bluuebunny/crossref_metadata_2025_split huggingface dataset:
Discharge threshold is enhanced for several seconds after a single interictal spike in a model of focal epileptogenesis
Authors: De Curtis Marco , Librizzi Laura , Biella Gerardo 
Published: March 2003

AbstractInterictal spikes (ISs) are typically observed between seizures in focal epilepsies. Whether ISs are causally involved or represent protective elements in the transition toward an ictal discharge is an open question. Previous studies suggested that inhibition or disfacilitation occurs during the period elapsing between two ISs induced by local application of either bicuculline or penicillin in the piriform cortex of the in vitro isolated guinea pig brain preparation. We further investigated this issue by studying responses to afferent stimulation during the interspike period (6.3 ± 2.5 s; mean ± SD). Properly set stimulation intensity of the lateral olfactory tract resets ISs exclusively (and not before) 4–10 s (5.6 ± 2.0 s; mean ± SD) after a preceding spontaneous spike. This finding demonstrates the existence of a period of enhanced threshold to stimulus‐evoked activation that coincides with the interspike interval in the absence of stimulation. Current source density analysis of depth laminar profiles demonstrated that both stimulus‐evoked and spontaneous ISs were generated by the activation of an identical cortical circuit. Our study suggests that interictal spiking could play a protective role or at least provide an effective restraint against the onset of a focal ictal discharge.
Patterns of colocalization of GABA, glutamate and glycine immunoreactivities in terminals that synapse on dendrites of noradrenergic neurons in rat locus coeruleus
Authors: Somogyi J. , Llewellyn‐Smith I. J. 
Published: March 2003

AbstractAmino acid transmitters play a key role in regulating the activity of noradrenergic neurons in the locus coeruleus. We investigated the anatomical substrate for this regulation by quantifying immunoreactivity for GABA, glutamate and glycine in terminals that contacted the dendrites of tyrosine hydroxylase‐immunoreactive principal neurons in rat locus coeruleus. Pre‐embedding peroxidase immunocytochemistry was used to detect tyrosine hydroxylase‐immunoreactivity in Vibratome sections of tissue perfused with 2.5% glutaraldehyde. GABA, glutamate and glycine were localized with postembedding immunogold labelling. Gold particle densities over terminals were measured in three semiserial ultrathin sections, each reacted for a different amino acid. More than 90% (range among rats, 89%−95%) of the terminals analyzed (n = 288) were immunoreactive for at least one amino acid. A high proportion (39%−49%) were positive for two or three amino acids. About two‐thirds (60%−69%) of the boutons contained GABA, of which more than half (51%−55%) also contained glycine. More than one‐third (36%−38%) of the terminals were positive for glycine. Terminals immunoreactive for glycine alone were rare (0%−2%). About one‐third of the terminals showed glutamate‐immunoreactivity (32%−37%). GABA and/or glycine occurred in one‐fifth to one‐third of these. These results show that amino acid‐immunoreactivity is present in almost all of the terminals that synapse on tyrosine hydroxylase‐positive dendrites in locus coeruleus. Glutamate provides a major excitatory input. The almost complete colocalization of glycine with GABA suggests that the inhibitory input to locus coeruleus is predominantly GABAergic with a contribution from glycine in about half of the GABAergic boutons.
Human brain activity in the control of fine static precision grip forces: an fMRI study
Authors: Kuhtz‐Buschbeck Johann P. , Ehrsson H. Henrik , Forssberg Hans 
Published: March 2003

AbstractDexterous manipulation of delicate objects requires exquisite control of fingertip forces. We have used functional magnetic resonance imaging to identify brain regions involved in the skilful scaling of these forces when normal human subjects (n = 8) held with precision grip a small object (weight 200 g) in the dominant right hand. In one condition, they used their normal, automatically scaled grip force. The object was held gently in a second condition; the isometric grip force was maintained just above the critical level at which the object would have slipped. In a third condition, the force was increased to hold the object with a more firm grip. The supplementary and cingulate motor areas were significantly more active during the gentle force condition than during either of the other conditions in all subjects, despite weaker contractions of the hand muscles. In addition, the left primary sensorimotor cortex, the ventral premotor cortex and the left posterior parietal cortex were more strongly activated during gentle than during normal grasping. These novel results suggest that these regions are specifically involved in dexterous scaling of fingertip forces during object manipulation.
Projections from the nociceptive area of the central nucleus of the amygdala to the forebrain: a PHA‐L study in the rat
Authors: Bourgeais Laurence , Gauriau Caroline , Bernard Jean‐François 
Published: March 2003

