bluuebunny/crossref_metadata_2025_split huggingface dataset:
Contributions of NMDA receptors to network recruitment and rhythm generation in spinal cord cultures
Authors: Legrand Jean‐Christophe , Darbon Pascal , Streit Jürg 
Published: January 2004

Abstract N‐methyl‐d‐aspartic acid (NMDA) receptors are implicated in fictive locomotion; however, their precise role there is not clear. In cultures of dissociated cells from foetal rat spinal cord, synchronous bursting (but not fictive locomotion) can be induced by disinhibition, which is produced by blocking glycinergic and γ‐aminobutyric acid (GABA)A‐dependent synaptic conductances. In this study, we investigate the role of NMDA‐R in rhythm generation during disinhibition with multielectrode arrays and patch‐clamp. We previously determined that bursting activity is generated by repetitive recruitment of a network through recurrent excitation. Blocking NMDA‐R with d(−)‐2‐amino‐5‐phosphonopentanoic acid (APV) decreased the burst duration, suggesting a role of such receptors in the maintenance of high network activity during the bursts. In addition, APV reduced burst rate in about a third of the experiments, suggesting a contribution of NMDA‐R in network recruitment. When (±)‐α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionic acid hydrate (AMPA)/kainate receptors were blocked with 6‐cyano‐7‐nitroquinoxaline‐2,3‐dione (CNQX) in the presence of disinhibition, the burst rate was reduced and burst onset was slowed in two‐thirds of the experiments. In the remaining experiments, bursting ceased completely with CNQX. Neither APV nor CNQX changed the spatial patterns of activity in the network, suggesting a co‐operation of both receptors in rhythm generation. While NMDA alone was not able to create a rhythm, it accelerated bursting in the presence of disinhibition, made it more regular and slowed down network recruitment. These effects were most likely due to the depolarization of the interneurons in the network. We conclude that NMDA‐R contribute to rhythm generation in spinal cultures by supporting recurrent excitation and network recruitment and by depolarizing the network.
Lesion‐dependent regulation of transgene expression in the rat brain using a human glial fibrillary acidic protein‐lentiviral vector
Authors: Jakobsson Johan , Georgievska Biljana , Ericson Cecilia , Lundberg Cecilia 
Published: January 2004

AbstractThe ability to regulate transgene expression will be crucial for development of gene therapy to the brain. The most commonly used systems are based on a transactivator in combination with a drug, e.g. the tetracycline‐regulated system. Here we describe a different method of transgene regulation by the use of the human glial fibrillary acidic protein (GFAP) promoter. We constructed a lentiviral vector that directs transgene expression to astrocytes. Using toxin‐induced lesions we investigated to what extent transgene expression could be regulated in accordance with the activation of the endogenous GFAP gene. In animals receiving excitotoxic lesions of the striatum we detected an eightfold increase of green fluorescent protein (GFP)‐expressing cells. The vast majority of these cells did not divide, suggesting that the transgene was indeed regulated in a similar fashion as the endogenous GFAP gene. This finding will lead to the development of lentiviral vectors with autoregulatory capacities that may be very useful for gene therapy to the brain.
Modulation of rhythmic patterns and cumulative depolarization by group I metabotropic glutamate receptors in the neonatal rat spinal cord in vitro
Authors: Taccola Giuliano , Marchetti Cristina , Nistri Andrea 
Published: January 2004

