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W Singer

Publications and source records attributed to W Singer.

At least 91 records · Page 5Linked to original sources

Development and plasticity of cortical processing architectures.

One of the basic functions of the cerebral cortex is the analysis and representation of relations among the components of sensory and motor patterns. It is proposed that the cortex applies two complementary strategies to cope with the combinatorial problem posed by the astronomical number of possible relations: (i) the analysis and representation of frequently occurring, behaviorally relevant relations by groups of cells with fixed but broadly tuned response properties; and (ii) the dynamic association of these cells into functionally coherent assemblies. Feedforward connections and reciprocal associative connections, respectively, are thought to underlie these two operations. The architectures of both types of connections are susceptible to experience-dependent modifications during development, but they become fixed in the adult. As development proceeds, feedforward connections also appear to lose much of their functional plasticity, whereas the synapses of the associative connections retain a high susceptibility to use-dependent modifications. The reduced plasticity of feedforward connections is probably responsible for the invariance of cognitive categories acquired early in development. The persistent adaptivity of reciprocal connections is a likely substrate for the ability to generate representations for new perceptual objects and motor patterns throughout life.

Action Potentials↗

All-or-none excitatory postsynaptic potentials in the rat visual cortex.

Intracellular recordings were obtained from supragranular neurons in slices of the rat visual cortex. In approximately 25% of the cells large (0.5-1.6 mV) excitatory postsynaptic potentials (EPSPs) of constant amplitude were observed after minimal, presumably single-fibre stimulation. The amplitude variance of these large EPSPs was surprisingly small and within the range of the variance of the noise. These EPSPs could be reduced in amplitude by paired-pulse and low-frequency stimulation or by raising extracellular Mg2+ concentration. Reduced EPSPs could either continue to behave as all-or-none responses, or they could fluctuate between several amplitude levels. Conversely, responses where the amplitude fluctuated from trial to trial under control conditions could be converted into large all-or-none responses by paired-pulse facilitation. This indicates that the large all-or-none EPSPs were composed of several subunits, probably reflecting the action of several different release sites. It is concluded that these release sites are either independent and operate with a probability close to 1 or, if operating with a lower probability, are coordinated by a mechanism which synchronizes release. Several observations suggest that release probabilities can switch from values close to 1 to 0 with repetitive stimulation or high Mg2+ concentration. Thus, a substantial fraction of single-fibre inputs to supragranular cells possess synapses which operate with high synaptic efficiency and extremely low variance under control conditions but can undergo drastic changes in efficacy when release probabilities are interfered with. Such modifications of release probability could serve as an effective mechanism to regulate the gain of synaptic transmission.

Animals↗

Involvement of serotonin in developmental plasticity of kitten visual cortex.

During a critical period of postnatal development, neuronal connections in the kitten visual cortex are susceptible to experience-dependent modifications. These modifications are facilitated by the neuromodulators noradrenaline and acetylcholine. To address the question of whether serotonin (5-hydroxytryptamine; 5-HT), the other major neuromodulator in the cerebral cortex, also plays a role in developmental plasticity, we investigated whether interference with serotoninergic transmission in the kitten visual cortex affects ocular dominance (OD) plasticity. The serotonin neurotoxin 5,7-dihydroxytryptamine or the serotonin receptor blockers ketanserin and methysergide were infused into the visual cortex of kittens undergoing monocular deprivation. We found that both methods of disrupting serotoninergic transmission reduced OD plasticity. However, to be effective, the receptor blockers ketanserin and methysergide had to be applied in combination, suggesting that coactivation of serotonin receptor subtypes of both the 5-HT1 and 5-HT2 families have a permissive function in OD plasticity. Since activation of 5-HT2 receptors stimulates phosphoinositide hydrolysis, our data suggest that second messengers from the phospholipid pathway may play an important role in developmental plasticity of visual cortex.

5,7-Dihydroxytryptamine↗

Metabolic mapping of visual areas in the behaving cat: a [14C]2-deoxyglucose study.

