bluuebunny/crossref_metadata_2025_split huggingface dataset:
High susceptibility of the anterior and posterior piriform cortex to induction of convulsions by bicuculline
Authors: Ebert Ulrich , Wlaź Piotr , Löscher Wolfgang 
Published: July 2009

AbstractAccumulating evidence suggests that the piriform cortex (PC) plays a critical role in the development of limbic motor seizures. In the anterior piriform cortex (aPC), a functionally defined, discrete epileptogenic site has been previously identified by unilateral microinjection of bicuculline in Sprague–Dawley (SD) rats and termed the ‘area tempestas’ (AT). Compared to this site in the aPC, more posterior PC sites, particularly a site in the transition zone between the posterior and aPC (central PC) exhibited a greater susceptibility to electrical stimulation. However, it is not known whether central and posterior sites in the PC differ from the aPC, including the AT, with regard to their sensitivity to bicuculline. In the present study, unilateral focal microinfusion of picomole quantities of bicuculline induced behavioural (focal and generalized) seizures in deep layers of all parts of the PC in two rat strains, Wistar and SD. The incidence of generalized seizures was higher in the AT of SD rats, but no such difference was seen in Wistar rats, arguing against the previous proposal that the rat AT is unique in its sensitivity to induction of seizures by bicuculline compared to other locations within or outside of the PC. Injection of biotin–dextran in PC seizure‐sensitive sites in SD rats showed clear differences in anterograde and retrograde labelling between the different PC sites. Therefore, although it was possible to evoke generalized seizures from all parts of the PC, the anatomical connections of the bicuculline injection sites were qualitatively different. The results suggest that the deep layers of the entire PC are highly sensitive to seizure induction by bicuculline, thus substantiating the notion that the PC may be important in seizure generation and propagation.
Cloning, distribution and functional analysis of the type III sodium channel from human brain
Authors: Chen Yu Hua , Dale Timothy J. , Romanos Michael A. , Whitaker William R. J. , Xie Xin Min , Clare Jeffrey J. 
Published: July 2009

AbstractThe type III voltage‐gated sodium channel was cloned from human brain. The full‐length cDNA has 89% identity with rat type III, and the predicted protein (1951 amino acids) has 55 differences. The expression pattern of human type III mRNA was determined in adult brain tissue and, in contrast to rat, was detected in many regions, including caudate nucleus, cerebellum, hippocampus and frontal lobe. The human type III channel was stably expressed in Chinese hamster ovary (CHO) cells and its biophysical properties compared to the human type II channel using identical conditions. The voltage dependence and kinetics of activation were found to be similar to that of type II. The kinetics of inactivation of the two human subtypes were also similar. However, type III channels inactivated at more hyperpolarized potentials and were slower to recover from inactivation than type II. When expressed in human embryonic kidney (HEK293T) cells, type III channels produced currents with a prominent persistent component, which were similar to those reported for rat type II [Ma et al. (1997) Neuron, 19, 443–452]. However, unlike type II, this was prominent even in the absence of coexpressed G‐proteins, suggesting type III may adopt this gating mode more readily. The distinct properties of the channel, together with its wide distribution in adult brain, suggest that in humans, type III may have important physiological roles under normal, and perhaps also pathological conditions.
Increased neuronal damage and apoE immunoreactivity in human apolipoprotein E, E4 isoform‐specific, transgenic mice after global cerebral ischaemia
Authors: Horsburgh Karen , McCulloch James , Nilsen Margaret , Roses Allen D. , Nicoll James A. R. 
Published: July 2009

AbstractApolipoprotein E (apoE, protein; APOE, gene) is expressed as three isoforms in humans (E2, E3, E4). The APOE‐ε4 allele is associated with a poor outcome in patients after head injury of which ischaemic brain damage is a contributor of mortality and morbidity. The aim of the study was to determine whether mice expressing human APOE‐ε4 displayed more extensive ischaemic neuronal damage 72 h after transient global ischaemia compared with mice which express human APOE‐ε3. APOE‐ε3 and ‐ε4 transgenic mice, under the control of a human promoter, were used which express human APOE in neurons and glia. Ischaemic neuronal damage in the CA1 pyramidal cell layer in the APOE‐ε4 transgenic mice was significantly greater than in the APOE‐ε3 mice after global ischaemia (36.4 ± 8.9%, 18.2 ± 7.3%; P < 0.05). This was associated with more extensive neuronal apoE immunoreactivity in the CA1 pyramidal cell layer in the APOE‐ε4 transgenic mice compared with APOE‐ε3 transgenic mice. In contrast, in the caudate nucleus, there were similar levels of ischaemic neuronal damage in the APOE‐ε3 and ‐ε4 transgenic mice (39.2 ± 10.1%; 44.6 ± 8.4%, P = 0.32). In the caudate, similar numbers of neurons were immunostained for apoE in the APOE‐ε3 and ‐ε4 transgenic mice. The present study demonstrated that the APOE‐ε4 allele is associated with an increased vulnerability of a specific brain region to the effects of global ischaemia, which is closely associated with an increase in neuronal apoE. The data extend previous work and are consistent with an association of the APOE‐ε4 allele with a poor outcome after acute brain injury in humans.
Electrical stimulation accelerates and increases expression of BDNF and trkB mRNA in regenerating rat femoral motoneurons
Authors: Al‐Majed Abdulhakeem A. , Brushart Thomas M. , Gordon Tessa 
Published: July 2009

