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The cat perigeniculate nucleus (PGN) is a visual sector of the thalamic reticular nucleus that consists of GABAergic neurons. It receives excitatory axon-collateral input from relay neurons of the dorsal lateral geniculate nucleus (LGN) to which it provides inhibitory input. Thus, it is usually argued that the PGN works as feedback inhibition to the LGN. At the single neuron level, however, this circuit can also provide lateral inhibition. Which inhibition dominates in the visual circuit of the thalamus has yet to be well characterized. In this study, we conducted cross-correlation analysis of single spike trains simultaneously recorded from PGN and LGN neurons in anesthetized cats. For 12 pairs of functionally connected PGN and LGN neurons with overlapped receptive fields (RF), we quantitatively compared RF properties including the spatial frequency (SF) and temporal frequency (TF) tunings of each neuron. We found the SF and TF tunings of PGN neurons and LGN neurons were similar when there was only excitatory input from the LGN neuron to the PGN neuron, but different when the PGN neuron returned inhibitory inputs back, suggesting the circuit between PGN and LGN neurons works as lateral inhibition for these properties.

In the primary visual cortex (V1), the spike synchronization seen in neuron pairs with non-overlapping receptive fields can be explained by similarities in their preferred orientation (PO). However, this is not true for pairs with overlapping receptive fields, as they can still exhibit spike synchronization even if their POs are only weakly correlated. Here, we investigated the relationship between spike synchronization and suppressive modulation derived from classical receptive-field surround (surround suppression). We found that layer 4 and layer 2/3 pairs exhibited mainly asymmetric spike synchronization that had non-zero time-lags and was dependent on both the similarity of the PO and the strength of surround suppression. In contrast, layer 2/3 and layer 2/3 pairs showed mainly symmetric spike synchronization that had zero time-lag and was dependent on the similarity of the strength of surround suppression but not on the similarity in POs. From these results, we propose that in cat V1 there exists a functional network that mainly depends on the similarity in surround suppression, and that in layer 2/3 neurons the network maintains surround suppression that is primarily inherited from layer 4 neurons.

It is generally thought that orientation selectivity first appears in the primary visual cortex (V1), whereas neurons in the lateral geniculate nucleus (LGN), an input source for V1, are thought to be insensitive to stimulus orientation. Here we show that increasing both the spatial frequency and size of the grating stimuli beyond their respective optimal values strongly enhance the orientation tuning of LGN neurons. The resulting orientation tuning was clearly contrast-invariant. Furthermore, blocking intrathalamic inhibition by iontophoretically administering γ-aminobutyric acid (GABA)A receptor antagonists, such as bicuculline and GABAzine, slightly but significantly weakened the contrast invariance. Our results suggest that orientation tuning in the LGN is caused by an elliptical classical receptive field and orientation-tuned surround suppression, and that its contrast invariance is ensured by local GABAA inhibition. This contrast-invariant orientation tuning in LGN neurons may contribute to the contrast-invariant orientation tuning seen in V1 neurons.

The brain dynamically changes its input-output relationship depending on the behavioral state and context in order to optimize information processing. At the molecular level, cholinergic/monoaminergic transmitters have been extensively studied as key players for the state/context-dependent modulation of brain function. In this paper, we review how cortical visual information processing in the primary visual cortex (V1) of macaque monkey, which has a highly differentiated laminar structure, is optimized by serotonergic and cholinergic systems by examining anatomical and in vivo electrophysiological aspects to highlight their similarities and distinctions. We show that these two systems have a similar layer bias for axonal fiber innervation and receptor distribution. The common target sites are the geniculorecipient layers and geniculocortical fibers, where the appropriate gain control is established through a geniculocortical signal transformation. Both systems exert activity-dependent response gain control across layers, but in a manner consistent with the receptor subtype. The serotonergic receptors 5-HT1B and 5HT2A modulate the contrast-response curve in a manner consistent with bi-directional response gain control, where the sign (facilitation/suppression) is switched according to the firing rate and is complementary to the other. On the other hand, cholinergic nicotinic/muscarinic receptors exert mono-directional response gain control without a sign reversal. Nicotinic receptors increase the response magnitude in a multiplicative manner, while muscarinic receptors exert both suppressive and facilitative effects. We discuss the implications of the two neuromodulator systems in hierarchical visual signal processing in V1 on the basis of the developed laminar structure.

Surround suppression is a phenomenon whereby stimulation of the extraclassical receptive field suppressively modulates the visual responses of neurons in the primary visual cortex (V1) (also known as area 17). It is known that surround suppression tunes to spatial frequencies (SFs) that are much lower and broader than the frequencies to which the classical receptive field tunes. In this study, we tested the effects of varying SFs on surround suppression by using a circular sinusoidal grating patch that covered both the classical receptive field and the extraclassical receptive field. Using area-summation tuning curves, we found high-SF-tuned surround suppression in the cat V1. This high-SF-tuned surround suppression causes the SF tuning to shift to low SF for large stimuli. By simulating a model neuron lacking a suppressive surround mechanism, we confirmed that these preferred SF shifts do not occur in the absence of surround suppression. We surmise that the high-SF-tuned suppression, which shifts the preferred SF according to size, functionally contributes to the scale-invariant processing of visual images in V1.

