Biomedical subjects

W Singer

Publications and source records attributed to W Singer.

At least 181 records · Page 10Linked to original sources

PubMed1988

Topographic relations between ocular dominance and orientation columns in the cat striate cortex.

In the visual cortex of four adult cats ocular dominance and orientation columns were visualized with (3H)proline and (14C)deoxyglucose autoradiography. The two columnar systems were reconstructed from serial horizontal sections or from flat-mount preparations and graphically superimposed. They share a number of characteristic features: In both systems the columns have a tendency to form regularly spaced parallel bands whose main trajectory is perpendicular to the border between areas 17 and 18. These bands frequently bifurcate or terminate in blind endings. The resulting irregularities are much more pronounced in the ocular dominance than in the orientation system. The periodicity of the columnar patterns was assessed along trajectories perpendicular to the main orientation of the bands and differed in the two columnar systems. The spacing of the ocular dominance stripes was significantly narrower than the spacing of orientation bands. The mean periodicity of a particular columnar system was virtually identical in the two hemispheres of the same animal but it differed substantially in different animals. However, the spacing of orientation columns covaried with that of the ocular dominance columns, the ratios of the mean spacings of the two columnar systems being similar in the four cats. The superposition of the two columnar systems revealed no obvious topographic relation between any of the organizational details such as the location of bifurcations, blind endings and intersections. We suggest the following conclusions: 1. The developmental processes generating the two columnar systems seem to obey the same algorithms but they act independently of each other. 2. The space constants of the two systems are rigorously specified and appear to depend on a common variable. 3. The main orientation of the bands in both columnar systems is related to a) the representation of the vertical meridian, b) the anisotropy of the cortical magnification factor, and c) the tangential spread of intracortical connections.

Animals↗

PubMed1988

Experience-dependent modifications of kitten striate cortex are not prevented by thalamic lesions that include the intralaminar nuclei.

It has been shown previously that surgical lesions of the antero-medial thalamus interfere with ocular dominance modifications that normally result from monocular deprivation in young kittens (Singer 1982). The aim of the present study was to determine whether this effect was due specifically to the destruction of the visual cortical projections of the anterior intralaminar nuclei. We report here that large excitotoxin lesions of the anterior dorsal thalamus have no effect on the cortical response to monocular deprivation. These data indicate that the intralaminar projection is not essential for ocular dominance plasticity.

Animals↗

PubMed1988

Developmental changes of the distribution of binding sites for organic Ca2+-channel blockers in cat visual cortex.

There are indications that during a critical period of visual cortex development Ca2+-fluxes from extra- to intracellular compartments serve as a trigger signal for experience-dependent changes of neuronal response properties. In this study we investigate the possibility of a relation between the time course of the critical period and age-dependent changes in the density and topographical distribution of Ca2+-channels. As a marker for the latter we used Ca2+-channel blockers of the 1,4-Dihydropyridine (1,4-DHP) class since these are supposed to bind to voltage-dependent Ca2+-channels. We used the tritiated 1,4-DHP derivative 3H-PN 200 110 for autoradiographic determination of 1,4-DHP binding sites in the visual cortex of adult cats and kittens ranging in age from two to ten weeks. The binding of 3H-PN 200 110 to slide-mounted tissue sections was saturable and of high affinity. The overall density of specific 3H-PN 200 110 binding sites decreased during development and their laminar distribution underwent marked changes: in young kittens specific binding was accentuated in lower layer IV, whereas in adult cats the supragranular layers were most intensely labeled. Dark rearing did not affect these developmental changes of 3H-PN 200 110 binding sites. The time course of the reduction of 1,4-DHP binding sites correlates well with that of the age-dependent decrease of the susceptibility to experience-dependent modifications. We consider this result as compatible with the hypothesis that use-dependent modifications of the response properties of cortical neurons involve changes in the Ca2+-fluxes from extra- to intracellular compartments.

Aging↗

PubMed1988

Localization of isoenzymes II/III of protein kinase C in the rat visual cortex (area 17), hippocampus and dentate gyrus.