AbstractElectrical stimulation promotes the speed and accuracy of motor axonal regeneration. The positive effects of stimulation are mediated at the cell body. Here we characterize the effect of electrical stimulation on motoneuronal expression of BDNF and its receptor, trkB, two genes whose expression levels in motoneurons correlate with regeneration and are regulated by electrical activity in a variety of neurons. We used semiquantitative in situ hybridization to measure expression of mRNA encoding BDNF and the full‐length trkB receptor at intervals of 8 h, 2 days and 7 days after unilateral femoral nerve cut, suture, and stimulation. Expression in regenerating motoneurons was compared to that of contralateral intact motoneurons. BDNF and trkB signals were not significantly upregulated 8 h and 2 days after femoral nerve suture and sham stimulation. By 7 days, there was a 2‐fold increase in both BDNF and trkB mRNA expression. In contrast, stimulation of cut and repaired nerves for only 1 h led to rapid upregulation of BDNF and trkB mRNA by 3‐fold and 2‐fold, respectively, within the first 8 h. The stimulation effect peaked at 2 days with 6‐fold and 4‐fold increases in the signals, respectively. Thereafter, the levels of BDNF and trkB mRNA expression declined to equal the 2‐fold increase seen at 7 days after nerve repair and sham‐stimulation. We conclude that brief electrical stimulation stimulates BDNF and trkB expression in regenerating motoneurons. Because electrical stimulation is known to accelerate axonal regeneration, we suggest that changes in the expression of BDNF and trkB correlate with acceleration of axonal regeneration.
APP is required during an early phase of memory formation
Authors: Mileusnic R. , Lancashire C. L. , Johnston A. N. B. , Rose S. P. R. 
Published: July 2009

AbstractThe amyloid β/A4 protein precursor (APP) has been shown to be implicated in age‐associated plastic changes at synapses that might contribute to memory loss in Alzheimer's disease. As APP has previously been reported to have multiple functions during normal development, we have employed a one‐trial passive avoidance task in day‐old chicks to study its role in the process of memory formation. Administration of anti‐APP antibodies, injected 30 min pretraining, prevented memory for a one‐trial passive avoidance task in day‐old chicks without effects on general behaviour or initial acquisition. Amnesia was apparent by 30 min post‐training and lasted for at least 24 h. The same result was obtained by down‐regulation of APP expression by APP‐antisense, injected 8–12 h pretraining. However, injections of anti‐APP antibodies or APP antisense at later post‐training time did not cause amnesia for the task. Unlike antibodies and antisense, injection of the APP328–332 pentapeptide, in either orientation, 30 min pretraining, rescued the memory and prevented antisense‐induced amnesia. The post‐training time within which the antibody‐ and antisense‐induced amnesia, and within which the APP peptides prevent amnesia, correspond to that during which memory formation is vulnerable to disruption of the putative signal transduction functions of APP. These results suggest that: (i) APP is required during an early phase of memory formation, and (ii) the memory enhancing effect of secretory APP is localized within a 5‐mer sequence of growth‐promoting domain.
Changes in the firing pattern of globus pallidus neurons after the degeneration of nigrostriatal pathway are mediated by the subthalamic nucleus in the rat
Authors: Ni Zhongge , Bouali‐Benazzouz Rabia , Gao Dongming , Benabid Alim‐Louis , Benazzouz Abdelhamid 
Published: July 2009

