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Activity-dependent receptive field changes in the surround of adult cat visual cortex lesions.

Extracellular single cell spike activity was recorded in the visual cortex of anaesthetized adult cats at identical sites before and 2 days after focal excitotoxic lesions induced by injections of ibotenic acid. In the surround of the lesions (up to 5 mm from the border of the lesion), the average postlesion receptive field (RF) sizes were not different from the prelesion RFs. However, RFs of neurons with increased postlesion excitability were slightly enlarged; such neurons were mainly found close to the anterior border of the lesion (< or = 1 mm). After applying a visual training procedure for 1 h to the postlesion RFs (repetitive, synchronous stimulation of a part of the RF and the neighbouring unresponsive part of the visual field), there was a small (0.4-0.8 degrees ) but significant and specific increase of RF size in about half of the tested neurons. This RF enlargement was similar to that observed with the same training procedure in the visual cortex of normal cats. Thus, small RF changes can be induced by visual stimulation within one hour in normal cells as well as in cells at the border of cortical lesions. Any differences between normal and lesioned animals appear to be related to lesion-induced changes of excitability.

Action Potentials↗

Morphology and distribution of neurons and glial cells expressing beta-adrenergic receptors in developing kitten visual cortex.

The morphology and distribution of cells expressing beta-adrenergic receptors has been studied in developing kitten visual cortex using a monoclonal antibody which recognizes both beta-1 and beta-2 adrenergic receptors. We found specific populations of neurons and glial cells which express beta-adrenergic receptor immunoreactivity in the kitten visual cortex. In adult animals, the receptors are most concentrated in the superficial and deep cortical layers (layers I, II, III and VI). About 50% of the stained neural cells in adult cat visual cortex are glial cells. Most of the immunoreactive neurons in layers III and V are pyramidal cells while those in layers II and IV are more likely to be nonpyramidal cells. In neonatal kittens, staining is weaker than that in adult cats and it appears to be concentrated in neurons of the deep cortical layers and in the subcortical plate and white matter. Only a few immunoreactive glial cells were found at this age. Receptor numbers increase after birth and by 24 days of age, the laminar distribution of beta-adrenergic receptors approaches that of adult animals. Immunoreactive glial cells in the white matter show a progressive increase in number throughout postnatal development.

Aging↗

Development and activity-dependent expression of neuronal marker proteins in organotypic cultures of rat visual cortex.

We are interested in activity-dependent mechanisms which govern the structural and functional maturation of neurons in the visual cortex. We have asked whether the expression of neuronal markers microtubule-associated proteins tau, MAP-2, synaptophysin (p38), and the growth-associated protein GAP-43 are dependent on cortical afferents or spontaneous activity. As a model system we have employed organotypic monocultures of rat visual cortex (OTCs, isolated from subcortical structures) in comparison with visual cortex in vivo (innervated by thalamic and other afferents) at different postnatal ages. We know from previous work that the OTCs, like the cortex in vivo, display a high rate of spontaneously generated action potentials. Therefore, as a third objective, we have analysed OTCs grown as monocultures under chronic blockade of spontaneous action potentials. Protein expression was detected by protein blots and/or immunohistochemistry. The proteins examined in this study are expressed in OTCs, even when grown under activity blockade. However, the pattern of expression differs from the cortex in vivo. Tau is expressed much weaker in OTCs than in cortex in vivo. The expression of the major band of about 50 kDa increases over time in vivo and in OTCs. Smaller isoforms of tau are dramatically downregulated, and larger (adult) isoforms do not appear within 35 days in vitro (DIV). Under activity blockade the expression of tau reaches a maximum by 21 DIV and decreases dramatically, so that the protein is hardly detectable by 47 DIV. MAP-2-immunoreactive proteins are localized in somata and dendrites, but also persist in axons. The expression in OTCs of p38 and GAP-43 correlates well with the expression observed in vivo. Synaptophysin (p38) occurs with a similar time course and amount in OTCs as in cortex in vivo. Synaptic boutons appear in all layers, and specialized terminal elements have been observed. Activity blockade slightly affects the p38 expression, although the late postnatal decline in p38 immunoreactivity observed on protein blots from cortex in vivo and in normal OTCs appears more accentuated in activity-blocked OTCs. The GAP-43 expression is prominent from birth onwards in vivo and in OTCs. However, in normal OTCs GAP-43 is not declining as it is in vivo, although it is downregulated in activity-blocked OTCs. As a major finding we report that neuronal markers which are normally expressed in immature neurons and axons during the period of differentiation and structural plasticity are continuously expressed in OTCs, suggesting that a monocultured cortex retains the ability for growth and structural changes longer than the cortex in vivo.

