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Biomedical subjects

M Brecht

Publications and source records attributed to M Brecht.

17 recordsLinked to original sources
PubMed2001

Synchronization of visual responses in the superior colliculus of awake cats.

Multi-unit responses to moving stimuli were recorded simultaneously from several sites in the superior colliculus of awake cats. Correlation analysis revealed that response synchronization was a prominent feature of visually evoked neural activity in both superficial and deep collicular layers. Responses at about half of the recordings separated by < or = 1 mm showed significant correlations. The synchronized responses oscillated in the gamma frequency range (30-70 Hz) which contrasts to conditions in anaesthetized cats where oscillations predominantly occurred in the alpha and beta frequency range (10-20 Hz). Response synchronization was most pronounced with coherent motion stimuli and broke down with incoherent stimuli. These results agree with previous findings on corticotectal synchronization and support the hypothesis that synchronization in the millisecond range serves to group collicular neurons into functionally coherent assemblies.

Animals↗
PubMed1999

Patterns of synchronization in the superior colliculus of anesthetized cats.

Sensorimotor transformations in the mammalian superior colliculus (SC) are mediated by large sets of distributed neurons. For such distributed coding systems, stimulus superposition poses problems attributable to the merging of neural populations coding for different stimuli. Such superposition problems could be overcome by synchronization of neuronal discharges, because it allows the selection of a subset of distributed responses for further joint processing. To assess the putative role of such a temporal binding mechanism in the SC, we have applied correlation analysis to visually evoked collicular activity. We performed recordings of single-unit and multiunit activity in the SC of anesthetized and paralyzed cats with multiple electrodes. Autocorrelation analysis revealed that collicular neurons often discharged in broad (20-100 msec) bursts or with an oscillatory patterning in the alpha- and beta-frequency range. Significantly modulated cross-correlograms were observed in 50% (128 of 258) of the collicular multiunit recording pairs, and for these pairs significant correlations occurred in 44% of the stimulation epochs. For the single-unit pairs, significant interactions were observed in 14 of 48 cases studied (29%). Collicular cross-correlograms were often oscillatory, and these oscillations covered a broad frequency range of up to 100 Hz, with a predominance of oscillation frequencies in the alpha- and beta-range. In the majority of the significant correlograms (64%) the phase lag of the center peak was <5 msec. The probability of collicular synchronization increased with the overlap of the receptive fields and the proximity of the recording sites. Correlations were also observed between cells in the superficial and deep SC layers. Collicular synchronization required activation of the respective cells with a single coherent stimulus and broke down when the neurons were activated with two different stimuli. These data are consistent with the notion that collicular synchrony could define assemblies of functionally related cells.

Anesthesia, General↗
PubMed1999

Temporal binding, binocular rivalry, and consciousness.

Cognitive functions like perception, memory, language, or consciousness are based on highly parallel and distributed information processing by the brain. One of the major unresolved questions is how information can be integrated and how coherent representational states can be established in the distributed neuronal systems subserving these functions. It has been suggested that this so-called "binding problem" may be solved in the temporal domain. The hypothesis is that synchronization of neuronal discharges can serve for the integration of distributed neurons into cell assemblies and that this process may underlie the selection of perceptually and behaviorally relevant information. As we intend to show here, this temporal binding hypothesis has implications for the search of the neural correlate of consciousness. We review experimental results, mainly obtained in the visual system, which support the notion of temporal binding. In particular, we discuss recent experiments on the neural mechanisms of binocular rivalry which suggest that appropriate synchronization among cortical neurons may be one of the necessary conditions for the buildup of perceptual states and awareness of sensory stimuli.

Arousal↗
PubMed1998

Changes in polysome profiles accompany trypanosome development.

Development of the protozoan pathogen Trypanosoma brucei involves regulated changes in parasite structure, biochemistry, and the cell cycle. The transition of slender blood forms into stumpy bloodforms includes cell cycle arrest and a decrease in protein synthesis. The next stage in the development cycle, the procyclic form, shows increased protein synthesis and proliferates. To address the mechanism of the cyclical changes in protein synthesis, we examined two parameters: polyadenylation of mRNA and ribosome loading. We developed a method for analytical polyribosome analysis in T. brucei which provided excellent results with regard to reproducibility, yield of mRNA densely loaded with ribosomes, and separation of mRNA associated with different numbers of polyribosomes. Use of this technique allowed us to determine that the polysome profiles of the different developmental stages are distinctly different, with higher ribosome loading in the proliferating stages. The lengths of the poly(A) tails on the total population of RNA from the different developmental stages showed no significant variation. These data indicate that changes in polysome loading of mRNAs accompany development, and that they do not reflect bulk changes in polyadenylation. We speculate that developmental changes in translation reflect reduced translational initiation.

