The entire population of ganglion cells in the retina of the toad Bufo marinus was labeled by retrograde transport of a lysine-fixable biotinylated dextran amine of 3000 molecular weight. Synaptic connections between bipolar, amacrine, and ganglion cells in the inner plexiform layer were quantitatively analyzed, with emphasis on synaptic inputs to labeled ganglion cell dendrites. Synapses onto ganglion cell dendrites comprised 47% of a total of 1234 identified synapses in the inner plexiform layer. Approximately half of the bipolar or amacrine cell synapses were directed onto ganglion cell dendrites, while the rest were made mainly onto amacrine cell dendrites. Most of the synaptic inputs to ganglion cell dendrites derived from amacrine cell dendrites (84%), with the rest from bipolar cell terminals. Synaptic inputs to ganglion cell dendrites were distributed relatively uniformly throughout all sublaminae of the inner plexiform layer. The present study provides unambiguous identification of ganglion cell dendrites including very fine processes, enabling a detailed analysis of the types and distribution of synaptic inputs from the bipolar and amacrine cell to the ganglion cells. The retrograde tracing technique used in the present study will prove to be a useful tool for identifying synaptic inputs to ganglion cell dendrites from neurochemically identified bipolar and amacrine cell types in the retina.

In the frog optic tectum, the spatiotemporal pattern of neuronal activity evoked by electrical stimulation of the optic tract was examined by means of a current source density (CSD) analysis. The CSD depth profile was highly reproducible in different experiments. In all seven CSD profiles, three current sinks A, B, and D were observed in the retinorecipient layers. Four out of the seven profiles show additional two sinks C and E below the retinorecipient layers. Very small and short lasting sinks related to afferent fiber activities precede sinks A and B by about 1 ms, which could be accounted for by monosynaptic delay, in the corresponding depth region. The earliest prominent sink A at the bottom of the retinorecipient layers reflects only excitatory monosynaptic activities derived from R3 and/or R4 retinal ganglion cells. The second prominent sink B in the superficial retinorecipient layer is composed partly of excitatory monosynaptic activity from medium-sized myelinated optic fibers. It may involve excitatory monosynaptic activity from unmyelinated optic fibers and further polysynaptic activity. The fourth prominent sink D in the intermediate retinorecipient layer partially reflects excitatory monosynaptic activity derived from unmyelinated optic fibers. It may also involve further polysynaptic activity. In contrast with these three sinks, the third prominent sink C and fifth sink E exclusively reflect intratectal polysynaptic activity that has not been reported in any previous CSD studies in the frog optic tectum. These sinks almost overlap spatially in the tectal layer. We also measured the intratectal resistance changes and computed inhomogeneous CSD depth profiles to show that the results from homogeneous CSD computation assuming constant conductivity are valid for our present study. Finally, we compared the present results with previously reported CSD studies on the frog optic tectum and discuss consistencies and discrepancies among these experiments.

During locomotion, observers respond to objects in the environment that may represent obstacles to avoid or landmarks for navigation. Although much is known about how visual cortical neurons respond to stimulus objects moving against a blank background, nothing is known about their responses when objects are embedded in optic flow fields (the patterns of motion seen during locomotion). We recorded from cells in the lateral suprasylvian visual area (LS) of the cat, an area probably analogous to area MT. In our first experiments, optic flow simulations mimicked the view of a cat trotting across a plain covered with small balls; a black bar lying on the balls served as a target object. In subsequent experiments, optic flow simulations were composed of natural elements, with target objects representing bushes, rocks, and variants of these. Cells did not respond to the target bar in the presence of optic flow backgrounds, although they did respond to it in the absence of a background. However, 273/423 cells responded to at least one of the taller, naturalistic objects embedded in optic flow simulations. These responses might represent a form of image segmentation, in that cells detected objects against a complex background. Surprisingly, the responsiveness of cells to objects in optic flow fields was not correlated with preferred direction as measured with a moving bar or whole-field texture. Because the direction of object motion was determined solely by receptive-field location, it often differed considerably from a cell's preferred direction. About a quarter of the cells responded well to objects in optic flow movies but more weakly or not at all to bars moving in the same direction as the object, suggesting that the optic flow background modified or suppressed direction selectivity.