Aging↗

Bihemispheric Collateralization of the Cortical and Subcortical Afferents to the Rat's Visual Cortex.

A fluorescent dye (usually fast blue or rhodamine tagged latex microspheres) was injected into cortical area 17 (or area 17 and the lateral part of area 18b) of adult and juvenile (15 - 22 day old) Sprague-Dawley albino rats. Another fluorescent dye (usually diamidino yellow) was injected into cortical areas 17, 18a and 18b of the opposite hemisphere. The injections involved only the cortical grey matter. After postinjection survival of 2 - 14 days the distribution of retrogradely labelled mesencephalic and prosencephalic cells was analysed. Both small and large injections labelled retrogradely a substantial number of cells in specific and nonspecific dorsal thalamic nuclei (lateral geniculate, lateral posterior, ventromedial, several intralaminar nuclei and nucleus Reuniens) as well as a small number of cells in the preoptic area of the hypothalamus and the mesencephalic ventral tagmental area (VTA). While labelled thalamic cells contained only the dye injected into the ipsilateral cortex, a small proportion of hypothalamic and VTA cells was labelled with the dye injected into the contralateral cortex. Virtually none of the cells in these areas were double labelled with both dyes. Both small and large injections labelled cells in the ipsilateral telencephalic magnocellular nuclei of the basal forebrain and the caudal claustrum. A substantial minority of labelled cells in these structures was labelled by the dye injected into the contralateral cortex. Furthermore, a small proportion (about 1%) of claustral cells projecting to the ipsilateral cortex were double labelled with both dyes. In several cortical areas ipsilateral to the injected area 17, associational neurons were intermingled with commissural neurons projecting to the contralateral visual cortex. A substantial proportion of associational neurons projecting to ipsilateral area 17 also projected to the contralateral visual cortex (associational-commissural neurons). Thus, in visual area 18a, the associational-commissural neurons were located in all laminae, with the exception of lamina 1 and the bottom of lamina 6, and constituted about 30% of the neurons projecting to ipsilateral area 17. In paralimbic association area 35/13, associational-commissural neurons were located in lamina 5 and constituted about 20% of neurons projecting to ipsilateral area 17. In the limbic area 29d, the associational-commissural neurons were located in laminae 4, 5 and the upper part of lamina 6 and constituted about 10% of the associational-commissural neurons projecting to ipsilateral area 17. In oculomotor area 8, double-labelled neurons were located in lamina 5 and constituted about 10% of the neurons projecting to ipsilateral area 17. Thus, it appears that the axons of mesencephalic and diencephalic neurons projecting to the visual cortex do not send collaterals into both hemispheres. The bihemispheric projection to the rat's visual cortex originates almost exclusively in the retinotopically organized cortical area 18a and in integrative cortical areas 35/13, 29d and 8.

Journal Article↗

Nerve growth factor and brain-derived neurotrophic factor increase neurotransmitter release in the rat visual cortex.

A number of experiments have shown that neurotrophins are involved in the development and plasticity of the visual cortex (Bonhoeffer, T., Curr. Op. Neurobiol., 6, 119, 1996). A possible mechanism underlying these effects is the neurotrophin modulation of synaptic transmission. We investigated whether nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) can modulate the release of neurotransmitter in the rat visual cortex at the peak of the critical period for plasticity (P23). The release of glutamate, acetylcholine and gamma-aminobutyric acid (GABA) from visual cortical synaptosomes was analysed in continuous perfusion conditions. We found that NGF enhances the depolarization-evoked release of glutamate (approximately 90%) and acetylcholine (approximately 35%) but not that of GABA. By contrast, BDNF enhances the depolarization-evoked release of all three neurotransmitters investigated (approximately 30%). BDNF and NGF were ineffective on basal release of neurotransmitters. The effect of NGF was not blocked by cholinergic antagonists atropine and mecamylamine. NGF and BDNF potentiation of transmitter release was strongly but not completely blocked by K252a, a tyrosine kinase inhibitor. The role of TrkA and p75NTR receptors was investigated in NGF-induced potentiation of glutamate release. Block of NGF binding to p75NTR using specific blocking antibodies (REX-IgG) slightly but significantly reduced the effect of NGF. Activation of TrkA in isolation by RTA-IgG, an antibody that specifically activates TrkA, was less effective than activation of both receptors by NGF. These results show that neurotrophin action on neurotransmitter release was mostly mediated by Trk receptors with p75NTR having a little but significant positive role. Antigen blot analysis showed the presence of TrkA, TrkB and p75NTR receptors in the visual cortex.