In primary visual cortex (V1) neurons, a stimulus placed in the extraclassical receptive field suppresses the response to a stimulus within the classical receptive field (CRF), a phenomenon referred to as surround suppression. The aim of the present study was to elucidate the mechanisms of surround suppression in V1. Using stationary-flashed sinusoidal grating as stimuli, we observed temporal changes of surround suppression in V1 and the lateral geniculate nucleus (LGN) and of the response to CRF stimulation in V1. The spatial frequency (SF) tuning of surround suppression in V1 neurons changed over time after the stimulus onset. In the early phase (< 50 ms), the SF tuning was low-pass, but later became band-pass that tuned to the optimal SF in response to CRF stimulation. On the other hand, the SF tuning of CRF responses in V1 was band-pass throughout the response time whereas the SF peak shifted slightly toward high SF. Thus, SF tuning properties of the CRF response dissociated from that of surround suppression in V1 only in the early phase. We also confirmed that the temporal changes of the SF tuning of surround suppression in the LGN occurred in the same direction as surround suppression in V1, but the shift from low-pass to band-pass SF tuning started later than that in V1. From these results, we suggest that subcortical mechanisms contribute to early surround suppression in V1, whereas cortical mechanisms contribute to late surround suppression.

In the primary visual cortex (V1), the response of a neuron to stimulation of its classical receptive field (CRF) is suppressed by concurrent stimulation of the extraclassical receptive field (ECRF), a phenomenon termed 'surround suppression'. It is also known that the orientation tuning of V1 neurons becomes sharper as the size of the stimulus increases beyond the CRF. However, there have been few quantitative investigations of the relationship between sharpening of orientation tuning and surround suppression. We examined this relationship in 73 V1 neurons recorded from anesthetized and paralysed cats using sinusoidal grating patches as stimuli. We found that sharpening of orientation tuning was significantly correlated with the strength of surround suppression for large stimuli that cover both CRF and ECRF. Furthermore, simulation analysis using a variety of tuning widths and most suppressive orientation of orientation-tuned surround suppression demonstrated that broadly orientation-tuned surround suppression sharpens orientation tuning for large gratings without shift in optimal orientation. Our findings suggest that one of the functional roles of surround suppression in V1 is enhancement of orientation discrimination for large and uniformly patterned objects.

To study the molecular mechanism how cortical areas are specialized in adult primates, we searched for area-specific genes in macaque monkeys and found striking enrichment of serotonin (5-hydroxytryptamine, 5-HT) 1B receptor mRNA, and to a lesser extent, of 5-HT2A receptor mRNA, in the primary visual area (V1). In situ hybridization analyses revealed that both mRNA species were highly concentrated in the geniculorecipient layers IVA and IVC, where they were coexpressed in the same neurons. Monocular inactivation by tetrodotoxin injection resulted in a strong and rapid (

We examined the spatiotemporal characteristics of metacontrast using sinusoidal grating stimuli as the target and mask for quantitative comparison with the functional properties of the visual cortex. The magnitude of metacontrast effects depended on the stimulus features such as the orientation and spatial frequency of the target and mask. The characteristics of metacontrast dynamically changed depending on the stimulus onset asynchrony (SOA). At short SOAs (0 to approximately 40 ms), metacontrast exhibited a high stimulus feature specificity and a low contrast sensitivity, whereas at long SOAs ( approximately 40 to 80 ms), metacontrast exhibited a low stimulus feature specificity and a high contrast sensitivity. We suggest that metacontrast is explained by the interaction between two parallel visual pathways: one with a low contrast sensitivity and a high feature specificity, and the other with a high contrast sensitivity and a low feature specificity.

In the primary visual cortex (V1), the responses of neurons to stimuli presented in their classical receptive fields (CRFs) are modulated by another stimulus concurrently presented in their surround (receptive field surround, SRF). We studied the nature of the modulatory effects of SRF stimulation with respect to stimulus contrast in cat V1. In 51 V1 neurons studied, large SRF stimuli (40 degreesx30 degrees ) induced only the suppression of responses to CRF stimulation and the suppressive effects became stronger as the contrast for SRF stimulation increased. The contrast sensitivity of SRF suppression did not correlate with that of CRF responses. By independently controlling contrast of CRF and SRF stimuli, we studied whether SRF effects vary with CRF response magnitude. Increasing contrast for CRF stimulation caused an upward shift of the range of effective contrasts for SRF stimulation, indicating that a high contrast for SRF stimulation is required for suppressing strong responses to CRF stimulation at high contrasts. To assess the possible origin of the suppressive SRF effect on V1 neurons, we also investigated the contrast dependency of SRF effects in 28 neurons from the lateral geniculate nucleus. Our results suggest that SRF effects obtained at the subcortical level strongly contribute to those in V1. Taken together, we conclude that along the thalamocortical projections, SRF modulation exhibits a gain-control mechanism that scales the suppressive SRF effect depending on the contrast for CRF stimulation. In addition, SRF effects can be facilitatory at low stimulus contrasts potentially due to the enlargement of the summation field.