AbstractThe lateral capsular division (CeLC) of the central nucleus (Ce) of the amygdala, in the rat, has been shown to be the main terminal area of a spino(trigemino)‐parabrachio‐amygdaloid nociceptive pathway [Bernard & Besson (1990)J. Neurophysiol.63,473–490; Bernardet al. (1992)J. Neurophysiol.68,551–569; Bernardet al. (1993)J. Comp. Neurol.329,201–229]. The projections to the forebrain from the CeLC and adjacent regions were studied in the rat by using microinjections ofPhaseolus vulgarisleucoagglutinin (PHA‐L) restricted in subdivisions of the Ce and the basolateral amygdaloid nucleus anterior (BLA). Our data showed that the entire CeLC projects primarily and extensively to the substantia innominata dorsalis (SId). The terminal labelling is especially dense in the caudal aspect of the SId. The other projections of the CeLC in the forebrain were dramatically less dense. They terminate in the bed nucleus of the stria terminalis (BST) and the posterior hypothalamus (pLH). No (or only scarce) other projections were found in the remaining forebrain areas. The Ce lateral division (CeL) and the Ce medial division (CeM), adjacent to the CeLC, also project to the SId with slightly lower density labelling. However, contrary to the case of the CeLC, both the CeL and the CeM extensively project to the ventrolateral subnucleus of the BST (BSTvl) with a few additional terminals found in other regions of the lateral BST. Only the CeM projects densely to both the interstitial nucleus of the posterior limb of the anterior commissure and the caudal most portion of the pLH. The projections of the BLA are totally different from those of the Ce as they terminate in the dorsal striatum, the accumbens nucleus, the olfactory tubercle, the nucleus of olfactory tract and the rostral pole of the cingulate/frontal cortex. This study demonstrates that the major output of the nociceptive spino(trigemino)‐parabrachio‐CeLC pathway is to the SId. It is suggested that the CeLC–SId pathway could have an important role in anxiety, aversion and genesis of fear in response to noxious stimuli.
Exogenous NT‐3 and NGF differentially modulate PACAP expression in adult sensory neurons, suggesting distinct roles in injury and inflammation
Authors: Jongsma H. , Danielsen N. , Johnston J.M. , Gratto K.A. , Karchewski L.A. , Verge V.M.K. 
Published: March 2003

AbstractExpression of pituitary adenylate cyclase‐activating polypeptide in sensory neurons varies with injury or inflammation. The neurotrophins NGF and NT‐3 are profound regulators of neuronal peptidergic phenotype in intact and injured sensory neurons. This study examined their potential for modulation of PACAP expression in adult rat with intact and injured L4–L6 spinal nerves with or without immediate or delayed intrathecal infusion of NT‐3 or NGF. Results indicate that in L5 DRG, few trkC neurons express high levels of PACAP mRNA in the intact state, but many do following injury. The elevated expression in injured neurons is mitigated by NT‐3 infusion, suggesting a role for NT‐3 in returning the ‘injured phenotype’ back towards an ‘intact phenotype’. NGF dramatically up‐regulated PACAP expression in trkA‐positive neurons in both intact and injured DRGs, implicating NGF as a positive regulator of PACAP expression in nociceptive neurons. Surprisingly, NT‐3 modulates PACAP expression in an antagonistic fashion to NGF in intact neurons, an effect most evident in the trkA neurons not expressing trkC. Both NT‐3 and NGF infusion results in decreased detection of PACAP protein in the region of the gracile nuclei, where central axons of the peripherally axotomized large sensory fibers terminate. NGF infusion also greatly increased the amount of PACAP protein detected in the portion of the dorsal horn innervated by small–medium size DRG neurons, while both neurotrophins appear able to prevent the decrease in PACAP expression observed in these afferents with injury. These results provide the first insights into the potential molecules implicated in the complex regulation of PACAP expression in sensory neurons.
Multiple pertussis toxin‐sensitive G‐proteins can couple receptors to GIRK channels in rat sympathetic neurons when expressed heterologously, but only native Gi‐proteins do soin situ
Authors: Fernández‐Fernández José M. , Abogadie Fe C. , Milligan Graeme , Delmas Patrick , Brown David A. 
Published: March 2003

