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Involvement of serotonin in developmental plasticity of kitten visual cortex.

During a critical period of postnatal development, neuronal connections in the kitten visual cortex are susceptible to experience-dependent modifications. These modifications are facilitated by the neuromodulators noradrenaline and acetylcholine. To address the question of whether serotonin (5-hydroxytryptamine; 5-HT), the other major neuromodulator in the cerebral cortex, also plays a role in developmental plasticity, we investigated whether interference with serotoninergic transmission in the kitten visual cortex affects ocular dominance (OD) plasticity. The serotonin neurotoxin 5,7-dihydroxytryptamine or the serotonin receptor blockers ketanserin and methysergide were infused into the visual cortex of kittens undergoing monocular deprivation. We found that both methods of disrupting serotoninergic transmission reduced OD plasticity. However, to be effective, the receptor blockers ketanserin and methysergide had to be applied in combination, suggesting that coactivation of serotonin receptor subtypes of both the 5-HT1 and 5-HT2 families have a permissive function in OD plasticity. Since activation of 5-HT2 receptors stimulates phosphoinositide hydrolysis, our data suggest that second messengers from the phospholipid pathway may play an important role in developmental plasticity of visual cortex.

5,7-Dihydroxytryptamine↗

Internal state of monkey primary visual cortex (V1) predicts figure-ground perception.

When stimulus information enters the visual cortex, it is rapidly processed for identification. However, sometimes the processing of the stimulus is inadequate and the subject fails to notice the stimulus. Human psychophysical studies show that this occurs during states of inattention or absent-mindedness. At a neurophysiological level, it remains unclear what these states are. To study the role of cortical state in perception, we analyzed neural activity in the monkey primary visual cortex before the appearance of a stimulus. We show that, before the appearance of a reported stimulus, neural activity was stronger and more correlated than for a not-reported stimulus. This indicates that the strength of neural activity and the functional connectivity between neurons in the primary visual cortex participate in the perceptual processing of stimulus information. Thus, to detect a stimulus, the visual cortex needs to be in an appropriate state.

Animals↗

Genesis of GABA-immunoreactive neurons in the ferret visual cortex.

The pattern of neurogenesis of GABA-immunoreactive neurons in the ferret primary visual cortex was determined using immunohistochemical and 3H-thymidine autoradiographic techniques. Neurons in the visual cortex of the ferret undergo their final cell division during a period extending from embryonic day 20 (E20) to postnatal day 14 (P14) and follow an inside-out pattern of neuronal production (Jackson et al., 1984) similar to that observed in other mammals. Earlier-generated neurons are found at deeper cortical positions in the adult than are those generated later. Layer I is an exception to this rule, since neurons destined for this layer are produced at both the beginning and end of neurogenesis. In this study, the pattern of neurogenesis of GABA-immunoreactive neurons is compared to the pattern observed for nonimmunoreactive neurons. The overall pattern of cortical neurogenesis (inside-out pattern) is similar for GABA-immunoreactive neurons and neurons that are not GABA-immunoreactive. However, the GABA-immunoreactive neurons born on a given day of development are more broadly distributed across the radial axis of the adult cortex than are nonimmunoreactive neurons generated on the same day. GABA-immunoreactive neurons generated later in neurogenesis are, on average, slightly smaller than those generated early. If GABA-immunoreactive neurons in the visual cortex are interneurons, then these findings suggest that interneurons follow the same pattern of neurogenesis as do projecting neurons in the visual cortex.

Animals↗

Naso-temporal asymmetry of visual perception and of the visual cortex.

The decrease of visual performance from the fovea towards the periphery depends upon the task tested. The slope of the decrease is generally steeper for hyperacuity than for spatial resolution and is steeper in the nasal than in the temporal hemifield. The naso-temporal asymmetry in the periphery of the visual field, beyond 20 deg eccentricity, is much more pronounced for hyperacuity than for spatial resolution. The psychophysical results show a close correlation to the cortical organization as revealed by autoradiography.

Adult↗

Stimulus novelty and emotion perception: the near absence of habituation in the visual cortex.

