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Noninvasive optical imaging in the visual cortex in young infants.

During the developmental stage, the brain undergoes anatomic, functional, and metabolic changes necessary to support the complex adaptive behavior of a mature individual. Estimation of developmental changes occurring in different regions of the brain would provide a means of relating various behavioral phenomena to maturation-specific brain structures, thereby providing useful information on structure-function relationships in both normal and disease states. We used multichannel near-infrared spectroscopy (MNIRS), a new noninvasive imaging technique for revealing the course of neural activity in selected brain regions, to monitor the activities of the visual cortex as mirrored by hemodynamic responses in infants subjected to photostimulation during natural sleep. In the infants, oxyhemoglobin and total hemoglobin decreased and deoxyhemoglobin increased in the visual cortex with photostimulation. This pattern of responses was different from the response pattern in adults reported previously. The different patterns of responses to photostimulation in the visual cortices of infants and adults might reflect developmental and behavioral differences. It may reflect a different functional organization of the visual cortex in infants or ongoing retinal development. Our results demonstrated that regional hemodynamic change could be detected in a small area around the visual cortex. MNIRS offers considerable potential for research and noninvasive clinical applications.

Adult↗

Functional organization of columns in damaged visual cortex of adult cats.

OBJECTIVE: The objective of the present study was to reveal the amount of preservation of the most prominent features of the visual cortex: orientation and ocular dominance columns. It has been assumed that because of its inherent organization, the fragment of cells that would survive following lesioning would preserve the orientation and ocular dominance properties, despite the distortion of the connectivity pattern. EXPERIMENTAL: The experiments were carried out on 13 anesthetized and paralyzed adult cats from which 1,186 single cells were recorded. The animals were divided into the following three experimental (operated) groups to observe the time lapse of changes after operation: Acute (immediately); Short Chronic (2 to 3 months), and Long Chronic (5 to 7 months). The operations were performed using microsurgical, stereotaxic, electrophysiological, and histological techniques. The disconnection was produced by making a surgical incision into the visual cortex perpendicular to the cortical columns as accurately as possible. The single-unit activity of cells was recorded in the areas proximal and distal to the lesion. RESULTS: In all groups, the visual responsiveness of the cells was significantly reduced and the percentage of binocular cells was significantly lower in all recording sites. The distribution of the cells according to their ocular dominance was similar to that in the normal control group. Surprisingly, most of the cells, that remained visually active, were found selective to orientation in all experimental groups as well as in the normal control group. CONCLUSION: Even though no improvement in function occurred because mature cells were involved, the inherent structure of the disrupted cortical columns in the visual cortex was preserved. Therefore, the disruption of cortical connections does not lead to remarkable distortion of the inherent connectivity pattern on the whole in visually active cortical fragments.

Animals↗

Alterations in the visual cortex receptor pattern by operant conditioning in a reward paradigm.

The aim of the study was to investigate the impact of operant conditioning on the receptor pattern in the visual cortex of calves. A reward paradigm was used to induce conditioned preference for colours. Binding sites in visual cortex specimens from conditioned and naive animals were assayed in vitro on cellular basis after dissociation of the tissue by collagenase, incubation with fluorescent ligands and flow-cytometry for fluorescence analysis. The cellular counts were subdivided according to sedimentation at 200 g as well as via the flow-cytometrical histogram by size and granularity. Binding sites of dopamine D1 and D2 receptor subtypes, glucocorticoids, opioids, casein as well as glycine and N-methyl-D-aspartic acid (NMDA) were detected by fluorescent molecular probes. In displacing naloxone fluorescein from NMDA- and mu-opioid receptors NMDA and meth-enkephalin were used. Comparisons between portions of fluorescent cellular counts from visual cortex tissue of conditioned and naive animals revealed a small increase (1.2-fold, P < 0.05) in opioid receptors of large and high granulated counts, bearing > 80% D1 receptors, and a decrease (0.70-fold, P < 0.05) in less granulated counts with variable portion of D1 receptors. Conditioning resulted in higher and lower displacing rates by meth-enkephalin and NMDA, resp., and in a reduce in counts with dopamine D1 (0.8-fold, P < 0.05), glycine and glucocorticoid binding sites (0.6-fold in both cases, P < 0.01). A tendency of elevated phagocyte marker expression occurred in high granulated counts. The data suggest that conditioning is accompanied with significant and in part marked change in binding sites studied. Induction of scavenger activity may parallel this process. As cellular portion with glycine and glucocorticoid receptors were most markedly altered by conditioning, the neurochemical needs of the used paradigm seem to focus to motility-related functions.