Monoclonal antibodies against type II and type III subspecies of protein kinase C PkC(II/III) were used to map the distribution of these isoenzymes in the visual cortex (area 17), hippocampus and dentate gyrus of the rat. PkC(II/III)-immunocytochemistry resulted in a specific staining of neuropil and of neuronal somata with their proximal dendrites. The majority of immunopositive cells exhibited a punctate distribution of reaction product, while only a few neurons were homogeneously labeled. In the visual cortex stained neurons were distributed throughout all laminae and reached a particularly high density in layers II/III. Moreover, PkC(II/III)-positive neurons were found within the strata pyramidale and radiatum of the hippocampus proper and in the stratum granulosum, the subgranular zone and the hilar region of the dentate gyrus. The present results suggest that PkC(II/III)-positive neurons constitute a distinct population of both projection and local circuit neurons that are not exclusively associated with any one neurotransmitter system.

Animals↗

PubMed1988

Long-term recordings and receptive field measurements from single units of the visual cortex of awake unrestrained kittens.

A method is described which allows simultaneous recording of the activity of several neurons in the visual cortex of awake unrestrained kittens for a period sufficiently long to follow experience-dependent changes in receptive field properties. The electrodes consisted of 25 microns thick Teflon-coated platinum-iridium wires whose tips were tapered and coated with platinum black. They were implanted individually into the striate cortex and fixed with tissue glue to the pia mater. The other end of the electrodes was connected to a 21-pin plug and fixed to the skull in a way which allowed the wires to follow freely any movements of the brain. With this arrangement single and multi unit activity could be recorded from up to 10 sites over several weeks. In fortuitous cases the activity of a single cell could be followed over several days. The receptive field properties of these neurons were determined in awake animals by computing response histograms to moving gratings that covered the whole visual field and whose orientation could be changed in small steps. Comparison with receptive field properties that were determined for the same neurons after the kittens had been lightly anesthetized, revealed that this method allowed reliable determination of the eye preference of the neurons as well as of their orientation and direction selectivity. Since this method allowed repeated non-invasive measurements of neuronal response properties in only lightly restrained kittens, it was possible to study, in individual units, the nature and time course of changes in receptive field properties such as result from monocular deprivation and reverse occlusion.

Animals↗

PubMed1988

Cholinergic mechanisms in the reticular control of transmission in the cat lateral geniculate nucleus.

1. We examined the hypothesis that the ascending reticular arousal system influences thalamic transmission through a cholinergic mechanism. Extra- and intracellular recordings were obtained from neurons of the dorsal lateral geniculate nucleus (LGNd) and the perigeniculate nucleus (PGN) of cats anesthetized either with N2O and pentobarbital or with N2O and halothane. We compared the effects that electrical stimulation of the mesencephalic reticular formation (MRF) and ionophoretically applied acetylcholine (ACh) have on spontaneous and evoked activity of individual neurons and tested whether these effects could be antagonized by ionophoretic administration of the muscarinic receptor blocker scopolamine. The effects of ionophoretically applied glutamate (GLU), N-methyl-D-aspartate, and bicuculline were examined in addition. 2. The prominent effects in LGNd relay cells of both ACh application and of MRF stimulation were an enhancement of the resting discharge, a facilitation of the excitatory responses to light, a reduction of the amplitude and duration of evoked inhibitory episodes, and a blockade of postinhibitory rebound burst. These latter effects resembled those induced with bicuculline. Under barbiturate anesthesia neither ACh application nor MRF stimulation elicited discharges when the excitatory input from the retina was blocked. Ionophoretic application of hte muscarinic antagonist scopolamine abolished the effects of ACh ionophoresis in all relay cells tested (n = 20), and in 10 cells it also antagonized completely the effects of MRF stimulation. In the remaining cells scopolamine reduced the effects of MRF stimulation. 3. Increasing the depth of anesthesia reduced or abolished the effects of ACh application and MRF stimulation on the cells' resting activity but did not interfere with the facilitation of evoked responses. 4. The effects of the excitatory amino acids GLU and NMDA differed from those of MRF stimulation and ACh application, since the former always enhanced both spontaneous and evoked discharges but neither shortened phases of evoked inhibition nor abolished postinhibitory rebound bursts. 5. There was a high correlation between the effectiveness of MRF stimulation and ACh application in individual neurons. On the average, the facilitation of evoked responses was more pronounced in X- than in Y-cells, and the fraction of cells responding with an increase of resting activity to both procedures was considerably higher among X- than among Y-cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetylcholine↗