AbstractAlthough many G‐protein‐coupled neurotransmitter receptors are potentially capable of modulating both voltage‐dependent Ca2+channels (ICa) and G‐protein‐gated K+channels (IGIRK), there is a substantial degree of selectivity in the coupling to one or other of these channels in neurons. Thus, in rat superior cervical ganglion (SCG) neurons, M2muscarinic acetylcholine receptors (mAChRs) selectively activateIGIRKwhereas M4mAChRs selectively inhibitICa. One source of selectivity might be that the two receptors couple preferentially to different G‐proteins. Using antisense depletion methods, we found that M2mAChR‐induced activation ofIGIRKis mediated by Giwhereas M4mAChR‐induced inhibition ofICais mediated by GoA. Experiments with the βγ‐sequestering peptides α‐transducin and βARK1C‐terindicate that, although both effects are mediated by G‐protein βγ subunits, the endogenous subunits involved inIGIRKinhibition differ from those involved inICainhibition. However, this pathway divergence does not result from any fundamental selectivity in receptor–G‐protein–channel coupling because bothIGIRKandICamodulation can be rescued by heterologously expressed Gior Goproteins after the endogenously coupled α‐subunits have been inactivated withPertussistoxin (PTX). We suggest instead that the divergence in the pathways activated by the endogenous mAChRs results from a differential topographical arrangement of receptor, G‐protein and ion channel.
Astrocytes down‐regulate neuronal β‐amyloid precursor protein expression and modify its processing in an apolipoprotein E isoform‐specific manner
Authors: Vincent Bruno , Smith Jonathan D. 
Published: March 2003

AbstractAlzheimer's disease is the most frequent neurodegenerative disorder in the aged population and is characterized by the deposition of the 40/42‐residue amyloid β protein (Aβ), a proteolytic fragment of the β‐amyloid precursor protein (APP). A common apolipoprotein E (apoE) polymorphism is associated with an increased risk of developing the disease. In order to assess the putative relationship between apoE and amyloidogenesis in the CNS, we prepared primary cortical neurons overexpressing humanized APP695 bearing the Swedish mutation (hAPP695sw) and we analysed APP expression and processing after: (i) coculture with primary astrocytes from wild‐type, apoE‐deficient (E0) mice, or mice overexpressing human apoE2, E3, or E4; (ii) treatment with conditioned media from apoE0, E2, E3 or E4 astrocytes; and (iii) treatment with human recombinant ApoE or human apoE purified from conditioned media of stably transfected RAW264 cells (E2, E3 and E4). Interestingly, a strong decrease in APP expression was observed only when neurons were cocultured with astrocytes (and independently of the apoE genotype considered), suggesting that cell–cell contact is required. Moreover, apoE4‐secreting astrocytes, but not recombinant or purified apoE4, significantly increased Aβ production and decrease sAPPα secretion only when cultured in direct contact with neurons, whereas apoE2 astrocytes had a protective effect. We conclude that astrocytes: (i) strongly regulate neuronal APP expression in primary neurons, and (ii) promote the amyloidogenic pathway in an apoE4‐dependent manner. Thus, apoE and astrocytic factor(s) may modulate the pathogenesis of Alzheimer's disease.
Effect of microiontophoretic application of dopamine on subthalamic nucleus neuronal activity in normal rats and in rats with unilateral lesion of the nigrostriatal pathway
Authors: Ni Zhongge , Gao Dongming , Bouali‐Benazzouz Rabia , Benabid Alim‐Louis , Benazzouz Abdelhamid 
Published: March 2003

AbstractThe subthalamic nucleus (STN) receives dopamine inputs from the substantia nigra but their implication in the pathophysiology of parkinsonism is still debated. Extracellular microrecordings were used to study the effect of microiontophoretic injection of dopamine and the D1 receptor agonist SKF 38393 on the activity of STN neurons in normal and 6‐hydroxydopamine‐lesioned rats under urethane anaesthesia. Dopamine and SKF induced an increase in the firing rate of the majority of STN neurons in both normal and 6‐OHDA rats. In rats with 6‐OHDA lesions, the percentage of firing rate increase did not differ from that of controls. When GABA, glutamate and dopamine were all applied to the same individual STN neurons, GABA induced an inhibitory effect and glutamate and dopamine caused an excitatory effect in both groups. This excitatory response was suppressed by the application of GABA. Systemic administration of apomorphine provoked a decrease in the firing rate of STN neurons in rats with 6‐OHDA lesions. These results show that dopamine exerts an excitatory influence on STN neurons, suggesting that the inhibitory effect induced by the systemic injection of apomorphine is due to the GABAergic inputs from the globus pallidus as predicted by the current model of basal ganglia organization. In addition, we show that dopamine, GABA and glutamate can act on the same STN neuron and that GABA can reverse the excitatory effect of dopamine and glutamate, suggesting the predominant influence of GABAergic inputs to the subthalamic nucleus.
Early behavioural changes in scrapie‐affected mice and the influence of dapsone
Authors: Guenther Katja , Deacon Robert M. J. , Perry V. Hugh , Rawlins J. Nicholas P. 
Published: March 2003

