bluuebunny/crossref_metadata_2025_split huggingface dataset:
Seizure prediction by non‐linear time series analysis of brain electrical activity
Authors: Elger Christian E. , Lehnertz Klaus 
Published: March 2003

AbstractBrain electrical activity of 16 patients with temporal lobe epilepsy, recorded intracranially during seizure‐free intervals as well as during transitions to the seizure state, was analysed using methods derived from the theory of non‐linear dynamics. Long‐lasting and marked changes towards low‐dimensional system states were found to occur specifically up to 25 min prior to epileptic seizures and allow to predict the occurrence of individual seizures in time. These findings reflect a continuous increase in the degree of synchronicity, and thus open a window for the study of mechanisms generating seizures in humans. This offers new possibilities for therapeutic interventions.
Polarized sorting of nicotinic acetylcholine receptors to the postsynaptic membrane in Torpedo electrocyte
Authors: Camus Gilles , Jasmin Bernard J. , Cartaud Jean 
Published: March 2003

AbstractSeveral regulatory mechanisms contribute to the accumulation and maintenance of high concentrations of acetylcholine receptors (AChR) at the postsynaptic membrane of the neuromuscular junction, including compartmentalized gene transcription, targeting, clustering and anchoring to the cytoskeleton. The targeting of the AChR to the postsynaptic membrane is likely to involve a polarized sorting in the exocytic pathway. In this work, we used the electrocyte of Torpedo marmorata electric organ to study the intracellular trafficking of neosynthesized AChR and its delivery to the postsynaptic membrane. Gradient centrifugation and immunoisolation techniques have led to the isolation of two populations of post‐Golgi transport vesicles (PGVs) enriched in proteins of either the innervated (AChR) or non‐innervated (Na,K‐ATPase) membrane domains of the cell. Immunolabelling of these vesicles at the EM level disclosed that very few PGVs contained both proteins. In AChR‐enriched vesicles, high sialylation of AchR molecules, an expected post‐translational modification of proteins exiting the trans‐Golgi network, and the presence of a marker of the exocytic pathway (Rab6p), indicate that these vesicles are carriers engaged in the Golgi‐to‐plasma membrane transport. These data suggest that AChR and Na,K‐ATPase are sorted intracellularly most likely within the trans‐Golgi network. Furthermore, EM analysis and immunogold‐labelling experiments provided in situ evidence that the AChR‐containing PGVs are conveyed to the postsynaptic membrane, possibly by a microtubule‐dependent transport mechanism. Our data therefore provide the first evidence that the targeting of receptors for neurotransmitters to synaptic sites could be contributed by intracellular sorting and polarized delivery in the exocytic pathway.
Mechanisms and functional significance of a slow inhibitory potential in neurons of the lateral amygdala
Authors: Danober Laurence , Pape Hans‐Christian 
Published: March 2003

AbstractA slow inhibitory potential (sIP) elicited upon synaptic activation in spiny, pyramidal‐like cells with properties indicative of projection neurons was investigated in slices of the rat and guinea‐pig lateral amygdala in vitro. The sIP succeeded the triphasic sequence of excitatory and fast/slow inhibitory postsynaptic potentials mediated via glutamate and GABAA/B receptors, respectively, was readily evoked upon repetitive stimulation of the external capsule and appeared to terminate epileptiform burst discharges during pharmacologically reduced GABAergic influence. The sIP reversed close to the Cl– equilibrium potential, but was not affected by altered transmembrane Cl– gradients and not abolished by antagonists to ligand‐gated Cl– channels. Intracellular injection of QX 314 and resulting blockade of sodium spikes had no effect, whereas the Ca2+ chelator BAPTA blocked the sIP concomitantly with slow hyperpolarizing afterpotentials following intrinsically generated spike firing, thereby indicating the contribution of Ca2+‐dependent mechanisms secondary to synaptic activation. During action of BAPTA and QX 314, an N‐methyl‐d‐aspartate (NMDA) receptor‐mediated potential was unmasked, which contributed to the sIP. The Ca2+‐dependent mechanisms of the sIP involved a membrane K+ conductance, as was indicated by the dependence on the K+ gradient and the shift of the reversal potential towards the K+ equilibrium potential during blocked NMDA receptors. During the presence of GABA receptor antagonists, reduction of the Ca2+‐activated K+ conductance through injection of BAPTA or application of dopamine induced a gradual shift of interictal‐like single bursts of spikes towards the generation of re‐occurring ictal‐like activity. It is concluded that pyramidal‐like projection cells in the AL can generate a sIP upon synaptic activation, which reflects the combined activation of an NMDA receptor‐mediated cation current and a K+ current that is secondary to the rise in intracellular Ca2+ concentration resulting from the preceding depolarizing response. The sIP may play an important role in controlling excitatory activity in the amygdala, particularly in preventing the transformation of interictal‐like activity towards recurrent epileptic discharges during periods of decreased GABAergic influence.
Tumour necrosis factor‐α and interleukin‐2 differentially affect hippocampal serotonergic neurotransmission, behavioural activity, body temperature and hypothalamic–pituitary–adrenocortical axis activity in the rat
Authors: Pauli Sabine , Linthorst Astrid C. E. , Reul Johannes M. H. M. 
Published: March 2003