Visually responsive cortical areas and subcortical nuclei were studied in the awake cat using the 2-deoxyglucose technique. Visual input was confined to one hemisphere by unilaterally sectioning the optic tract, the corpus callosum and the commissura anterior. Within the intact hemisphere, numerous cortical regions were distinguishable in the autoradiographs due to differential labelling. Comparison of the intact with the visually deafferented hemisphere confirmed the visual character of eighteen cortical areas (areas 17, 18, 19, 20a, 20b, 21a, 21b, the posteromedial lateral, posterolateral lateral, anteromedial lateral, anterolateral lateral, dorsal lateral, ventral lateral, and posterior suprasylvian areas, the splenial and anterior ectosylvian sylvian areas, insular visual area and posterior area 7) and revealed the visual nature of an area in the posterior cingulate gyrus which had not been described previously. We refer to this area as cingulate visual area (CVA). This area exhibits a gradient in interhemispheric differences along a caudorostral axis similar to that observed in posterior area 7 which is in keeping with the strong and topographic connections between CVA and posterior area 7. These results support the validity of metabolic mapping for the characterisation of cortical areas.

Animals↗

Relation between oscillatory activity and long-range synchronization in cat visual cortex.

Recent theoretical studies have suggested that oscillatory firing patterns with frequencies in the gamma band (30-70 Hz) may be instrumental for the establishment of synchrony among widely distributed neurons if synchrony is to be achieved by reciprocal connections. We have now investigated the relationship between synchrony and oscillations in cat visual cortex. Our results show that when synchronization of neuronal activity occurs over distances of > 2 mm in primary visual cortex, or occurs between the two hemispheres, it is almost always associated with oscillatory firing patterns, whereas synchronization over short distances occurs also in the absence of oscillations. Furthermore, our results indicate that short-range interactions affect both the firing rate of the respective neurons and the timing of their discharges, whereas only the latter is influenced by long-range interactions. These data support the hypothesis that oscillatory activity can contribute to the establishment of long-range synchrony in a network of reciprocally coupled neurons.

Animals↗

Thyroid hormone treatment of depression.

The use of thyroid hormones in the treatment of depression is reviewed. The studies examining the use of triodothyronine (T3) alone as well as combination with antidepressants are discussed. The data suggest that there is little evidence that T3 alone has antidepressant efficacy but that this hormone may be used to enhance therapeutic effects of antidepressants in treatment refractory depressed patients. The different theories to explain the antidepressant effects of T3 are summarized.

Antidepressive Agents↗

How precise is neuronal synchronization?

Recent work suggests that synchronization of neuronal activity could serve to define functionally relevant relationships between spatially distributed cortical neurons. At present, it is not known to what extent this hypothesis is compatible with the widely supported notion of coarse coding, which assumes that features of a stimulus are represented by the graded responses of a population of optimally and suboptimally activated cells. To resolve this issue we investigated the temporal relationship between responses of optimally and suboptimally stimulated neurons in area 17 of cat visual cortex. We find that optimally and suboptimally activated cells can synchronize their responses with a precision of a few milliseconds. However, there are consistent and systematic deviations of the phase relations from zero phase lag. Systematic variation of the orientation of visual stimuli shows that optimally driven neurons tend to lead over suboptimally activated cells. The observed phase lag depends linearly on the stimulus orientation and is, in addition, proportional to the difference between the preferred orientations of the recorded cells. Similar effects occur when testing the influence of the movement direction and the spatial frequency of visual stimuli. These results suggest that binding by synchrony can be used to define assemblies of neurons representing a coarse-coded stimulus. Furthermore, they allow a quantitative test of neuronal network models designed to reproduce physiological results on stimulus-specific synchronization.

Anesthesia↗

Reduced synchronization in the visual cortex of cats with strabismic amblyopia.

Synchronous firing of spatially separate neurons was studied with multi-electrode recordings in area 17 of the visual cortex of strabismic cats which had developed behaviourally verified amblyopia of the deviated eye. Responses of neurons were evoked with moving light bars or gratings of different spatial frequency. Neurons driven by the normal eye displayed stronger synchronization of their responses than neurons dominated by the amblyopic eye. These interocular differences were highly significant and particularly pronounced for grating stimuli of high spatial frequency. No interocular differences were noted with respect to the amplitudes of responses to the light bars and gratings. These results suggest reduced synchronization of population responses as a neurophysiological correlate of strabismic amblyopia and underline the importance of correlated firing of spatially separate cortical neurons for normal processing of visual information.

Amblyopia↗

Induction of LTP and LTD in visual cortex neurones by intracellular tetanization.