Animals↗

A Golgi study of the early postnatal development of the visual cortex of the hooded rat.

Although neuroanatomical plasticity has been demonstrated in the rat visual cortex, no systematic data on the dendritic development of the area are available. In the present study, the visual cortex of hooded rats at 1, 3, 5, 7, 10 and 15 postnatal days of age (P1-P15) was impregnated with the rapid Golgi method. The cortex was divided into the superficial layers, II-IV, and the middle layer V. At P1, pyramidal neurons had apical shafts and the beginning of the apical terminal arch. Analysis of both basilar and oblique dendritic number showed that pyramidal neurons of the middle layer developed more quickly than those in the superficial layers. The number of lower order basilar dendritic branches reached asymptote over the examined time period, whereas the higher order branches were still increasing in number but at a decelerating rate by P15. Dendrites at all ages exhibited varicosities which were especially prominent on the thin dendritic branches of the earlier ages. Some thin, filamentous processes, termed protospines, were found on dendrites and cell bodies at P1 to P5. They seemed to decrease by P7, when a few mature spines appeared. Spines increased in number on days P10 and P15. A comparison of the data from this study with quantified Golgi studies in adult rats indicates that by P10 and P15 the number of basilar branches is in the range seen in the adult.

Age Factors↗

The development of beta-adrenergic receptors in the visual cortex of the rat.

The development of beta-adrenergic receptors in the rat visual cortex was examined and the density of beta-receptors and associated subtypes (beta 1 and beta 2) was compared between visual and non-visual or whole cortical tissues using radioreceptor assays employing [125I]iodohydroxybenzylpindolol and [125I]iodocyanopindolol as ligands. Saturation assays revealed not only similar affinities of beta-receptors for [125I]iodohydroxybenzylpindolol in visual cortical samples at 10, 24 and 160 days after birth but also practically identical saturation curves for visual and non-visual cortical samples at 160 days of age. Displacement of [125I]iodohydroxybenzylpindolol with propranolol in visual cortical membranes at various postnatal ages showed a gradual increase in receptor density from day 4 to day 24 with no change thereafter. No significant differences were observed in the overall density of beta-receptors or in the distribution and density of beta 1 and beta 2-receptors between visual and non-visual or whole cortical samples; however, there was a definite decline in the density of beta-receptors in these samples between 40 and 160 days of age. The results indicate that the developmental pattern of beta-receptor density and the distribution of beta 1 and beta 2-receptors are similar between visual and whole cortical tissues. In addition, the results emphasize the importance of maintaining the dissociation constant at a fixed value when comparing receptor densities between experiments, and also show the utility of employing the high-affinity ligand, [125I]iodocyanopindolol, with a combination of serotoninergic, dopaminergic and alpha-adrenergic antagonists to examine beta-adrenergic receptors in a specific region of the brain. Study of beta-receptors in the visual cortex may be beneficial in elucidating the role of norepinephrine in this region.

Animals↗

Postsynaptic calcium and calcium-dependent processes in synaptic plasticity in the developing visual cortex.