In the primary visual cortex (V1), the single-neuron response to a grating stimulus placed in the classical receptive field (CRF) is suppressed by a similar stimulus presented in the CRF surround. To assess the input mechanism underlying the surround suppression, we tested the effects of iontophoretically administered GABAA-receptor antagonist, bicuculline methiodide (BMI), for the 46 V1 neurons in anesthetized cats. First, the stimulus-size tuning curves were studied, with or without BMI administration, for each neuron by changing the size of the grating patch. During the BMI administration, the shape of the normalized size tuning curve did not change considerably. Second, the dependency of surround suppression on the orientation of the surround grating was examined. In the control, the surround suppression showed the clear orientation tuning that peaked at an orientation the same as the optimal orientation of the CRF response. The BMI administration did not change the orientation dependency of surround suppression. We also estimated the relative contribution of excitation and inhibition to the size and orientation tuning of surround suppression. It was concluded that cortical excitation and inhibition were well balanced, having similar tuning profiles for both stimulus size and orientation of the surround grating. Furthermore, surround stimuli used for V1 neurons suppressed the CRF response of neurons in the lateral geniculate nucleus. These results suggest that surround suppression is not primarily attributable to the intracortical inhibition, but because of a reduction of thalamocortical inputs, which drive the cortical excitation and inhibition, and a subsequent decrease in the cortical excitatory interactions.

In the primary visual cortex (V1), a neuronal response to stimulation of the classical receptive field (CRF) is predominantly suppressed by a stimulus presented outside the CRF (extraclassical receptive field, ECRF), a phenomenon referred to as ECRF suppression. To elucidate the neuronal mechanisms and origin of ECRF suppression in V1 of anesthetized cats, we examined the temporal properties of the spatial extent and orientation specificity of ECRF suppression in V1 and the lateral geniculate nucleus (LGN), using stationary-flashed sinusoidal grating. In V1, we found three components of ECRF suppression: 1) local and fast, 2) global and fast, and 3) global and late. The local and fast component, which resulted from within 2° of the boundary of the CRF, started no more than 10 ms after the onset of the CRF response and exhibited low specificity for the orientation of the ECRF stimulus. These spatiotemporal properties corresponded to those of geniculate ECRF suppression, suggesting that the local and fast component of V1 is inherited from the LGN. In contrast, the two global components showed rather large spatial extents ∼5° from the CRF boundary and high specificity for orientation, suggesting that their possible origin is the cortex, not the LGN. Correspondingly, the local component was observed in all neurons of the thalamocortical recipient layer, while the global component was biased toward other layers. Therefore, we conclude that both subcortical and cortical mechanisms with different spatiotemporal properties are involved in ECRF suppression.

Acetylcholine (ACh) is known to modulate neuronal activity in the rodent primary visual cortex (V1). Although cholinergic modulation has been extensively examined in vitro, far less is understood regarding how ACh modulates visual information processing in vivo. We therefore extracellularly recorded visual responses to drifting sinusoidal grating stimuli from V1 of anesthetized rats and tested the effects of ACh administered locally by microiontophoresis. ACh exerted response facilitation or suppression in individual neurons across all cortical layers without any laminar bias. We assessed ACh effects on the stimulus contrast-response function, finding that ACh increased or decreased the response to varying stimulus contrasts in proportion to the magnitude of the control response without changing the shape of the original contrast-response function, which describes response gain control but not contrast gain control. Our results indicate that ACh serves as a gain controller in the visual cortex of rodents.

Acetylcholine (ACh) is secreted from cholinergic neurons in the basal forebrain to regions throughout the cerebral cortex, including the primary visual cortex (V1), and influences neuronal activities across all six layers via a form of diffuse extrasynaptic modulation termed volume transmission. To understand this effect in V1, we performed extracellular multi-point recordings of neuronal responses to drifting sinusoidal grating stimuli from the cortical layers of V1 in anesthetized rats and examined the modulatory effects of topically administered ACh. ACh facilitated or suppressed the visual responses of individual cells with a laminar bias: response suppression prevailed in layers 2/3, whereas response facilitation prevailed in layer 5. ACh effects on the stimulus contrast-response function showed that ACh changes the response gain upward or downward in facilitated or suppressed cells, respectively. Next, ACh effects on the signal-to-noise (S/N) ratio and the grating-phase information were tested. The grating-phase information was calculated as the F1/F0 ratio, which represents the amount of temporal response modulation at the fundamental frequency (F1) of a drifting grating relative to the mean evoked response (F0). In facilitated cells, ACh improved the S/N ratio, while in suppressed cells it enhanced the F1/F0 ratio without any concurrent reduction in the S/N ratio. These effects were predominantly observed in regular-spiking cells, but not in fast-spiking cells. Electrophysiological and histological findings suggest that ACh promotes the signaling of grating-phase information to higher-order areas by a suppressive effect on supragranular layers and enhances feedback signals with a high S/N ratio to subcortical areas by a facilitatory effect on infragranular layers. Thus, ACh distinctly and finely controls visual information processing in a manner that is specific for the modulation and cell type and is also laminar dependent.

Although it is thought that orientation selectivity first emerges in the primary visual cortex, several studies have reported that neurons in the cat lateral geniculate nucleus (LGN) are sensitive to stimulus orientation, especially for high spatial frequency (SF) stimuli. To understand how this orientation sensitivity emerges, we investigated the spatiotemporal structures of linear receptive fields (RFs) of LGN neurons. Orientation tunings at several SFs were measured using sinusoidal drifting grating stimuli. Fine spatiotemporal structures of the linear RFs were measured using a reverse correlation technique and two-dimensional dynamic Gaussian white noise stimuli. A non-linear response modulation function was estimated by comparing measured responses with responses predicted from a linear RF structure. Although we found that a population of LGN neurons exhibited significantly elongated linear RF centers and that the angles of the long axes corresponded well to the preferred orientations, the orientation tunings predicted from the linear RFs were significantly broader than those measured. These results suggest that orientation-tuned non-linear response modulation induced by stimulation outside the classical RF contributes to the sharp orientation tuning seen in LGN neurons.

