Biomedical subjects

W Singer

Publications and source records attributed to W Singer.

At least 55 records · Page 3Linked to original sources

PubMed1989

Blockade of NMDA-receptors prevents ocularity changes in kitten visual cortex after reversed monocular deprivation.

We investigated in the striate cortex of kittens whether the recovery from the effects of monocular deprivation that occurs after reverse occlusion requires activation of N-methyl-D-aspartate (NMDA) receptors. The right eye of 3-4-week-old kittens was closed by lid suture for one week. Subsequently this eye was reopened and the left eyelid sutured closed for another week. During this second week, the NMDA-receptor antagonist, 2-amino-5-phosphonovaleric acid (APV), was infused from an osmotic minipump into the left visual cortex (50 nmol/h), while the right visual cortex was infused only with vehicle solution (saline) as control. At the end of the second week, the ocular dominance of striate cortical neurons was assessed with single unit recording. In the control hemispheres, the large majority of neurons was dominated by the newly opened eye, while in the APV-treated hemispheres most neurons were still dominated by the newly deprived eye. In addition, neurons in the APV-treated hemispheres were less responsive and showed a reduction of orientation tuning. These data confirm that chronic blockade of cortical NMDA-receptors disrupts the disconnection of deprived pathways after monocular deprivation and reduces both responsiveness and orientation selectivity of cortical neurons. In addition they indicate that blockade of NMDA-receptors prevents also vision-dependent recovery of deprived pathways after reverse occlusion.

2-Amino-5-phosphonovalerate↗

PubMed1989

Acetylcholine-induced inhibition in the cat visual cortex is mediated by a GABAergic mechanism.

The influence of iontophoretically applied acetylcholine (ACh) on single-unit activity in the visual cortex was studied in anesthetized cats. The dominant effect consisted of a slow facilitation of neuronal responses to moving light bars. This cholinergic action was sometimes paralleled by a decrease of the cells' selectivity to the direction of stimulus movement. In about one-third of the neurons studied ACh-iontophoresis suppressed maintained and visually driven activity within a few hundred milliseconds from the onset of its application. This effect was antagonized by concurrent iontophoresis of the muscarinic ACh-receptor antagonist scopolamine and the GABAA-receptor antagonist bicuculline methiodide. In 7% of the units studied a fast excitation was elicited by ACh application showing a similar time course as the rapid suppressive effect. It is concluded that ACh-induced inhibition is mediated by an activation of GABAergic interneurons. The role of cholinergic depression and facilitation in cortical information processing is discussed.

Acetylcholine↗

PubMed1989

The development of N-methyl-D-aspartate receptors in cat visual cortex.

During a critical period of early postnatal development, the visual cortex of kittens is susceptible to experience-dependent modifications of neuronal response properties. Recently, the activation of N-methyl-D-aspartate (NMDA) receptors has been identified as an indispensable prerequisite for the induction of such modifications. We therefore investigated developmental changes in the density and distribution of NMDA receptors and questioned whether these showed a relation to the time course of the critical period. We determined the proportion of [3H]glutamate binding sites that were displaced by the NMDA receptor antagonist 2-amino-5-phosphonovalerate (APV) on 10-microns-thick cryostat sections of the primary visual cortex. The overall density of APV-sensitive [3H]glutamate binding sites increased dramatically between the second and the fourth week and stayed at this level throughout the critical period. Towards the end of the critical period, these binding sites decreased and finally reached adult values that were slightly above those of 2-week-old kittens. APV-sensitive binding sites were present in all cortical layers of the age groups investigated. While the general pattern of developmental changes was similar in all layers, slight differences existed in the time course. These observations are compatible with the notion that NMDA receptor activation is required for the expression of use-dependent change of response properties in the kitten visual cortex. Furthermore, they suggest as a possible reason for the decline of malleability towards the end of the critical period the reduction of NMDA receptors.

2-Amino-5-phosphonovalerate↗

PubMed1989

Oscillatory responses in cat visual cortex exhibit inter-columnar synchronization which reflects global stimulus properties.

A fundamental step in visual pattern recognition is the establishment of relations between spatially separate features. Recently, we have shown that neurons in the cat visual cortex have oscillatory responses in the range 40-60 Hz (refs 1, 2) which occur in synchrony for cells in a functional column and are tightly correlated with a local oscillatory field potential. This led us to hypothesize that the synchronization of oscillatory responses of spatially distributed, feature selective cells might be a way to establish relations between features in different parts of the visual field. In support of this hypothesis, we demonstrate here that neurons in spatially separate columns can synchronize their oscillatory responses. The synchronization has, on average, no phase difference, depends on the spatial separation and the orientation preference of the cells and is influenced by global stimulus properties.

Animals↗

PubMed1989

The role of muscarinic acetylcholine receptors in ocular dominance plasticity.