AbstractThe role of group I metabotropic glutamate receptors (mGluRs), and their subtypes 1 or 5, in rhythmic patterns generated by the neonatal rat spinal cord was investigated. Fictive locomotor patterns induced by N‐methyl‐d‐aspartate + serotonin were slowed down by the subtype 1 antagonists (RS)‐1‐aminoindan‐1,5‐dicarboxylic acid (AIDA) or 7‐(hydroxyimino)cyclopropa[b]chromen‐1a‐carboxylate ethyl ester (CPCCOEt) and unaffected by the subtype 5 antagonist 2‐methyl‐6‐(phenylethynyl)pyridine hydrochloride (MPEP). The group I agonist (RS)‐3,5‐dihydroxyphenylglycine (DHPG) depolarized ventral roots and disrupted fictive locomotion, an effect blocked by AIDA (or CPCCOEt) and reversed by increasing the N‐methyl‐d‐aspartate concentration. Cumulative depolarization induced by low frequency trains of dorsal root stimuli was attenuated by DHPG and unchanged by AIDA or MPEP while rhythmic patterns or motoneuron spike wind‐up persisted. Disinhibited bursting induced by strychnine + bicuculline was accelerated by DHPG, slowed down by AIDA (which prevented the action of DHPG), unaffected by MPEP and counteracted by the selective group II agonist (2S,2′R,3′R)‐2‐(2′,3′‐dicarboxycyclopropyl)glycine. The DHPG transformed regular bursting into arrhythmic bursting, a phenomenon also produced by the group II mGluR antagonist (2S)‐α‐ethylglutamic acid. These results indicate that, during fictive locomotion or disinhibited bursting, endogenous glutamate could activate discrete clusters of subtype 1 mGluRs to facilitate discharges. Diffuse activation by the exogenous agonist DHPG of group I mGluRs throughout spinal networks had an excitatory effect overshadowed by its much stronger depressant action due to concomitant facilitation of glycinergic transmission. Irregular disinhibited bursting caused by activation of subtype 1 receptors or block of group II receptors suggests that mGluRs could control not only the frequency but also the periodicity of bursting patterns, outlining novel mechanisms contributing to burst duration.
Developmental changes in GABAergic actions and seizure susceptibility in the rat hippocampus
Authors: Khazipov Roustem , Khalilov Ilgam , Tyzio Roman , Morozova Elena , Ben‐Ari Yezekiel , Holmes Gregory L. 
Published: January 2004

AbstractThe immature brain is prone to seizures but the underlying mechanisms are poorly understood. We explored the hypothesis that increased seizure susceptibility during early development is due to the excitatory action of GABA. Using noninvasive extracellular field potential and cell‐attached recordings in CA3 of Sprague‐Dawley rat hippocampal slices, we compared the developmental alterations in three parameters: excitatory actions of GABA, presence of the immature pattern of giant depolarizing potentials (GDPs) and severity of epileptiform activity generated by high potassium. The GABA(A) receptor agonist isoguvacine increased firing of CA3 pyramidal cells in neonatal slices while inhibiting activity in adults. A switch in the GABA(A) signalling from excitation to inhibition occurred at postnatal day (P) 13.5 ± 0.4. Field GDPs were present in the form of spontaneous population bursts until P12.7 ± 0.3. High potassium (8.5 mm) induced seizure‐like events (SLEs) in 35% of slices at P7–16 (peak at P11.3 ± 0.4), but only interictal activity before and after that age. The GABA(A) receptor antagonist bicuculline reduced the frequency or completely blocked SLEs and induced interictal clonic‐like activity accompanied by a reduction in the frequency but an increase in the amplitude of the population spikes. In slices with interictal activity, bicuculline typically caused a large amplitude interictal clonic‐like activity at all ages; in slices from P5–16 rats it was often preceded by one SLE at the beginning of bicuculline application. These results suggest that, in the immature hippocampus, GABA exerts dual (both excitatory and inhibitory) actions and that the excitatory component in the action of GABA may contribute to increased excitability during early development.
Localization of endoplasmic reticulum and plasma membrane Ca2+‐ATPases in subcellular fractions and sections of pig cerebellum
Authors: Sepúlveda M. Rosario , Hidalgo‐Sánchez Matías , Mata Ana M. 
Published: January 2004

AbstractSubcellular fractions and sections of the cerebellum were analysed to evaluate the relative activity and distribution of organellar and plasma membrane Ca2+‐ATPases (SERCA and PMCA). Western blot analysis of the fractions with IID8 or Y/1F4 SERCA‐specific antibodies or else with 5F10 or pbPMCA antibodies, specific to PMCA pump, revealed a major content of SERCA protein in microsomes and of PMCA protein in plasma membrane vesicles. The Ca2+‐ATPase activity of microsomes was more sensitive to thapsigargin, a SERCA‐specific inhibitor, whereas the activity of the plasma membrane vesicle fraction was inhibited more by vanadate, a blocker of PMCA activity. The SERCA and PMCA distribution analysed in cerebellar sections revealed IID8 antibody reactions in Purkinje cell cytoplasm, granule cells and cerebellar glomeruli. Y/1F4 gave immunostaining in Purkinje cells, molecular layer interneurons (basket and stellate cells) and glomeruli, but granule cells were not labelled. The 5F10 antibody reacted with Purkinje cells, including their dendritic spines, as well as cerebellar glomeruli, whereas the pbPMCA antibody labelled several processes in all three layers and some synaptic interaction sites. The differential content and localization of the two types of Ca2+ pumps in specific neuronal areas of pig cerebellum indicate precise Ca2+ requirements of specific cellular regions.
Opposing roles of the nucleus accumbens and anterior lateral hypothalamic area in the control of sexual behaviour in the male rat
Authors: Kippin Tod E. , Sotiropoulos Veneta , Badih Julia , Pfaus James G. 
Published: January 2004