PubMed1988

A novel type of pituitary adenoma: morphological features and clinical correlations.

Twenty patients with a novel, frequently aggressive type of pituitary adenoma, termed silent subtype 3 adenoma on the basis of fine structural criteria, are reported. The surgically removed tumors were studied by morphological techniques, and the findings were correlated with clinical and biochemical data. All tumors were macroadenomas, often with parasellar extension. The histologically diffuse tumors frequently exhibited focal immunopositivity for one or more adenohypophysial hormones, although the majority of adenoma cells were negative. The tumors had characteristic electron microscopic features, assuring specific diagnosis and delineating this tumor type as a distinct ultrastructural entity. The tumors were removed from 9 women and 11 men (median ages, 27 and 41 yr, respectively). In all women, mild to moderate hyperprolactinemia and its sequelae were present from the early phase of the disease, leading to the erroneous diagnosis of prolactinoma. Bromocriptine therapy (3 patients) reduced serum PRL levels to normal, but failed to halt tumor growth. In men, most adenomas were nonfunctioning; 4 men had mild to moderate hyperprolactinemia. Three men had elevated serum GH levels and acromegaly, suggestive of multidirectional differentiation. Although the putative cell type giving rise to silent subtype 3 adenomas is not known, the tumor should be recognized to avoid erroneous diagnosis and inappropriate treatment.

Adenoma↗

PubMed1988

Suprasellar craniopharyngioma associated with hyperprolactinemia, pituitary lactotroph hyperplasia, and microprolactinoma. Case report.

A case with the coexistence of a microprolactinoma and suprasellar craniopharyngioma lactotroph hyperplasia is presented. Loss of inhibitory hypothalamic dopaminergic input may have played a role in hyperprolactinemia and the proliferation of pituitary lactotrophs. This is believed to be the first published case of suprasellar craniopharyngioma with this association.

Brain Neoplasms↗

PubMed1988

Structure-function correlations of human pituitary gonadotroph adenomas in vitro.

Two pituitary gonadotroph adenomas were studied in vitro to characterize structure-function correlations. Both tumors were from men, aged 63 and 69 years, who had elevated blood levels of follicle-stimulating hormone (FSH) and normal blood luteinizing hormone (LH) and testosterone values. The surgically resected adenomas contained diffuse immunohistochemical positivity for beta-FSH, beta-LH, and alpha-subunit of glycoprotein hormones; by electron microscopy they were composed of well-differentiated gonadotrophs. In vitro, both tumors released FSH, LH, and alpha-subunit. Morphometric studies were performed on surgically resected and cultured adenoma cells. Compared with the surgical specimens, the cultured cells had decreased cytoplasmic volume densities of endoplasmic reticulum and Golgi apparatus and slightly increased cytoplasmic volume densities of secretory granules. Incubation with gonadotropin-releasing hormone (GnRH) for 2 and 24 hours increased FSH, LH, and alpha-subunit release by both tumors; morphometry after 2 consecutive days of exposure confirmed significant increases in cytoplasmic volume densities of endoplasmic reticulum and Golgi regions and marked decreases in that of secretory granules. There was no significant change in cell size, nuclear/cytoplasmic ratio, or secretory granule diameter. The two tumors differed in their response to gonadal steroids. Estradiol, testosterone, and progesterone stimulated release of FSH, LH, and alpha-subunit by one tumor and the morphologic changes paralleled the biochemical response; addition of testosterone suppressed the secretory and morphologic response to GnRH. The other tumor showed no significant response to estradiol or testosterone and addition of these steroids did not alter the response to GnRH. The results are consistent with the interpretation that GnRH stimulates not only release but also synthesis of gonadotropins by gonadotroph adenomas of men. The data also indicate variable sensitivity of these tumors to gonadal steroids with paradoxical stimulation alone and inhibition of response to GnRH. The structural changes correlate with the hormone release response in vitro.