Gamma-aminobutyric acid (GABA) modulates the pattern of correlated spontaneous bursting activity between amacrine cells and ganglion cells of the ferret retina during the first postnatal month. Here, we demonstrate the presence of an anatomical network which may underlie these interactions throughout the period when correlated bursting activity is observed, by immunolabelling the neonatal ferret retina for GABA, GABAA receptors, and synapse-associated proteins. GABA immunoreactivity was detected in cell somata in the ganglion cell layer (GCL), in amacrine cells, and in the inner plexiform layer (IPL) by embryonic day 38. This pattern remained largely unchanged throughout neonatal development and in the adult. By contrast to other mammals, the outer plexiform layer (OPL) was only very weakly labelled for GABA, at all ages studied. Strong, punctate, immunolabelling for the β2/3 subunit of the GABAA receptor was apparent in the IPL by birth, and appeared in the OPL by the second postnatal week. The possibility that synaptic interactions in the IPL occur during bursting activity was examined by immunolabelling for synapse-associated proteins. Strong immunoreactivity for synaptic vesicle proteins, Synapsin I and II, and synaptic vesicle-2 (SV2), a synaptic vesicle transporter protein, was observed in the IPL by birth. Immunoreactivity for SNAP-25, a protein associated with vesicle fusion, was also intense at the level of the IPL and in the nerve fiber layer of the retina at birth. Taken together, these patterns of immunoreactivity suggest the presence of a GABAergic network in the IPL of the ferret retina by birth, coinciding with the appearance of correlated bursting activity in the inner retina.

Immunocytochemistry and retrograde labeling were used to define the thalamic projections of calbindin- and parvalbumin-containing cells in superficial layers of the rat's superior colliculus (SC). Quantitative analysis revealed that 90.8 ± 2.2% (mean ± standard deviation) of the calbindin-immunoreactive neurons in the stratum griseum superficiale (SGS) projected to the dorsal lateral geniculate nucleus (LGNd) and that 91.3 ± 4.3% of calbindin-immunoreactive neurons in the stratum opticum (SO) projected to the lateral posterior nucleus (LP). In contrast, only 17.3 ± 2.5% of parvalbumin-immunoreactive neurons in the SGS were found to project to the LGNd and 16.5 ± 3.1% of the parvalbumin-immunoreactive SO cells were retrogradely labeled after LP injections. Few of the parvalbumin-immunoreactive neurons in either the SGS (7.2 ± 2.5%) or the SO (9.2 ± 2.5%) were GABA positive. The retrograde-labeling results suggest that parvalbumin-immunoreactive neurons in the rat's SO and SGS may either be primarily interneurons or have descending projections, while calbindin-containing cells are primarily thalamic projection neurons. These results are consistent with data from other rodents, but almost exactly the opposite of data that have been reported for the cat for these same populations of SC projection neurons. Such interspecies differences raise questions regarding the functional importance of expressing one calcium-binding protein versus another in a specific neuronal population.

Unilateral eyelid suture, a model for amblyopia induced by congenital cataract, produces shrinkage of the deprived eye's ocular dominance columns in the striate cortex. Loss of geniculocortical projections are thought to account for the poor vision in the amblyopic eye. It is uncertain whether ocular dominance columns become shrunken in other forms of amblyopia. We examined the striate cortex in a pigtailed macaque with natural anisometropia discovered at age 5 months. Amblyopia in the left eye was documented at 1 year by behavioral testing. At age 6 years, the left eye was injected with [3H]proline and the striate cortex was processed for autoradiography and cytochrome oxidase (CO). The ocular dominance columns in layer IVc labelled with [3H]proline were normal. CO staining showed a novel pattern of thin dark bands in layer IV. These bands occupied the core zones at the center of the ocular dominance columns. Their appearance resulted from relative loss of CO activity along the borders of the ocular dominance columns, regions specialized for binocular processing. These findings indicate that not all forms of amblyopia are accompanied by shrinkage of ocular dominance columns. The unusual pattern of CO staining in layer IVc reflected a subtle alteration in metabolic activity which may have resulted from impairment of binocular function in anisometropic amblyopia.