ACh modulates neuronal activity throughout the cerebral cortex, including the primary visual cortex (V1). However, a number of issues regarding this modulation remain unknown, such as the effect and its function and the receptor subtypes involved. To address these issues, we combined extracellular single-unit recordings and microiontophoretic administration of ACh and measured V1 neuronal responses to drifting sinusoidal grating stimuli in anesthetized macaque monkeys. ACh was found to have mostly facilitatory effects on the visual responses, although some cases of suppressive effects were also seen. To assess the functional role of ACh, we further examined how ACh modulates the stimulus contrast-response function, finding that the response gain increased with the facilitatory effect. The response facilitation was completely or strongly blocked by atropine (At), a muscarinic ACh receptor (mAChR) antagonist, in almost all neurons (96% of cells), whereas any residual effect after At administration was fully removed by mecamylamine, a nicotinic AChR (nAChR) antagonist, suggesting a predominant role for mAChRs in this mechanism. Furthermore, we found no laminar distribution bias for the facilitatory modulation, although the relative contribution of mAChRs was smaller in layer 4C than in other layers. The suppressive effect was blocked completely by At. These results demonstrate that ACh plays an important role in visual information processing in V1 by controlling the response gain via mAChRs across all cortical layers and via nAChRs, mainly in layer 4C.

Surround suppression is a phenomenon whereby stimulation of the extraclassical receptive field suppressively modulates the visual responses of neurons in the primary visual cortex (V1) (also known as area 17). It is known that surround suppression tunes to spatial frequencies (SFs) that are much lower and broader than the frequencies to which the classical receptive field tunes. In this study, we tested the effects of varying SFs on surround suppression by using a circular sinusoidal grating patch that covered both the classical receptive field and the extraclassical receptive field. Using area-summation tuning curves, we found high-SF-tuned surround suppression in the cat V1. This high-SF-tuned surround suppression causes the SF tuning to shift to low SF for large stimuli. By simulating a model neuron lacking a suppressive surround mechanism, we confirmed that these preferred SF shifts do not occur in the absence of surround suppression. We surmise that the high-SF-tuned suppression, which shifts the preferred SF according to size, functionally contributes to the scale-invariant processing of visual images in V1.

In primary visual cortex (V1) neurons, a stimulus placed in the extraclassical receptive field suppresses the response to a stimulus within the classical receptive field (CRF), a phenomenon referred to as surround suppression. The aim of the present study was to elucidate the mechanisms of surround suppression in V1. Using stationary-flashed sinusoidal grating as stimuli, we observed temporal changes of surround suppression in V1 and the lateral geniculate nucleus (LGN) and of the response to CRF stimulation in V1. The spatial frequency (SF) tuning of surround suppression in V1 neurons changed over time after the stimulus onset. In the early phase (50 ms), the SF tuning was low-pass, but later became band-pass that tuned to the optimal SF in response to CRF stimulation. On the other hand, the SF tuning of CRF responses in V1 was band-pass throughout the response time whereas the SF peak shifted slightly toward high SF. Thus, SF tuning properties of the CRF response dissociated from that of surround suppression in V1 only in the early phase. We also confirmed that the temporal changes of the SF tuning of surround suppression in the LGN occurred in the same direction as surround suppression in V1, but the shift from low-pass to band-pass SF tuning started later than that in V1. From these results, we suggest that subcortical mechanisms contribute to early surround suppression in V1, whereas cortical mechanisms contribute to late surround suppression.

We have studied the effect of dark rearing on the development of excitatory amino acid transmission in 6-week-old kittens. In normal kittens, the NMDA component of the visual response decreases between 3 and 6 weeks of age for cells located in layers IV, V, and VI (Fox et al., 1991). Dark rearing to 6 weeks of age prevents this decrease. Subsequent exposure to light allows the decrease to proceed. Ten days in the light after 6 weeks in the dark was sufficient to decrease the NMDA component of the visual response to the same levels seen in light- reared animals of the same age. Comparison of the effect of the non- NMDA antagonist 6-cyano-7-dinitroquinoxaline-2,3-dione with the NMDA antagonist aminophosphonovalerate showed that the changes were due to the relative contributions of NMDA and non-NMDA receptors to the visual response rather than the overall contribution of glutamate receptors. We also studied the receptive field properties of the cells in the various groups of kittens. Cells given 4 d in the light after 6 weeks in the dark showed increased direction selectivity but little change in response firing rate. After 10 d in the light, visual responses did show some recovery toward adult values, but neither average firing rates nor the proportion of direction-selective cells reached the levels found in normal 6-week-old animals, contrary to the suggestion that a short period in the light can reverse the effect of dark rearing completely. These results show that the decrease in the NMDA component of the visual response seen during normal development of the cortex is caused by visual experience. Changes in NMDA receptors and developmental events such as geniculocortical afferent segregation and acquisition of orientation tuning covary as a function of visual experience rather than age, strongly suggesting that NMDA receptors are involved in experience-dependent developmental processes.