AbstractBehavioural testing can reveal effects in scrapie‐infected mice long before overt clinical signs appear (Betmouni et al., 1999, Psychobiology, 27, 63–71). These effects may be partly attributable to an early, atypical inflammatory response in the brain (Betmouni et al., 1996, Neuroscience, 74, 1–5). The present study replicated and extended these findings, and examined the effect of chronic treatment with dapsone. This anti‐inflammatory compound has been reported to delay disease onset in a rat model of Creutzfeldt–Jakob disease (Manuelidis et al., 1998, Lancet, 352, 456). Although the doses used in the present study were higher than those of Manuelidis et al. (1998), no attenuation of the disease was seen in either behavioural or subsequent histological tests. Burrowing, i.e. displacing food pellets from a tube in the home cage, decreased from around week 12 in scrapie‐infected mice, as did consumption of palatable glucose solution. Concurrently, ambulation in an open field increased, as did rearing at around week 17. Spontaneous alternation was impaired around this time. Around 18 weeks, motor performance on an inverted screen, horizontal bar, rotating rod and static rods decreased. Nest construction was impaired at 20 weeks. Overt clinical signs (reduction in mobility, hunched posture, poor coat condition, bladder enlargement) only occurred after week 20, when the mice were prepared for histology. The ME7 scrapie‐infected mice thus showed a characteristic complex of neurological and behavioural changes during the course of the disease that were not ameliorated by dapsone. These changes appeared well before clinical signs were prominent.
A common inhibitory binding site for zinc and odorants at the voltage‐gated K+ channel of rat olfactory receptor neurons
Authors: Seebungkert Benchamaporn , Lynch Joseph W. 
Published: March 2003

AbstractThis study compared the effects of zinc and odorants on the voltage‐gated K+ channel of rat olfactory neurons. Zinc reduced current magnitude, depolarized the voltage activation curve and slowed activation kinetics without affecting inactivation or deactivation kinetics. Zinc inhibition was potentiated by the NO compound, S‐nitroso‐cysteine. The pH‐ and diethylpyrocarbonate‐dependence of zinc inhibition suggested that zinc acted by binding to histidine residues. Cysteine residues were eliminated as contributing to the zinc‐binding site. The odorants, acetophenone and amyl acetate, also reduced current magnitude, depolarized the voltage activation curve and selectively slowed activation kinetics. Furthermore, the diethylpyrocarbonate‐ and pH‐dependence of odorant inhibition implied that the odorants also bind to histidine residues. Zinc inhibitory potency was dramatically diminished in the presence of odorants, implying competition for a common binding site. These observations indicate that the odorants and zinc share a common inhibitory binding site on the external surface of the voltage‐gated K+ channel.
Interleukin‐6 (IL6) and cellular response to facial nerve injury: effects on lymphocyte recruitment, early microglial activation and axonal outgrowth in IL6‐deficient mice
Authors: Galiano Matthias , Liu Zhi Qiang , Kalla Roger , Bohatschek Marion , Koppius Andrea , Gschwendtner Andreas , Xu ShengLi , Werner Alexander , Kloss Christian U.A. , Jones Leonard L. , Bluethmann Horst , Raivich Gennadij 
Published: March 2003