We characterized the light response, morphology, and receptive-field structure of a distinctive amacrine cell type (Dacey, 1989), termed here the Al amacrine, by applying intracellular recording and staining methods to the macaque monkey retina in vitro. A1 cells show two morphologically distinct components: a highly branched and spiny dendritic tree, and a more sparsely branched axon-like tree that arises from one or more hillock-like structures near the soma and extends for several millimeters beyond the dendritic tree. Intracellular injection of Neurobiotin reveals an extensive and complex pattern of tracer coupling to neighboring A1 amacrine cells, to two other amacrine cell types, and to a single ganglion cell type. The A1 amacrine is an ON-OFF cell, showing a large (10–20 mV) transient depolarization at both onset and offset of a photopic, luminance modulated stimulus. A burst of fast, large-amplitude (Σ60 mV) action potentials is associated with the depolarizations at both the ON and OFF phase of the response. No evidence was found for an inhibitory receptive-field surround. The spatial extent of the ON-OFF response was mapped by measuring the strength of the spike discharge and/or the amplitude of the depolarizing slow potential as a function of the position of a bar or spot of light within the receptive field. Receptive fields derived from the slow potential and associated spike discharge corresponded in size and shape. Thus, the amplitude of the slow potential above spike threshold was well encoded as spike frequency. The diameter of the receptive field determined from the spike discharge was Σ10% larger than the spiny dendritic field. The correspondence in size between the spiking receptive field and the spiny dendritic tree suggests that light driven signals are conducted to the soma from the dendritic tree but not from the axon-like arbor. The function of the axon-like component is unknown but we speculate that it serves a classical output function, transmitting spikes distally from initiation sites near the soma.

We investigated a putative local angiotensin II (AngII) system in the rabbit retina by examining AngII contents in the retina, vitreous humor, and choroid by radioimmunoassays and AngII synthesis in the retina and choroid by detection of angiotensin converting enzyme (ACE) mRNA. An antibody directed against AngII was used to localize possible cellular sources of AngII in the retina. To enhance immunoreactivity and to further examine AngII metabolism, tissues were preincubated in medium containing either protease inhibitors (PI), PI together with the AngII-precursor AngI, or PI and AngII. In some experiments the conversion of AngI to AngII was blocked by an ACE inhibitor. AngII concentration in the vitreous humor was only about 10% of the plasma concentration; in the retina and the choroid, however, AngII concentrations were 10 and 86 times higher, respectively, than in the plasma. ACE mRNA was present in both retina and choroid. Immunohistochemistry for AngII revealed faintly labeled amacrine cells at the inner border of the inner nuclear layer of the retina. Preincubation with PI resulted in an enhanced immunoreaction and in the labeling of fibers in the inner and outer plexiform layer; Müller cells and their processes as well as ganglion cells were now stained as well but the specificity of ganglion cell staining remains questionable. The immunoreaction was further enhanced when AngI or AngII was added to the incubation medium, whereas labeling totally disappeared when the conversion of AngI to AngII was blocked. No immunoreactive cells were detected in the choroid. In conclusion, the synthesizing enzyme for AngII is expressed in the retina and a specific AngII concentration is maintained there; AngII is localized in distinct cell types and can be metabolized within these cells. These data point to a local retinal AngII system that is protected and independent of blood-borne AngII.