AbstractIntraperitoneal endotoxin injection and central administration of interleukin (IL)‐1β profoundly activate hippocampal serotonergic neurotransmission. This study was designed to investigate, using in vivo microdialysis, the effects of another endotoxin‐induced proinflammatory cytokine, tumour necrosis factor‐α, and the effects of the non‐inflammatory cytokine, IL‐2, on hippocampal extracellular levels of serotonin. To compare the effects of these cytokines on neurotransmission with the effects on physiological parameters and behaviour, hypothalamic–pituitary–adrenocortical (HPA) axis activity, body temperature and behavioural activity were monitored as well. Time‐dependent changes in serotonergic neurotransmission and HPA axis activity were determined by measuring serotonin, its metabolite 5‐hydroxyindoleacetic acid and free corticosterone in dialysates. Total behavioural activity was scored by assessing the time during which rats were active. Core body temperature was measured by biotelemetry. Intracerebroventricular injection of 50 or 100 ng recombinant murine tumour necrosis factor‐α exerted no effect on hippocampal serotonergic neurotransmission, and induced no signs of sickness behaviour. However, these doses produced a dose‐dependent increase in body temperature and free corticosterone levels. In contrast, intracerebroventricular administration of 500 ng, but not of 50 ng, recombinant human IL‐2 produced a marked increase in hippocampal extracellular concentrations of serotonin and 5‐hydroxyindoleacetic acid, accompanied by a pronounced behavioural inhibition and other signs of sickness. Moreover, both doses of IL‐2 caused a dose‐dependent increase in body temperature and free corticosterone levels. Interestingly, intracerebroventricular pretreatment with the IL‐1 receptor antagonist showed that the effects of IL‐2 on hippocampal serotonin were completely dependent on endogenous brain IL‐1. However, IL‐1 seemed to play only a minor role in the IL‐2‐induced increase in free corticosterone. Taken together, the results show that cytokines produce partially overlapping brain‐mediated responses, but are selectively effective in stimulating hippocampal serotonergic neurotransmission and inducing sickness behaviour. Moreover, we postulate that activation of hippocampal serotonin release is instrumental in the full development of behavioural inhibition.
Reciprocal modulation of TrkA and p75NTR affinity states is mediated by direct receptor interactions
Authors: Ross Gregory M. , Shamovsky Igor L. , Lawrance Gail , Solc Mark , Dostaler Suzanne M. , Weaver Donald F. , Riopelle Richard J. 
Published: March 2003

AbstractEquilibrium binding of 125I‐nerve growth factor (125I‐NGF) to cells coexpressing the tyrosine kinase receptor A (TrkA) and common neurotrophin receptor (p75NTR), cells coexpressing both receptors where p75NTR is occupied, and cells expressing only p75NTR, revealed reciprocal modulation of receptor affinity states. Analysis of receptor affinity states in PC12 cells, PC12 cells in the presence of brain‐derived neurotrophic factor (BDNF), and PC12nnr5 cells suggested that liganded and unliganded p75NTR induce a higher affinity state within TrkA, while TrkA induces a lower affinity state within p75NTR. These data are consistent with receptor allosterism, and prompted a search for TrkA/p75NTR complexes in the absence of NGF. Chemical crosslinking studies revealed high molecular weight receptor complexes that specifically bound 125I‐NGF, and were immunoprecipitated by antibodies to both receptors. The heteroreceptor complex of TrkA and p75NTR alters conformation and/or dissociates in the presence of NGF, as indicated by the ability of low concentrations of NGF to prevent heteroreceptor crosslinking. These data suggest a new model of receptor interaction, whereby structural changes within a heteroreceptor complex are induced by ligand binding.
Characterization of a nicotinic acetylcholine receptor from the insect Manduca sexta
Authors: Eastham Helen M. , Lind Robert J. , Eastlake Jane L. , Clarke Barry S. , Towner Paul , Reynolds Stuart E. , Wolstenholme Adrian J. , Wonnacott Susan 
Published: March 2003