Animals↗

Substrates for coincidence detection and calcium signaling for induction of synaptic potentiation in the neonatal visual cortex.

Regulation of the efficacy of synaptic transmission by activity-dependent processes has been implicated in learning and memory as well as in developmental processes. We previously described transient potentiation of excitatory synapses onto layer 2/3 pyramidal neurons in the visual cortex that is induced by coincident presynaptic stimulation and postsynaptic depolarization. In the adult visual cortex, activation of N-methyl-d-aspartate (NMDA) glutamate receptors is necessary to induce this plasticity. These receptors act as coincidence detectors, sensing presynaptic glutamate release and postsynaptic depolarization, and cause an influx of Ca(2+) that is necessary for the potentiation. In the neurons of the neonatal visual cortex, on the other hand, coincident presynaptic stimulation and postsynaptic depolarization induce stable long-term potentiation (LTP). In addition, reduced but significant LTP can be induced in many neurons in the presence of the NMDA receptor (NMDAR) antagonist, 2-amino-5-phosphonovaleric acid despite the Ca(2+) requirement. Therefore there must be an alternative postsynaptic Ca(2+) source and coincidence detection mechanism linked to the LTP induction mechanism in the neonatal cortex operating in addition to NMDARs. In this study, we find that in layer 2/3 pyramidal neurons, release of Ca(2+) from inositol trisphosphate (InsP(3)) receptor-mediated intracellular stores and influx through voltage-gated Ca(2+) channels (VGCCs) provide alternative postsynaptic Ca(2+) sources. We hypothesize that InsP(3)Rs are coincidence detectors, sensing presynaptic glutamate release through linkage with group I metabotropic glutamate receptors (mGluRs), and depolarization, through VGCCs. We also find that the downstream protein kinases, PKA and PKC, have a role in potentiation in layer 2/3 pyramidal neurons of the neonatal visual cortex.

Animals↗

Motility of dendritic spines in visual cortex in vivo: changes during the critical period and effects of visual deprivation.

Cortical dendritic spines are highly motile postsynaptic structures onto which most excitatory synapses are formed. It has been postulated that spine dynamics might reflect synaptic plasticity of cortical neurons. To test this hypothesis, we have investigated spine dynamics during the critical period in mouse visual cortex in vivo with and without sensory deprivation. The motility of spines on apical dendrites of layer 5 neurons was assayed by time-lapse two-photon microscopy. Spines were motile at the ages examined, postnatal days (P)21-P42, although motility decreased between P21 and P28 and then remained stable through P42. Binocular deprivation from before the time of eye-opening up-regulated spine motility during the peak of the critical period (P28), without affecting average spine length, class distribution, or density. Deprivation at the start of the critical period had no effect on spine motility, whereas continued deprivation through the end of the critical period appeared to reduce spine motility slightly. We conclude that spine motility might be involved in critical-period plasticity and that reduction of activity during the critical period enhances spine dynamics.

Aging↗

Where is 'dorsal V4' in human visual cortex? Retinotopic, topographic and functional evidence.

In flattened human visual cortex, we defined the topographic homologue of macaque dorsal V4 (the 'V4d topologue'), based on neighborhood relations among visual areas (i.e. anterior to V3A, posterior to MT+, and superior to ventral V4). Retinotopic functional magnetic resonance imaging (fMRI) data suggest that two visual areas ('LOC' and 'LOP') are included within this V4d topologue. Except for an overall bias for either central or peripheral stimuli (respectively), the retinotopy within LOC and LOP was crude or nonexistent. Thus the retinotopy in the human V4d topologue differed from previous reports in macaque V4d. Unlike some previous reports in macaque V4d, the human V4d topologue was not significantly color-selective. However, the V4d topologue did respond selectively to kinetic motion boundaries, consistent with previous human fMRI reports. Because striking differences were found between the retinotopy and functional properties of the human topologues of 'V4v' and 'V4d', it is unlikely that these two cortical regions are subdivisions of a singular human area 'V4'.

Animals↗

Interconnections of the visual cortex with the frontal cortex in the rat.