In rapid serial visual presentation of pictures, an early event-related brain potential component shows enlarged negativity over occipital regions for emotional pictures compared with neutral pictures. The present study examined whether the processing of emotional target pictures varies as a function of stimulus repetition. Accordingly, pictures of erotica, neutral contents, and mutilations were repeatedly presented (90 times) while the electroencephalogram was recorded with a 129 dense sensor array. As in previous studies, emotional pictures were associated with a larger posterior negativity than neutral pictures. Furthermore, differential emotion processing did not vary as a function of stimulus repetition and was similarly expressed across blocks of picture presentation. These findings suggest the near absence of habituation in differential emotion processing during perceptual processing.

Adult↗

Dynamic model of visual recognition predicts neural response properties in the visual cortex.

The responses of visual cortical neurons during fixation tasks can be significantly modulated by stimuli from beyond the classical receptive field. Modulatory effects in neural responses have also been recently reported in a task where a monkey freely views a natural scene. In this article, we describe a hierarchical network model of visual recognition that explains these experimental observations by using a form of the extended Kalman filter as given by the minimum description length (MDL) principle. The model dynamically combines input-driven bottom-up signals with expectation-driven top-down signals to predict current recognition state. Synaptic weights in the model are adapted in a Hebbian manner according to a learning rule also derived from the MDL principle. The resulting prediction-learning scheme can be viewed as implementing a form of expectation-maximization (EM) algorithm. The architecture of the model posits an active computational role of the reciprocal connections between adjoining visual cortical areas in determining neural response properties. In particular, the model demonstrates the possible role of feedback from higher cortical areas in mediating neurophysiological effects due to stimuli from beyond the classical receptive field. Simulations of the model are provided that help explain the experimental observations regarding neural responses in both free viewing and fixation conditions.

Animals↗

[Interhemispheric relations of the cat visual cortex following unilateral polarization of the secondary visual area].

In 40 anesthetized cats, evoked potentials following light flashes during unilateral polarization of the secondary cortical visual area with DC anode (2-10 mcA) were studied in symmetrical centers of the 17th and 18th fields. Four phases of interhemisphere interrelationships between the 18th field's symmetrical centers were shown: 1 -- extracallosal phase of synergic depression; 2 -- callosal phase of dominant interrelationships; 3 -- callosal phase of synergic depression; 4 -- callosal-extracallosal phase of dominant interrelationships. In symmetrical centers of the 17th field, the only 1 extracallosal phase of synergic depression was observed during which the transcallosal modulation of nervous processes occurred. The data obtained are interpreted from the standpoint of the role of dominanta in interhemisphere interrelationships.

Animals↗

Noradrenergic control of ocular dominance plasticity in the visual cortex of dark-reared cats.

In the visual cortex of cats which had been dark-reared for several months since the time before natural eye opening, a cortical infusion of 6-hydroxydopamine (6-OHDA), a noradrenaline (NA)-related neurotoxin, partially suppressed a usual shift in ocular dominance following brief monocular lid suture, causing a significant loss of binocular cells. This partial shift in ocular dominance (U-shaped histogram) was also observed typically in the control hemisphere of cats which were subjected to dark-rearing for more than a year. Furthermore, the expected shift in ocular dominance following monocular deprivation was blocked by a direct cortical infusion of D,L-metoprolol, a selective beta 1-adrenergic receptor antagonist. The blockade was not obtained by D-metoprolol, a biologically inert stereo-isomer, under the comparable condition. In contrast, exogenous L-NA gave rise to an obvious shift in ocular dominance toward the non-deprived eye. The present results suggest that the NA-beta 1 adrenoreceptor system was necessary to maintain the ocular dominance plasticity in the visual cortex of dark-reared cats.

Animals↗

Heterogeneous oxygen extraction in the visual cortex during activation in mild hypoxic hypoxia revealed by quantitative functional magnetic resonance imaging.