AbstractManduca sexta is a nicotine‐insensitive insect, the larval form of which feeds on tobacco. It has been postulated that its nicotine insensitivity may reflect the presence of a modified nicotinic acetylcholine receptor whose α subunits lack the amino acid residues necessary for binding nicotine: we have performed ligand binding assays and molecular cloning to examine this hypothesis. [125I]α‐Bungarotoxin bound specifically to both larval and adult membranes, with Kd values of 7.6 and 6.5 nm and Bmax values of 119 and 815 fmol/mg protein, respectively. The pharmacological profile of [125I]α‐bungarotoxin binding was similar in both tissues. In particular, nicotine (Ki values: 1.6 μm and 2 μm for larvae and adults, respectively) competed with an affinity similar to that found for nicotine‐sensitive insects. No α‐bungarotoxin‐insensitive binding sites labelled by [3H]epibatidine could be detected. Using the α‐like subunit from the locust Schistocerca gregaria to probe two cDNA libraries, and by inverse PCR on circularized genomic DNA from Manduca sexta, we have obtained overlapping cDNA clones that contain the complete coding sequence of a putative nicotinic subunit from Manduca sexta (MARA1). No other α‐subunit cDNAs were isolated using this probe, although it hybridized to multiple bands on Southern blots. The sequence of MARA1 is consistent with an α‐like subunit capable of binding α‐bungarotoxin, and it retains all those amino acids implicated in nicotine binding to vertebrate nicotinic receptors. Taken together, these findings provide no support for the hypothesis that the nicotine insensitivity of Manduca sexta is the result of a nicotinic receptor with diminished nicotine binding.
Gamma frequency oscillation in the hippocampus of the rat: intracellular analysis in vivo
Authors: Penttonen Markku , Kamondi Anita , Acsády László , Buzsáki György 
Published: March 2003

AbstractGamma frequency field oscillations reflect synchronized synaptic potentials in neuronal populations within the ≈ 10–40 ms range. The generation of gamma activity in the hippocampus was investigated by intracellular recording from principal cells and basket cells in urethane anaesthetized rats. The recorded neurones were verified by intracellular injection of biocytin. Gamma frequency field oscillations were nested within the slower theta waves. The phase and amplitude of intracellular gamma were voltage dependent with an almost complete phase reversal at Cl– equilibrium potential in pyramidal cells. Basket cells fired at gamma frequency and were phase‐locked to the same phase of the gamma oscillation as pyramidal cells. Current‐induced depolarization coupled with synaptically induced inhibition resulted in gamma frequency discharge (30–80 Hz) of pyramidal cells without accommodation. These observations suggest that at least part of the gamma frequency field oscillation reflects rhythmic hyperpolarization of principal cells, brought about by the rhythmically discharging basket neurones. Resonant properties of pyramidal cells might facilitate network synchrony in the gamma frequency range.
Origin of the synchronized network activity in the rabbit developing hippocampus
Authors: De La Prida L. Menendez , Bolea  , Sanchez‐Andres  
Published: March 2003

AbstractRhythmic spontaneous bursting is a fundamental hallmark of the immature hippocampal activity recorded in vitro. These bursts or giant depolarizing potentials (GDPs) are GABA‐ and glutamatergic‐driven events. The mechanisms of GDPs generation are still controversial, since although a hilar origin has been suggested, GDPs were also recorded from isolated CA3 area. Here, we have investigated the origin of GDPs in hippocampal slices from newborn rabbits. Simultaneous intracellular recordings were performed in CA3, CA1 and the fascia dentata. We found a high degree of correlation between the spontaneous GDPs present in CA3 and CA1 regions. Cross‐correlation analysis demonstrated that CA3 firing precedes CA1 by about 192 ms, although a significant population of discharges was recorded first in CA1 (20%). Granule cells (GCs) in the fascia dentata also showed GDPs. The frequency of these events (1.46 ± 1.25 GDPs/min, n = 7) is significantly lower when compared with that from CA3 (3.13 ± 1.43 GDPs/min, n = 10) or CA1 (2.94 ± 1.36 GDPs/min, n = 17). Dual recordings from CA3 and fascia dentata cells showed synchronous bursts in both regions with no prevalent preceding area. By recording from isolated areas we found that CA1, CA3 and the fascia dentata can produce GDPs, suggesting that they emerge as a property of local circuits present throughout the hippocampus.
Expression of small‐conductance calcium‐activated potassium channels (SK) in outer hair cells of the rat cochlea
Authors: Dulon Didier , Luo Lin , Zhang Chunyan , Ryan Allen F. 
Published: March 2003