AbstractChanges in the neuronal activity of globus pallidus (GP) have been shown in animal models of parkinsonism. In order to study the implication of the subthalamic nucleus (STN) in these changes, the effects of STN lesions alone or in combination with 6‐hydroxydopamine (6‐OHDA) ‐induced damage to the substantia nigra compacta (SNc) were examined in rats using electrophysiological recordings of GP cells. In normal rats, the firing rate was 22.1 ± 1.4 spikes/s. The pattern was regular in 45%, irregular in 49% and bursty in 6% of the cases. In rats with STN lesions, the firing rate of GP units (20.15 ± 1.25 spikes/s) did not differ from that of normal rats and only regular (46%) and irregular (54%) cells were found; a bursty pattern was not observed. 6‐OHDA lesions of the SNc induced no change in the firing rate of GP neurons (21.5 ± 1.4 spikes/s, P > 0.05) but a significant decrease in the percentage of regular cells (27%, P < 0.001), a significant increase in burst cells (21%, P < 0.001) with no change in the percentage of irregular units (52%) were observed. In rats with combined SNc and STN lesions, the firing pattern did not change from that of normal rats. The present results show that STN lesions induced the disappearance of bursts in normal rats and normalization of firing pattern in the GP units of rats with 6‐OHDA lesions suggesting that the STN plays an important role in the modulation of the pattern of activity of GP neurons which may account for the therapeutic effect of STN lesions in Parkinson's disease.
Cortical cholinergic inputs mediate processing capacity: effects of 192 IgG‐saporin‐induced lesions on olfactory span performance
Authors: Turchi Janita , Sarter Martin 
Published: July 2009

AbstractAn olfactory span task that required rats to discriminate an olfactory stimulus added to an increasing list of such stimuli (nonmatching‐to‐sample; NMTS) was employed to assess the role of the basal forebrain cholinergic system in the animals' olfactory working memory capacity. A separate group of animals was trained in a matching‐to‐sample (MTS) version of this task that did not tax span performance. NMTS animals required significantly more sessions to reach an olfactory span of 18 stimuli than MTS rats. Infusions of the cholino‐immunotoxin 192 IgG‐saporin into the basal forebrain resulted in decreases of cortical acetylcholinesterase (AChE)‐positive fibre density ranging from 80% in frontodorsal and frontoparietal regions to 35% in the pyriform cortex and 24% in the olfactory bulb. Postsurgery span performance was significantly reduced in lesioned NMTS but not MTS animals. Span performance in lesioned NMTS animals recovered following 4 weeks of postoperative training; however, these animals' span remained vulnerable to the effects of increased intertrial intervals. The distribution of errors in lesioned animals indicated a recency effect. In NMTS animals, olfactory span performance during the initial two postoperative weeks correlated significantly with AChE‐positive fibre density in neocortical but not olfactory areas. The privileged, automatic processing of olfactory stimuli in rats may have contributed to the transience of the lesion effect. The results support the crucial role of cortical cholinergic input in the mediation of aspects of processing capacity.
Morphological evidence for selective modulation by serotonin of a subpopulation of dorsal horn cells which possess the neurokinin‐1 receptor
Authors: Stewart W. , Maxwell D. J. 
Published: July 2009

AbstractSerotonin selectively depresses transmission of nociceptive information through the spinal dorsal horn but the mechanisms of this depression are poorly understood. In this study we report that serotonin‐containing axons form basket‐like clusters which are intimately woven around cell bodies and proximal dendrites of a subpopulation (≈ 50%) of laminae III/IV neurons which possess the neurokinin‐1 receptor. Statistical analysis confirms that cells belonging to this subpopulation have significantly higher numbers of serotoninergic contacts on proximal dendrites when compared with the population of neurokinin‐1 cells that are not associated with clusters (mean ± SD = 13 ± 5.8 and 5 ± 2.9, respectively). Neurokinin‐1 cells in laminae III/IV project to regions of the brain which are involved in nociceptive processing and are likely to be activated predominantly by nociceptive input. The concentration of serotoninergic axons around proximal regions of some of these cells indicates that serotonin may have a powerful influence on transmission through this pathway. This type of arrangement could be a morphological correlate for at least part of the selective antinociceptive actions of serotonin.
Differential targeting of components of the dystrophin complex to the postsynaptic membrane
Authors: Marchand Sophie , Stetzkowski‐Marden Françoise , Cartaud Jean 
Published: July 2009