In this paper we describe some of the results obtained from recent experiments on mechanisms underlying long-term potentiation (LTP) and long-term depression (LTD) in the visual cortex of young rats. In particular, we focus on experiments which tested the hypotheses that the induction of LTP in the visual cortex is of Hebbian type and that an input-associated Ca2+ rise at postsynaptic sites and subsequent activation of protein kinases or protein phosphatases may play roles in the induction of LTP or LTD in the developing visual cortex.

Animals↗

Lesions of nonvisual inputs affect plasticity, norepinephrine content, and acetylcholine content of visual cortex.

1. The depletion of both norepinephrine (NE) and acetylcholine (ACh) in the visual cortex can decrease plasticity. This decrease in plasticity, although dramatic under some circumstances, fails to occur under others. 2. We depleted cortical NE and ACh in 35- to 42-day-old kittens by making a lesion of the white matter behind the cingulate gyrus. One eye was sutured on the day of the lesion. We recorded from the visual cortex 7 days or 2-3 mo later and used the influence of the deprived eye on the cortical cells as a measure of plasticity. 3. We measured NE content by high-pressure liquid chromatography (HPLC) and inferred ACh depletion from depletion of choline acetyltransferase (ChAT) activity. NE depletion averaged 60% in the successfully depleted animals. Depletion of ChAT activity was consistent with NE depletion. 4. When recording occurred 7 days after the lesion and the sutured eye was contralateral to the lesion, plasticity was decreased on the side with the lesion; 70% of the cells were driven by the deprived eye. On the control, uninjured side only 15% of the cells were driven by the deprived eye. 5. In two circumstances the lesion did not cause a decrease in plasticity. In animals with suture ipsilateral to the lesion, the cortex remained plastic. In these animals only 26% of the cells in the hemisphere with the lesion were driven by the deprived eye. The cortex also retained its plasticity if the contralateral eye remained sutured for several months after the lesion, even though there was no recovery from NE and ACh depletion. 6. We conclude that depletion of NE and ACh does decrease plasticity; that is, it protects the deprived eye from losing its ability to drive cortical cells, at least for a short period of time. Depletion protects only the normally dominant contralateral pathway; the ipsilateral visual pathway remains plastic. 7. Perhaps the importance of the side of the deprived eye can be explained by assuming that depletion of NE and ACh removes facilitatory input. This would decrease the ability of cortical cells on the side with lesion to potentiate the input from the nondeprived eye relative to the deprived eye; that is, it would decrease the molecular deprivation (MD) effect. A removal of facilitation would also increase the visual input required to drive cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetylcholine↗

Ramification patterns of vasoactive intestinal polypeptide (VIP)-cells in the rat primary visual cortex. An immunohistochemical study.

Vasoactive intestinal polypeptide (VIP)-immunoreactive cells in the primary visual cortex of the rat were classified on the basis of ramification pattern of cell processes. The distribution of cells over cortical layers, and proportions of cell classes relative to total cell numbers were evaluated by means of quantitative methods. Two main types of VIP-positive neurons, the bipolar and the multipolar were distinguished constituting 76% and 24% of the VIP populations, respectively. The axons of vertically oriented bipolars were observed to ramify within a column around the descending dendrite. By contrast, multipolar cells have a non-oriented ramification pattern. The two overlapping axonal systems form the VIP-innervation of the rat visual cortex.

Animals↗

Glutamic acid decarboxylase and somatostatin immunoreactivities in rat visual cortex.