In the human eye, domination of the electroretinogram (ERG) by the b−wave and other postreceptor components ordinarily obscures all but the first few milliseconds of the rod photoreceptor response to a stimulating flash. However, recovery of the rod response after a bright test flash can be analyzed using a paired-flash paradigm in which the test flash, presented at time zero, is followed at time t by a bright probe flash that rapidly saturates the rods (Birch et al., 1995). In ERG experiments on normal subjects, the hypothesis that a similar method can be used to obtain the full time course of the rod response to test flashes of subsaturating intensity was tested. Rod-only responses to probe flashes presented at varying times t after the test flash were used to derive a family of amplitudes A(t) that represented the putative rod response to the test flash. These rod-only responses to the probe flash were obtained by computational subtraction of the cone-mediated component of each probe flash response. With relatively weak test flashes (11–15 scot-td-s), the time course of the rod response to the test flash derived in this manner was consistent with a four-stage impulse response function of time-to-peak ≃170 ms. A(170), the amplitude of the derived response at 170 ms, increased with test flash intensity (Itest) to a maximum value Amo and exhibited a dependence on Itest given approximately by the relation, A(170)/Amo = 1 - exp(-kItest), where k = 0.092 (scot-td-s)−1. In steady background light, the falling (i.e. recovery) phase of the derived response began earlier, and the sensitivity parameter k was reduced several-fold from its dark-adapted value. As the sensitivity, kinetics, and light-adaptation properties of the derived response correspond closely with those of photocurrent flash responses previously obtained from isolated rods in vitro, it was concluded that the response derived here from the human ERG approximates the course of the massed in vivo rod response to a test flash.

A descriptive function method was used to measure the detection, discrimination, and identification performance of a large population of single neurons recorded from within the primary visual cortex of the monkey and the cat, along six stimulus dimensions: contrast, spatial position, orientation, spatial frequency, temporal frequency, and direction of motion. First, the responses of single neurons were measured along each stimulus dimension, using analysis intervals comparable to a normal fixation interval (200 ms). Second, the measured responses of each neuron were fitted with simple descriptive functions, containing a few free parameters, for each stimulus dimension. These functions were found to account for approximately 90% of the variance in the measured response means and response standard deviations. (A detailed analysis of the relationship between the mean and the variance showed that the variance is proportional to the mean.) Third, the parameters of the best-fitting descriptive functions were utilized in conjunction with Bayesian (optimal) decision theory to determine the detection, discrimination, and identification performance for each neuron, along each stimulus dimension. For some of the cells in monkey, discrimination performance was comparable to behavioral performance; for most of the cells in cat, discrimination performance was better than behavioral performance. The behavioral contrast and spatial-frequency discrimination functions were similar in shape to the envelope of the most sensitive cells; they were also similar to the discrimination functions obtained by optimal pooling of the entire population of cells. The statistics which summarize the parameters of the descriptive functions were used to estimate the response of the visual cortex as a whole to a complex natural image. The analysis suggests that individual cortical neurons can reliably signal precise information about the location, size, and orientation of local image features.

The lateral geniculate nucleus (LGN) of primates contains three classes of relay cells, the magnocellular (M), parvocellular (P), and koniocellular (K) cells. At present, very little is known about either the structure or function of the K relay cells in New or Old World monkeys (simian primates). In monkeys, K cells are located between the main LGN layers and adjacent to the optic tract. For convenience, these intercalated cell layers are numbered K1-K4 starting closest to the optic tract with K1. The objective of this study was to examine the details of K axon morphology in the primary visual cortex (V1) of owl monkeys and to determine if different K layers give rise to distinct axon types. For this purpose, injections of WGA-HRP or PHA-L were made into specific K LGN layers and the distribution and morphology of the resulting labeled axons were analyzed. Injections of fluorescent tracers also were made within the superficial layers of V1 to further document connections via analysis of the patterns of retrogradely labeled cells in the LGN. Our main finding is that K axons in owl monkeys terminate as delicate focused arbors within single cytochrome oxidase (CO) blob columns in cortical layer III and within cortical layer I. Overall, the morphology of the K axons in these monkeys is quite similar to what we described previously for K geniculocortical axons in the distantly related bush baby (prosimian primate), suggesting that the basic features of this pathway are common to all primates. Our results also provide evidence that the axon arbors from different K layers are morphologically distinct; axons from LGN layer K1 project mainly to cortical layer I, while axons from LGN layer K3 chiefly terminate in cortical layer III. Taken together, these results imply that the basic features of axons within the K pathway are conserved across primates, and that the K axons from different K layers are likely to differ in function based upon their different morphologies.