Animals↗
PubMed1998

Correlation analysis of corticotectal interactions in the cat visual system.

We have studied the temporal relationship between visual responses in various visual cortical areas [17, 18, postero medial lateral suprasylvian (PMLS), postero lateral lateral suprasylvian (PLLS), 21a]) and the superficial layers of the cat superior colliculus (SC). To this end, simultaneous recordings were performed in one or several visual cortical areas and the SC of anesthetized paralyzed cats, and visually evoked multiunit responses were subjected to correlation analysis. Significant correlations occurred in 117 (24%) of 489 cortex-SC pairs and were found for all cortical areas recorded. About half of the significant correlograms showed an oscillatory modulation. In these cases, oscillation frequencies covered a broad range, the majority being in the alpha- and beta-band. On average, significant center peaks in cross-correlograms had a modulation amplitude of 0.34. Our analysis revealed a considerable intertrial variability of correlation patterns with respect to both correlation strength and oscillation frequency. Furthermore, cortical areas differed in their corticotectal correlation patterns. The percentage of cells involved a corticotectal correlation, as well as the percentage of significantly modulated correlograms in such cases, was low for areas 17 and PMLS but high for areas 18 and PLLS. Analysis of the cortical layers involved in these interactions showed that consistent temporal relationships between cortical and collicular responses were not restricted to layer V. Our data demonstrate a close relationship between corticotectal interactions and intracortical or intracollicular synchronization. Trial-by-trial analysis from these sites revealed a clear covariance of corticotectal correlations with intracortical synchronization. The probability of observing corticotectal interactions increased with enhanced local cortical and collicular synchronization and, in particular, with interareal cortical correlations. Corticotectal correlation patterns resemble in many ways those described among areas of the visual cortex. However, the correlations observed are weaker than those between nearby cortical sites, exhibit usually broader peaks and for some cortical areas show consistent phase-shifts. Corticotectal correlations represent population phenomena that reflect both the local and global temporal organization of activity in the cortical and collicular network and do not arise from purely monosynaptic interactions. Our findings show that both striate and extrastriate inputs affect the superficial SC in a cooperative manner and, thus, do not support the view that responses in the superficial SC depend exclusively on input from the primary visual areas as implied by the concept of "two corticotectal systems." We conclude that the corticotectal projections convey temporal activation patterns with high reliability, thus allowing the SC evaluation of information encoded in the temporal relations between responses of spatially disseminated cortical neurons. As a consequence, information distributed across multiple cortical areas can affect the SC neurons in a coherent way.

Animals↗
PubMed1997

Functional architecture of the mystacial vibrissae.

We investigated the transduction operation and function of the mystacial vibrissae, using a comparative morphological analysis and behavioral experiments in rats. Vibrissal architecture was documented in a series of mammals to identify evolutionary conserved features of vibrissal organization. As a result of this analysis, we distinguish between a frontal microvibrissal system and macrovibrissal system of the mystacial pad. The latter was invariably comprised of whiskers aligned in regular rows. In each row, whiskers were oriented perpendicular to the animal's rostrocaudal axis; all shared a specific dorsoventral orientation. In all species, progressing from rostral to caudal in any vibrissal row, there was a precisely exponential increase in whisker length. Each whisker appeared to act as a lever-like transducer, providing information as to whether or not--but not where--an individual vibrissa had been deflected. The rat's frontal microvibrissae system was found to have a vibrissa tip density that was about 40 times higher than that of the mystacial macrovibrissae. In behavioral studies spatial tasks and object recognition tasks were used to investigate (a) search behaviors; (b) single whisker movements; (c) object recognition ability; and (d) effects of selective macro- or microvibrissae removal on task performances. A clear distinction between the functional roles of macro- and microvibrissae was demonstrated in these studies. Mystacial macrovibrissae were critically involved in spatial tasks, but were not essential for object recognition. Microvibrissae were critically involved in object recognition tasks, but were not essential for spatial tasks. A synthesis of these morphological and behavioral data led to the following functional concept: The mystacial macrovibrissae row is a distance decoder. Its function is to derive head centered obstacle/opening contours at the various dorsoventral angles represented by vibrissal rows. This distance detector model is functionally very different from traditional concepts of whisker function, in which the mystacial whiskers were hypothesized to form a fine grain skin-like object-recognizing tactile surface.