Horseradish peroxidase conjugated to wheat germ agglutinin (WGA-HRP) and autoradiography of tritiated leucine were used to trace the cortical origins and terminations of the connections between the visual and frontal cortices in the rat. Ipsilateral reciprocal connections between each subdivision of the visual cortex (areas 17, 18a and 18b) and the posterior half of the medial part of the frontal agranular cortex (PAGm), and their laminar organizations were confirmed. These connections did not appear to have a significant topographic organization. Although in areas 17 and 18b terminals or cells of origin in this fiber system were confined to the anterior half of these cortices, in area 18a they were observed spanning the anteroposterior extent of this cortex, with in part a column like organization. No evidence could be found for the participation of both the posterior parts of areas 17 and 18b and the anterior half of this frontal agranular cortex in these connections. Fibers from each subdivision of the visual cortex to the PAGm terminated predominantly in the lower part of layer I and in layer II. In area 17, this occipito-frontal projection was found to arise from the scattered pyramidal cells in layer V and more prominently from pyramidal cells in layer V of area 17/18a border. In area 18a, the fibers projecting to the PAGm originated mainly from pyramidal cells primarily in layer V and to a lesser extent in layers II, III and VI. Whereas in area 18b, this projection was found to arise mainly from pyramidal cells in layers II and III, to a lesser extent in layers V and VI, and less frequent in layer IV. On the other hand, the reciprocal projection to the visual cortex was found to originate largely from pyramidal cells in layers III and V of the PAGm. In areas 17 and 18a, these fibers terminated in layers I and VI, and in layers I, V and VI, respectively. Whereas in area 18b, they were distributed throughout all layers except layer II.

Animals↗

Development of blobs in the visual cortex of macaques.

We have examined the area of the primary visual cortex and the number and size of blobs within it in 10 neonatal and 11 adult rhesus monkeys. The average area of the primary visual cortex (V1) increases from 919 mm2 in newborns to 1,069 mm2 in adult animals (16%). The number of blobs decreases per unit area from an average of 5.2/mm2 at birth to 4.3/mm2 in maturity (18%). As a consequence, the number of blobs remains approximately the same during maturation, at about 4,800/hemisphere. These observations correct a preliminary report on a subset of the animals studied here (Purves and LaMantia: Proc Natl Acad Sci 87:5765, '90), in which it appeared that blob number might increase between birth and maturity. As in other regions of the developing postnatal brain, we found no net loss of modular circuitry.

Animals↗

Localization of calcium-binding protein parvalbumin-immunoreactive neurons in mouse and hamster visual cortex.

Calcium-binding proteins are thought to play important roles in regulating intracellular calcium in the central nervous system. In the present study, we investigated the distribution and morphology of neurons containing parvalbumin in the visual cortex of mouse and hamster. The calcium-binding proteins were localized using immunocytochemistry. Parvalbumin-immunoreactive neurons were located in all layers except layer I. The highest density of parvalbumin immunoreactivity was found in layer V of both mouse and hamster. The labeled neurons varied in morphology. The majority of the parvalbumin-immunoreactive neurons both in mouse and hamster visual cortex was stellate and round, or oval with multipolar dendrites. These results indicate that the calcium-binding protein parvalbumin is contained in specific layers and in selective cell types of the mouse and hamster visual cortex. The distribution of parvalbumin in the mouse visual cortex is very similar to that of hamster.

Animals↗

Processing capability of the primary visual cortex and possible physiologic basis for an apparent motion illusion.

The primary visual cortex is known to process stimuli in a given part of the visual field such that divisions of the cortical column into orientation and ocular dominance minicolumns are present. Applying a model incorporating both the Hebb learning hypothesis and a Mountcastle-like organizational structure to the visual cortex, we predicted that the processing capabilities of the column involve dynamic interactions among minicolumns and are much greater than presently documented. In particular, processing of rotational stimuli in area 17 was suggested by the model. Motivated by this, a psychophysics experiment was conducted that demonstrated a spatial-temporal filling-in process in apparent motion. We have now presented this "human illusion" to cats and recorded from units in area 17 with results which clearly demonstrate striking phenomena not simply understood. The purpose of this note is to present our experimental paradigm with the preliminary results.

Animals↗

Unilateral eyelid suture increases GABAA receptors in cat visual cortex.

We have examined the number, characteristics and distribution of GABAA receptor in the visual cortex of normal cats and in cats monocularly deprived by unilateral eyelid suture from early in postnatal life. Receptor densities were about 100% higher in the deprived animals than in their normal counterparts. No changes in receptor affinity were noted. The GABAA receptor increase appeared to affect all laminae in the visual cortex. The results suggest that an increase in GABAA receptors may underlie or result from the physiological consequences of early monocular deprivation.