Functional magnetic resonance imaging (fMRI) techniques were used to study haemodynamic and metabolic responses in human visual cortex during varying arterial blood oxygen saturation levels (Y(sat), determined by pulse-oximeter) and stimulation with contrast-reversing checkerboards. The visual-evoked potential amplitude remained constant at lowered Y(sat) of 0.82+/-0.03. Similarly, fMRI cerebral blood flow (CBF) responses were unchanged during reduced Y(sat). In contrast, visual cortex volume displaying blood oxygen level-dependent (BOLD) fMRI response decreased as a function of Y(sat), but the BOLD signal change of 3.6%+/-1.4% was constant. Oxygen extraction ratio (OER) during visual activation showed values of 0.26+/-0.03 for normal Y(sat). At lowered Y(sat), two OER patterns were observed. Firstly, a reduced OER of 0.14+/-0.03 in the visual cortex structures showing BOLD in hypoxia was observed. Secondly, signs of much higher OER in other parts of visual cortex were obtained. T2*-weighted magnetic resonance imaging revealed signal increases by 0.8%+/-0.4% with visual activation during lowered Y(sat) in the visual cortex structures, which showed BOLD of 3.6% in magnitude under normoxia. Because the CBF response in the visual cortex was quantitatively similar during stimulation in normoxia and hypoxia, attenuated T2*-weighted signal increase in parts of visual cortex indicated high OER during visual activation in hypoxia, which was close to that encountered in the resting brain. These spatially localised regions of tissue oxygen extraction and metabolism argue for dissociation between CBF and BOLD fMRI signals in mild hypoxia. The findings point to heterogeneity with regard to oxygen requirement and its coupling to the haemodynamic response in the brain.

Adult↗

Development of orientation selectivity in ferret visual cortex and effects of deprivation.

The orientation selectivity of cells in ferret primary visual cortex was studied during normal development and in animals deprived of vision or of visual cortical activity. In normal animals from the age when visual responses were first recorded (postnatal day 23) through postnatal week 5, only about 25% of cells showed orientation-selective responses. By postnatal week 7, cortical responses had matured to an adult-like state, with approximately 75% of cells clearly selective for orientation. This development of orientation selectivity was not merely a reflection of the development of cortical cell responsiveness: at all ages studied, there was no correlation between responsiveness and selectivity. Infusion of TTX into visual cortex to silence neuronal activity completely blocked the maturation of orientation selectivity. Visual deprivation by bilateral lid suture impaired but did not completely block the normal development of orientation selectivity. We conclude that the maturation of orientation-selective responses in ferret primary visual cortex requires cortical neuronal activity, and that normal development requires visually driven activity.

Animals↗

N-methyl-D-aspartate subunit R1 involvement in the postnatal organization of the primary visual cortex of Callithrix jacchus.

It has been demonstrated that the primary visual cortex is highly sensitive to manipulations of the visual environment during a specific, early, postdevelopmental period: the critical period. Pharmacological studies have shown that N-methyl-D-aspartate (NMDA) receptors are involved in the plasticity of the visual cortex just as they are involved in the induction of long-term potentiation (LTP), another activity-dependent form of plasticity. The setting up of synaptic connectivity in the neocortex may rely on LTP-like mechanisms. By using immunohistochemistry techniques, we tested the hypothesis of the role of subunit R1 of NMDA (NMDAR1) receptors in the thalamocortical afferent segregation into ocular-dominance columns in the New World monkey, Callithrix jacchus. We employed early and short (2 weeks) monocular-deprivation periods at different ages of postnatal development (17, 46, 67, 107, and 188 postnatal days). We observed heterogeneous distribution of NMDAR1 in the layer IVC receiving the thalamic inputs if the deprivation was realized between the ages of 46 and 107 days. Layers IVCalpha and IVCbeta were involved differently as a function of the deprivation age. The striped pattern lost its differential intensity with the postnatal age. These results are compared with the ocular-dominance pattern evolution described in other works on this primate. They provide evidence of the NMDAR1 role in the modular organization, within time limits, during the postnatal development of the primary visual cortex.

Aging↗

Negative BOLD in the visual cortex: evidence against blood stealing.

The positive BOLD (blood oxygen level-dependent) response elicited in human visual cortex by a localized visual stimulus is accompanied by a reduction in the BOLD response in regions of the visual cortex that represent unstimulated locations in the visual field. We have suggested previously that this negative BOLD reflects attention-related suppression of neural activity, but it might also be explained in terms of "blood stealing," i.e., hemodynamic changes that have no neural correlate. We distinguish two possible hemodynamic effects of this type: (1). blood flow reduction caused by locally reduced pressure in vessels that share their blood supply with nearby dilated vessels; and (2). blood flow reduction caused by active constriction of vessels under neural control. The first is ruled out as an explanation of negative BOLD by showing that a visual stimulus that stimulates primary visual cortex in one hemisphere can cause extensive suppression in the other hemisphere i.e., it is not a local phenomenon. Negative BOLD most likely reflects suppression of neural activity, but could also reflect an active blood flow control system.