The phototransduction cascade in invertebrates involves the coupling of rhodopsin activation to the action of the enzyme phospholipase C. This step is performed by G-proteins. An antibody against the α-subunit of a mouse Gq type G-protein recognized protein bands in Western blots of lateral eye and ventral nerve photoreceptors of Limulus. The protein bands had an apparent molecular mass of about 42 kDa. The antibody also recognized protein bands of a similar molecular mass in immunoblots of brain and intestine tissue. Immunoreactivity was found in lateral eye frozen sections where it was confined to the rhabdom region. When the antibody was applied to ultrathin sections of ventral nerve photoreceptors, the highest density of labeling was found on the rhabdomeral microvilli, but gold particles were also scattered in the cytoplasm. We conclude that a G-protein of the type Gq participates in the phototransduction of Limulus.

The compound eye of the tobacco hornworm moth Manduca sexta contains green-, blue-, and ultraviolet-sensitive photoreceptors. Electroretinogram spectral-sensitivity measurements were recorded from different regions of the retina in order to broadly map the distribution of the three receptor types. The relative contribution of the three receptors to spectral-sensitivity curves was estimated by fitting theoretical curves based on the absorption spectra of the three rhodopsins. This analysis indicated that the dorsal retina is green and ultraviolet dichromatic, with green-sensitive cells greatly predominating. The ventral retina is trichromatic with a substantial population of blue- and ultraviolet-sensitive receptors. We previously showed that flower visitation for nectar feeding is mediated mainly by blue-sensitive cells. Their localization in the ventral retina seems an appropriate adaptation of the receptor mosaic, since the moths hover above flowers as they feed.

Population-based studies of ganglion cells in retinal flatmounts have helped to reveal some of their natural types in mammals, teleost fish and, recently, the aquatic mesobatrachian frog Xenopus laevis. Here, ganglion cells of the semiterrestrial neobatrachian frogs Rana esculenta and Rana pipiens have been studied similarly. Ganglion cells with large somata and thick dendrites could again be divided into three mosaic-forming types with distinctive stratification patterns. Cell dimensions correlated inversely with density, being smallest in the visual streak. Cells of the αa mosaic (<0.2% of all ganglion cells) had the largest somata at each location (often displaced) and their trees were confined to one shallow plane within sublamina a of the inner plexiform layer. In regions of high regularity, many trees were symmetric. Elsewhere, asymmetric, irregular trees predominated and their dendrites, although sparsely branched, achieved consistent coverage by intersecting in complex ways. Cells of the αab mosaic were more numerous (≈0.7%) and had large somata, smaller (but still large) trees, and dendrites that branched extensively in two separate shallow planes in sublaminae a and b. The subtrees did not always match in symmetry, and each subtree tessellated independently with its neighbors. Cells of the αc mosaic (≈0.1%) had large, orthotopic somata and large, sparse trees (often asymmetric and irregular) close to the ganglion cell layer. Nearest-neighbor analyses and spatial correlograms confirmed that each mosaic was regular and independent. Densities, proportions, sizes, and mosaic statistics are tabulated for all three types, which are compared with types defined by size and symmetry in R. pipiens, by discriminant analysis in R. temporaria, by physiological response in both, and by mosaic analysis in Xenopus and several teleosts. The variable stratification of these otherwise similar types across species is consistent with other evidence that stratification may be determined, in part, by functional interactions.

