bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neural interactions between motor cortical hemispheres during bimanual and unimanual arm movements
Authors: Cardoso de Oliveira S. , Gribova A. , Donchin O. , Bergman H. , Vaadia E. 
Published: March 2003

AbstractCortico‐cortical connections through the corpus callosum are a major candidate for mediating bimanual coordination. However, aside from the deficits observed after lesioning this connection, little positive evidence indicates its function in bimanual tasks. In order to address this issue, we simultaneously recorded neuronal activity at multiple sites within the arm area of motor cortex in both hemispheres of awake primates performing different bimanual and unimanual movements. By employing an adapted form of the joint peri‐stimulus time histogram technique, we discovered rapid movement‐related correlation changes between the local field potentials (LFPs) of the two hemispheres that escaped detection by time‐averaged cross‐correlation methods. The frequency and amplitude of dynamic modifications in correlations between the hemispheres were similar to those within the same hemisphere. As in previous EEG studies, we found that, on average, correlation decreased during movements. However, a subset of recording site pairs did show transiently increased correlations around movement onset (57% of all pairs and conditions in monkey G, 39% in monkey P). In interhemispheric pairs, these increases were consistently related to the mode of coupling between the two arms. Both the correlations between the movements themselves and the interhemispheric LFP correlation increases were strongest during bimanual symmetric movements, and weaker during bimanual asymmetric and unimanual movements. Increased correlations occurred mainly around movement onset, whilst decreases in correlation dominated during movement execution. The task‐specific way in which interhemispheric correlations are modulated is compatible with the notion that interactions between the hemispheres contribute to behavioural coupling between the arms.
Neuroprotective effect of interleukin‐6 and IL6/IL6R chimera in the quinolinic acid rat model of Huntington's syndrome
Authors: Bensadoun Jean‐Charles , De Almeida Luis Pereira , Dréano Michel , Aebischer Patrick , Déglon Nicole 
Published: March 2003

AbstractCiliary neurotrophic factor prevents behavioural deficits and striatal degeneration in rat and primate models of Huntington's disease. Interleukin‐6, another member of the cytokine family, and the chimeric molecule (IL6/IL6R) in which interleukin‐6 and its soluble receptor are fused, have been shown to exert trophic action on various neuronal populations in the central nervous system. Therefore, we investigated the neuroprotective effect of these two molecules in the quinolinic acid model of Huntington's disease. LacZ‐, interleukin‐6‐ and IL6/IL6R‐expressing lentiviral vectors were stereotaxically injected into the striatum of Wistar rats. Three weeks later the animals were lesioned through the intrastriatal injection of 180 nmol of quinolinic acid. The extent of the striatal damage was significantly diminished in the rats that had been treated with interleukin‐6 or IL6/IL6R. The neuroprotective effect was, however, more pronounced with the IL6/IL6R chimera than with interleukin‐6 as indicated by the volume of the lesions (38.6 ± 10% in the IL6/IL6R group, 63.3 ± 3.6% in the IL‐6 group and 84.3 ± 2.9% in the control group). Quantitative analysis of striatal interneurons further demonstrated that the IL6/IL6R chimera is more neuroprotective than IL‐6 on ChAT‐ and NADPH‐d‐immunoreactive neurons. These results suggest that the IL6/IL6R chimera is a potential treatment for Huntington's disease.
Temporally controlled targeted somatic mutagenesis in the mouse brain
Authors: Weber Philipp , Metzger Daniel , Chambon Pierre 
Published: March 2003

AbstractTo develop spatio‐temporally controlled somatic mutagenesis in the adult mouse nervous system, we established transgenic mice expressing the tamoxifen‐inducible Cre‐ERT recombinase under the control of the mouse prion protein (PrP) promoter. Cre‐ERT was expressed in most regions of the brain and in the retina of one transgenic line, whereas its expression was mostly restricted to the hippocampus and the cerebellum in another line. As tamoxifen efficiently induced Cre‐mediated recombination in the various neuronal cell types expressing Cre‐ERT in the brain of adult mice, the PrP‐Cre‐ERT lines should be valuable tools to study the functions of genes involved in neurodegenerative diseases or regeneration, and in complex processes such as behaviour, learning and memory. Some limitations of presently available reporter lines for Cre‐mediated recombination in adult mouse CNS are discussed.
Alterations in behaviour and glutamate transmission following presentation of stimuli previously associated with cocaine exposure
Authors: Hotsenpiller Gregory , Giorgetti Marco , Wolf Marina E. 
Published: March 2003

