Neural mechanisms for color perception in the primary visual cortex

New neurophysiological results show the existence of multiple transformations of color signals in the primary visual cortex (V1) in macaque monkey. These different color mechanisms may contribute separately to the perception of color boundaries and colored regions. Many cells in V1 respond to color and to black-white (luminance) patterns. These neurons are spatially selective and could provide signals about boundaries between differently colored regions. Other V1 neurons that prefer color over luminance respond without much spatial selectivity to colored stimuli, and could be the neural basis for the response to local color modulation within a region. How these different types of color cells combine inputs from cone photoreceptors is what gives them their different spatial selectivities for color.     

Cellular mechanisms underlying cutaneous pressure-induced vasodilation: in vivo involvement of potassium channels

In the skin of humans and rodents, local pressure induces localized cutaneous vasodilation, which may be protective against pressure-induced microvascular dysfunction and lesion formation. Once activated by the local pressure application, capsaicin-sensitive nerve fibers release neuropeptides that act on the endothelium to synthesize and release nitric oxide (NO) and prostaglandins, leading to the development of the cutaneous pressure-induced vasodilation (PIV). The present study was undertaken to test in vivo the hypothesis that PIV is mediated or modulated by differential activation of K+ channels in anesthetized rats using pharmacological methods. Local pressure was applied at 11.1 Pa/s. Endothelium-independent and -dependent vasodilation were tested using iontophoretic delivery of sodium nitroprusside (SNP) and acetylcholine (ACh), respectively, and was correlated with PIV response. PIV was reduced after systemic administration of tetraethylammonium (a nonspecific K+ channel blocker), iberiotoxin [a specific large-conductance Ca2+-activated K+ (BKCa) channel blocker], and glibenclamide [a specific ATP-sensitive K+ (KATP) channel blocker], whereas PIV was unchanged by apamin (a specific small-conductance Ca2+-activated K+ channel blocker) and 4-aminopyridine (a specific voltage-sensitive K+ channel blocker). The responses to SNP and ACh were reduced by iberiotoxin but were unchanged by glibenclamide. We conclude that the cellular mechanism of PIV in skin involves BKCa and KATP channels. We suggest that the opening of BKCa and KATP channels contributes to the hyperpolarization of vascular smooth muscle cells to produce PIV development mainly via the NO and prostaglandin pathways, respectively.     

Adaptive coincidence detection and dynamic gain control in visual cortical neurons in vivo

Several theories have proposed a functional role for response synchronization in sensory perception. Critics of these theories have argued that selective synchronization is physiologically implausible when cortical networks operate at high levels of activity. Using intracellular recordings from visual cortex in vivo, in combination with numerical simulations, we find dynamic changes in spike threshold that reduce cellular sensitivity to slow depolarizations and concurrently increase the relative sensitivity to rapid depolarizations. Consistent with this, we find that spike activity and high-frequency fluctuations in membrane potential are closely correlated and that both are more tightly tuned for stimulus orientation than the mean membrane potential. These findings suggest that under high-input conditions the spike-generating mechanism adaptively enhances the sensitivity to synchronous inputs while simultaneously decreasing the sensitivity to temporally uncorrelated inputs.     

Mapping of contextual modulation in the population response of primary visual cortex

We review the evidence of long-range contextual modulation in V1. Populations of neurons in V1 are activated by a wide variety of stimuli outside of their classical receptive fields (RF), well beyond their surround region. These effects generally involve extra-RF features with an orientation component. The population mapping of orientation preferences to the upper layers of V1 is well understood, as far as the classical RF properties are concerned, and involves organization into pinwheel-like structures. We introduce a novel hypothesis regarding the organization of V1’s contextual response. We show that RF and extra-RF orientation preferences are mapped in related ways. Orientation pinwheels are the foci of both types of features. The mapping of contextual features onto the orientation pinwheel has a form that recapitulates the organization of the visual field: an iso-orientation patch within the pinwheel also responds to extra-RF stimuli of the same orientation. We hypothesize that the same form of mapping applies to other stimulus properties that are mapped out in V1, such as colour and contrast selectivity. A specific consequence is that fovea-like properties will be mapped in a systematic way to orientation pinwheels. We review the evidence that cytochrome oxidase blobs comprise the foci of this contextual remapping for colour and low contrasts. Neurodynamics and motion in the visual field are argued to play an important role in the shaping and maintenance of this type of mapping in V1.     

