Biomedical subjects

W Singer

Publications and source records attributed to W Singer.

At least 91 records · Page 5Linked to original sources

PubMed1987

Functional and neuronal binocularity in kittens raised with rapidly alternating monocular occlusion.

1. In order to determine the degree of synchrony of binocular activation required for the development of binocularity we reared 11 kittens with rapidly alternating monocular occlusion. Alternating occlusion was achieved with microprocessor-controlled electrooptic solid-state shutters, which were fitted to individually moulded goggles. The intervals of alternating occlusion were varied from 50 to 1,000 ms. Two normally reared kittens and three kittens that were reared with the shutters operating synchronously with open/close intervals of 50/50 ms, 200/200 ms, and 400/100 ms, respectively, were used as controls. Toward the end of the critical period we examined the kittens' ability for binocular depth discrimination and tested binocular luminance summation of the pupillary light reflex. Single-cell recordings were made from the visual cortex in order to determine the percentages of binocularly excitable neurons. 2. There was a good correlation between the degree of asynchrony of binocular experience, the impairment of depth discrimination, and the percentage of binocular neurons. Kittens reared with alternation rates of 200, 330, and 400 ms, respectively, had developed normal binocularity and were indistinguishable from the controls. Alternation rates of 500 ms or longer prevented the development of normal depth discrimination and luminance summation and resulted in reduced cortical binocularity. 3. A linear relationship between depth discrimination, binocular luminance summation, and percentages of binocular neurons was found. 4. Our findings indicate that an asynchrony of binocular activation of several hundred milliseconds is compatible with the development of normal binocularity in the kitten visual system.

Animals↗

PubMed1987

Pancreatic endocrine tumour producing growth hormone-releasing hormone associated with multiple endocrine neoplasia type I syndrome.

We report the first documentation of GHRH production by a tumour associated with proven multiple endocrine neoplasia (MEN). A 30-year-old woman had hypoglycaemia, hyperparathyroidism, and pituitary adenoma with hyperprolactinaemia. Serum growth hormone elevation was attributed to hypoglycaemia but plasma GHRH was elevated. Subtotal pancreatectomy revealed multiple endocrine tumours and nesidioblastosis. Immunohistochemistry demonstrated insulin, glucagon, and somatostatin in several tumours. GHRH was localized in the largest one and was released from that tumour in vitro. Post-operative plasma GH returned to normal. Excess secretion of humoural factors by one tumour may stimulate growth of other tumours in MEN syndromes. The prevalence of GHRH in MEN-I tumours remains to be established.

Adult↗

PubMed1986

Cholinergic innervation of the cat striate cortex: a choline acetyltransferase immunocytochemical analysis.

In area 17 of adult cats the morphology, distribution, and synaptology of cholinergic elements were examined by immunocytochemical methods with a monoclonal antibody against choline acetyltransferase (ChAT). ChAT(+) fibers are present throughout the entire depth of the cortex but are particularly dense in layer I. Typically these fibers are very thin and possess numerous irregularly spaced varicosities. Except in layer I and deep layer VI, where the fibers tend to run parallel to the pial surface, they appear to be randomly oriented. At the electron microscope level, immunolabeling was present in unmyelinated fibers of irregular contour and diameter. Most of the ChAT(+) varicose profiles contained mitochondria and round vesicles. Synaptic complexes were relatively infrequent and tended to be of the symmetrical type. They were located mostly on dendritic shafts and only rarely on cell bodies and dendritic spines. Both pyramidal and nonpyramidal cells were found to be innervated by cholinergic afferents. These anatomical data are consistent with the known physiology of acetylcholine in the visual cortex, which indicates that it acts as a modulator of cortical excitability.

Animals↗

PubMed1986

Development of horizontal intrinsic connections in cat striate cortex.