During a critical period of postnatal development neuronal connections in the visual cortex are susceptible to experience-dependent modifications. In normally reared kittens the majority of neurons respond to visual stimulation of either eye. A few days of monocular deprivation, however, are sufficient to render most cortical neurons unresponsive to visual stimuli presented to the deprived eye. Among other factors the cholinergic projection to striate cortex has been identified as having a permissive role in this use-dependent modification of synaptic transmission. In order to analyze further the influence of acetylcholine in cortical plasticity, we tested whether the blockade of muscarinic or nicotinic receptors interfered with ocular dominance plasticity. At four weeks of age kittens had one eyelid sutured closed and osmotic minipumps implanted, which delivered scopolamine (1 nmol/h) or hexamethonium (1 or 10 nmol/h) into the striate cortex of one hemisphere and vehicle solution (saline) into the other. After one week, ocular dominance distributions were determined in area 17 with single unit recording. In the control hemispheres, most neurons became unresponsive to the deprived eye, while in the scopolamine-treated hemispheres most neurons remained binocular. In contrast to the effects of scopolamine, the intracortical infusion of hexamethonium had no effect on ocular dominance plasticity. These results demonstrate that blockade of muscarinic, but not nicotinic receptors renders kitten striate cortex resistant to the effects of monocular deprivation.

Animals↗

PubMed1989

The callosal projection in cat visual cortex as revealed by a combination of retrograde tracing and intracellular injection.

The neuronal composition of callosally projecting cells in cat visual cortex was determined with a combination of retrograde labelling and intracellular injection. Fluorescent tracers were stereotaxically injected into the proximity of the area 17/18 border, corresponding to the representation of the visual vertical meridian. In fixed slice preparations of homotopic regions of the contralateral hemisphere retrogradely labelled cells were filled with Lucifer Yellow. Of more than a hundred injected cells a morphological variety of pyramidal cells, located in cortical layers II-IV and VI, constituted the prevalent cell class in the contralateral projection. A minor proportion of spiny stellate cells was encountered in layer IV. Despite the presence of a contralaterally projecting smooth stellate cell, presumed to be a basket cell, it is concluded that the efferents to contralateral visual cortex predominantly arise from pyramidal and spiny stellate cells. Thus, in agreement with findings from anterograde degeneration studies, the interhemispheric pathway most likely conveys a direct excitatory input to postsynaptic target cells.

Animals↗

PubMed1989

Combining retrograde tracing, intracellular injection, anterograde degeneration and electron microscopy to reveal synaptic links.

Synaptic circuitry was investigated by combining retrograde tracing, intracellular staining, anterograde degeneration and electron microscopy in the same piece of tissue. This methodological procedure was successfully applied to disentangle a disynaptic neuronal chain, which originated in the olfactory bulb, was synaptically relayed in the entorhinal cortex and terminated in the ipsilateral hippocampus. Presumed entorhinal relay cells were retrogradely labelled from their hippocampal termination site by means of a fluorescent tracer. Subsequently, the marked projection neurones were intracellularly injected with Lucifer yellow in fixed slice preparations. Following a simple photo-conversion procedure, dye filled cells were processed for electron microscopy. The origin of presynaptic afferents to identified relay cells was revealed ultrastructurally after lesion induced anterograde degeneration of olfactory mitral cell axons. Due to its reliability, technical simplicity and a high degree of selectivity the new approach is considered an appropriate tool for unravelling neuronal networks.

Animals↗

PubMed1989

Stimulus-specific neuronal oscillations in orientation columns of cat visual cortex.

In areas 17 and 18 of the cat visual cortex the firing probability of neurons, in response to the presentation of optimally aligned light bars within their receptive field, oscillates with a peak frequency near 40 Hz. The neuronal firing pattern is tightly correlated with the phase and amplitude of an oscillatory local field potential recorded through the same electrode. The amplitude of the local field-potential oscillations are maximal in response to stimuli that match the orientation and direction preference of the local cluster of neurons. Single and multiunit recordings from the dorsal lateral geniculate nucleus of the thalamus showed no evidence of oscillations of the neuronal firing probability in the range of 20-70 Hz. The results demonstrate that local neuronal populations in the visual cortex engage in stimulus-specific synchronous oscillations resulting from an intracortical mechanism. The oscillatory responses may provide a general mechanism by which activity patterns in spatially separate regions of the cortex are temporally coordinated.

Animals↗

PubMed1989

Chronic recordings from single sites of kitten striate cortex during experience-dependent modifications of receptive-field properties.