AbstractTo study the role of glutamate in cocaine‐conditioned responses, we developed a rat model in which conditioned locomotion is produced by repeated pairing of cocaine with discrete stimuli (flashing light and metronome). ‘Paired’ subjects received cocaine (15 mg/kg) prior to six exposures to stimuli for 30 min in the test environment. ‘Unpaired’ subjects received equivalent presentations of the stimuli yet received cocaine in home cages. Tests with the stimuli alone demonstrated that the conditioned locomotion displayed by Paired subjects was evident at 3 or 10 days post‐training and resistant to two sessions of testing. The degree of conditioned locomotion was not correlated with the subjects' response to novelty or cocaine. Administration of the noncompetitive AMPA receptor antagonist GYKI 52466 (2.5 mg/kg, a dose without effect on spontaneous activity) attenuated the expression of conditioned activity. In vivo microdialysis revealed that Paired subjects had significantly lower basal glutamate levels in the nucleus accumbens (NAc) than did Unpaired subjects when no stimuli were presented. Presentation of the conditioned stimuli resulted in significant increases in glutamate levels in the NAc in the Paired group whilst glutamate levels in the Unpaired group remained unchanged. The associative control of glutamate levels in the NAc by stimuli formerly paired with a drug of abuse is an unprecedented finding. It is likely to reflect the convergence of excitatory inputs that the NAc receives from limbic structures.
Changes in P2X receptor responses of sensory neurons from P2X3‐deficient mice
Authors: Zhong Yu , Dunn Philip M. , Bardini Michelle , Ford Anthony P. D. W. , Cockayne Debra A. , Burnstock Geoffrey 
Published: March 2003

AbstractDorsal root ganglion (DRG) neurons respond to ATP with transient, persistent or biphasic inward currents. In contrast, the ATP responses in nodose neurons are persistent. These sustained currents are also heterogeneous, with one component being accounted for by P2X2/3 receptors, and the residual response probably mediated by P2X2 receptors, although the direct evidence for this has been lacking. In the present study, we examined the P2X receptors on DRG and nodose neurons from P2X3‐deficient (P2X3−/−) mice, using whole cell voltage‐clamp recording and immunohistochemistry. We found that all P2X3−/− DRG neurons lacked rapidly desensitizing response to ATP, and both DRG and nodose neurons from P2X3‐null mutant mice no longer responded to α,β‐methylene ATP (αβmeATP). In contrast, ATP evoked persistent inward current in 12% of DRG neurons and 84% of nodose neurons from P2X3−/− mice. This retained persistent response to ATP on nodose neurons had an EC50 for ATP of 77 µm, was antagonized by Cibacron blue and pyridoxal‐5‐phosphate‐6‐azophenyl‐2′,4′‐disulphonic acid, potentiated by Zn2+ and acidification, but not enhanced by ivermectin or diinosine pentaphosphate. 2′,3′‐O‐Trinitrophenyl‐ATP antagonized this response with an IC50 of 8 µm. All these properties are consistent with those of recombinant P2X2 homomeric receptors. Furthermore, specific P2X2 receptor immunoreactivity detected in wild‐type sensory neurons was unaltered in null mutant mice. Therefore, the αβmeATP‐insensitive persistent responses on nodose neurons are likely to be mediated by P2X2 homomers, which contribute to 60% of currents evoked by 100 µm ATP in the wild type.
The ubiquitin–proteasome cascade is required for mammalian long‐term memory formation
Authors: Lopez‐Salon Mariella , Alonso Mariana , Vianna Monica R. M. , Viola Haydee , E Souza Tadeu Mello , Izquierdo Ivan , Pasquini Juana M. , Medina Jorge H. 
Published: March 2003

AbstractIt has been recently demonstrated that ubiquitin–proteasome‐mediated proteolysis is required for long‐term synaptic facilitation in Aplysia. Here we show that the hippocampal blockade of this proteolytic pathway is also required for the formation of long‐term memory in the rat. Bilateral infusion of lactacystin, a specific proteasome inhibitor, to the CA1 region caused full retrograde amnesia for a one‐trial inhibitory avoidance learning when given 1, 4 or 7h, but not 10 h, after training. Proteasome inhibitor I produced similar effects. In addition, inhibitory avoidance training resulted in an increased ubiquitination and 26S proteasome proteolytic activity and a decrease in the levels of IkappaB, a substrate of the ubiquitin–proteasome cascade, in hippocampus 4 h after training. Together, these findings indicate that the ubiquitin–proteasome cascade is crucial for the establishment of LTM in the behaving animal.
Cholinergic and noncholinergic septal neurons modulate strategy selection in spatial learning
Authors: Cahill Jonathan F. X. , Baxter Mark G. 
Published: March 2003