Intracortical injections of horseradish peroxidase conjugated with wheat-germ agglutinin (WGA-HRP) reveal a characteristic patchy staining pattern within the superficial layers of cat striate cortex. The patches consist of a dense accumulation of labeled neurons and axonal arborizations. We have investigated the tangential organization and the development of these intrinsic cortical connections by using a flat-mount preparation of area 17. The diameter of the patches varied from 200 to 400 micron, the center-to-center distance ranged from 400 to 800 micron, and the spread of patches extended further in the anterior-posterior than in the medial-lateral direction. The expression of these horizontal patchy connections is age- and experience-dependent. From ten days to six weeks of age patches are exuberant and on occasion fuse to beaded bands extending radially from the injection site. From 6 weeks onwards the number and the tangential spread of the patches decreases to one or two rows of isolated clusters. Long-term binocular deprivation disrupts this pattern of intrinsic connections nearly completely. We infer from these results that there is an inborn pattern of discrete horizontal connections in striate cortex which is shaped by visual experience and requires contour vision for its maintenance.

Animals↗

PubMed1986

The brain as a self-organizing system.

Clinical evidence and numerous results from animal experimentation indicate that cognitive functions have to be learned. Brain structures subserving these functions require sensory experience for their maturation. Genetic instructions are in principle not sufficient to specify neuronal connections with sufficient precision. Self-organization processes are implemented in addition which allow to optimize genetically determined blue prints of connectivity by making use of functional criteria. Thus, neuronal activity becomes an important shaping factor in the development of the structural and functional architecture of the forebrain. To the extent that this neuronal activity is modulated by sensory signals, environmental factors can influence the development of neuronal networks. Recent experiments indicate that these shaping processes are additionally controlled by modulatory systems. Both, the noradrenergic projection from the locus coeruleus and the cholinergic projection from the basal forebrain facilitate activity-dependent long-term changes of neuronal connections during development. The activity of these modulatory systems in turn depends on central states such as arousal, attention, and perhaps also motivation. It is inferred from this evidence that experience-dependent self-organization should not be considered as a passive imprinting process but rather as an active dialogue between the brain and its environment. The hypothesis is discussed that many developmental disturbances which are commonly attributed to deprivation are in fact due to defaults of the CNS which either lead to the formulation of wrong questions or to the reduction of exploratory drive.

Animals↗

PubMed1986

Temporal integration in the visual system: influence of temporal dispersion on figure-ground discrimination.

Psychophysical measurements were carried out with a microcomputer-controlled matrix of 32 X 32 light emitting diodes to determine temporal parameters of figure-ground separation processes. The task was to detect a figure that was dispersed in time. Between each two figure elements n noise elements were interspersed. The results of these experiments indicate that the discrimination of figures hidden in dynamic noise is possible even if figure elements are dispersed in time over several hundred milliseconds. The maximal dispersion time still compatible with figure discrimination (Tmax) depends critically on the number n of interspersed noise elements, on the subject's expectancy and on the number of elements used for the generation of the figure. For simple figures such as triangles Tmax could be as long as 1.5 sec when n was 4. Our experimental results suggest that the neuronal representation of the briefly displayed (less than 6 msec) pattern elements outlasts their physical presence by at least 400 msec. This persistence of neuronal representations must occur at a level of processing where retinotopy is still preserved, since the only cue for figure-ground discrimination is the difference in the local density of figure and noise elements.

Afterimage↗

PubMed1986

Temporal integration in amblyopic vision.

Amblyopic subjects were tested on different visual tasks which required temporal integration of successively presented stimuli: a figure had to be detected whose components were displayed successively and hidden in spatio-temporal noise. The time interval T over which the figure elements were dispersed was varied and the longest T value still compatible with figure detection was determined. In all subjects these T values were considerably longer for the normal than for the amblyopic eye. A missing square had to be detected in a checker-board of 3 X 3 squares that was presented in two successive frames, each frame containing 4 squares. With the normal eye, identification of the missing square was possible over considerably longer interstimulus intervals (ISIs) than with the amblyopic eye. Changes had to be detected in two patterns of randomly distributed squares that were presented successively with varying ISI whereby one square was added or subtracted in the second pattern. With the normal eye, detection of changes was possible over much longer ISIs than with the amblyopic eye. These experiments show a deficit of the amblyopic visual system to integrate temporally separated stimuli. We conclude that amblyopia is associated with a marked reduction of the duration of visual persistence and suggest that this is due to shortening of normally sustained neuronal responses.

Afterimage↗

PubMed1986

Critical period plasticity of kitten visual cortex is not associated with enhanced susceptibility to electrical kindling.