Stimulus-specific response properties, such as direction or orientation selectivity, were studied intracellularly in cells recorded from area 17 of the cat. In all 5 direction selective complex cells and one orientation selective simple cell successfully studied, visually evoked excitatory postsynaptic potentials (EPSPs) were tuned to the preferred direction or orientation. Visually evoked inhibitory postsynaptic potentials (IPSPs) were also tuned to the preferred direction/orientation of stimulus. IPSPs evoked by the non-preferred stimulus when present were smaller than those evoked by the preferred stimulus. IPSPs were undetected in two of the 5 cells tested. These results suggest that directionally/orientationally tuned EPSPs make a major contribution to stimulus specificity in visual cortical neurons but IPSPs evoked by a stimulus with null-direction/orientation may sharpen the stimulus specificity.

We previously suggested that orientation-tuned surround suppression of responses of cells in the primary visual cortex (V1) is primarily caused by a decrease in geniculocortical input for the cell [Ozeki H, Sadakane O, Akasaki T, Naito T, Shimegi S, Sato H (2004) Relationship between excitation and inhibition underlying size tuning and contextual response modulation in the cat primary visual cortex. J Neurosci 24:1428-1438]. To further test this hypothesis, we compared the strength of orientation and spatial phase selectivity of surround suppression, and the spatial extent of the extraclassical receptive field (ECRF) between the lateral geniculate nucleus (LGN) and V1 neurons of anesthetized cats. Extraclassical surround suppression in the LGN was well tuned to orientation-contrast and relative spatial phase between the classical receptive field (CRF) and ECRF stimuli. Significant orientation-tuned surround suppression was observed in 72.6% of the LGN neurons and the 66.7% of the V1 neurons tested. The degree of orientation selectivity of ECRF in LGN was comparable to that in V1; however, the strength of the relative spatial phase selectivity of ECRF in LGN was higher than that previously reported for V1 [Akasaki T, Sato H, Yoshimura Y, Ozeki H, Shimegi S (2002) Suppressive effects of receptive field surround on neuronal activity in the cat primary visual cortex. Neurosci Res 43:207-220; DeAngelis GC, Freeman RD, Ohzawa I (1994) Length and width tuning of neurons in the cat's primary visual cortex. J Neurophysiol 71:347-374]. In 70% of the LGN neurons that exhibited significant orientation-tuned extraclassical surround suppression, the effective orientation of the suppression varied according to a change in the orientation of CRF stimulus, while the remaining 30% exhibited a fixed preferred orientation of the suppression regardless of the orientation of the CRF grating. These results suggest that the basic properties of surround suppression, such as orientation and spatial phase tuning, already exist in cat LGN and that a decrease of surround suppression in excitatory inputs from LGN by surround suppression is the primary cause of surround suppression in V1. Corticogeniculate feedback may further elaborate the properties of surround suppression in LGN.

In the primary visual cortex (V1), the responses of neurons to stimuli presented in their classical receptive fields (CRFs) are modulated by another stimulus concurrently presented in their surround (receptive field surround, SRF). We studied the nature of the modulatory effects of SRF stimulation with respect to stimulus contrast in cat V1. In 51 V1 neurons studied, large SRF stimuli (40 degreesx30 degrees ) induced only the suppression of responses to CRF stimulation and the suppressive effects became stronger as the contrast for SRF stimulation increased. The contrast sensitivity of SRF suppression did not correlate with that of CRF responses. By independently controlling contrast of CRF and SRF stimuli, we studied whether SRF effects vary with CRF response magnitude. Increasing contrast for CRF stimulation caused an upward shift of the range of effective contrasts for SRF stimulation, indicating that a high contrast for SRF stimulation is required for suppressing strong responses to CRF stimulation at high contrasts. To assess the possible origin of the suppressive SRF effect on V1 neurons, we also investigated the contrast dependency of SRF effects in 28 neurons from the lateral geniculate nucleus. Our results suggest that SRF effects obtained at the subcortical level strongly contribute to those in V1. Taken together, we conclude that along the thalamocortical projections, SRF modulation exhibits a gain-control mechanism that scales the suppressive SRF effect depending on the contrast for CRF stimulation. In addition, SRF effects can be facilitatory at low stimulus contrasts potentially due to the enlargement of the summation field.

Monocular deprivation (MD) during the critical period for the development of visual cortex causes a loss of binocular response of neurons and a shift to the open eye, a normal ocular dominance (OD) shift. However, when MD is combined with chronic inactivation of the visual cortex by muscimol, the OD distribution of the neurons shifts to the deprived eye (reverse OD shift). We have previously shown that the normal OD shift is abolished by chronic infusion of the protein kinase A (PKA) inhibitor, 8-chloroadenosine-3′, 5′-cyclic monophosphorothioate, Rpisomer (Rp-8-Cl-cAMPS), into kitten visual cortex. In this study, we investigated the effect of this inhibitor on the reverse OD shift. Combination of MD and muscimol infusion into the visual cortex of 6-wk-old kittens caused a reverse OD shift that was comparable to that seen in previous studies. However, a reverse OD shift was also seen with concurrent infusion of the PKA inhibitor with muscimol. The strongest OD shift was observed in layer IV regardless of the presence or absence of the PKA inhibitor. This suggests that the dissociation of pre- and postsynaptic activities, which occurs mainly at thalamocortical synapses, induces the reverse OD shift and that inhibition of PKA does not prevent it. Presumably, an inhibition of PKA has no effect in silent cortex. We conclude that 1) an activation of PKA is not required for the induction of the reverse OD shift, and 2) the intracellular signaling mechanism underlying MD-induced OD plasticity differs between normal and reverse OD shifts.