AbstractNerve injury triggers numerous changes in the injured neurons and surrounding non‐neuronal cells. Of particular interest are molecular signals that play a role in the overall orchestration of this multifaceted cellular response. Here we investigated the function of interleukin‐6 (IL6), a multifunctional neurotrophin and cytokine rapidly expressed in the injured nervous system, using the facial axotomy model in IL6‐deficient mice and wild‐type controls. Transgenic deletion of IL6 caused a massive decrease in the recruitment of CD3‐positive T‐lymphocytes and early microglial activation during the first 4 days after injury in the axotomized facial nucleus. This was accompanied by a more moderate reduction in peripheral regeneration at day 4, lymphocyte recruitment (day 14) and enhanced perikaryal sprouting (day 14). Motoneuron cell death, phagocytosis by microglial cells and recruitment of granulocytes and macrophages into injured peripheral nerve were not affected. In summary, IL6 lead to a variety of effects on the cellular response to neural trauma. However, the particularly strong actions on lymphocytes and microglia suggest that this cytokine plays a central role in the initiation of immune surveillance in the injured central nervous system.
Subcellular localization of calcium‐permeable AMPA receptors in spinal motoneurons
Authors: Vandenberghe Wim , Bindokas Vytautas P. , Miller Richard J. , Robberecht Wim , Brorson James R. 
Published: March 2003

AbstractActivation of Ca2+‐permeable α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionic acid (AMPA) receptors has been linked to potent effects on survival and dendritic outgrowth of spinal motoneurons. Ca2+ permeability of AMPA receptors is controlled by the GluR2 subunit. Whole‐cell electrophysiological studies have suggested that GluR2‐containing and GluR2‐lacking AMPA receptors may coexist in individual motoneurons. However, there has not been a direct demonstration of heterogeneity in AMPA receptor subunit composition in single motoneurons, nor of distinct subcellular distributions of GluR2‐containing and GluR2‐lacking receptors. In the present study, we have used confocal microscopy, immunocytochemistry and Ca2+ imaging to characterize the subcellular localization of AMPA receptors in cultured rat spinal motoneurons. Immunoreactivity for GluR2 and GluR4 was concentrated in clusters, the vast majority of which were found in dendrites at synapses. Double‐labelling for GluR2 and GluR4 revealed variability in relative expression of GluR2 and GluR4 between clusters within individual motoneurons; most AMPA receptor clusters were immunoreactive for both GluR2 and GluR4, but a significant minority of clusters were immunoreactive for GluR2 only or for GluR4 only. The majority of GluR2‐immunonegative AMPA receptor clusters was present in dendrites, but the relative proportion of GluR2‐immunonegative and GluR2‐immunopositive clusters was similar in dendrites and soma. Imaging of [Ca2+]i rises triggered by AMPA receptor activation confirmed Ca2+ influx in motoneuron dendrites. These findings strongly support a model in which GluR2‐containing and GluR2‐lacking AMPA receptors coexist in motoneurons, clustered at synapses, and mixed in a relative proportion that varies considerably between cell membrane microdomains.
Astrocytic factors protect neuronal integrity and reduce microglial activation in an in vitro model of N‐methyl‐d‐aspartate‐induced excitotoxic injury in organotypic hippocampal slice cultures
Authors: Hailer Nils P. , Wirjatijasa Florentina , Roser Nadine , Hischebeth Gunnar T. R. , Korf Horst‐Werner ,   Faramarz Dehghani
Published: March 2003

AbstractAcute CNS lesions lead to neuronal injury and a parallel glial activation that is accompanied by the release of neurotoxic substances. The extent of the original neuronal damage can therefore be potentiated in a process called secondary damage. As astrocytes are known to secrete immunomodulatory and neuroprotective substances, we investigated whether astrocytic factors can attenuate the amount of neuronal injury as well as the degree of microglial activation in a model of excitotoxic neurodegeneration. Treatment of organotypic hippocampal slice cultures with N‐methyl‐d‐aspartate (NMDA) resulted in a reproducible loss of viable granule cells, partial destruction of the regular hippocampal cytoarchitecture and a concomitant accumulation of amoeboid microglial cells at sites of neuronal damage. Astrocyte‐conditioned media reduced the amount of NMDA‐induced neuronal injury by 45.3%, diminished the degree of microglial activation and resulted in an improved preservation of the hippocampal cytoarchitecture. Transforming growth factor (TGF)‐β failed to act as a neuroprotectant and even enhanced the amount of neuronal injury by 52.5%. Direct effects of astrocytic factors on isolated microglial cells consisted of increased microglial ramification and down‐regulated expression of intercellular adhesion molecule‐1, whereas incubation with TGF‐β had no such effects. In summary, our findings show that hitherto unidentified astrocyte‐derived factors that are probably not identical with TGF‐β can substantially enhance neuronal survival, either by eliciting direct neuroprotective effects or by modulating the microglial response to neuronal injury.