Attention↗

Intracortical origins of interocular suppression in the visual cortex.

The response of neurons in the primary visual cortex to an optimally oriented grating is usually suppressed quite dramatically when a second grating of, for example, orthogonal orientation is superimposed. Such "cross-orientation suppression" has been implicated in the generation of cortical orientation selectivity and local response normalization. Until recently, little experimental evidence was available concerning the neurophysiological substrate of this phenomenon, although an involvement of intracortical inhibition was commonly assumed. However, Freeman et al. (2002) proposed that cortical cross-orientation suppression is caused by suppression in the thalamus and depression at geniculocortical synapses. Here, we examine a dichoptic form of cross-orientation suppression, termed interocular suppression and thought to be involved in binocular rivalry (Sengpiel et al., 1995a). We show that its dependency on the drift rate of the suppressing stimulus is consistent with a cortical origin; unlike monocular cross-orientation suppression, it cannot be evoked by very fast-moving stimuli. Moreover, we find that previous adaptation to the orthogonal stimulus essentially eliminates interocular suppression. Because adaptation is a cortical phenomenon, this result also argues in favor of a cortical locus of suppression, again unlike monocular cross-orientation suppression, which is not affected by adaptation to the suppressor (Freeman et al., 2002). Finally, interocular suppression is greatly reduced in the presence of the GABA antagonist bicuculline. Together, our study demonstrates that interocular suppression is substantially different from monocular cross-orientation suppression and is mediated by inhibitory circuitry within the visual cortex.

Action Potentials↗

The neurophysiology of figure-ground segregation in primary visual cortex.

The activity of neurons in the primary visual cortex of the awake macaque monkey was recorded while the animals were viewing full screen arrays of either oriented line segments or moving random dots. A square patch of the screen was made to perceptually pop out as a circumscribed figure by virtue of differences between the orientation or the direction of motion of the texture elements within that patch and the surround. The animals were trained to identify the figure patches by making saccadic eye movements towards their positions. Almost every cell gave a significantly larger response to elements belonging to the figure than to similar elements belonging to the background. The figure-ground response enhancement was present along the entire extent of the patch and was absent as soon as the receptive field was outside the patch. The strength of the effect had no relation with classical receptive field properties like orientation or direction selectivity or receptive field size. The response enhancement had a latency of 30-40 msec relative to the onset of the neuronal response itself. The results show that context modulation within primary visual cortex has a highly sophisticated nature, putting the image features the cells are responding to into their fully evaluated perceptual context.

Animals↗

Development of human visual cortex: a balance between excitatory and inhibitory plasticity mechanisms.

Formation of neural circuitry in the developing visual cortex is shaped by experience during the critical period. A number of mechanisms, including N-methyl-D-aspartate (NMDA) receptor activation and gamma-aminobutyric acid (GABA)-mediated inhibition, are crucial in determining onset and closure of the critical period for visual plasticity. Animal models have shown that a threshold level of tonic inhibition must be reached for critical period plasticity to occur and that NMDA receptors contribute to Hebbian synaptic plasticity in the developing visual cortex. There are a number of developmental changes in these glutamatergic and GABAergic mechanisms that have been linked to plasticity; however, those changes have been shown only in animal models, and their development in the human visual cortex is not known. We have addressed this question by studying the expression of the major glutamatergic receptors, GABA(A) receptors, and glutamic acid decarboxylase (GAD) isoforms during the first 6 years of postnatal development of human visual cortex. There are significant changes in the expression of these proteins during postnatal development of human visual cortex. The time course of the changes is quite prolonged and suggests that it may set the pace for the prolonged critical period in human visual development. The changes also affect the nature of spatial and temporal integration in visual cortical neurons and thereby contribute to the maturation of visual functions.

Blotting, Western↗

Pyramidal neurons in layer 5 of the rat visual cortex. I. Correlation among cell morphology, intrinsic electrophysiological properties, and axon targets.