Neurons of the primary visual cortex (V1) respond to stimuli presented at the classical receptive field (CRF), and the responses are suppressively modulated by stimuli simultaneously presented at the receptive field surround (SRF) [1, 2]. The response modulation by an SRF stimulus depends on the stimulus orientation and spatial frequency; thus, it was suggested that intracortical mechanisms contribute to this phenomenon [2]. We recently reported that this suppressive modulation is not due to a direct inhibition to the cell by the intracortical inhibition [3] (also see the chapter by H. Ozeki et al., this volume).

In neurons of the primary visual cortex (V1), the response to the grating stimulus presented in the classical receptive field (CRF) is suppressively modulated by the grating presented at the receptive field surround (SRF). This surround suppression (SS) depends on the relationship of stimulus parameters, such as orientation and spatial frequency, between the CRF and SRF gratings. The strength of SS depends on the stimulus contrast of both CRF and SRF. To assess the input mechanism underlying this stimulus-context-dependent suppression, we performed two series of experiments on the contribution of intracortical inhibition to SS and the nature of the contrast-gain control mechanism of SS.

To assess the network dynamics in the primary visual cortex, we performed simultaneous recordings of neuronal activity from cell pairs within 1 mm apart in anesthetized and paralyzed cats. Cross-correlograms (CCs) were calculated for the responses to grating stimuli with varying orientations and sizes for the 30 cell pairs to date. There were three patterns of cell pairs in respect of tuning property to stimulus sizes. First, both cells exhibited strong suppression of firings with stimuli larger than their classical receptive field (CRF). Second, only one cell exhibited suppression to the large stimuli while the other did not. In these two patterns, the contribution of the peak CCs became smaller when the grating stimulus was larger than the CRFs. And third, both cells did not significantly reduce activity to the grating patch larger than their CRFs. In this case, the peak contribution in CCs did not vary with an increase of the stimulus size. We concluded that the strength of firing interaction is positively correlated with the change in firing rate of cell pairs because of the change of stimulus sizes. We also analyzed CCs in respect of orientation preference of cell pairs. Although the significant peak CCs were most often observed for the common and optimal orientation of the cell pairs, there were some pairs that showed strong peaks for the nonpreferred orientation (more than 60° apart from the optimal) of stimulus, which evoked responses with low firing levels. This result suggests that the strength of firing correlation of cell pairs does not simply depend on the firing rate when the stimulus orientation is varied.

The response of neurons in the primary visual cortex (V1) is modulated by the stimulus presented at the surround of the classical receptive field (CRF), and the predominant effect of this surround stimulation is suppressive [1–5]. The strength of the surround suppression is dependent on the relationship of stimulus parameters, such as orientation and spatial frequency, between grating stimuli at the inside and outside of the CRF [1, 2]. Although properties of the surround suppression have been well characterized, input mechanisms underlying the stimulus-context-dependent response modulation and the size-tuning properties of V1 neurons have not been clarified yet. There is evidence that the surround suppression in VI is both sub-cortical [5] and intracortical [2, 4] in origin.

Effects of sinusoidal grating stimulus presented outside the classical receptive field (CRF) on neuronal responses were studied in the primary visual cortex of anaesthetized cats. Among 101 cells electrophysiologically recorded, the predominant effect of the stimulus in the receptive field surround (SRF) was the suppression of responses to the CRF stimulation, and the SRF grating suppressed them up to 56% of the responses (44% suppression) to the CRF stimulus alone. The strong suppression was observed more often in layer II/III cells than in other layers and in complex cells more often than in simple cells. The modulatory effects by SRF stimulus might be enhanced by the cortical recurrent excitation particularly in the superficial layers. We also examined whether the modulation by the surround grating exhibits a differential effect according to the presence or absence of figure-ground segregation in the stimulus configuration. For this purpose, effects of stimulus configuration with orientation-, direction-contrast or relative spatial phase difference between CRF and SRF stimuli (figure-ground segregated configuration) were compared with those of uniform configuration of stimulus (non-segregated configuration). There was a population of cells, which exhibited significantly stronger suppression with non-segregated configuration than with figure-ground segregated configuration. Such differential modulation of response by the SRF stimulus in the primary visual cortex is a possible basis of perceptual figure-ground segregation.

The purpose of this study is to elucidate the integrative input mechanisms of pyramidal cells receiving horizontally projecting axon collaterals (horizontal projection) and vertical input from layer IV. We performed whole-cell recordings from pyramidal cells in layer II/III and focally activated other single pyramidal cells monosynaptically connected via long-distance horizontal (LH) projections (the distance between presynaptic and postsynaptic cells was 350–1200 μm) in slice preparations of the kitten primary visual cortex. In addition, presynaptic single fibers in layer IV (vertical input) and/or short-distance horizontal (SH) inputs from neighboring single pyramidal cells (distance within 100 μm) in layer II/III were activated. Unitary EPSPs evoked by the activation of LH and SH connections had smaller amplitude and larger coefficient of variation than those evoked by stimulating the vertical input. Paired-pulse stimulation of the LH and SH inputs caused the depression of the second EPSP, whereas that of vertical inputs caused either facilitation or depression of the second EPSP. The EPSPs evoked by simultaneous activation of LH and vertical inputs summated linearly at the resting membrane potential. However, the EPSPs evoked by stimulation of the two inputs were nonlinearly (supralinearly) summated when the postsynaptic membrane was depolarized to a certain level. Similar EPSP interaction was observed in response to simultaneous activation of the LH and SH inputs.