AbstractRats solving a simple spatial discrimination task in a plus maze initially employ a place‐learning strategy, then switch to a motor response strategy. The hippocampus is required for the use of a place‐learning strategy in this task. Rats with 192 IgG‐saporin lesions of the medial septum/vertical limb of the diagonal band (MS/VDB), that selectively removed cholinergic neurons projecting to the hippocampus, were significantly facilitated in acquisition of the spatial discrimination, and switched from place to response strategies just as control rats did. Rats with ibotenic acid lesions of the MS/VDB, that produced cell loss in the MS/VDB but little damage to cholinergic neurons, were significantly impaired in acquiring the spatial discrimination and did not reliably employ either a place or response strategy at any point in training. This suggests that the MS/VDB modulates hippocampal involvement in place learning, but that cholinergic MS/VDB neurons are neither necessary nor sufficient for using a place strategy to solve a spatial discrimination.
HIV‐1 protein Tat reduces the glutamate‐induced intracellular Ca2+ increase in cultured cortical astrocytes
Authors: Köller Hubertus , Schaal Heiner , Freund Marcel , Garrido Sanuk Rafaela , Von Giesen Hans‐Jürgen , Ott Melanie , Rosenbaum Claudia , Arendt Gabriele 
Published: March 2003

AbstractThe trans‐activator protein Tat of the human immunodeficiency virus type 1 (HIV‐1) is regarded as an injurious molecule in the pathogenesis of HIV‐1 associated encephalopathy (HIVE). We investigated the effects of Tat on neuroligand‐induced intracellular Ca2+ increase in cultured astroglial cells. Rat cortical astrocytes, human glioblastoma cells and glial restricted precursor cells, from a human embryonic teratocarcinoma cell line, were incubated with recombinant Tat (100 ng/mL for 60 min) which induced a significant reduction of glutamate or ATP‐induced intracellular Ca2+ increase (‘glutamate response’, ‘ATP response’). The reduction of the glutamate response was also observed following cell incubation with cell extracts of HeLa‐T4+ cells transiently transfected with an expression plasmid coding for Tat. However, inactivation of the transcriptional trans‐activity of Tat, by using a mutant form of Tat, as well as inhibition of de novo protein synthesis by cycloheximide abolished the effect on the glutamate response. This suggests that Tat acts upon induction of a so far unknown cellular gene whoes gene product causes the reduction of glutamate responses. As the effect of Tat resembles the effect of TNFα on glutamate responses [Köller et al. (2001) Brain Res., 893, 237–243] which is locally released within the brains of HIVE patients, we also tested for synergistic effects of Tat and TNFα on the glutamate response. Low concentrations of Tat in combination with subthreshold concentrations of TNFα also elicited a marked reduction of astroglial glutamate responses. Our data suggest that Tat and TNFα, both by itself and synergistically, induce astroglial dysfunction.
Evidence that interleukin‐1β and reactive oxygen species production play a pivotal role in stress‐induced impairment of LTP in the rat dentate gyrus
Authors: Vereker Emily , O'Donnell Eamonn , Lynch Aileen , Kelly Áine , Nolan Yvonne , Lynch Marina A. 
Published: March 2003

AbstractLong‐term potentiation (LTP) in both area CA1 and the dentate gyrus is attenuated by stress and the evidence is consistent with the view that this is a consequence of increased activation of glucocorticoid receptors, in the hippocampus, following the stress‐induced increase in circulating corticosterone. It has been shown that expression of the pro‐inflammatory cytokine, interleukin‐1β (IL‐1β), is increased in hippocampus in response to stress; this finding together with the observation that IL‐1β exerts an inhibitory effect on LTP, suggests that IL‐1β may play a key role in mediating this inhibitory effect of stress on LTP. In this study, we explore this possibility and report that stress is also associated with increased reactive oxygen species production. The evidence presented supports the view that this is secondary to the stress‐induced increase in IL‐1β concentration, as IL‐1β increased activity of superoxide dismutase and increased reactive oxygen species accumulation in hippocampus in vitro. We report that the inhibitory effect of stress on LTP is mimicked by H2O2, which increases reactive oxygen species accumulation, and by IL‐1β, the effect of which is overcome by the antioxidant, phenylarsine oxide. The hypothesis that the stress‐induced increase in reactive oxygen species production may underlie the suppression of LTP is further supported by the finding that the effect of stress is abrogated by dietary manipulation with antioxidant vitamins E and C.
Associative effects of Pavlovian differential inhibition of behaviour
Authors: Jones Dirk , Gonzalez‐Lima F. 
Published: March 2003