Adenoma↗

PubMed1987

Blockade of "NMDA" receptors disrupts experience-dependent plasticity of kitten striate cortex.

Intracortical infusion of the "N-methyl-D-aspartate" (NMDA) receptor blocker D,L-2-amino-5-phosphonovaleric acid (APV) renders kitten striate cortex resistant to the effects of monocular deprivation. In addition, 1 week of continuous APV treatment (50 nanomoles per hour) produces a striking loss of orientation selectivity in area 17. These data support the hypothesis that crucial variables for the expression of activity-dependent synaptic modifications are a critical level of postsynaptic activation and calcium entry through ion channels linked to NMDA receptors.

2-Amino-5-phosphonovalerate↗

PubMed1987

Immunohistochemical localization of calcium-binding proteins, parvalbumin and calbindin-D 28k, in the adult and developing visual cortex of cats: a light and electron microscopic study.

In the cat primary visual cortex, we investigated with immunohistochemical techniques the developmental changes in the cellular and subcellular localization of the Ca2+-binding proteins parvalbumin (PV) and calbindin-D 28K (CBP), in order to determine whether there is a correlation between the expression of Ca2+-dependent processes and the time course of the critical period for use-dependent plasticity. On the 54th day of gestation and at 1 week postnatally, both calcium-binding proteins were present only in a subpopulation of neurons in layers V and VI. During subsequent maturation, the number of PV(+) and CBP(+) neurons increased significantly and labeled cells were detected in more superficial layers. Moreover, the homogeneous labeling of some CBP(+) neurons in layers IV to VI decreased and changed to a punctate pattern. In adult cats PV(+) neurons were evenly distributed throughout layers II to VI, whereas CBP(+) neurons were concentrated in layers II/III. Only a few immunoreactive cells had morphological features characteristic of pyramidal cells; the large majority were nonpyramidal. Electron microscopy confirmed the presence of PV- and CBP-reaction product within the perikarya, axons, and dendrites of labeled cells. It was associated preferentially with microtubules, postsynaptic densities, and intracellular membranes. Immunoreactive neurons received immunonegative asymmetric synapses on their dendritic shafts and made symmetric synaptic contacts with labeled and unlabeled somata and with unlabeled dendritic shafts. The large number and widespread distribution of immunoreactive neurons implies that PV and CBP play an important role in the regulation of calcium-dependent processes in the visual cortex. Furthermore, the developmental redistribution of PV and CBP points to changes in the organization of Ca2+-dependent processes during maturation.

Aging↗

PubMed1987

The brainstem projection to the lateral geniculate nucleus in the cat: identification of cholinergic and monoaminergic elements.