Animals↗
PubMed1997

Role of the temporal domain for response selection and perceptual binding.

Most cognitive functions are based on highly parallel and distributed information processing by the brain. A paradigmatic example is provided by the vertebrate visual system where numerous cortical areas have been described which analyse different types of visual information. At present, it is unclear how information can be integrated and how coherent representational states can be established in such distributed systems. We suggest that this so-called 'binding problem' may be solved in the temporal domain. The hypothesis is that synchronization of neuronal discharges can serve for the integration of distributed neurons into cell assemblies and that this process may underlie the selection of perceptually and behaviourally relevant information. We review experimental results, mainly obtained in the visual system, which support this temporal binding hypothesis.

Animals↗
PubMed1995

The use of genomic DNA probes for in-gel hybridization.

Hybridization within agarose gels using oligonucleotide probes has been described in several publications; genomic DNA probes, however, have been used rarely and only with limited success. Here we present a simple and convenient procedure for in-gel hybridization using radiolabeled genomic DNA fragments. The protocol was improved by the use of formamide in the hybridization as well as in the washing step. This method was compared with the conventional Southern blotting technique and was shown to produce good results in restriction pattern analysis, as well as in chromosomal localization with the help of pulsed field gel electrophoresis.

Blotting, Southern↗
PubMed1994

[Changes in cytosol Ca(2+)-, Mg(2+)-, H(+)-, N(+)-, and K(+)-concentrations in cultivated hepatocytes in hypoxic conditions].

AIM: It is assumed that disturbances of cellular ion homeostasis, especially an increase in the cytosolic Ca2+ concentration, are of decisive importance for hypoxic cell injury. The aim of this study is the determination of alterations in the cytosolic Ca2+, Mg2+, H+, Na+ and K+ concentration in cultured hepatocytes during hypoxia. METHODS: The alterations of ion homeostasis under hypoxic conditions were studied in primary cultures of isolated rat hepatocytes by using fluorescence microscopy. RESULTS: The measurements of cytosolic Ca2+ concentration showed no alterations during the first 3-4 h of hypoxia. About 1-2 h before cell injury became evident Ca2+ increased from 147 +/- 28 to 385 +/- 31 nM. Similarly the cytosolic Mg2+ concentration increased from 0.63 +/- 0.05 to 1.42 +/- 0.11 mM in a late stage of hypoxia. In contrast, the cytosolic Na+ concentration increased continuously from 16 +/- 2 mM at start to 76 +/- 9 mM after 5 h of hypoxic conditions. The cytosolic K+ concentration remained constant for 2 h (129 +/- 7 mM) but then decreased down to 31 +/- 18 mM. The intracellular H+ concentration increased slightly under hypoxic conditions, the pH decreased from 7.35 +/- 0.02 to 7.19 +/- 0.04. CONCLUSION: The results indicate that cytosolic Ca2+ plays only a minor role in the pathomechanism of hypoxic hepatocellular injury but suggest an important role of the cytosolic Na+ concentration in this process.

Acid-Base Equilibrium↗
PubMed1993

Cloning and sequencing of glutamate mutase component E from Clostridium tetanomorphum.

The nucleotide sequence of the large subunit E of glutamate mutase of Clostridium tetanomorphum was determined. The protein consists of 483 amino acids and is not made in a precursor form, thus excluding the possibility of subunit E being a pyruvoyl enzyme. It shows no homology to any other protein in the database, and while binding coenzyme B12, a conspicuous B12 binding motif, shared amongst other proteins, is not detectable at the sequence level.

Amino Acid Isomerases↗
PubMed1993

Improvement of the energy status of hypoxic hepatocytes by calcium channel blockers.