AbstractOpposing roles have been implicated for the nucleus accumbens (NAc) and anterior portion of the lateral hypothalamic area (aLHA) in the regulation of sexual behaviour in male rats based on in vivo neurochemical correlates. The present study provides functional evidence supporting this hypothesis by examining the effects of lesions to these structures on copulation, noncontact erection and receptive female preference. Sexually naïve male Long‐Evans rats received either bilateral 1.0‐µL injections of NMDA (10 µg/µL/side) or vehicle (shams) into either the aLHA or the NAc. During repeated tests of copulation most of the sham‐lesioned males, but few of the aLHA‐lesioned and NAc‐lesioned males, copulated to ejaculation. Most of the NAc‐lesioned males also failed to intromit, whereas the majority of the aLHA‐lesioned males intromitted repeatedly. During exposure to an inaccessible receptive female behind a wire‐mesh screen, aLHA‐lesioned males displayed facilitation of noncontact erections, whereas NAc‐lesioned males displayed impaired noncontact erections. Conversely, during simultaneous exposure to inaccessible receptive and nonreceptive females in different compartments, all males spent more time in the proximity of the receptive female. These findings indicate that the aLHA plays an inhibitory role in the regulation of sexual arousal and an excitatory role in the regulation of ejaculation. Conversely, the NAc plays an excitatory role in the regulation in sexual arousal.
Synaptology of the proximal segment of pyramidal cell basal dendrites
Authors: Alonso‐Nanclares L. , White E. L. , Elston G. N. , DeFelipe J. 
Published: January 2004

AbstractPyramidal neurons are covered with dendritic spines, the main postsynaptic targets of excitatory (asymmetrical) synapses. However, the proximal portion of both the apical and basal dendrites is devoid of spines, suggesting a lack of excitatory inputs to this region. In the present study we used electron microscopy to analyse the proximal region of the basal dendrites of supra‐ and infragranular pyramidal cells to determine if this is the case. The proximal region of 80 basal dendrites sampled from the rat hindlimb representation in the primary somatosensory cortex was studied by electron microscopy. A total of 317 synapses were found within this region of the dendrites, all of which were of the symmetrical type. These results suggest that glutamate receptors, although present in the cytoplasm, are not involved in synaptic junctions in the proximal portion of the dendrites. These data further support the idea that inhibitory terminals exclusively innervate the proximal region of basal dendrites.
ZD7288 inhibits postsynaptic glutamate receptor‐mediated responses at hippocampal perforant path–granule cell synapses
Authors: Chen Chu 
Published: January 2004

AbstractHyperpolarization‐activated channels (Ih) are widely expressed in the nervous system and believed to play an important role in the regulation of membrane excitability and rhythmic activity. Recent evidence suggests that Ih may be involved in long‐term potentiation (LTP) in the hippocampus; however, the results are controversial. To explore the possible causes of these differing results, the effects of Ih blockers on synaptic activity were evaluated in mouse hippocampal slices. ZD7288 (20 µm), a selective Ih blocker, apparently prevented the induction of LTP, while Cs+ (1 mm), a commonly used Ih blocker, had no effect on LTP at hippocampal perforant path–dentate granule cell synapses. In addition, ZD7288 but not Cs+ abolished basal synaptic transmission. Results from voltage‐clamp experiments showed that ZD7288 produced a very little inhibition on hyperpolarization‐activated currents, indicating a weak expression of the Ih in granule neurons. Outside‐out patch recordings revealed that ZD7288 inhibited glutamate receptor‐mediated responses, while Cs+ had no effect on them. Meanwhile, ZD7288 reduced both α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionate and N‐methyl‐d‐aspartate receptor‐mediated excitatory postsynaptic currents. The results suggest that ZD7288‐induced reduction of synaptic transmission may result from its inhibition of the postsynaptic glutamate receptors on dentate granule neurons.
Comparison of learning‐related neuronal activity in the dorsal premotor cortex and striatum
Authors: Brasted Peter J. , Wise Steven P. 
Published: January 2004