The pontomesencephalic projection to the dorsal lateral geniculate nucleus (dLGN) of the cat was analyzed by combining retrograde transport of rhodamine-labeled latex spheres and immunohistochemistry. After injections of latex beads into the dLGN, sections of the brainstem were treated immunohistochemically for choline acetyltransferase (ChAT), serotonin (Ser), tyrosine hydroxylase (TH), and dopamine-beta-hydroxylase (DBH). Essentially, six regions in the brainstem contained retrogradely labeled cells: the superior colliculus, the parabigeminal nucleus, the dorsal raphe nuclei, the parabrachial area of the central tegmental field, the marginal nucleus of the brachium conjunctivum, and the nucleus coeruleus. Furthermore, isolated retrogradely labeled cells were present in the central nucleus of the raphe, in the cuneiform nucleus, and in the periaqueductal gray. Most serotoninergic double-labeled cells were found in the medial and lateral divisions of the dorsal raphe nuclei, but a few were also present in the central nucleus of the raphe. In the sections immunostained for ChAT, double-labeled cells were located in the central tegmental field, in the marginal nucleus of the brachium conjunctivum, and in the nucleus coeruleus. In the sections treated for TH and DBH, double-labeled cells showed a similar distribution, and like the ChAT(+) cells, they were located mainly in the central tegmental field, in the marginal nucleus of the brachium conjunctivum, and in the nucleus coeruleus. In these regions the cholinergic and noradrenergic cells that projected to the lateral geniculate nucleus were intermingled, the former predominating rostrally and the latter caudally. The majority of retrogradely labeled cells were located in the region of the central tegmental field in the vicinity of the brachium conjunctivum, and most of these cells were also ChAT-immunoreactive. We, therefore, conclude that the cholinergic projection is the most important of the central core projections ascending to the dLGN.

Animals↗

PubMed1987

The serotoninergic fibers in the dorsal lateral geniculate nucleus of the cat: distribution and synaptic connections demonstrated with immunocytochemistry.

The distribution, morphology, and synaptic contacts of serotoninergic fibers were studied with immunocytochemical methods in the lateral geniculate complex of the cat. The serotonin-immunoreactive fibers are diffusely distributed throughout the main laminae of the dorsal lateral geniculate nucleus (dLGN) and the perigeniculate nucleus (PGN) and reach a particular density in the ventral lateral geniculate nucleus (vLGN). The labeled fibers are in most cases very thin and sometimes varicose. There is no obvious order in their distribution pattern except that they sometimes partially encircle the unlabeled cell bodies of the dLGN. The synaptic connections of the serotoninergic fibers were investigated mainly in the A laminae of the dLGN. Few synaptic complexes were found, most of them with asymmetric morphology. The postsynaptic elements were small dendritic profiles. Perisomatic serotoninergic fibers were seen, but no convincing synaptic contacts were found between labeled fibers and cell somata. In the dLGN, serotoninergic profiles were almost exclusively confined to the extraglomerular neuropile. In the PGN serotoninergic fibers also contacted dendritic profiles and formed asymmetrical synapses, but as in the geniculate, synaptic specializations were very rare.

Animals↗

PubMed1987

Quantitative analysis of the choline acetyltransferase-immunoreactive axonal network in the cat primary visual cortex: I. Adult cats.

The laminar distribution of cholinergic axons was analyzed quantitatively in the visual cortex of adult cats by using immunocytochemistry with a monoclonal antibody against choline acetyltransferase (ChAT). ChAT(+) fibers and varicosities were counted at different locations within area 17 and the distribution patterns in various animals were compared. Choline acetyltransferase-immunoreactivity was localized in fine, varicose fibers, which were present in all layers of the visual cortex. The density of labeled fibers was highest in layer I, which contained 14% of all fibers and 19.5% of all varicosities, and decreased toward deeper layers. The number of varicosities decreased more markedly toward deeper layers than the frequency of fibers. These distribution patterns were very consistent, showing only slight intra- and interindividual variability.

Animals↗

PubMed1987

Quantitative analysis of the choline acetyltransferase-immunoreactive axonal network in the cat primary visual cortex: II. Pre- and postnatal development.

The pre- and postnatal development of cholinergic projections was investigated in the cat striate cortex by applying immunohistochemical methods based on a monoclonal antibody against choline acetyltransferase (ChAT). The earliest age investigated was gestational day 54. At this stage a sparse network of ChAT(+) fibers was distributed throughout the striate cortex. Subsequent postnatal maturation of ChAT(+) fibers was characterized by an increase in fiber density that started in layer VI and gradually progressed toward more superficial layers. By 4 weeks of age the density of ChAT(+) fibers and varicosities had reached adult levels in layers V and VI but was still subnormal in layers I-IV. The mature pattern of cholinergic innervation was established by 13 weeks of age. There was no evidence for developmental gradients in the anteroposterior and mediolateral directions within area 17. These results indicate that the cholinergic projection to striate cortex develops continuously in an inside-out sequence as is characteristic for most cortical maturation processes. There was no indication that striate cortex receives an especially dense cholinergic input during the critical period.