To explore functional connectivity between area 17 and posteromedial lateral suprasylvian (PMLS) area of the cat cerebral cortex, we carried out cross-correlation analysis of spike trains of neurons recorded simultaneously from both areas of anesthetized, paralyzed cat. Most of correlated pairs had peaks which indicate that PMLS cells were activated earlier than or simultaneously with their partners in area 17, suggesting that ‘backward’ as well as synchronous activation operates between these cortical areas.

To test the possibility of cross-talk between parallel pathways dealing with different aspects of visual information, such as orientation, direction of motion and colour in cortical area V2, we quantitatively analysed visual responses of 121 V2 cells recorded from anaesthetized and paralysed macaques and compared them with those of 147 V1 cells. A selectivity index of visual responses was calculated for each neuron, which was then classified as selective or not to a particular attribute of visual stimuli. Twenty-one percent of the V2 neurons had dual selectivity to both colour and direction of stimulus motion (C&D cells). In V1, only 5% of the cells were C&D cells. Thus, the proportion of C&D cells significantly increased from V1 to V2. We also carried out cross-correlation analysis of spike trains recorded simultaneously from pairs of V2 neurons or pairs of V1 neurons. In V2, correlated firings could be observed between cells with completely different optimal orientation, such as orthogonal, while it was never observed in V1. The cross-correlation analysis further indicated that functional interactions in V2 were more widespread than those in V1. These results suggest that neurons which have different functional properties become less segregated, and that functional interactions become more widespread in V2 than in V1.

Some features of the visual cortex develop postnatally in mammals. For example, geniculocortical axons that initially overlap throughout cortical layer IV segregate postnatally into two sets of interleaved eye-specific bands. NMDA (N-methyl-D-aspartate) receptors are necessary for eye-specific axon-segregation in the frog tectum, and as NMDA receptors play a greater part in synaptic transmission in early life and decrease in function during the period of axon segregation, they may be involved in the segregation of geniculocortical axons: they are well placed to do so as they transduce retinally derived signals essential for segregation. Rearing animals in the dark in early life delays segregation and prolongs the critical period for plasticity. We now report that dark-rearing of kittens also delays the loss of NMDA receptor function in the visual cortex, supporting the view that they play an important part in neuronal development and plasticity.

Effects of iontophoretic application of γ-aminobutyric acid (GABA) and its antagonist, N-methyl-bicuculline (BIC), on visual responses of striate cortical neurons were studied in kittens 6–13 days old. Visually responsive cells were classified into 3 groups, i.e., orientation-selective, orientational bias and non-oriented cells. In almost all of the orientation-selective cells their responses were completely suppressed by GABA while the majority of the others were not significantly or only weakly suppressed. BIC abolished or reduced the selectivity of all the orientation-selective cells while it did not affect any of the non-oriented cells tested. These results suggest that GABAergic inhibition already operates on a group of cortical neurons to make them orientation-selective at the time of eye opening.

The role of N-methyl-D-aspartate (NMDA) receptors in cat visual cortex was studied as a function of both layer and age by iontophoresis of the NMDA antagonist (D)-2-amino-5-phosphonovaleric acid (APV). Effects on both visual responses and spontaneous activity were observed. In superficial layers (II and III), D-APV reduced visual responses substantially at all ages. Iontophoresis of D-APV with 10 nA of ejecting current for 2–3 min was sufficient to reduce the response to approximately one third of control levels. The magnitude of the reduction did not vary with age. In granular and deep layers (IV, V, and VI), D-APV affected the visual response in young animals but only spontaneous activity in older animals. On average, visual responses were reduced to about half at 20–23 days of age and to about 75% at 4 weeks of age but in most cases were not significantly affected in adults. The rapid change in the functional effect of NMDA receptors over the third and fourth week in granular and deep layers suggests a role in development. There was a reasonable age correlation between the change in effect and the period of geniculocortical afferent segregation. Further experiments will be necessary to determine whether NMDA receptors are necessary for segregation to occur. The presence of an NMDA component to the visual response in the adult in layers II and III argues either that these layers retain some form of plasticity in the adult or that NMDA receptors play a role in the transmission of normal visual input to these layers.

Effects of iontophoretic application of gamma-aminobutyric acid (GABA) and its antagonist, N-methyl-bicuculline (BIC), on visual responses of striate cortical neurons were studied in kittens 6-13 days old. Visually responsive cells were classified into three groups, i.e. orientation-selective, orientation-bias and nonoriented cells. In almost all of the orientation-selective cells, their responses were completely suppressed by GABA while the majority of the others were not significantly or only weakly suppressed. An application of BIC abolished or reduced the selectivity of all the orientation-selective cells but did not affect any of the nonoriented cells tested. These results suggest that GABAergic inhibition already operates on a group of cortical neurons to make them orientation-selective at the time of eye opening, but such an action of GABA on other groups of neurons develops later.