Simulation of mechanisms of tuning to incomplete cross-like figures in neurons of visual cortex

We performed a digital simulation of the receptive fields (RF) of cat cortical neurons in the area 17 that are able to detect cross-like figures with partly masked central or peripheral fragments. It was shown that the reciprocal interaction between the RF center and periphery may produce sharp, selective, and pronounced tuning to a cross shape and orientation due to blocking the end-stopping inhibition in the RF by its side-disinhibitory zone. Under conditions of cooperative interaction between the RF center and periphery the sensitivity index (cross/bar response ratio) was typically lower than in the reciprocal model. Features of the model that are critical for sensitivity to cross in cases of small or incomplete figures (the shape, localization, and weight of the RF zones) are specified.     

Local synchronized activity of neurons of different classes in cat primary visual cortex

The goal of the present study was to investigate the local synchronized neuronal activity in the cat visual cortex and the role of different classes of neurons in neural synchrony. Four classes of neurons were identified on the basis of electrophysiological properties of extracellularly recorded cells: RS, FS, IB, and FRB. It was revealed that neurons with short spikes and FRB type of activity were first engaged in synchronization. The model study revealed that neurons with the short action potential had more stable synchronized activity.     

Cellular and biochemical mechanisms underlying circadian rhythms in vertebrates

Circadian clocks organize neural processes, such as motor activities, into near 24-hour oscillations and adaptively synchronize these rhythms to the solar cycle. Recently, the first mammalian clock genes have been found. Unpredicted diversity in signaling pathways and clock-controlled gating of signals that modulate timekeeping has been discovered. A diffusible clock output has been found to control some behavioral rhythms. Consensus is emerging that circadian mechanisms are conserved across phylogeny, but that mammals have developed a great complexity of controls.     

Cellular mechanisms underlying the development of diabetic neuropathies

The data of recent studies of fundamental mechanisms underlying the development of diabetic neuropathies are summarized in the Review. The importance of a sorbitol-polyol pathway of glucose metabolism, as well as the roles of production of peroxide radicals and activation of the processes of non-enzymatic glycosilation in the nerve cells are analyzed. Special attention is paid to the roles of growth factors in morphological modifications of the neuronal structures and to that of intracellular signalization in functional disturbances in the nerve cells. Changes in intracellular homeostasis of Ca ions are of considrable importance for the development of peripheral diabetic neuropathies.     

Locomotion-induced gain of visual responses cannot explain visuomotor mismatch responses in layer 2/3 of primary visual cortex

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Orientation-selective neurons in the squirrel visual cortex

The organization of receptive fields of neurons sensitive to orientation of visual stimuli was investigated in the squirrel visual cortex. Neurons with mutually inhibitory on- and off-areas of the receptive field, with partially and completely overlapping excitatory and inhibitory mechanisms, were distinguished. Neurons of the second group are most typical. They exhibit orientation selectivity within the excitatory area of the receptive field because, if the stimulus widens in the zero direction, perpendicular to the preferred direction, lateral inhibition is much stronger than if it widens in the preferred direction. Additional inhibitory areas (outside the excitatory area) potentiate this inhibition and increase selectivity. It is suggested that there is no strict separation of simple (with separate excitatory and inhibitory mechanisms in the receptive field) and complex (with overlapping of these mechanisms) neurons in the squirrel visual cortex.A. N. Severtsov Institute of Evolutionary Morphology and Ecology of Animals, Academy of Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 11, No. 6, pp. 540–549, November–December, 1979.     

Cellular and molecular mechanisms underlying LPS-associated myocyte impairment

Recently we reported that Toll-like receptor 4 (TLR4)-positive immune cells of unknown identity were responsible for the LPS-induced depression of cardiac myocyte shortening. The aim of this study is to identify the TLR4-positive cell type that is responsible for the LPS-induced cardiac dysfunction. Neither neutrophil depletion alone nor mast cell deficiency had any impact on the impairment of myocyte shortening during LPS treatment. In contrast, LPS-treated, macrophage-deficient mice demonstrated a partial reduction in shortening compared with saline-treated, macrophage-deficient mice. Because the removal of macrophages could only partially restore myocyte shortening, we also investigated the effects of removing both neutrophils and macrophages on myocyte shortening. Interestingly, endotoxemic, neutrophil-depleted, and macrophage-deficient mice had completely restored myocyte shortening. Because both macrophages and neutrophils can produce nitric oxide (NO) and TNF-alpha, we examined LPS-treated inducible NO synthase knockout (iNOSKO) mice and TNF receptor (TNFR)-deficient mice. Eliminating both TNFR1 and TNFR2 was required to restore myocyte shortening during LPS treatment, whereas iNOS deficiency had no effect. These data suggest that macrophages and to a lesser degree neutrophils cause cardiac impairment, presumably via TNF-alpha.     