AbstractPrevious studies have reported learning‐related changes in neuronal activity during conditional visuomotor learning, also known as arbitrary sensorimotor mapping, conditional visual discrimination, and symbolic or endogenous mapping. Qualitatively similar observations have been reported for the dorsal premotor cortex, the supplementary eye field, the prefrontal cortex, the hippocampus, the striatum and the globus pallidus. The fact that cells in both the dorsal premotor cortex (PMd) and the basal ganglia show changes in activity during associative learning enables a test of the hypothesis that cortex and basal ganglia function in distributed architectures known as cortical–basal ganglionic modules or ‘loops’. We reasoned that if these loops represent functional entities, as proposed, then learning‐related changes in activity should occur simultaneously in both the cortical and striatal nodes of a loop. The present results confirmed this prediction; as monkeys learned conditional visuomotor associations, neurons in the premotor cortex and associated parts of the putamen changed their rates at approximately the same time. For the largest number of neurons, the evolution in neural activity occurred in close correspondence to the monkeys' learning curves. As a population, however, learning‐related changes in activity continued after the monkeys reached an asymptote in performance.
Dissociation of function between the dorsal and the ventral hippocampus in spatial learning abilities of the rat: a within‐subject, within‐task comparison of reference and working spatial memory
Authors: Pothuizen Helen H. J. , Zhang Wei‐Ning , Jongen‐Rêlo Ana L. , Feldon Joram , Yee Benjamin K. 
Published: January 2004

AbstractLesions restricted to the dorsal, but not the ventral, hippocampus severely impair the formation of spatial memory. This dissociation was first demonstrated using the water maze task. The present study investigated whether the dorsal and the ventral hippocampus are involved differentially in spatial reference and spatial working memory using a four‐baited/four‐unbaited version of the eight‐arm radial maze task. This test allows the concurrent evaluation of reference and working memory with respect to the same set of spatial cues, and thereby enables a within‐subjects within‐task comparison between the two forms of memory functions. Rats with N‐methyl‐d‐aspartic acid‐induced excitotoxic lesions of the dorsal hippocampus, ventral hippocampus or both were compared with sham and unoperated controls. We showed that dorsal lesions were as effective as complete lesions in severely disrupting both reference and working spatial memory, whereas rats with ventral lesions performed at a level comparable with controls. These results lend further support to the existence of a functional dissociation between the dorsal and the ventral hippocampus, with the former being preferentially involved in spatial learning.
Hippocampal gene expression is modulated by hypergravity
Authors: Del Signore A. , Mandillo S. , Rizzo A. , Di Mauro E. , Mele A. , Negri R. , Oliverio A. , Paggi P. 
Published: January 2004

AbstractWe used the cDNA microarray technique to monitor simultaneously possible changes induced by hypergravity in the expression level of thousands of hippocampal genes. We tested the mRNA level of about 5000 genes in the hippocampus of mice subjected to 1.09 g (1g) or to 1.85 g (2g) for five repeated 1‐h daily rotations in a centrifuge (g = 9.81 m/s2). Data were compared with those obtained for mice kept stationary (C). The ratios 1g/C and 2g/C identified genes affected by rotation and rotation + hypergravity, respectively, whereas 2g/1g ratio identified those affected by hypergravity. We found that about 200 genes were affected by rotation and/or rotation + hypergravity. Almost all the genes affected by rotation + hypergravity were up‐regulated, only five being down‐regulated. The modulated genes code for proteins involved in a wide range of cellular functions (DNA/RNA metabolism, protein processing, intermediate metabolism, cytoskeleton and motility, cell cycle and apoptosis, signal transduction, neuronal structure/function), suggesting that rotation + hypergravity may affect several aspects of the hippocampal function in order to compensate for environmental changes. Six genes directly or indirectly involved in synaptic transmission and plasticity (proSAAS, neuroblastoma ras oncogene, ESTs moderately similar to thymosin beta‐10, syndet, inhibin beta E and Ngfi‐A binding protein 2) were found to be significantly modulated by hypergravity and unaffected or only slightly affected by rotation. The modulation by hypergravity of these genes suggests that this stimulus might induce plastic remodelling of the hippocampal circuits, possibly both at structural and functional level.
Effects of coadministration of cannabinoids and morphine on nociceptive behaviour, brain monoamines and HPA axis activity in a rat model of persistent pain
Authors: Finn D. P. , Beckett S. R. G. , Roe C. H. , Madjd A. , Fone K. C. F. , Kendall D. A. , Marsden C. A. , Chapman V. 
Published: January 2004