Postnatal development of striate cortical neurons projecting to the superior colliculus (SC) was studied in cats, ranging in age from newborn to adult, by injection of horseradish peroxidase (HRP) into the SC. At birth, HRP-labelled cells were widely distributed throughout the cortex between the splenial and suprasylvian sulci, although a very rough topographic correspondence seemed to exist between the striate cortex and SC. The labelled cells were confined to layer V of the cortex, as in the adult. They were very densely packed and their somas were already pyramidal in shape although very slender. During the third to eighth days, apical dendrites of a substantial number of cells, mostly locatcd in the upper bank of the splenial sulcus, were filled with HRP up to layer I and their somas were larger than those of cells located near the crown of the lateral and postlateral gyri. At the eighth day and thereafter, the distribution of the labelled cells across the visual cortex was not so widespread as that seen in the newborn kittens. The dendritic arborization pattern of labelled cells became nearly adultlike at the fourth week, and its full maturation was seen at the eighth week. A quantitative analysis of the cross-sectional areas of the cells and their packing density in layer V of the cortex revealed that (1) the size of cells increased very rapidly during the second week and became almost adultlike at the fifth week; (2) the density of cells reduced dramatically during the second week and thereafter at a low rate until the eighth week; and (3) the ratio of the labelled to unlabelled cells in layer V decreased remarkably also during the second week. These results suggest that an elimination of axon collaterals of corticotectal cells or their death may take place mostly during the second week of age, when eye-opening occurs in kittens. By comparison with previous data on functional development of the SC, it is also suggested that the maturation of visual response properties of SC neurons may depend on postnatal development of corticotectal cells.

1. We studied the effect of electrically stimulating the locus coeruleus (LC) and iontophoresing noradrenergic antagonists on visual responses and spontaneous activity of individual cells in the cat primary visual cortex. 2. A bilateral projection from LC to visual cortex was demonstrated anatomically, by retrograde labeling using horseradish peroxidase. Where electrical stimulation of both ipsilateral and contralateral LC affected a cortical neuron, the effect induced by stimulating each side was similar. 3. One hundred and two cells were recorded in area 17: 52% of them had their activity suppressed and 36% had their activity facilitated by LC stimulation. The suppressive effect was predominant in cortical layers II + III and IV, whereas most cells in layer V and one-half of the cells in layer VI were facilitated by LC stimulation. This suggests that LC neurons innervate each cortical layer in a different manner. 4. Simple and complex cells were equally sensitive to LC stimulation. For simple cells, the suppressive effect of LC stimulation was dominant throughout all layers. For complex cells, the suppressive effect was dominant in layers II + III and IV, whereas the facilitatory effect was dominant in layers V and VI. 5. The suppressive effect of LC stimulation was blocked by iontophoretic application of beta-adrenergic receptor antagonists and the facilitatory effect was blocked by either alpha- or beta-adrenergic receptor antagonists. 6. Nonselective alpha-, and selective alpha 1- and alpha 2-receptor antagonists suppressed visual and spontaneous activity in almost all neurons tested, suggesting that these receptors are either facilitatory at a postsynaptic site or inhibitory at a site presynaptic to an inhibitory synapse in the visual cortex. 7. beta-Receptor antagonists facilitated activity in 45% and suppressed activity in 36% of the cells tested, suggesting there are both suppressive and facilitatory types of beta-receptors. 8. The effectiveness of alpha- and beta-antagonists on the activity of neurons without LC stimulation also suggested that spontaneously released noradrenaline activated noradrenergic receptors in the visual cortex even in the anesthetized and paralyzed cat. 9. In most cells tested, both alpha- and beta-receptor antagonists exerted effects on single neurons suggesting that endogenous noradrenaline acts on both alpha- and beta-receptors on the same cell. 10. The activation of LC did not improve the signal- (visual response)to-noise (spontaneous discharge) ratio of neurons in the visual cortex. 11. LC seemed to control the activity of each cortical layer differently, by activating different kinds of noradrenergic receptors in different layers.

1. A study was made of the relative contribution of N-methyl-D-aspartate (NMDA) and non-NMDA receptors to the visual responses of cells in different layers of the cat visual cortex at different levels of excitatory drive (which was varied by altering the stimulus contrast). 2. Receptive fields were mapped for 121 cells in area 17 of cat cortex. Cells were characterized to determine the optimal visual stimulus, the brightness of which was then varied relative to background luminance to construct a contrast-response (C-R) curve for each cell. Curves were made during control conditions and during application of agonists (NMDA and quisqualate) and/or antagonists [(D)-2-amino-5-phosphonovaleric acid (D-APV) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX)] to examine the excitatory amino acid components of the visual response. 3. Threshold responses were obtained with stimuli between 1/60 and 1.8 X background luminance. The cell response, measured by firing rate, was linearly related to stimulus contrast over 1-2 decades and saturated at higher contrasts. 4. Application of APV reduced the slope of the linear portion of the C-R curve for cells located in layers II and III (average reduction, 59% of control). APV did not decrease the threshold to stimulation. The "just suprathreshold" responses to stimulation were reduced by the same proportion as the saturation responses for individual cells. The principal effect was therefore to reduce the gain of the C-R curve in these layers. 5. Application of APV reduced the spontaneous activity of cells located in layers IV, V, and VI with little if any effect on the gain of the C-R curve. This suggests a tonic background level of NMDA-receptor activation in these layers, which is not directly related to the visual response. 6. Low levels of NMDA increased the gain of the C-R curve in layers II/III and V/VI. On the other hand, low levels of quisqualate increased the overall level of firing without affecting the gain of the C-R curve. NMDA did not increase the gain of the curve in layer IV. 7. These experiments show that visual stimuli that produce just suprathreshold responses activate NMDA receptors. The degree of activation is proportionally the same for small responses and large responses for an individual cell. Rather than finding a threshold for NMDA-receptor activation, a continuous range of NMDA-receptor influence was observed over the entire response range.(ABSTRACT TRUNCATED AT 250 WORDS)