1. With the use of chronically implanted floating microelectrodes, we obtained simultaneous single-unit recordings from multiple sites in the kitten striate cortex and followed experience-dependent modifications of receptive-field properties. For induction of experimental modifications, we used the paradigm of monocular deprivation and reverse occlusion. Kittens were implanted when 4-5 wk old. During the following 2 days, receptive-field properties of the recorded units were determined once under light ketamine anesthesia and repeatedly while the kittens were awake and only lightly restrained. Subsequently, one eye was patched, and the resulting changes in neuronal eye preference were followed by repeated measurements of response properties. For investigation of the effects of reverse occlusion, the deprived eye was opened and the previously open eye closed when the neurons had become unresponsive to the initially deprived eye. Alternatively, kittens were monocularly deprived for 1 wk by lid suture before implantation. The closed eye was then opened, the other eye patched, and the effects of reverse occlusion were studied for up to 1 wk by repeated measurements of receptive-field properties. 2. The earliest effect of monocular deprivation was the disappearance of binocular summation, i.e., binocular responses ceased to be superior over monocular responses. Overt changes of ocular dominance were observed as early as 6 h after the beginning of monocular deprivation. These consisted of a gradual decrease of the excitatory response to deprived eye stimulation and, on occasions, of an additional moderate increase of responses to the normal eye. A complete loss of excitatory responses to deprived-eye stimulation was seen as early as 12 h after occlusion. In numerous cells, however, stimulation of the deprived eye continued to evoke inhibitory responses even after excitatory responses had vanished completely. During this shift in ocularity, neurons preserved their orientation and direction selectively. 3. The minimal time required for the manifestation of ocular dominance changes was similar regardless of whether the animals were stimulated continuously or were asleep part of the time, suggesting the existence of an experience-independent consolidation period for ocular dominance changes. 4. The first change after reverse occlusion was a reduction of the response to the newly deprived eye. The time course of this inactivation was similar to that observed after initial deprivation, whereas the recovery of responses to the previously deprived eye had a considerably slower time course.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1989

The effects of SMS 201-995 (sandostatin) on metabolic profiles in insulin-dependent diabetes mellitus.

GH has been implicated in the pathophysiology of various acute and chronic complications of diabetes mellitus. As a consequence, there has been a great deal of interest in developing methods for suppressing GH secretion in diabetes. SMS 201-995 is a long-acting somatostatin analog which inhibits the secretion of numerous hormones, including GH. To determine the metabolic and hormonal responses to SMS 201-995 independent of endogenous insulin suppression, we studied six patients with insulin-dependent diabetes mellitus while they received 150 micrograms SMS 201-995, sc, daily for an 8-week period. This treatment resulted in no change in 24-h glucose profiles, although the mean insulin dose decreased by 19%, while hemoglobin A1c decreased significantly (0.084 +/- 0.023 to 0.067 +/- 0.011, P = 0.04). The 24-h profiles of blood lactate, plasma free insulin, glucagon, FFA, blood glycerol, and beta-hydroxybutyrate were unchanged, whereas that of blood alanine increased significantly (7.8 +/- 0.4 to 10.6 +/- 0.9 mmol/L.h; P = 0.01). GH secretion declined in five of the six patients; the mean values before and during SMS 201-995 treatment were 102 +/- 23 and 68 +/- 12 micrograms/L.h, respectively (P = NS), for the six patients. [In the five patients in whom GH secretion declined, the mean values before and during SMS 201-995 treatment were 115 +/- 23 and 63 +/- 14 micrograms/L.h, respectively (P = 0.01).] These results suggest that SMS 201-995 may be administered to patients with insulin-dependent diabetes mellitus without a deleterious effect on metabolic control.

Adult↗

PubMed1988

Pharmacological induction of use-dependent receptive field modifications in the visual cortex.

Lasting modifications of the receptive fields of neurons in the visual cortex can be induced by pairing visual stimuli with iontophoretic application of the neuromodulators acetylcholine and noradrenaline or the excitatory amino acids N-methyl-D-aspartate (NMDA) and L-glutamate. The modifications are obtained in less than 1 hour and persist for more than 40 minutes. Thus, acetylcholine and norepinephrine have a permissive role in use-dependent neuronal plasticity. These results support the notion of a postsynaptic threshold for neuronal malleability that differs from that of sodium-dependent action potentials.

Acetylcholine↗

PubMed1988

Light and electron microscopic immunocytochemical localization of parvalbumin in the dorsal lateral geniculate nucleus of the cat: evidence for coexistence with GABA.

The coexistence in individual neurons of parvalbumin and gamma-aminobutyric acid (GABA) was studied in the dorsal lateral geniculate nucleus (dLGN) of the cat using pre- and postembedding immunocytochemical methods. PV(+) cell bodies and processes were found in the perigeniculate nucleus (PGN) and throughout all laminae of the dLGN. PV(+) neurons were relatively small and had circular to fusiform shapes. Electron microscopy revealed PV(+) reaction product within the perikarya, axons, and dendrites of labeled cells. It was associated preferentially with microtubules, postsynaptic densities, and intracellular membranes. PV(+) presynaptic boutons were identified on the basis of their synaptic relations and ultrastructure as retinal terminals (RLP) and as profiles originating from inhibitory interneurons (F1 and F2). Immunopositive somata and dendrites received asymmetric synaptic contacts from labeled RLP and non-identified, non-immunoreactive synaptic boutons. Moreover, PV(+) dendrites were postsynaptic to labeled F profiles. In the PGN all neurons were both PV(+) and GABA-immunoreactive and in the dLGN the vast majority of PV(+) neurons showed GABA-immunoreactivity. It is suggested that the high incidence of PV in GABAergic neurons is related to the particular activation patterns of these neurons and the resulting demand for calcium buffer systems.

Animals↗

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↗