Isolated hepatocytes from rat liver in primary culture rapidly lost viability under hypoxic conditions. Hypoxic injury was significantly decreased by the calcium channel blockers nifedipine (5 microM) and diltiazem (10 microM). The concentrations of the inhibitors which afforded maximum protection also produced the maximum increase in the energy level of the hypoxic hepatocytes, as evidenced by their ATP, ADP, AMP, and total adenine nucleotide content and by their energy charge. The increased hypoxic energy level caused by these calcium channel blocking agents was not due to an increased rate of anaerobic glycolysis; nifedipine did not have any effect on lactate production while diltiazem slightly decreased its rate. During the first 2 h under hypoxic conditions the cytosolic Ca2+ concentration remained constant around 100 nM, subsequently increasing to 400 nM first slowly and later more rapidly. The calcium channel blockers delayed the Ca2+ increase by about 1 h but were without any effect on the rate of this increase. The results suggest that the well-known beneficial effects of calcium channel blockers on hypoxic liver injury are due in large measure to an improved energetic situation of the hepatocytes rather than to the increase in the cytosolic Ca2+ concentration being blocked.

Adenine Nucleotides↗
PubMed1992

Late steady increase in cytosolic Ca2+ preceding hypoxic injury in hepatocytes.

Upon initiation of hypoxia, the ATP content of hepatocytes in monolayer cultures fell within 5 min from 22 to 12 nmol of ATP/10(6) cells. This decrease in ATP was not followed by early alterations in the cytosolic Ca2+ concentration; for up to 60 min it remained around 100 nM. However, after the period cytosolic free Ca2+ steadily increased, up to 400 nM. This increase began around 60 min before the cells lost their viability, and primarily resulted from an influx of extracellular Ca2+. Likewise, in experiments where the mitochondrial respiratory chain was blocked by KCN and glycolysis was blocked by iodoacetate, the ATP content fell within minutes to 10 nmol/10(6) cells, whereas the cytosolic Ca2+ concentration only began to increase 30 min later (up to 600 nM). However, also under these conditions of 'chemical hypoxia' this increase was clearly (about 10 min) earlier than the loss of viability.

Adenosine Triphosphate↗
PubMed1991

Reoxygenation injury in rat hepatocytes: mediation by O2/H2O2 liberated by sources other than xanthine oxidase.

The mechanism of reoxygenation injury was studied in primary cultures of isolated hepatocytes from rat liver. Reoxygenation injury, which affected up to 80% of the hepatocytes, was only inducible within a certain time window of the anaerobic incubation. Reintroduction of oxygen before this vulnerable period ensured the survival of the hepatocytes. After the vulnerable period upon reintroduction of oxygen the hepatocytes continued to die in the same way as the anaerobic control. Allopurinol had no effect on reoxygenation injury. From the inhibitors of the mitochondrial respiratory chain, both cyanide and antimycin A increased injury while rotenone was without significant effect on injury. Reoxygenation injury was significantly diminished by superoxide dismutase, but not by catalase. When added together, superoxide dismutase and catalase completely prevented reoxygenation injury. The results demonstrate that reoxygenation injury in hepatocytes is mediated by the combined action of both O2- and H2O2. These reduced oxygen species are not liberated by xanthine oxidase but possibly originate from the mitochondrial respiratory chain.

Allopurinol↗
PubMed1990

Evidence for a factor protective against hypoxic liver parenchymal cell injury in a protein-free blood extract.

The effect of a protein-free extract from calf blood on hypoxic cell injury was studied in experiments with primary cultures of isolated hepatocytes. At concentrations above 1 mg/ml the extract produced marked protection. At 4 h of anaerobic incubation at 37 degrees C only 20% of cells were damaged as compared to 50% of the anaerobic control incubation. These data demonstrate the presence of a factor in the blood extract which protects against hypoxic cell injury.

Animals↗
PubMed1986

Increased hyaluronate synthesis is required for fibroblast detachment and mitosis.

Human-embryo fibroblasts were synchronized by means of colchicine and cytochalasin, and the production of hyaluronate was determined by [3H]glucosamine incorporation and ion-exchange chromatography. Cells arrested by colchicine synthesized small amounts of hyaluronate, whereas cells blocked by cytochalasin were stimulated in hyaluronate production. When the colchicine block was released, there was an increased synthesis of hyaluronate, which appeared first in the cellular fraction and was then shed into the culture medium. After release of the cytochalasin block, the hyaluronate production declined to that found with unsynchronized cells. A comparable increase of hyaluronate synthase activity was observed during mitosis. When hyaluronate synthesis was blocked by periodate-oxidized UDP-glucuronic acid, the cells were arrested in mitosis before rounding of cells. These results suggest that hyaluronate synthesis is required for detachment and rounding of cells during mitosis.

Cell Cycle↗