The goal of this study was to determine whether the use-dependent malleability of visual cortex functions which is particularly pronounced in 4-week-old kittens correlates with enhanced susceptibility to kindling. For that purpose the effects of high-frequency electrical stimulation were compared in the visual cortex of 4-week-old kittens and of adult cats. The striate cortex of one hemisphere was stimulated with a single train of pulses whose intensity was set just above the threshold for the elicitation of afterdischarges (ADs). In kittens the AD thresholds were consistently higher than in adults and with repeated stimulation, the ADs tended to disorganize, to decrease in amplitude and duration and to become more restricted to the site of stimulation after about 6 stimulations. In the adult, by contrast, the ADs remained well organized and constant in duration throughout 30 stimulations. They showed an increase in amplitude and spike frequency and spread with increasing consistency to the other hemisphere. No electrographic or behavioural signs of epileptic activity developed in kittens, while in adults ADs were on occasion followed by irregular spike activity associated with behavioural states resembling absences. We conclude that the visual cortex possesses powerful mechanisms to prevent the development of supracritical excitatory states, these mechanisms being more effective in the kitten than in the adult.

Age Factors↗

PubMed1986

Gonadotropin secretion in vitro by human pituitary null cell adenomas and oncocytomas.

Pituitary null cell adenomas and oncocytomas are tumors not associated with clinical or biochemical evidence of hormone excess; morphological studies have not hitherto revealed their origin or the nature of their hormone production, if any. We examined the in vitro secretory activity of seven null cell adenomas and five oncocytomas which caused symptoms of a mass lesion and variable degrees of hypopituitarism. All tumors were classified at the time of surgical resection using immunohistochemistry and electron microscopy. RIA revealed the presence of FSH, LH, and alpha-subunit of pituitary glycoprotein hormones in the culture medium of eight tumors, FSH and alpha-subunit in the medium of one tumor, and TSH, FSH, LH, and alpha-subunit in the medium of three adenomas. Morphological examination of cultured tissues confirmed the presence of tumor resembling those in the initial surgical specimen. Thus, we conclude that null cell adenomas and oncocytomas contain cells that can produce pituitary glycoprotein hormones, and that the majority produce gonadotropins.

Adenoma↗

PubMed1986

Microscopic peliosis of pancreatic islets in a woman with MEN-1 syndrome.

We report herein a case of histologically identified peliosis of pancreatic islets in the surgically removed portion of the pancreas of a 30-year-old woman with multiple endocrine neoplasm, type 1 (MEN-1) syndrome. In addition to microscopic peliosis, the pancreas contained multiple endocrine tumors producing insulin, glucagon, somatostatin, and growth hormone-releasing factor and showed evidence of widespread nesidioblastosis. It is uncertain whether peliosis of pancreatic islets and MEN-1 syndrome were coincidental or whether the two diseases were causally related. Since hormonal factors can result in hepatic peliosis, it is tempting to speculate that the endocrine imbalance secondary to MEN-1 syndrome might have played a role in the genesis of peliosis in this case. Although no direct proof of vascular damage was encountered, it is conceivable that escape of red blood cells from the circulation and their accumulation in tissue spaces was due to abnormal islet blood flow and increased capillary permeability.

Adult↗

PubMed1985

Organization and morphological characteristics of choline acetyltransferase-containing fibers in the visual thalamus and striate cortex of the cat.

The morphological characteristics and the distribution of cholinergic fibers in the cat visual system were studied with immunohistochemical methods employing monoclonal antibodies directed against choline acetyltransferase (ChAT). ChAT-positive fibers form dense meshworks within the main laminae of the dorsal lateral geniculate nucleus (LGNd), the perigeniculate nucleus (PGN) and the visual cortex. The fibers are of fine caliber, branch extensively and possess numerous varicosities in close contact with cellular elements. The density of ChAT + fibers is not uniform and is particularly high in cortical laminae I-III, the PGN complex and laminae A and A1 of the LGNd.

Animals↗

PubMed1985

Ultrastructural identification of somata and neural processes immunoreactive to antibodies against glutamic acid decarboxylase (GAD) in the dorsal lateral geniculate nucleus of the cat.