AbstractThe associative inhibitory control of behaviour is a major component of Pavlovian learning theory, but little is known about its functional neuroanatomy. The associative effects of differential inhibition of conditioned behaviour were investigated by mapping learning‐related changes in brain activity of the rat with fluorodeoxyglucose autoradiography. Of interest was how a tone is processed in auditory and extra‐auditory systems of the rat brain under similar behavioural, but different associative conditions. Conditioned emotional suppression to drink was used to assess training, and summation tests were used to verify that the tone became an inhibitor of conditioned behaviour. In the Inhibitor group, presentations of a tone stimulus alone were intermixed with presentations of a light stimulus followed by footshock. In the Pseudorandom group, the same numbers of tone, light and footshock presentations were used, but they were presented in a pseudorandom fashion. After training, fluorodeoxyglucose uptake was measured during tone presentations. Behavioural responding to the tone was similar during fluorodeoxyglucose uptake in the two groups, yet associative effects were found in brain activity. In the auditory system, the tone produced reduced fluorodeoxyglucose uptake in major relay nuclei (cochlear nucleus and inferior colliculus) in the Inhibitor group relative to the Pseudorandom group. The tone inhibitor produced similar decreases in the septohippocampal system and the retrosplenial cortex. In contrast, the tone inhibitor produced activity increases in somatosensory and reticulocerebellar systems. The findings provide the first detailed map of neural regions involved in the learned associations controlling differential inhibition of conditioned behaviour.
Acute modulation of synaptic transmission to motoneurons by BDNF in the neonatal rat spinal cord
Authors: Arvanian Victor L. , Mendell Lorne M. 
Published: March 2003

AbstractWe investigated the acute effects of bath applied BDNF on synaptic input to motoneurons in the hemisected spinal cord of the neonatal rat. Motoneurons were recorded intracellularly, and BDNF‐induced modulation of the synaptic response to stimulation of the homologous dorsal root (DR) and the ventrolateral funiculus (VLF) was examined. All motoneurons exhibited long‐lasting (up to several hours) depression of the DR‐activated monosynaptic AMPA/kainate‐receptor mediated EPSP in response to BDNF but in about half of the motoneurons this was preceded by facilitation. VLF‐evoked AMPA/kainate EPSPs in the same motoneurons were unaffected. BDNF effects were blocked by K252a and were not observed in neonates older than 1 week. Bath applied NMDA antagonists APV and MK‐801 abolished both facilitatory and inhibitory actions of BDNF on the AMPA/kainate responses indicating the requirement for functional NMDA receptors. The pharmacologically isolated, DR‐evoked, NMDA receptor‐mediated response exhibited the same pattern of changes after BDNF superfusion. When introduced into the motoneuron through the recording microelectrode, MK‐801 selectively blocked the facilitatory action of BDNF. Furthermore, BDNF enhanced NMDA‐induced depolarization of the motoneuron in the presence of tetrodotoxin (TTX), thus, confirming its facilitatory effect on motoneuron NMDA receptors. Bath application of either BDNF or NMDA depressed the monosynaptic EPSP after selective blockade of postsynaptic NMDA receptors indicating a role for presynaptic NMDA receptors in BDNF‐induced inhibitory action. Thus, BDNF‐induced facilitation of monosynaptic EPSPs in neonatal rats is mediated by direct effects on postsynaptic NMDA receptors, while its inhibitory action occurs presynaptically.
Increased cannabinoid CB1 receptor binding and activation of GTP‐binding proteins in the basal ganglia of patients with Parkinson's syndrome and of MPTP‐treated marmosets
Authors: Lastres‐Becker I. , Cebeira M. , de Ceballos M.L. , Zeng B. ‐Y. , Jenner P. , Ramos J. A. , Fernández‐Ruiz J. J. 
Published: March 2003