AbstractThe antinociceptive effects of Δ9‐tetrahydrocannabinol (Δ9‐THC) have been widely described; however, its therapeutic potential may be limited by secondary effects. We investigated whether coadministration of low doses of cannabinoids or cannabinoids and morphine produced antinociception in the absence of side‐effects. Effects of preadministration (i.p.) of Δ9‐THC (1 or 2.5 mg/kg), cannabidiol (5 mg/kg), morphine (2 mg/kg), Δ9‐THC + morphine, Δ9‐THC + cannabidiol or vehicle on formalin‐evoked nociceptive behaviour were studied over 60 min. Trunk blood and brains were collected 60 min after formalin injection and assayed for corticosterone and tissue levels of monoamines and metabolites, respectively. Drug effects on locomotor activity, core body temperature and grooming were assessed. Δ9‐THC reduced both phases of formalin‐evoked nociceptive behaviour, enhanced the formalin‐evoked corticosterone response and increased the 4‐hydroxy‐3‐methoxyphenylglycol : noradrenaline ratio in the hypothalamus. Cannabidiol alone had no effect on these indices and did not modulate the effects of Δ9‐THC. Morphine reduced both phases of formalin‐evoked nociceptive behaviour. Coadministration of Δ9‐THC and morphine reduced the second phase of formalin‐evoked nociceptive behaviour to a greater extent than either drug alone, and increased levels of thalamic 5‐hydroxytryptamine. While the antinociceptive effects of Δ9‐THC and morphine alone occurred at doses devoid of effects on locomotor activity, coadministration of Δ9‐THC and morphine inhibited locomotor activity. In conclusion, coadministration of a low dose of morphine, but not cannabidiol, with Δ9‐THC, increased antinociception and 5‐hydroxytryptamine levels in the thalamus in a model of persistent nociception. Nevertheless, these enhanced antinociceptive effects were associated with increased secondary effects on locomotor activity.
Histological findings after angioplasty using conventional balloon, radiofrequency thermal balloon, and stent for experimental aortic coarctation
Authors: Ohkubo Mataichi , Takahashi Ken , Kishiro Masahiko , Akimoto Katsumi , Yamashiro Yuichiro 
Published: January 2004

Abstract
Background
: Use of balloon angioplasty or stent implantation has been reported to be effective in relieving coarctation of the aorta. However, restenosis frequently occurs after balloon angioplasty for native aortic coarctation in small infants, and sometimes develops after stent implantation because of vessel growth. The causes of restenosis remain uncertain. The purpose of this study was to assess the histologic differences in vascular responses to angioplasty using conventional balloon, radiofrequency thermal balloon (RFTB), or stent for experimental aortic coarctation.
Methods
: The authors surgically created an aortic coarctation model using 14 puppies. Angioplasty using conventional balloon, RFTB, or stent was performed 1 month after the initial operation. At the acute or chronic phase after angioplasty, the animals were killed and histologic studies were performed.
Results
: More vascular injuries were noted in the specimens from animals undergoing conventional angioplasty than in those with RFTB or stent. However, neointimal hyperplasia was seen more often after RFTB or stent because of the proliferation of smooth muscle cells from the tunica media, caused by secretion of growth factors. Apoptosis reached a peak 1−2 weeks after angioplasty, regardless of the type of intervention.
Conclusions
: The authors conclude that angioplasty with RFTB or stent can provide relatively small injuries in the vessel wall for aortic coarctation, but care must be taken to prevent restenosis caused by intimal hyperplasia, because neointima hyperplasia is more frequent after RFTB or stent.