The perception of dynamic random-dot stereograms (RDS) depends on the physiological fusion of horizontally disparate binocular visual input. Thus, the use of RDS offers the possibility to study selectively cortical processing of visual information in man. We investigated the influence of horizontal disparity on the scalp topography of RDS evoked brain activity in 33 healthy subjects. Stereoscopic checkerboard patterns were presented in the center or lateralized in the left or right visual field with horizontal disparities changing at temporal frequencies of six or eight depth reversals/s using different disparity values ranging from 3.5 to 28 min of arc. In 11 subjects evoked potential fields were recorded from 16 electrodes, and 21 subjects participated in 30-channel recordings with electrodes located over the parietal and occipital brain areas. Stimulation frequency-related brain activity was obtained with all disparity values; however, with large or small disparities the potential field strength decreased significantly while largest responses were obtained with intermediate disparities. Significant differences were observed in RDS evoked brain activity when central and lateralized stimulus locations were compared. With lateral stimuli (extending from the fovea to 17.1-deg eccentricity) maximal amplitudes were obtained at larger disparities than with central stimuli. In addition there were pronounced differences between brain activity evoked with stimuli presented in the left or right visual field; however, there were very similar evoked potential signals recorded from electrodes located over the left and right hemispheres. Our findings indicate that the processing of disparity information with lateralized stimuli is different from the processing in the center of the visual field. In addition, lateralized stimulation yields a significant disparity tuning mainly with stereoscopic targets occurring to the right from the fixation point (but not with stimuli to the left) suggesting a functional difference between the visual half-fields.

Macaque monkeys are widely used as a model species for investigations of the biology of human vision. Previous measurements suggest that the cone-based spectral sensitivity of these two primates is greatly similar, but perhaps not identical. We measured the photopic spectral sensitivity of 42 male macaque monkeys from two species (Macaca mulatto, M. fascicularis) using an objective index, electroretinogram flicker photometry. The variations among individuals and between the two species were very small and there was no evidence for any significant cone pigment polymorphism in this sample. There are small but systematic differences in spectral sensitivity between macaque monkeys and equivalently tested human subjects–the monkeys were slightly more sensitive to short wavelengths (<520 nm) and slightly less sensitive to wavelengths longer than this value. The results obtained from the curve fitting of standard photopigment absorption spectra to the spectral-sensitivity functions suggest that the difference between human and macaque monkey spectral sensitivity principally reflects differences in the relative proportions of the long- and middle-wavelength cones in the retinas of the two species.

The developing cerebral cortex is likely to exhibit synaptic circuitries differing from those in adulthood, due to the asynchronous maturation of the various neurotransmitter systems. Two antisera directed against mammalian β-adrenergic receptors (βAR), βAR248 and βAR404, were used to characterize the laminar, cellular, and subcellular distributions of βAR in postnatally developing visual cortex of rats. The antigenic sites were the receptor's third intracellular loop for βAR248 and the C-terminus for βAR404. During week 1, most of the βAR404- and βAR248-immunoreactive sites were dendritic. Morphologically identifiable synapses were rare, even in layer 1: yet, semiquantitative analysis revealed that βAR404-immunoreactive synapses comprise half of those in layer 1. During week 2, the two antisera began to diverge in their immunoreactivity patterns. With βAR248, there was an overall decline in immunoreactivity, while with βAR404, there was an increase in immunoreactive sites, primarily due to labeled astrocytic processes that increased 200-fold in areal density by week 3. In contrast, the areal density of synaptic labeling by βAR404 barely doubled, in spite of the 30-fold increase in areal density of synapses. These results suggest that βAR undergo conformational changes during early postnatal periods, causing alterations in their relative antigenicity to the two antisera. Furthermore, the first 2 weeks appear to be characterized by modulation of earliest-formed synapses, and the subsequent phase is marked by addition of astrocytic responses that would be more diffuse temporally and spatially. Activation of βAR is recognized to increase visually evoked activity relative to spontaneous activity. Moreover, astrocytic βAR are documented to regulate extracellular concentrations of glutamate, ATP, and neurotrophic factors important for the formation of binocular connections. Thus, neuronal and astrocytic responses may, together and in tandem, facilitate strengthening of intracortical synaptic circuitry during early life.