Antibodies to glutamic acid decarboxylase (GAD) and somatostatin (SS) were used to determine the laminar distribution and morphology of GAD- and SS-immunoreactive neurons and terminals in rat visual cortex. The present study demonstrates that GAD-immunoreactive neurons constitute several morphologically distinct subclasses of neurons in rat visual cortex. These subclasses of neurons can be distinguished by differences in soma size, soma shape, dendritic branching patterns, axonal arborizations, and location in the neuropil. GAD-immunoreactive neurons are found throughout all layers of visual cortex. They have nonpyramidal morphology and constitute roughly 15% of the total neuronal population. The laminar pattern of GAD-immunoreactive puncta is uneven, with a prominent band of terminals in layer IV. Numerous large GAD-positive puncta surround the somata and proximal dendrites of pyramidal cells in layers II, III, and V. SS-immunoreactive neurons constitute a less numerous and more restricted population of nonpyramidal neurons. Their somata are located mainly in layers II, III, V, and VI. Very few, if any, SS-immunoreactive neurons are found in layers I and IV. SS-immunoreactive terminals are arranged along vertical and diagonal collateral branches that have a beaded appearance. Finally, many neurons in the supra- and infragranular layers and in the white matter are immunoreactive to both glutamic acid decarboxylase and somatostatin. This coexistence of immunoreactivity to both GAD and SS may characterize a broad subclass of cortical nonpyramidal neurons.

Animals↗

An inhibitor for calcineurin, FK506, blocks induction of long-term depression in rat visual cortex.

Long-term depression (LTD) of synaptic transmission, often used as an essential component in synaptic models for learning, memory and forgetting, can be produced in layer II/III of the visual cortex by a prolonged, low-frequency stimulation (LFS) of layer IV. The activation of Ca2+/calmodulin-dependent protein phosphatase, calcineurin, has been postulated to play a role in the induction of LTD. The recent introduction of a specific inhibitor for calcineurin, FK506, prompted the investigation of the involvement of this phosphatase in the induction of LTD in visual cortex. Thus, we administered FK506 at 1 microM to visual cortical slices of young rats, and found that it did not significantly affect field responses of layer II/III evoked by test stimulation of layer IV at 0.1 Hz, but prevented LTD of the responses from being induced by LFS (1 Hz for 15 min) in all the 10 slices tested. Without FK506, significant LTD was induced by the same parameters of LFS in 8 of the 12 slices. These results suggest the critical involvement of calcineurin in producing LTD in visual cortex.

Animals↗

Interhemispheric connections of visual cortex in the owl monkey, Aotus trivirgatus, and the bushbaby, Galago senegalensis.

Anatomical techniques have been used to map within visual cortex th pattern of degenerating axonal terminals produced by surgical section of the splenium of the corpus callosum in the owl monkey, Aotus trivirgatus, and the bushbaby, Galago senegalensis. Previous studies in other species have shown that callosal inputs terminate preferentially in regions where the vertical meridian of the visual field is represented. Such a correspondence can serve as a useful aid for locating the boundaries of visual areas. The goals of this study have been (1) to assess the degree of correspondence between callosal inputs and previously identified vertical meridian representations in the owl monkey and bushbaby, and (2) to gain information from the pattern of callosal inputs concerning the existence and organization of as yet unidentified extrastriate visual areas. In both the owl monkey and the bushbaby, a discrete band of degenerating axonal terminals corresponds precisely to the vertical meridian representation at the V1-V2 border, and a less precise increase in the density of degenerating axonal terminals corresponds to the vertical meridian representation of extrastriate area MT. A well-defined band of degeneration on the ventral surface of the owl monkey's cerebral hemisphere corresponds to a previously unknown vertical meridian representation which is shared by two newly identified extrastriate visual areas. Elsewhere in visual cortex the pattern of callosal connections is more complex. Although this pattern may still reflect visual topography, it is not immediately useful for distinguishing areal boundaries.

Animals↗

Nerve growth factor favours long-term depression over long-term potentiation in layer II-III neurones of rat visual cortex.

