Hironobu Osaki

Cholinergic modulation of response gain in the primary visual cortex of the macaque.

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.

Enriched Expression of Serotonin 1B and 2A Receptor Genes in Macaque Visual Cortex and their Bidirectional Modulatory Effects on Neuronal Responses

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 (<3 h) downregulation of these mRNAs, suggesting the retinal activity dependency of their expression. Consistent with the high expression level in V1, clear modulatory effects of 5-HT1B and 5-HT2A receptor agonists on the responses of V1 neurons were observed in in vivo electrophysiological experiments. The modulatory effect of the 5-HT1B agonist was dependent on the firing rate of the recorded neurons: The effect tended to be facilitative for neurons with a high firing rate, and suppressive for those with a low firing rate. The 5-HT2A agonist showed opposite effects. These results suggest that this serotonergic system controls the visual response in V1 for optimization of information processing toward the incoming visual inputs.

Surround suppression sharpens orientation tuning in the cat primary visual cortex

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.

Surround suppression by high spatial frequency stimuli in the cat primary visual cortex

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.

Effects of stimulus spatial frequency, size, and luminance contrast on orientation tuning of neurons in the dorsal lateral geniculate nucleus of cat

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.

Receptive field properties of cat perigeniculate neurons correlate with excitatory and inhibitory connectivity to LGN relay neurons

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.

Interaction between the lateral geniculate nucleus and the perigeniculate nucleus of the cat

The perigeniculate nucleus (PGN) is a layer of inhibitory GABAergic neurons lying over the dorsal surfaces of the lateral geniculate nucleus (LGN). It receives axon-collateral input from the principal cells of LGN and axon-collaterals of cortico-geniculate projections. PGN neuron sends back inhibitory projection to the LGN. It is known that these projections are organized in retinotopic manner. However, little is known about the relationship between visual receptive field properties of the PGN and LGN neurons, which are connected each other. To explore this point, we conducted a crosscorrelation analysis of single neuronal activity simultaneously recorded from the PGN and LGN neurons in anesthetized cats. For 15 pairs of functionally connected PGN and LGN neurons, we compared the receptive field properties, such as the spatial frequency tuning and temporal frequency tuning, of each neuron. Correlated firings were observed only in neuron pairs whose receptive fields were partially or entirely overlapped. We found a pattern of connection between these neurons, that is, the receptive field properties of the PGN neurons and the LGN neurons are similar when there is only excitatory connection from LGN to PGN (4 pairs), but different when the PGN neurons send inhibitory inputs to the LGN neurons (8 pairs). We also found that the inhibitory input from PGN neuron serves for sharpening the orientation selectivity of LGN neuron, which shows the orientation preference different from that of PGN neuron. These results suggest the inhibitory role of PGN neurons on the elaboration of the receptive field properties of LGN neurons.

Acetylcholine enhances response gain via muscarinic receptor in the macaque primary visual cortex

Mammalian visual system exhibits significant experience-induced plasticity during a restricted period of early postnatal life. Expression of the plasticity is retarded in animals raised in darkness, suggesting the necessity of visual experience in cortical development. Growing evidences suggest a role of endocannnabinoid system in the plasticity of central nervous system. To explore a possible role of endocannnabinoid system in the developmental plasticity of visual cortex, we examined the developmental regulation of the expression of Type 1 cannabinoid receptor (CB1) and diacylglycerol lipase(DGL), which synthesizes a major endocannabinoid 2-arachidonoylglycerol, in the primary visual cortex (V1) of mice at various ages and those raised in darkness, using immunohistochemistry and western blot analysis. CB1 immunoreactivity was rather faint and mainly existed in layer VI of V1 at postnatal days (P)10. In animals from P20 to P100, intense CB1 immunoreactivity was observed in layer II/III and VI of V1. The CB1 signal was mainly colocalized with inhibitory nerve terminals containing vesicular GABA transporter rather than with the terminals containing vesicular glutamate transporters. Relative amount of CB1 protein in V1 did not change significantly from P10 to P100. On the other hand, DGL, which is assumed to localize at post synaptic sites, distributed at lower part of layer II/III and layer IV from P30 to P100. DGLprotein level in V1 significantly increased during development from P10 to P40 and then decreased to P100 in V1. Mice rearing in the dark from birth to P30 exhibited similar layer distribution of CB1 and DGLimmunoreactivity to those in normal animal at P30. Therefore, the postnatal maturation of laminar distribution of CB1 and DGLwould not require sensory experience.

Functional effects of 5-HT1B and 5-HT2A receptors in macaque V1

Single neuron recordings have shown that there are many color-sensitive neurons in the inferior temporal (IT) cortex, but it is still unclear how they distribute in this area. We examined color-related responses in broad brain area, including the IT cortex, by using fMRI in the alert macaque monkey. We measured the BOLD responses to chromatic stimuli (colored gratings and Mondrian-like patterns) and achromatic stimluli (same patterns without color) while the monkey was performing a fixation task. Color-biased responses were observed in LGN, V1, V2, V3 and V4. In addition, some color-biased patches were distributed in the IT cortex; around the posterior middle temporal sulcus, in the posterior bank of the superior temporal sulcus and in the anterior middle temporal sulcus. Their positions were partly overlapped with shape-biased patches detected in a separate experiment. Our results support the hypothesis that color-sensitive neurons are concentrated in multiple sub-regions in the IT cortex.