Visual feature integration and the temporal correlation hypothesis.
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Animals↗
Biomedical subjects
W Singer
Publications and source records attributed to W Singer.
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↗
Neurobiology. A new job for the thalamus.
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Cortical Synchronization↗
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↗
Coherence as an organizing principle of cortical functions.
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Amblyopia↗
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↗
Effects of intracortical infusion of anticholinergic drugs on neuronal plasticity in kitten striate cortex.
During a critical period of postnatal development the mammalian visual cortex is highly susceptible to experience-dependent alterations of neuronal response properties. These modifications are facilitated by the neuromodulators noradrenaline and acetylcholine. To identify the cholinergic mechanisms responsible for this facilitation, muscarinic and nicotinic antagonists were infused into the visual cortex of kittens while the animals were subject to monocular deprivation. Subsequently the ocular dominance of cortical cells was assessed by single-unit recording. Ocular dominance changes were suppressed by scopolamine and pirenzepine but not by gallamine, hexamethonium and mecamylamine. This blocking effect was concentration-dependent, and control experiments revealed that it was not due to suppression of neuronal responses to light. It is concluded from these results that acetylcholine facilitates neuronal plasticity in the visual cortex through mechanisms activated by muscarinic M1 receptors.
Animals↗
Squint affects synchronization of oscillatory responses in cat visual cortex.
As shown previously, neurons in various areas of the cat's visual cortex respond to appropriate visual stimuli with oscillatory activity in the frequency range of 30-70 Hz. It has been suggested that synchronization of such responses serves to define assemblies of coherently active cells which represent individual visual objects. In this study, we have investigated this putative binding mechanism in the visual cortex of strabismic cats. We used six adult cats in which divergent squint had been induced surgically at the age of 3 weeks. Multiunit activity was recorded from area 17 with arrays of four or five closely spaced microelectrodes. Subsequently, auto- and cross-correlation functions were computed for all spike trains. To quantify the oscillatory nature of the responses and the strength of synchronization between spatially remote sites, damped sine wave functions were fitted to the correlograms. Analysis of responses obtained from 202 recording sites showed that the vast majority of cells had become monocular. Auto-correlation analysis revealed that the proportion of oscillatory firing patterns was similar to that observed in normal cats. However, cross-correlation analysis of 153 response pairs demonstrated that synchronization was reduced significantly between cells dominated by different eyes while it was as frequent and strong as in normal cats between cells dominated by the same eye. These findings indicate that strabismus not only causes a reorganization of afferent inputs but also affects intracortical interactions.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Cytochemical redistribution of 5'-nucleotidase in the developing cat visual cortex.
The adenosine-producing ectoenzyme 5'-nucleotidase has recently been shown to undergo a marked redistribution during development of the cat visual cortex and to be involved in the remodelling of ocular dominance columns (Schoen et al., J. Comp. Neurol., 296, 379-392, 1990). Using an enzyme-cytochemical technique, we now investigate the developmental redistribution of 5'-nucleotidase activity in area 17 of kittens at the ultrastructural level. Between postnatal days 35 and 42, when 5'-nucleotidase is concentrated in layer IV, enzyme reaction product occupies the clefts of asymmetrical synapses within the neuropil. During later development (9th and 13th postnatal weeks), when 5'-nucleotidase spreads over all cortical laminae, the enzyme disappears from its synaptic localization and becomes increasingly associated with astrocytic membranes. The transient appearance of 5'-nucleotidase at synapses parallels the time-course and laminar profile of the synaptic remodelling which takes place during the critical period of visual cortex development. This suggests that synapse-bound 5'-nucleotidase activity plays a role in synaptic malleability, whereas its later association with glial profiles is likely to reflect other functions of the enzyme.
5'-Nucleotidase↗
A placebo-controlled comparison of lithium and triiodothyronine augmentation of tricyclic antidepressants in unipolar refractory depression.
OBJECTIVE: To directly compare the efficacy of lithium carbonate and liothyronine sodium (triiodothyronine) in the augmentation of therapeutic response in antidepressant nonresponders. DESIGN: A randomized, double-blind, placebo-controlled study of 2 weeks' duration. SETTING: The Mood Disorders Program, Clarke Institute of Psychiatry and the University of Toronto, Ontario. PATIENTS: Fifty outpatients, males and females, with unipolar, nonpsychotic major depression who had failed to respond to treatment with desipramine hydrochloride or imipramine hydrochloride. RESULTS: Both liothyronine and lithium were more effective than placebo in reducing scores on the Hamilton Rating Scale for Depression. However, the antidepressant augmenting effect of these two compounds did not differ from each other. When response was defined as a 50% or more reduction in the Hamilton Rating Scale for Depression scores and a final score less than 10, we found that 10 of 17 subjects responded to liothyronine, nine of 17 responded to lithium and three of 16 responded to placebo. CONCLUSIONS: Our study suggests that both lithium and liothyronine may be considered as alternatives in augmenting antidepressant response in patients who do not respond to treatment with a tricyclic antidepressant.
Adult↗
Reticular facilitation of cat visual cortical responses is mediated by nicotinic and muscarinic cholinergic mechanisms.
Stimulation of the mesencephalic reticular formation facilitates responses in the visual cortex elicited from the optic radiation. Using intravenous administration of cholinergic antagonists we investigated in adult cats and two kittens whether this effect is mediated by cholinergic mechanisms. When administered alone the muscarinic antagonists atropine and scopolamine and the nicotinic antagonist mecamylamine failed to block reticular facilitation and sometimes even enhanced the effects of reticular stimulation. However, when administered in combination muscarinic and nicotinic antagonists eliminated or significantly reduced the facilitation. This was even true when the two antagonists were administered with a time lag of several hours. These results support the notion that reticular facilitation of cortical responses is mediated by cholinergic mechanisms and suggest that this effect is mediated either by a receptor with a mixed pharmacological property or by two independent pathways acting via nicotinic and muscarinic receptors. This hypothesis is discussed in the context of recent evidence on cholinergic transmission and earlier data on the pharmacology of reticular arousal.
Animals↗
Structures mediating cholinergic reticular facilitation of cortical responses in the cat: effects of lesions in immunocytochemically characterized projections.
Cholinergic afferents to the neocortex controlled by the mesencephalic reticular formation (MRF) are known to transiently facilitate cortical excitability. In an attempt to identify the pathway mediating this effect in the cat visual cortex we combined retrograde tracing techniques with immunocytochemical methods to visualize the acetylcholine-synthesizing enzyme choline acetyltransferase (ChAT). In addition we examined, in acute electrophysiological experiments, whether local neurotoxin injections into nuclei of the basal forebrain interfered with the reticular facilitation of cortical evoked potentials. Cholinergic projections to area 17 originate from different centers in the homolateral substantia innominata/internal capsule, the septal nuclei, and the nuclei of the diagonal band of Broca. No direct cholinergic projection from the MRF to the visual cortex was observed. Retrogradely labelled cells intermingled with ChAT-positive neurons in the brainstem generally revealed immunopositivity for catecholaminergic markers. Local injections of neurotoxins in the substantia innominata blocked reticular facilitation, whereas local lesions of the septal nuclei and the nuclei of the diagonal band had no effect on MRF-induced facilitation. The blockage of the reticular facilitation of cortical evoked responses after unilateral lesions of the substantia innominata was bilateral, suggesting a cooperative interaction between basal forebrain structures of the two hemispheres. The anatomical and physiological data are discussed with respect to possible mechanisms of transient brainstem influences on cortical excitability.
Animals↗