Age Factors↗

Modulatory and inhibitory processes in the visual cortex.

The functional role of three putative neurotransmitter systems in the visual cortex is compared; the GABAergic inhibitory interneurons, the interneurones containing somatostatin and the cholinergic input originating from the nucleus basalis of Meynert (nbM). Evidence is presented to support the role of GABAergic processes in the generation of the functional structure of the visual cortex and the view that the cholinergic input exerts a neuromodulatory influence enhancing stimulus selective responses. Although the neuropeptide somatostatin produces facilitatory and inhibitory effects on visual cortical cells there is no clear functional pattern to its action. The possible significance of this data and the interaction of SSt with GABA is discussed in the light of evidence that they may coexist in some cells.

Acetylcholine↗

Identification of complex-cell intensive nonlinearities in a cascade model of cat visual cortex.

Complex cells in the cat's visual cortex show nonlinearities in processing of image luminance and movement. To study mechanisms, initially we have represented the chain of neurons from retina to cortex as a black-box model. Independent information about the visual system has helped us cast this "Wiener-kernel" model into a dynamic-linear/static-nonlinear/dynamic-linear (LNL) cascade. We then use system identification techniques to define the nature of these transformations directly from responses of the neuron to a single presentation of a stimulus composed of a sequence of white-noise-modulated luminance values. The two dynamic linear filters are mainly low-pass, and the static nonlinearity is mainly of even polynomial degree. This approximate squaring function may be effected in the animal by soft-thresholding each of the linear ON- and OFF-channel signals and then summing them, which account for "ON-OFF" responses and for the squaring operation needed for computation of "motion energy", both observed in these neurons.

Animals↗

Development of MK-801, kainate, AMPA, and muscimol binding sites and the effect of dark rearing in rat visual cortex.

We used quantitative autoradiography to determine whether the development of glutamate receptors correlates with the plastic period for monocular deprivation in rat visual cortex. To study glutamate receptors, we incubated sections of rat visual cortex with tritiated (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]-cyclohepten-5,10imin e maleate (MK-801), tritiated kainate, and tritiated amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA). [3H]MK-801 is a noncompetitive ligand for the N-methyl-D-aspartate (NMDA) receptor. [3H]kainate and [3H]AMPA are competitive ligands for non-NMDA receptors. To compare glutamate binding sites with a nonglutamate binding site, we studied [3H]muscimol, which binds to gamma-aminobutyric acid (GABA)A receptors. [3H]MK-801 binding was maximal at postnatal day 26 (P26) and decreased in adulthood. [3H]AMPA binding was maximal at P18. [3H]kainate binding and [3H]muscimol binding were not age dependent. Dark rearing partially prevented the age-dependent decrease in [3H]MK-801 binding but had no effect on [3H]kainate or [3H]AMPA binding. Dark rearing decreased muscimol binding in adult animals. These results suggest that NMDA receptors, but not other glutamate receptors or GABAA receptors, are likely to be critical for developmental plasticity in rat visual cortex.

Animals↗

Renal cortex visualization and analysis of dynamic CT curves of the kidney.

Renal cortex visualization and dynamic renal computed tomography (CT) were carried out by bolus injection of contrast medium. In vivo renal cortex visualization showed that renal cortex volume and cortex thickness are both inversely correlated with age. The percentage volumes of cortex and columns of Bertin are correlated inversely in non renal-failure subjects. Percentage volumes of cortex tend toward low values in renal failure and status after renal transplantation. In analyzing dynamic renal CT curves, the corticomedullary junction time is a good index of mild impairment of renal function.

Acute Kidney Injury↗

Maintained activity of single neurons in the cat visual cortex at different levels of retinal adaptation.

The influence of ambient illumination on the maintained electrical activity of single neurons of the cat visual cortex was studied by using the closed chamber technique for extracellular recordings. Several levels of light background within the scotopic-mesopic range were explored. Phasic and tonic changes in firing rate were observed following a background change. The former were irregular and unpredictable variations lasting up to 15-20 min. The latter, which usually followed the phasic changes, showed the constant characteristic of being in direct relation to luminance variations for neurons isolated in the striate area and in inverse relation for units recorded from the two non-striate areas of the visual cortex; in all cases, they lasted until a new luminous level was set. Changes in firing rate were not dependent upon either the neuron receptive field organization or the EEG pattern, simultaneously recorded. The background-locked firing rate variations recorded at the visual cortex seem to be the result of a particular cortical distribution of afferent fibers carrying luminance information. Applications to vision research are also suggested.

Action Potentials↗