AbstractRecent evidence obtained in rat models of Parkinson's disease showed that the density of cannabinoid CB1 receptors and their endogenous ligands increase in basal ganglia. However, no data exists from post‐mortem brain of humans affected by Parkinson's disease or from primate models of the disorder. In the present study, we examined CB1 receptor binding and the magnitude of the stimulation by WIN55,212‐2, a specific CB1 receptor agonist, of [35S]GTPγS binding to membrane fractions from the basal ganglia of patients affected by Parkinson's disease. In Parkinson's disease, WIN55,212‐2‐stimulated [35S]GTPγS binding in the caudate nucleus, putamen, lateral globus pallidus and substantia nigra was increased, thus indicating a more effective activation of GTP‐binding protein‐coupled signalling mechanisms via CB1 receptors. This was accompanied by an increase in CB1 receptor binding in the caudate nucleus and the putamen, although no changes were observed in the lateral globus pallidus and the substantia nigra. Because Parkinson's disease patients had been chronically treated with l‐DOPA, brains were studied from normal common marmosets and 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐treated animals with and without chronic L‐DOPA treatment. MPTP‐lesioned marmosets had increased CB1 receptor binding in the caudate nucleus and the putamen compared to control marmosets, as well as increased stimulation of [35S]GTPγS binding by WIN55,212‐2. However, following l‐DOPA treatment these parameters returned towards control values. The results indicate that a nigro‐striatal lesion is associated with an increase in CB1 receptors in the basal ganglia in humans and nonhuman primates and that this increase could be reversed by chronic l‐DOPA therapy. The data suggest that CB1 receptor blockade might be useful as an adjuvant for the treatment of parkinsonian motor symptoms.
Neuronal coordination of arm and leg movements during human locomotion
Authors: Dietz V. , Fouad K. , Bastiaanse C. M. 
Published: March 2003

AbstractWe aimed to study the neuronal coordination of lower and upper limb muscles. We therefore evaluated the effect of small leg displacements during gait on leg and arm muscle electromyographic (EMG) activity in walking humans. During walking on a split‐belt treadmill (velocity 3.5 km/h), short accelerations or decelerations were randomly applied to the right belt during the mid or end stance phase. Alternatively, trains of electrical stimuli were delivered to the right distal tibial nerve. The EMG activity of the tibialis anterior (TA), gastrocnemius medialis (GM), deltoideus (Delt), triceps (Tric) and biceps brachii (Bic) of both sides was analysed. For comparison, impulses were also applied during standing and sitting. The displacements were followed by specific patterns of right leg and bilateral arm muscle EMG responses. Most arm muscle responses appeared with a short latency (65–80 ms) and were larger in Delt and Tric than in Bic. They were strongest when deceleration impulses were released during mid stance, associated with a right compensatory TA response. A similar response pattern in arm muscles was obtained following tibial nerve stimulation. The arm muscle responses were small or absent when stimuli were applied during standing or sitting. The arm muscle responses correlated more closely with the compensatory TA than with the compensatory GM responses. The amplitude of the responses in most arm muscles correlated closely with the background EMG activity of the respective arm muscle. The observations suggest the existence of a task‐dependent, flexible neuronal coupling between lower and upper limb muscles. The stronger impact of leg flexors in this interlimb coordination indicates that the neuronal control of leg flexor and extensor muscles is differentially interconnected during locomotion. The results are compatible with the assumption that the proximal arm muscle responses are associated with the swinging of the arms during gait, as a residual function of quadrupedal locomotion.
Sciatic nerve regeneration in rats induced by transplantation of in vitro differentiated bone‐marrow stromal cells
Authors: Dezawa Mari , Takahashi Izumi , Esaki Michiyo , Takano Masahiko , Sawada Hajime 
Published: March 2003

AbstractBone marrow stromal cells (MSCs) are multipotent stem cells that have the potential to differentiate into bone, cartilage, fat and muscle. We now demonstrate that MSCs can be induced to differentiate into cells with Schwann cell characteristics, capable of eliciting peripheral nervous system regeneration in adult rats. MSCs treated with beta‐mercaptoethanol followed by retinoic acid and cultured in the presence of forskolin, basic‐FGF, PDGF and heregulin, changed morphologically into cells resembling primary cultured Schwann cells and expressing p75, S‐100, GFAP and O4. The MSCs were genetically engineered by transduction with retrovirus encoding green fluorescent protein (GFP), and then differentiated by treatment with factors described above. They were transplanted into the cut ends of sciatic nerves, which then responded with vigorous nerve fibre regeneration within 3 weeks of the operation. Myelination of regenerated fibers by GFP‐expressing MSCs was recognized using confocal and immunoelectron microscopy. The results suggest that MSCs are able to differentiate into myelinating cells, capable of supporting nerve fibre re‐growth, and they can therefore be applied to induce nerve regeneration.