Nerve growth factor (NGF) has been shown to regulate plasticity in the visual cortex of monocularly deprived animals. However, to date, few attempts have been made to investigate the role of NGF in synaptic plasticity at the cellular level. In the study reported here we looked at the effects of exogenously applied NGF on synaptic plasticity of layer II-III regular spiking (RS) neurones in visual cortex of 16- to 18-day-old rats. We found that local application of NGF converted high frequency stimulation (HFS)-induced long-term potentiation (LTP) into long-term depression (LTD). We showed that this shift of synaptic plasticity was also obtained with bath application of NGF during HFS. Application of NGF subsequent to HFS left LTP unaffected, conferring temporal constraints on NGF efficacy. NGF effects on LTP were mediated by TrkA receptors. Indeed, blockade of TrkA by monoclonal antibody prevented NGF from inducing LTD following HFS. Low frequency stimulation (LFS) elicited LTD in RS cells. We found that NGF or blockade of NGF signalling by anti-TrkA antibody did not change the amplitude of the LTD induced by LFS. Thus, the NGF effect is selective for synaptic modifications induced by HFS in RS cells. The present results indicate that NGF may modulate the sign of long-term changes of synaptic efficacy in response to high frequency inputs.

Animals↗

Properties of place cell firing after damage to the visual cortex.

Hippocampal place cells were recorded while rats with lesions of the striate visual cortex foraged for food pellets in a cylindrical arena. Compared to control rats, rats with striate damage had place cells whose firing was less well organized in space, according to a measurement of spatial coherence. More importantly, the spatial location of firing fields in rats with striate lesions was poorly controlled by three-dimensional objects, unlike the fields of either normal sighted rats or early blind rats. These findings suggest a possible contribution of the striate visual cortex to the selection of cues used for anchoring place cell firing fields in space.

Action Potentials↗

An immunohistochemical study of neurotransmitter profiles in developing human visual cortex.

The temporal pattern of development and distribution of gamma aminobutyric acid, serotonin, substance P and neuropeptide Y immunoreactive profiles was studied in the human visual cortex from 16 to 26 weeks of gestation, using an immunohistochemical technique. The immunoreactive profiles showed an increase in number and a change in their morphology and distribution pattern over the time period studied. A large number of neurons, fibers and terminals were stained with GABA antibody at 17-18 weeks and were distributed throughout the five zones of the developing visual cortex. GABA neurons were non-pyramidal and bipolar in form at 17-18 weeks while at 18-19 and 20-21 weeks the cells of subplate and intermediate zones were multipolar. Substance P and serotonin immunopositive fibers were present mainly in the intermediate zone at 16 and 17-18 weeks, where they were oriented in a horizontal manner. At subsequent ages they invaded the other zones also. Substance P positive neurons could be visualized only at 26 weeks of gestation in the intermediate, subventricular and ventricular zones; no cell bodies, however, stained with serotonin antibody. Neuropeptide Y immunoreactive cells and fibers were first seen in the intermediate zone but later were found to be distributed in other zones too. The observations indicate that the intermediate zone of the visual cortex in which the transmitters and peptides appear earlier assumes importance in the normal development as also noted in other mammals.

Female↗

The morphology and distribution of peptide-containing neurons in the adult and developing visual cortex of the rat. I. Somatostatin.

Using conventional immunocytochemical techniques, we have examined the morphology and distribution of somatostatin-like immunoreactive neurons in the visual cortex of albino rats between the first postnatal day and maturity. In the adult, somatostatin-immunoreactive neurons were observed in layers II to VI but were concentrated in layers II and III. These cells displayed morphological features characteristic of the multipolar and bitufted varieties of cortical non-pyramidal neurons as described in Golgi preparations of rat visual cortex. On the first postnatal day and in the subsequent few days, immunoreactivity was confined to immature bipolar and multipolar neurons concentrated in layers V and VI. Labelled cells first appeared in the more superficial layers at the beginning of the second postnatal week and attained a distribution similar to that observed in adult animals at the end of this week. At this time they closely resembled their adult counterparts from which they appeared indistinguishable by the end of the third postnatal week. The late appearance of labelled cells in the superficial layers, where they are predominantly located in adult animals, suggests that the somatostatin immunoreactivity exhibited by most of these neurons develops several days after they have completed their migration and assumed their positions in the visual cortex.