Contour saliency in primary visual cortex

Contour integration is an important intermediate stage of object recognition, in which line segments belonging to an object boundary are perceptually linked and segmented from complex backgrounds. Contextual influences observed in primary visual cortex (V1) suggest the involvement of V1 in contour integration. Here, we provide direct evidence that, in monkeys performing a contour detection task, there was a close correlation between the responses of V1 neurons and the perceptual saliency of contours. Receiver operating characteristic analysis showed that single neuronal responses encode the presence or absence of a contour as reliably as the animal's behavioral responses. We also show that the same visual contours elicited significantly weaker neuronal responses when they were not detected in the detection task, or when they were unattended. Our results demonstrate that contextual interactions in V1 play a pivotal role in contour integration and saliency.     

Clustered organization of neurons with similar extra-receptive field properties in the primary visual cortex

The primary visual cortex is organized into clusters of cells having similar classical receptive field (CRF) properties. Nonclassical, extra-receptive fields (ERFs) can either inhibit or facilitate the response elicited by stimulation within the CRF. Here, we report that in the primary visual cortex of cat, neurons with similar inhibitory or facilitatory ERF properties are also grouped into clusters. These clusters are randomly distributed in all cortical layers, with no detectable relationship with orientation and ocular dominance columns. This functional organization of neurons with respect to ERF properties may allow an efficient processing of global visual information.     

Molecular mechanisms underlying specificity of excitotoxic signaling in neurons

The central role of glutamate receptors in mediating excitotoxic neuronal death in stroke, epilepsy and trauma has been well established. Glutamate is the major excitatory amino acid transmitter within the CNS and it's signaling is mediated by a number of postsynaptic ionotropic and metabotropic receptors. Although calcium ions are considered key regulators of excitotoxicity, new evidence suggests that specific second messenger pathways rather than total Ca(2+) load, are responsible for mediating neuronal degeneration. Glutamate receptors are found localized at the synapse within electron dense structures known as the postsynaptic density (PSD). Localization at the PSD is mediated by binding of glutamate receptors to submembrane proteins such as actin and PDZ containing proteins. PDZ domains are conserved motifs that mediate protein-protein interactions and self-association. In addition to glutamate receptors PDZ-containing proteins bind a multitude of intracellular signal molecules including nitric oxide synthase. In this way PDZ proteins provide a mechanism for clustering glutamate receptors at the synapse together with their corresponding signal transduction proteins. PSD organization may thus facilitate the individual neurotoxic signal mechanisms downstream of receptors during glutamate overactivity. Evidence exists showing that inhibiting signals downstream of glutamate receptors, such as nitric oxide and PARP-1 can reduce excitotoxic insult. Furthermore we have shown that uncoupling the interaction between specific glutamate receptors from their PDZ proteins protects neurons against glutamate-mediated excitotoxicity. These findings have significant implications for the treatment of neurodegenerative diseases using therapeutics that specifically target intracellular protein-protein interactions.     

Dynamics underlying synaptic gain between pairs of cortical pyramidal neurons

Changes in connectivity between pairs of neurons can serve as a substrate for information storage and for experience-dependent changes in neuronal circuitry. Early in development, synaptic contacts form and break, but how these dynamics influence the connectivity between pairs of neurons is not known. Here we used time-lapse imaging to examine the synaptic interactions between pairs of cultured cortical pyramidal neurons, and found that the axon-dendrite contacts between each neuronal pair were composed of both a relatively stable and a more labile population. Under basal conditions, loss and gain of contacts within this labile population was well balanced and there was little net change in connectivity. Selectively increasing the levels of activated CaMKII in the postsynaptic neuron increased connectivity between pairs of neurons by increasing the rate of gain of new contacts without affecting the probability of contact loss, or the proportion of stable and labile contacts, and this increase required Calcium/calmodulin binding to CaMKII. Our data suggest that activating CaMKII can increase synaptic connectivity through a CaM-dependent increase in contact formation, followed by stabilization of a constant fraction of new contacts.