Animals↗

PubMed1987

A search for choline acetyltransferase-like immunoreactivity in neurons of cat striate cortex.

The goal of this study was to determine whether cat striate cortex contains neurons with choline acetyltransferase-like immunoreactivity. Two different monoclonal antibodies were applied with various fixation protocols. As controls served selected regions of the cat brain and the rat neocortex where cholinergic neurons had been demonstrated previously with independent methods. All experimental protocols labelled the presumptive cholinergic neurons in the central regions but revealed only a few weakly stained neurons in cat striate cortex. These had a non-pyramidal morphology and were scattered throughout all layers.

Animals↗

PubMed1987

Topographic organization of the orientation column system in large flat-mounts of the cat visual cortex: a 2-deoxyglucose study.

We developed a flat-mount technique in order to visualize, without additional reconstruction, the system of orientation columns in the cat visual cortex by using 2-deoxyglucose-autoradiography. Experimental animals were injected with 2-deoxyglucose and then stimulated for 45-60 minutes either with vertical or horizontal or oblique gratings alone or with vertical and horizontal gratings presented in alternation. In both areas 17 and 18 stimulation with either vertical or horizontal or oblique stripes produced similar and highly ordered patterns of parallel bands of increased 2-deoxyglucose uptake that were perpendicular to the boundaries of the areas. In area 17 they occasionally extended without interruption from the 17/18 border on the top of the lateral gyrus to the monocular segment in the splenial sulcus. Superposition of serial sections revealed that these bands were present in all cortical layers and in precise register along lines orthogonal to the lamination. The center-to-center spacing of the bands was 1.0-1.1 mm in area 17 and 1.2-1.4 mm in area 18. Stimulation with alternating vertical and horizontal contours led to a pattern the general organization of which resembled that induced by a single orientation but the spacing of which was reduced by a factor of 0.5. This strongly supports the concept that orientation is mapped in a system of parallel bands and argues against a recently formulated hypothesis that iso-orientation bands extend like spokes from centers that lack orientation selectivity (Braitenberg and Braitenberg, Biol. Cybern. 33:179-186, '79). Another characteristic feature, revealed by the flat-mount technique, was a periodic variation of 2-deoxyglucose uptake along the bands that gave them a beaded appearance. The mean center-to-center distance between adjacent beads on the same band was in the range of 0.9-1.2 mm and remained unchanged when horizontal and vertical gratings were presented in alternation. We propose that these beads reflect another columnar system whose features have yet to be determined.

Animals↗

PubMed1987

Neuronal dynamics in the visual corticothalamic pathway revealed through binocular rivalry.

Single unit activity was recorded from principal cells in the A-laminae of the cat dorsal lateral geniculate nucleus (dLGN). A steady state pattern of afferent activation was induced by presenting a continuously drifting square wave grating of constant spatial frequency to the eye (the dominant eye) that provided the excitatory input to the recorded cell. Intermittently, a second grating stimulus was presented to the other, nondominant, eye. In most neurones nondominant eye stimulation led to inhibition of relay cell responses. The latency of this suppressive effect was unusually long (up to 1 s) and its intensity and duration depended critically on the similarity between the gratings that were presented to the two eyes. Typically suppression was strongest when the gratings differed in orientation, direction of movement and contrast and when the nondominant eye stimulus was moving rather than stationary. Ablation of visual cortex abolished these long latency and feature-dependent interferences. We conclude that the visual cortex and the corticothalamic projections are involved in the mediation of these interocular interactions. We interpret our results as support for the hypothesis that corticothalamic feedback modifies thalamic transmission as a function of the congruency between ongoing cortical activation patterns and afferent retinal signals.

Animals↗