Aging↗

A current source density analysis of evoked responses in slices of adult rat visual cortex: implications for the regulation of long-term potentiation.

In slices of visual cortex, long-term potentiation (LTP) of synaptic responses in layer III can be evoked by high-frequency stimulation of a site in the middle of the cortical thickness, corresponding mainly to layer IV. In contrast, stimulation of the white matter-layer VI border typically fails to evoke LTP in adult visual cortex unless GABAA receptors are partially blocked. We performed current-source density (CSD) analysis to determine how the patterns of cortical activation compare under these different stimulation conditions. Single-pulse stimulation of the middle layers (corresponding to layer IV and superficial V) and the deep layers (corresponding to white matter and deep layer VI) yielded very similar CSD patterns. The major current sinks were located within 500 mu m of the pia, corresponding to layers II and III, regardless of the stimulation site. The amplitude of all current sinks was diminished, and the latency was increased, in the presence of high concentrations of divalent cations (12 mM Ca2+ and 12 mM mg2+). Nonetheless, the major synaptic current sink was still present at a depth of approximately 400 microns regardless of the site of stimulation, indicating that stimulation of either site leads to monosynaptic EPSCs in layer III. However, superficial sinks, at a depth of approximately 200 microns, were virtually eliminated by high concentrations of divalent cations after deep layer stimulation, but not after middle layer stimulation, suggesting that stimulation at the two sites recruits different monosynaptic circuits. This conclusion was supported by experiments using paired-pulse stimulation of the two sites (12.5 ms interstimulus interval). While there was little evidence of a paired-pulse interaction after stimulation of the middle layers, there was marked paired-pulse suppression of superficial layer III current sinks after stimulation of the deep layers. Taken together, the data suggest a model in which deep layer stimulation activates the dendrites of layer III cells by a monosynaptic route and by a disynaptic route. The disynaptic input originates in the middle cortical layers and is controlled by inhibition. Differences in synaptic plasticity evoked from the different sites could be explained if the recruitment of middle layer inputs were required for the generation of LTP in layer III.

Animals↗

Investigations of origins of serotonergic projection to developing rat visual cortex: a combined retrograde tracing and immunohistochemical study.

The present study investigated whether the raphe neurons which give rise to the transient serotonergic fibers in the visual cortex of neonatal rats persist or disappear as the rats mature. Three experiments were performed employing the WGA-apoHRP-Au retrograde transport technique in conjunction with 5-HT or WGA-HRP immunohistochemical staining. WGA-apoHRP-Au was injected into the primary visual cortex of all rats 9 days postnatally. In the first experiment, the animals were examined after 2 days; retrogradely labeled cells were observed in the dorsal raphe nucleus (DR), the median raphe nucleus (MR), and in the B9 and B6 cell groups; the majority (82.5%) of the cells was serotonergic. In the second experiment, the examinations took place following a survival time of 8 weeks: virtually all of the original raphe-visual cortical serotonergic neurons were found to the present. In the third experiment, also performed after 8 weeks relabeling the raphe-visual cortical neurons by WGA-HRP, it was found that 37.2% of the raphe neurons which had projected to the neonatal visual cortex no longer possessed such projections.

Aging↗

Heterogeneity of synaptic density in the adult pigmented rabbit's visual cortex.

In the adult pigmented rabbit, synaptic density in the lateral and medial part of the visual cortex was estimated along the projection area of the visual streak. A higher synaptic density distribution was observed in the lateral cortex (projection area of the nasal visual field) than in the medial cortex (projection area of the temporal visual field). This shows that there is a higher synaptic density in the region of the visual cortex receiving input from a retinal area with a high ganglion cell concentration than the area of the cortex receiving input from the retina with a low concentration of such cells. The regions of the visual cortex with higher and lower synaptic densities are the areas having a higher and lower magnification factor respectively.

Animals↗