Previous work has established two structure/function correlations for pyramidal neurons of layer 5 of the primary visual cortex of the rat. First, cells projecting to the superior colliculus have thick apical dendrites with a florid terminal arborization in layer 1, whereas those projecting to the visual cortex of the opposite hemisphere have thinner apical dendrites that terminate below layer 1, without a terminal tuft (e.g., Hallman et al.: J Comp Neurol 272:149, '90). Second, intracellular recording combined with dye injection has revealed two classes of cells: the first has a thick, tufted apical dendrite and fires a distinctive initial burst of two or more impulses, of virtually fixed, short interspike interval, in response to current injection; and the other, with a slender apical dendrite lacking a terminal tuft, tends to have a longer membrane time constant and higher input resistance, and does not fire characteristic bursts (e.g., Larkman and Mason: J Neurosci 10:1407, '90). The present study combined intracellular recording in isolated slices of rat visual cortex and injection of carboxyfluorescein, to reveal soma-dendritic morphology, with prior injection of rhodamine-conjugated microspheres into the superior colliculus or contralateral visual cortex to label neurons according to the target of their axons. This permitted a complete correlation of morphology, intrinsic electrophysiological properties, and identity of the projection target for individual pyramidal cells. Neurons retrogradely labeled from the opposite visual cortex were found in all layers except layer 1 while those labeled from the superior colliculus lay exclusively in layer 5. Within layer 5 interhemispheric cells were more concentrated in the lower half of the layer but extensively overlapped the distribution of corticotectal cells. Every cell studied that projected to the superior colliculus was of the bursting type and had a thick apical dendrite with a terminal tuft. Every cell in this study projecting to the opposite visual cortex was a "nonburster" and had a slender apical dendrite with fewer oblique branches that ended without a terminal tuft, usually in the upper part of layer 2/3. Interhemispheric cells also had rounder, less conical somata and generally had fewer basal dendrites than corticotectal neurons. Many cells with the physiological and morphological characteristics of interhemispheric cells were not back-labeled from the opposite visual cortex, implying that pyramidal cells of this type can have other projection targets (e.g., other cortical sites in the ipsilateral hemisphere).(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

Relation between retinotopical and orientation maps in visual cortex.

A recent study of cat visual cortex reported abrupt changes in the positions of the receptive fields of adjacent neurons whose preferred orientations strongly differed (Das & Gilbert, 1997). Using a simple cortical model, we show that this covariation of discontinuities in maps of orientation preference and local distortions in maps of visual space reflects collective effects of the lateral cortical feedback.

Animals↗

Plasticity in cat visual cortex restored by electrical stimulation of the locus coeruleus.

It has been proposed that the presence of noradrenaline (NA)-containing terminals and NA-related receptors within the visual cortex is necessary to maintain the high level of neuronal plasticity in the immature visual cortex of kittens. In the present study we wanted to show whether electrical stimulation of the locus coeruleus (LC), which contains the somata of these cortical NA fibers, can restore neuronal plasticity to the normally aplastic visual cortex of juvenile and adult cats. We consistently found a significant loss of binocular cells in the visual cortex of mature animals which had monocular vision for only 12 h dispersed over 6 days (2 h a day, otherwise kept in the dark) in combination with concurrent LC stimulation. This result was interpreted as indicating that endogenous NA released from NA terminals restored susceptibility to monocular vision in the mature visual cortex. We next examined how long the restored plasticity lasts in the same animals after the LC stimulation was ended. The animals revived from the first recording session were either returned to the same daily schedule of brief monocular exposure (light/dark = 2/22 h) as before, or subjected to the usual monocular lid suture and kept in a cat colony environment (light/dark = 16/8 h). The LC electrodes had been removed and no more electrical stimulation was delivered at this stage. In the animals subjected to reiteration of brief monocular exposure, the state of reduced binocularity gradually returned to normal over a period of 2-3 weeks after stopping LC stimulation. We calculated that the revived plasticity disappeared at an average rate of a 22% loss every 7 days. This result sharply contrasted with the result obtained in the animals subjected to usual monocular lid suture. In this test the state of reduced binocularity continued for at least the next 3 weeks, suggesting that the restored plasticity was sustained throughout a period of 3 weeks (longest term tested). The different results obtained in the two paradigms may be explained by the different strength of binocular imbalance in the two tests imposed on the visual cortex in which neuronal plasticity was restored partially.

Animals↗