AbstractPhysiological evidence suggests that SK‐type Ca2+‐activated K+ channels participate in ACh‐induced hyperpolarization of OHCs (outer hair cells). Based on the sequences published by Köhler et al. (1996, Science, 273: 1709), we designed degenerated primers recognizing cDNA subunits of rSK1, rSK2 and rSK3. Using this concensus set of primers, we probed by PCR a rat organ of Corti cDNA library. Two PCR products of 707 base pairs with sequence identical to rSK3 and rSK2 were obtained and cloned to generate RNA probes for in situ hybridization in the rat cochlea. The subunit rSK2 showed hybridization in the organ of Corti, at the location of the OHCs. The expression of rSK2 by OHCs was confirmed by probing with PCR a poly(A) amplified OHC cDNA library. During development, rSK2 hybridization in the organ of Corti was negative at embryonic days E16, E18 and at P0, weak at P4 and stronger from P8 to adulthood. The subunit rSK2 could also be detected in the spiral ganglion from P4 to the adult stage. Contrary to rSK2, the subunit rSK3 did not show specific hybridization in the organ of Corti at the adult stage (P120) and only a weak expression was observed at P10 and P21. Our study demonstrates expression of rSK2 in OHCs. These potassium channels are good candidates to underlie the ACh‐activated K+ currents recorded during patch‐clamp recordings in isolated OHCs. The expression of rSK2 in the cochlear ganglion at the adult stage suggests that SK Ca2+‐activated K+ channels may also participate in the repolarization of the auditory neurons after the action potential and may influence their firing patterns.
Structural diversity of the voltage‐dependent Ca2+ channel α1E‐subunit
Authors: Pereverzev A. , Klöckner U. , Henry M. , Grabsch H. , Vajna R. , Olyschläger S. , Viatchenko‐Karpinski S. , Schröder R. , Hescheler J. , Schneider T. 
Published: March 2003

AbstractVoltage‐operated Ca2+ channels are heteromultimeric proteins. Their structural diversity is caused by several genes encoding homologous subunits and by alternative splicing of single transcripts. Isoforms of α1 subunits, which contain the ion conducting pore, have been deduced from each of the six cDNA sequences cloned so far from different species. The isoforms predicted for the α1E subunit are structurally related to the primary sequence of the amino terminus, the centre of the subunit (II–III loop), and the carboxy terminus. Mouse and human α1E transcripts have been analysed by reverse transcription–polymerase chain reaction and by sequencing of amplified fragments. For the II–III loop three different α1E cDNA fragments are amplified from mouse and human brain, showing that isoforms originally predicted from sequence alignment of different species are expressed in a single one. Both predicted α1E cDNA fragments of the carboxy terminus are identified in vivo. Two different α1E constructs, referring to the major structural difference in the carboxy terminus, were stably transfected in HEK293 cells. The biophysical properties of these cells were compared in order to evaluate the importance in vitro of the carboxy terminal insertion found in vivo. The wild‐type α1E subunit showed properties, typical for a high‐voltage activated Ca2+ channel. The deletion of 43 amino acid residues at the carboxy terminus does not cause significant differences in the current density and the basic biophysical properties. However, a functional difference is suggested, as in embryonic stem cells, differentiated in vitro to neuronal cells, the pattern of transcripts indicative for different α1E isoforms changes during development. In human cerebellum the longer α1E isoform is expressed predominantly. Although, it has not been possible to assign functional differences to the two α1E constructs tested in vitro, the expression pattern of the structurally related isoforms may have functional importance in vivo.
Basic and acidic fibroblast growth factors protect spinal motor neurones in vivo after experimental spinal cord injury
Authors: Teng Yang Dong , Mocchetti Italo , Wrathall Jean R. 
Published: March 2003