Tyrosine hydroxylase (TH) expression was used as a marker to study the dopaminergic cells in the Cebus monkey retina. Two types of dopaminergic cells were identified by cell body size and location, level of arborization in the inner plexiform layer, and amount of immunolabeling. Type 1 cells displayed intense immunoreactivity and larger somata (12–24 μm) located in the inner nuclear layer or ganglion cell layer, whereas type 2 had smaller cell bodies (8–14 μm) found either in the inner plexiform layer or ganglion cell layer and were more faintly labeled. Interplexiform cells were characterized as type 1 dopaminergic cells. Immunoreactive axon-like processes were seen in the nerve fiber layer, and a net of fibers was visible in the foveal pit and in the extreme periphery of the retina. The population of TH+ cells was most numerous in the temporal superior quadrant and its density peaked at 1–2 mm from the fovea. Type 1 TH+ cells were more numerous than type 2 cells at any eccentricity. Along the horizontal meridian, type 1 cell density was slightly higher in temporal (29 cells/mm2) than in nasal (25 cells/mm2) retina, while type 2 cells had a homogeneous distribution (4.5 cells/mm2). Along the vertical meridian, type 1 cells reached lower peak density (average 17.7 cells/mm2) in the inferior retina (central 4 mm), compared to the superior portion (23.7 cells/mm2). Type 2 cell density varied from 4.5 cells/mm2 in the superior region to 9.4 cells/mm2 in the inferior region. The spatial density of the two cell types varied approximately inversely while the total density of TH+ cells was virtually constant across the retina. No correlation between dopaminergic cells and rod distribution was found. However, we suggest that dopaminergic cells could have a role in mesopic and/or photopic vision in this species, since TH+ fibers are present in cone-dominated regions like the foveola and extreme nasal Periphery.

Single neurons were recorded in cat primary visual cortex, and the effect of iontophoresis of the metabotropic glutamate agonist 1S,3R-aminocyclopentane-1.3-dicarboxylic acid (ACPD) was observed. In nearly all cases (41/43), ACPD reduced the visual response. In some cases ACPD also reduced spontaneous activity (24/43), and in other cases ACPD increased spontaneous activity (18/43). Increases were generally seen in infragranular layers (V and VI), and decreases in supragranular layers (II and III). The reduction in the visual response was also largest in supragranular layers. We conclude that activation of metabotropic glutamate receptors has both facilitatory and depressive effects in visual cortex, and the effect depends on the layer of the cell recorded.

In almost every study of the linearity of spatiotemporal summation in simple cells of the cat's visual cortex, there have been systematic mismatches between the experimental observations and the predictions of the linear theory. These mismatches have generally been explained by supposing that the initial spatiotemporal summation stage is strictly linear, but that the following output stage of the simple cell is subject to some contrast-dependent nonlinearity. Two main models of the output nonlinearity have been proposed: the threshold model (e.g. Tolhurst & Dean, 1987) and the contrast-normalization model (e.g. Heeger, 1992a, b). In this paper, the two models are fitted rigorously to a variety of previously published neurophysiological data, in order to determine whether one model is a better explanation of the data. We reexamine data on the interaction between two bar stimuli presented in different parts of the receptive field; on the relationship between the receptive-field map and the inverse Fourier transform of the spatial-frequency tuning curve; on the dependence of response amplitude and phase on the spatial phase of stationary gratings; on the relationships between the responses to moving and modulated gratings; and on the suppressive action of gratings moving in a neuron's nonpreferred direction. In many situations, the predictions of the two models are similar, but the contrast-normalization model usually fits the data slightly better than the threshold model, and it is easier to apply the equations of the normalization model. More importantly, the normalization model is naturally able to account very well for the details and subtlety of the results in experiments where the total contrast energy of the stimuli changes; some of these phenomena are completely beyond the scope of the threshold model. Rigorous application of the models' equations has revealed some situations where neither model fits quite well enough, and we must suppose, therefore, that there are some subtle nonlinearities still to be characterized.