The cat dorsal lateral geniculate nucleus (LGN) was examined at the light- and electron-microscopic level after immunocytochemistry for GAD (the synthesizing enzyme of the inhibitory neurotransmitter GABA), to identify cells and processes with GAD-like immunoreactivity. GAD-positive perikarya were distributed throughout the A and C laminae, constituting a moderate proportion of cells in the LGN. Labeled cells were characterized by small size, scant cytoplasm, relatively large nuclei with common indentations, small mitochondria, few organelles and few strands of rough endoplasmic reticulum. Unlabeled cells were of large, medium and small size. GAD-positive terminals were identified as F1 and F2 types (Guillery's nomenclature) on the basis of their synaptic relations and ultrastructure. Labeled F2 terminals were postsynaptic to retinal (RLP) boutons and presynaptic to unlabeled dendrites in synaptic glomeruli. Labeled F1 terminals made synapses on unlabeled somata and dendrites, and on labeled dendrites and F2 terminals. Presumably, most labeled F1 terminals originate from GABAergic perigeniculate axons. Retinal (RLP) and cortico-geniculate (RSD) boutons remained unlabeled in the reactive zone. These terminals made synapses with labeled and unlabeled dendrites and with labeled F2 boutons. In conjunction with previous studies on GAD-positive cells in the perigeniculate nucleus, these results provide immunocytochemical and morphological evidence suggesting that the GABAergic intrinsic and extrinsic (perigeniculate) interneurons mediate the different inhibitory phenomena which occur in relay cells of the cat LGN. The ultrastructural features and synaptic relations of GABAergic cells and processes in the cat LGN are similar to those of equivalent neural elements in the LGN of rat and monkey, suggesting general principles of organization and morphology for GABAergic neurons in the thalamus of different mammals.

Animals↗

PubMed1985

The cholinergic innervation of the visual thalamus: an EM immunocytochemical study.

In this study we demonstrate at the ultrastructural level that both the dorsal lateral geniculate nucleus (dLGN), the visual relay of the thalamus, and the perigeniculate nucleus (PGN), the visual segment of the thalamic reticular nucleus (TRN), are densely innervated by fibres with Choline-Acetyl-Transferase (ChAT) like immunoreactivity. These axons make synaptic contacts with interneurones considered to be inhibitory, both in the PGN and within the synaptic glomeruli of the dLGN. In addition, Chat positive terminals form intra- and extraglomerular synapses with dendrites thought to arise from relay cells. We interpret these results as evidence for direct cholinergic modulation of both relay cells and inhibitory interneurones.

Animals↗

PubMed1985

Central control of developmental plasticity in the mammalian visual cortex.

Visual experience influences the development of visual cortex functions. By manipulating retinal activity the efficacy of excitatory connections between the eyes and cortical neurones can be modified dramatically. A criterion for the enhancement or impairment of transmission is the temporal contiguity of pre- and postsynaptic activation. For a change to occur it is necessary that the cortical cells respond to retinal activity but this condition is not sufficient. Further permissive gating signals of nonretinal origin are required. It is proposed that these "now print" signals act by controlling the Ca2+-conductance of cortical dendrites. The possible role of these activity dependent modifications is discussed in the context of the development of cooperatively coupled cell assemblies.

Action Potentials↗

PubMed1984

Ultrastructure and synaptic relations of neural elements containing glutamic acid decarboxylase (GAD) in the perigeniculate nucleus of the cat. A light and electron microscopic immunocytochemical study.