Neurones from supragranular layers of rat visual cortex slices were activated by intracellular tetanization (IT) without concomitant presynaptic stimulation. The effect of IT was examined on EPSPs evoked at low stimulation intensity from two subsets of afferents by electrodes positioned in layers II and IV, respectively. In 17 of 23 inputs to 15 cells IT led to changes in EPSP amplitudes which persisted throughout the recording period (from at least 40 min to 3 h). For 10 potentiated inputs (nine cells) and eight depressed inputs (seven cells), EPSP amplitudes measured 30 min after tetanization were 167 +/- 14% and 55 +/- 14% of the pretetanic controls, respectively. In seven cells both inputs changed, in five cases modifications were of the opposite and in two cases of the same polarity.

Animals↗

Neuroscience in Europe: the European Neuroscience Association.

The number of neuroscientists in Europe is large enough to match that of the neuroscientific community in North America. However, the degree of cohesiveness in the former is hampered by, among other things, the lack of a common language, the existence of geopolitical boundaries, and the dearth of pan-European funding initiatives. In this article, Wolf Singer, President of the European Neuroscience Association (ENA), discusses these issues and describes how the ENA is changing its organization, in particular the way in which its annual meeting is to be organized, in an effort to counteract the current deficiencies in European neuroscience.

Europe↗

Insulin levels, blood pressure and sleep apnea.

This report concerns the relative contributions of body weight and sleep apnea to the following cardiovascular risk factors: blood pressure, fasting insulin and fasting glucose. We cross-sectionally examined the relationship of various levels of apneic activity [apnea-hypopnea index (AHI)] and a measure of obesity [body mass index (BMI)] to mean morning blood pressure and fasting serum insulin and fasting blood glucose concentrations sampled the morning after polysomnography. Subjects were 261 males (age 47 +/- 13 years, mean +/- SD), who were referred to a sleep laboratory for symptoms of sleep-disordered breathing. The dependent variables, mean morning blood pressure, insulin and fasting blood glucose (FBG) levels, were significantly related to both AHI (eta'2 = 0.10) and BMI (eta'2 = 0.18). AHI and BMI combined to account for approximately 30% of the variability in the best linear combination of these three factors. Further analysis indicated that mean morning blood pressure and fasting insulin levels each correlated positively with BMI and AHI, whereas FBG correlated only with BMI. We conclude that, although these data do not prove a causal relationship, there is evidence for an independent association between sleep apnea and not only blood pressure, but also fasting insulin levels.

Adult↗

Pituitary gland MR: a comparative study of healthy volunteers and patients with microadenomas.

PURPOSE: To compare the MR appearance of the pituitary glands of healthy volunteers with that of patients with microadenomas. METHODS: Unenhanced coronal T1-weighted MR of the pituitary gland was performed on 52 healthy adult volunteers and 14 consecutive patients with evidence of pituitary adenomas. The MRs were interpreted in a randomized, blinded fashion. Notation was made of pituitary gland size, symmetry, stalk position, and the gland's signal uniformity. RESULTS: Focal pituitary gland hypointensities were seen in 20 of 52 volunteers and in all 14 patients. In the volunteers, on average the areas of low signal were smaller and not as dark as in the patient group, but there was some overlap between the two groups. Pituitary gland size, symmetry, and stalk position did not differ between the two groups. CONCLUSIONS: Focal hypointensities are common incidental MR findings in the healthy population. On average they appear smaller and not as dark as microadenomas.

Adenoma↗

Transient association of the HNK-1 epitope with 5'-nucleotidase during development of the cat visual cortex.

During early postnatal development of the kitten visual cortex the ectoenzyme 5'-nucleotidase undergoes a characteristic redistribution. Until about postnatal week 6 it is essentially confined to synaptic contacts in input layer IV and its expression is related to the use-dependent segregation of thalamic afferents into ocular dominance columns. Subsequently, 5'-nucleotidase becomes distributed uniformly throughout all layers and is then associated selectively with glial cells. Here we describe an age-dependent alteration in the expression of a carbohydrate epitope of 5'-nucleotidase which correlates with the developmental change of the enzyme's localization. We have isolated 5'-nucleotidase from the occipital cortex of kittens of varying age and from adult cats and investigated by immunoblotting the association of the HNK-1 carbohydrate epitope with the protein. 5'-Nucleotidase carries the HNK-1 epitope in kittens of 3-9 weeks but the epitope is absent from 12-week-old kittens or adult cats. Thus, the appearance of the HNK-1 epitope correlates with the transient localization of the enzyme at synapses. The HNK-1 carrying 5'-nucleotidase may be involved in synaptogenesis and use-dependent modifications of synaptic connections.

