensitive (M/LWS) cone opsins, respectively. SWS cones were concentrated in dorso-temporal retina in the dunnart with a shallow decreasing gradient extending to the periphery (2300–1500/mm2). In the honey possum, SWS cones showed a uniform distribution (2700/mm2), except for a slight increase in a narrow peripheral band (3100/mm2). In both species, M/LWS cones dominated and their distributions were similar to those of retinal ganglion cells: a horizontal streak in the dunnart (31,000–21,000/mm2) and a shallow mid-ventral to peripheral gradient in the honey possum (37,000–26,000/mm2). A low number of cones remained unlabeled when the antisera were combined revealing further minority cone population(s). We discuss cone distributions in relation to visual capabilities and requirements of the species.

Contours and surface textures provide powerful cues used in image segmentation and the analysis of object shape. To learn more about how the visual system extracts and represents these visual cues, we studied the responses of V2 neurons in awake, fixating monkeys to complex contour stimuli (angles, intersections, arcs, and circles) and texture patterns such as non-Cartesian gratings, along with conventional bars and sinusoidal gratings. Substantial proportions of V2 cells conveyed information about many contour and texture characteristics associated with our stimuli, including shape, size, orientation, and spatial frequency. However, the cells differed considerably in terms of their degree of selectivity for the various stimulus characteristics. On average, V2 cells responded better to grating stimuli but were more selective for contour stimuli. Metric multidimensional scaling and principal components analysis showed that, as a population, V2 cells show strong correlations in how they respond to different stimulus types. The first two and five principal components accounted for 69% and 85% of the overall response variation, respectively, suggesting that the response correlations simplified the population representation of shape information with relatively little loss of information. Moreover, smaller random subsets of the population carried response correlation patterns very similar to the population as a whole, indicating that the response correlations were a widespread property of V2 cells. Thus, V2 cells extract information about a number of higher order shape cues related to contours and surface textures and about similarities among many of these shape cues. This may reflect an efficient strategy of representing cues for image segmentation and object shape using finite neuronal resources.

Whole-cell recordings of tiger salamander ganglion cells were obtained using a superfused retinal slice preparation. Membrane current fluctuations were recorded under voltage-clamp conditions with cells usually held at −70 mV. Current fluctuations at rest (Mg2+ = 1 mM) were reduced by adding d-2-amino-7-phosphonoheptanoate (d-AP7). Resting fluctuations were increased by adding N-methyl-D-aspartate (NMDA) or by removing extracellular Mg2+. These increased fluctuations were blocked by d-AP7. Blocking NMDA receptors under control conditions also reduced a tonic inward current by −1 to −15 pA. Fluctuation analysis of current noise shows that the noise power spectrum measured in the presence of NMDA is similar to that measured under Mg2+-free conditions. We conclude that NMDA receptors are active in cells held at −70 mV even in the presence of 1 mM Mg2+. We believe this activation is due to the presence of endogenous glutamate in the retina. The observations of this study strongly suggest that NMDA receptors contribute to the resting noise and conductance properties of retinal ganglion cells. Our results suggest NMDA receptors are activated by an ambient level of extracellular glutamate whose source has yet to be determined.

Neural activity in the optic tectum was compared with activity in the nucleus isthmi (NI) of both goldfish and sunfish with the aim of understanding how the two brain structures interact to process visual information. The two species yielded very similar results. Superficial tectum responds reliably to visual stimulation with topographically organized receptive fields; deep tectum and NI respond to stimulation throughout the field of the contralateral eye and habituate rapidly. Bursts of large-amplitude spiking in NI occur spontaneously and in response to contralateral visual stimulation. These NI bursts correlate with activity bursts across the tectal lobe on the same side, especially in the deeper layers. NI bursts may also synchronize with spiking activity in deep tectum. Trains of small-amplitude spikes in NI can be elicited by both ipsilateral and contralateral stimulation, but are not reflected in tectal activity. Simultaneous recordings from two sites in one NI were almost identical, suggesting that NI operates as a functional unit, broadcasting the same message across the ipsilateral tectal lobe.

MacDRP is a Macintosh application that calculates Density Recovery Profiles.