The perigeniculate nucleus of the cat (PGN) was examined at light and electron microscopic levels after immunocytochemical labeling for the gamma-aminobutyric acid (GABA) synthesizing enzyme, glutamic acid decarboxylase (GAD). In light microscopic sections, virtually all perikarya were found to be labeled (GAD+), as well as proximal dendrites, fibres and punctiform elements. Cells in the thalamic reticular nucleus (TRN) dorsal to PGN were also labeled. Ultrastructural analysis of PGN showed immunoreactivity in all somata, in dendrites and in the following vesicle containing profiles: 1.) F1 terminals, which are characterized by large size, dark mitochondria, and pleomorphic vesicles. These terminals form symmetrical synaptic contacts with somata, somatic spines and with dendrites of GAD+ PGN cells. 2.) F2 terminals, which are smaller than F1 terminals, contain also pleomorphic vesicles and frequently make serial synapses of the symmetric type with other F2 terminals. Presumably, F1 terminals are formed by collaterals of PGN-cell axons and F2 terminals by vesicle containing dendrites of PGN cells. Terminals devoid of immunoreactivity included: 1.) RLD terminals characterized by large size, round vesicles, dark mitochondria, and by asymmetric synaptic contacts with somata, especially with somatic spines, and with dendrites of GAD+ perigeniculate neurons; 2.) RSD terminals, characterized by small size, round vesicles and dark mitochondria, which make asymmetric synapses with GAD+ dendrites of medium and small size; 3.) Multivesicular (MV) terminals with variably shaped vesicles including dense core vesicles synapsing on GAD+ dendrites. There are reasons to believe that RSD terminals belong to corticofugal axons and RLD terminals to collateral axons of LGN relay cells. The origin of MV terminals remains to be determined. The GABAergic nature of the PGN cells conforms with the presumed function of these cells as mediators of inhibition of LGN relay cells. The complex synaptic relations observed between GAD+ elements in the PGN would allow for reciprocal inhibition between perigeniculate cells.

Animals↗

PubMed1984

A case for hypothalamic acromegaly: a clinicopathological study of six patients with hypothalamic gangliocytomas producing growth hormone-releasing factor.

We report the histological, ultrastructural, and immunocytochemical features of six hypothalamic gangliocytomas associated with pituitary GH cell adenomas and/or acromegaly. In four patients, the gangliocytoma was intrasellar, and no hypothalamic investigation was performed; in two patients, autopsy confirmed hypothalamic involvement. Four patients had a gangliocytoma associated with pituitary GH cell adenoma and acromegaly; electron microscopy demonstrated an intimate association between neurons and adenomatous GH cells. One patient had a gangliocytoma and a GH cell adenoma but no clinical evidence of acromegaly. In the sixth patient, clinical and biochemical acromegaly was manifest, but no pituitary adenoma was demonstrated. Using immunocytochemistry, human pancreatic tumor GRF (hptGRF-40) was localized in the majority of neurons of all six gangliocytomas. The pituitary adenomas and nontumorous adenohypophyses were negative for hptGRF-40. In addition, somatostatin, glucagon, and GnRH were demonstrated within some neurons of several tumors; insulin and gastrin stains were equivocal. These findings confirm previous proposals of production of a GRF by such gangliocytomas. While the significance of other peptides found in some of the tumors is uncertain, the presence of hptGRF-40 in neurons of these gangliocytomas supports the theory that GRF excess is the mechanism responsible for over-production of GH and provides evidence for a syndrome of hypothalamic acromegaly.

Acromegaly↗

PubMed1984

Immunohistochemical localization of neuron-specific enolase in the human hypophysis and pituitary adenomas.

Neuron-specific enolase (NSE) was localized, using the immunoperoxidase technique, in the cytoplasm of the five adenohypophyseal hormone-secreting cell types, and in nerve fibers of the pars nervosa of the human pituitary. Crooke's hyaline material was negative. Neuron-specific enolase was found in all pituitary adenoma types; there was no correlation between degree of granularity or differentiation of tumor cells and intensity of NSE immunopositivity. One hypothalamic hamartoma was positive for NSE; a craniopharyngioma and a neurohypophyseal granular cell tumor were not. Neuron-specific enolase was present in peptide hormone-producing endocrine cells outside the pituitary and in their tumors; the majority of other tumors were negative for NSE, although one breast carcinoma, one ovarian cystadenocarcinoma, and one lymphoma were positive for NSE. In control studies, absorption of NSE antisera with growth hormone abolished immunoreactivity; there was no immunologic cross-reaction demonstrable by radioimmunoassay.

Adenoma↗

PubMed1983

Pituitary and hypothalamic dysfunction in a patient with a basal encephalocele.

A 31 year old Chinese man was found to have a large basal encephalocele extending into the nasopharynx associated with a cleft palate and chiasmal damage producing visual field defects. He was found to have marked hypothalamic-pituitary dysfunction including deficiencies of growth hormone, thyrotropin, adrenocorticotropic hormone and gonadotropins, diabetes insipidus, adipsia with essential hypernatremia and poikilothermia. This man illustrates the importance of careful assessment of patients with craniofacial anomalies and outlines a simple investigational protocol.

Adult↗