AbstractWe studied the effect of a single focal injection of recombinant basic (FGF2) or acidic (FGF1) fibroblast growth factor on the survival of spinal motor neurones at 24 h after a standardized spinal cord contusion injury (SCI) in the rat. Both FGF2 and FGF1 (3 μg), microinjected into the injury site at 5 min post‐injury (p.i.), protected at least two functionally important classes of spinal motor neurones, autonomic preganglionic neurones in the intermediolateral (IML) column and somatic motor neurones in the ventral horn (VH). Moreover, there was enhanced choline acetyltransferase (ChAT) immunoreactivity in surviving VH and IML neurones, suggesting an improved functional status. Thus, neurotrophic factors such as FGF2 and FGF1 may contribute to an overall strategy to treat acute SCI and improve recovery of function.
Temporal limits of spatial working memory in humans
Authors: Ploner Christoph J. , Gaymard Bertrand , Rivaud Sophie , Agid Yves , Pierrot‐Deseilligny Charles 
Published: March 2003

AbstractAn essential feature attributed to working memory is the labile and transient nature of its representations. Using an oculomotor task, we examined the stability of spatial working memory in 16 normal human subjects. Eye movements towards remembered spatial cues (memory‐guided saccades) were electro‐oculographically recorded after memorization delays that varied unpredictably between 0.5 and 30 s. A peaked time‐course of saccadic targeting errors, with maximal errors around 20 s delay, was found, showing that delay‐dependent decay of spatial information in working memory occurs, but is time‐limited and reverts significantly beyond delays of about 20 s. These data (i) indicate temporal limits of spatial working memory and (ii) provide the first behavioural evidence for the existence of two parallely generated mental representations of space that successively control memory‐guided behaviour in humans.
Spectral envelope coding in cat primary auditory cortex: linear and non‐linear effects of stimulus characteristics
Authors: Calhoun Barbara M. , Schreiner Christoph E. 
Published: March 2003

AbstractElectrophysiological studies in mammal primary auditory cortex have demonstrated neuronal tuning and cortical spatial organization based upon spectral and temporal qualities of the stimulus including: its frequency, intensity, amplitude modulation and frequency modulation. Although communication and other behaviourally relevant sounds are usually complex, most response characterizations have used tonal stimuli. To better understand the mechanisms necessary to process complex sounds, we investigated neuronal responses to a specific class of broadband stimuli, auditory gratings or ripple stimuli, and compared the responses with single tone responses. Ripple stimuli consisted of 150–200 frequency components with the intensity of each component adjusted such that the envelope of the frequency spectrum is sinusoidal. It has been demonstrated that neurons are tuned to specific characteristics of those ripple stimulus including the intensity, the spacing of the peaks, and the location of the peaks and valleys (C. E. Schreiner and B. M. Calhoun, Auditory Neurosci. 1994; 1: 39–61). Although previous results showed that neuronal response strength varied with the intensity and the fundamental frequency of the stimulus, it is shown here that the relative response to different ripple spacings remains essentially constant with changes in the intensity and the fundamental frequency. These findings support a close relationship between pure‐tone receptive fields and ripple transfer functions. However, variations of other stimulus characteristics, such as spectral modulation depth, result in non‐linear alterations in the ripple transformation. The processing between the basilar membrane and the primary auditory cortex of broadband stimuli appears generally to be non‐linear, although specific stimulus qualities, including the phase of the spectral envelope, are processed in a nearly linear manner.
Opioid withdrawal activates MAP kinase in locus coeruleus neurons in morphine‐dependent rats in vivo
Authors: Schulz Stefan , Höllt Volker 
Published: March 2003

AbstractOpioid dependence is widely believed to result from neuroadaptations in specific brain regions. However, the precise molecular mechanisms underlying these adaptations are not yet clear. Our aim was to explore the role of mitogen‐activated protein kinase (MAPK) in μ opioid receptor signalling in vivo. Using anti‐phospho MAPK antibodies, activated MAPK was detected in cortical neurons (layers II/III), median eminence, amygdaloid and hypothalamic nuclei in untreated animals. Dense nuclear and cytoplasmic staining was observed resulting in full visualization of processes in these cells. Chronic, but not acute, administration of morphine greatly diminished this staining pattern while μ opioid receptor levels and levels of MAPkinase as detected with a phosphorylation state‐independent antibody were unchanged. When opioid withdrawal was precipitated with naloxone a dramatic increase in MAPkinase phosphorylation was observed in somata and fibres of locus coeruleus, solitary tract and hypothalamic neurons. Thus, the differential activation state of MAPK could have important implications for understanding the mechanisms underlying opioid tolerance and dependence.