5'-Nucleotidase↗

Monocularly induced 2-deoxyglucose patterns in the visual cortex and lateral geniculate nucleus of the cat: I. Anaesthetized and paralysed animals.

Extending previous investigations of the topographic relationship between ocular dominance and orientation columns in the cat visual cortex the two systems were visualized with transneuronally transported [3H]proline and with activity-dependent uptake of [14C]2-deoxyglucose, respectively. In addition, we used the 2-deoxyglucose method for a functional assay of both columnar systems. To this end, cats were injected with [3H]proline in the right eye. Two weeks later, they were stimulated monocularly through this eye by presenting contours of only a single orientation in the left and contours of many different orientations in the right visual hemifield while 2-deoxyglucose was injected. The patterns of increased 2-deoxyglucose uptake and of terminal labelling were analysed in flat-mount sections of the visual cortices and in frontal sections of the lateral geniculate nuclei. In the lateral geniculate nucleus, regions of increased 2-deoxyglucose uptake are in register with the [3H]proline-labelled laminae of the open eye. In the visual cortex, the hemispheres stimulated with many different orientations showed a rather homogeneous accumulation of 2-deoxyglucose over the entire extent and throughout all layers of area 17. The hemispheres stimulated with a single orientation displayed columnar patterns of orientation domains essentially similar to those obtained with binocular presentation of a single orientation. In particular and despite monocular stimulation, regions of increased 2-deoxyglucose uptake were neither in register with the [3H]proline-labelled terminals of the increased 2-deoxyglucose uptake were neither in register with the [3H]proline-labelled terminals of the stimulated eye in layer IV nor confined to columns of neural tissue above and below these terminals. The maximal horizontal offset between the termination sites of thalamic afferents and activated orientation columns was in the order of 400 microns. These findings suggest several conclusions. (i) In the cat visual cortex, binocular convergence seems to occur so early in cortical processing that monocular stimulation with many orientations leads to a rather homogeneous activation of cortical tissue. (ii) From the termination zones of geniculate afferents activity is apparently distributed already within layer IV to the respective orientation columns. (iii) This horizontal spread of activity could be assured by target cells with radially extending dendrites and/or tangentially oriented fibres.

Animals↗

Monocularly induced 2-deoxyglucose patterns in the visual cortex and lateral geniculate nucleus of the cat: II. Awake animals and strabismic animals.

In the course of experiments studying the organization of ocular dominance columns in the visual cortex of cats, we noticed that--contrary to common belief--labelling with 2-deoxyglucose after monocular stimulation failed to induce a pattern of ocular dominance columns but resulted in a rather homogenous 2-deoxyglucose uptake throughout area 17 in anaesthetized and paralysed animals. We wondered whether 2-deoxyglucose columns could be obtained in awake animals and/or in strabismic animals, which have a more pronounced segregation of ocular dominance columns. To this end, we investigated 2-deoxyglucose patterns after monocular stimulation in three groups of animals: (i) in awake normally reared cats, (ii) in awake strabismic cats and (iii) in anaesthetized and paralysed strabismic cats. Additionally, we labelled ocular dominance columns with intraocular [3H]proline injections. In all cats, monocular stimulation induced 2-deoxyglucose patterns that were in precise register with the proline-labelled ocular dominance columns in layer IV. Regions of increased 2-deoxyglucose uptake extended in a columnar fashion through all cortical layers. In contrast to normally reared animals, in strabismic cats, the expression of 2-deoxyglucose labelled ocular dominance columns was not abolished by anaesthesia or paralysis. However, there was a difference between the 2-deoxyglucose patterns in the awake normally reared cats and the strabismic animals. In the former, the patches of 2-deoxyglucose labelling were smaller and occupied less territory than the afferents of the stimulated eye in layer IV. Together with the results of the previous study, these data indicate that in awake normally reared and in awake and anaesthetized strabismic cats, but not in anaesthetized and paralysed normally reared animals, monocular stimulation activates selectively neurons in columns that are in register with the termination sites of afferents from the stimulated eye. This suggests the existence of a mechanism in normally reared animals which restricts cortical activation after monocular stimulation to territories that are in register with the afferents from the stimulated eye. This mechanism appears to be effective only when the animals are awake and actively exploring their environment. This and the fact that the active columns were narrower than the terminal fields of the stimulated eye suggest an active inhibitory process, perhaps related to mechanisms of selective attention. The observation that ocular dominance columns persist in strabismic cats even under anaesthesia can be accounted for by the lack of binocular convergence in these animals.

Animals↗