AbstractAccumulating evidence points to the participation of dystroglycan in the clustering of nicotinic acetylcholine receptors at the neuromuscular junction [Côtéet al.. (1999) Nature Genet., 3, 338–342]. Dystroglycan is part of a multimolecular complex, either associated with dystrophin (the dystrophin‐associated protein complex) at the sarcolemma or with utrophin (the utrophin‐associated protein complex) at the neuromuscular junction. Understanding the assembly of this complex at the developing synapse led us to investigate, in Torpedo electrocyte, the intracellular routing and the targeting of several of its components, including dystroglycan, syntrophin, dystrophin and dystrobrevin. We previously demonstrated that acetylcholine receptors and rapsyn, the 43‐kDa receptor‐associated protein at the synapse, are cotargeted to the postsynaptic membrane via the exocytic pathway [Marchand et al.. (2000) J. Neurosci., 20, 521–528]. Using cell fractionation, immunopurification and immuno‐electron microscope techniques, we show that β‐dystroglycan, an integral glycoprotein that constitutes the core of the dystrophin‐associated protein complex localized at the innervated membrane, is transported together with acetylcholine receptor and rapsyn in post‐Golgi vesicles en route to the postsynaptic membrane. Syntrophin, a peripheral cytoplasmic protein of the complex, associates initially with these exocytic vesicles. Conversely, dystrophin and dystrobrevin were absent from these post‐Golgi vesicles and associate directly with the postsynaptic membrane. This study provides the first evidence for a separate targeting of the various components of the dystrophin‐associated protein complex and a step‐by‐step assembly at the postsynaptic membrane.
p35/cdk5 binds and phosphorylates β‐catenin and regulates β‐catenin/presenilin‐1 interaction
Authors: Kesavapany Sashi , Lau Kwok‐Fai , McLoughlin Declan M. , Brownlees Janet , Ackerley Steven , Leigh P. Nigel , Shaw Christopher E. , Miller Christopher C. J. 
Published: July 2009

AbstractThe neuronal cyclin‐dependent kinase p35/cdk5 comprises a catalytic subunit (cdk5) and an activator subunit (p35). To identify novel p35/cdk5 substrates, we utilized the yeast two‐hybrid system to screen for human p35 binding partners. From one such screen, we identified β‐catenin as an interacting protein. Confirmation that p35 binds to β‐catenin was obtained by using glutathione S‐transferase (GST)–β‐catenin fusion proteins that interacted with both endogenous and transfected p35, and by showing that β‐catenin was present in p35 immunoprecipitates. p35 and β‐catenin also displayed overlapping subcellular distribution patterns in cells including neurons. Finally, we demonstrated that p35/cdk5 phosphorylates β‐catenin. β‐catenin also binds to presenilin‐1 and altered β‐catenin/presenilin‐1 interactions may be mechanistic in Alzheimer's disease (AD). Abnormal p35/cdk5 activity has also been suggested to contribute to AD. We therefore investigated how modulation of p35/cdk5 activity influenced β‐catenin/presenilin‐1 interactions. Inhibition of p35/cdk5 with roscovitine did not alter the steady state levels of either β‐catenin or presenilin‐1 but reduced the amount of presenilin‐1 bound to β‐catenin. Thus, p35/cdk5 binds and phosphorylates β‐catenin and regulates its binding to presenilin‐1. The findings reported here therefore provide a novel molecular framework to connect p35/cdk5 with β‐catenin and presenilin‐1 in AD.
The integration of parallel and serial processing mechanisms in visual search: evidence from eye movement recording
Authors: Maioli Claudio , Benaglio Irene , Siri Simona , Sosta Katiuscia , Cappa Stefano 
Published: July 2009

AbstractWe examined timing and scanning paths of eye movements during a visual search task, in which subjects had to detect, as quickly as possible, the presence or absence of a target among distractors [Q‐like element among O stimuli (QvsO) and vice‐versa (OvsQ)]. According to an influential theory [Treisman, A. & Gelade, G. (1980) Cognitive Psychol, 12, 97–136; Treisman, A. & Sato, S. (1990) J. Exp. Psychol. Hum. Percept. Perform., 16, 459–478], only tasks yielding nonflat search functions (OvsQ) involve focal attention. Alternative models propose that all kinds of visual search are resolved by a biased competitive process, working in parallel across the visual field. Data show that QvsO and OvsQ tasks are characterized by quantitative rather than by qualitative differences in search strategy. No differences between the two tasks were found regarding either the percentage of saccades foveating single stimulus items or the timing of the button response with respect to the onset of the last foveation saccade within a trial. Furthermore, the number of saccades made during search predicted very accurately the time required to accomplish the task and fixation times were independent of the number of stimulus items. On the basis of our results there is no reason to postulate the occurrence of shifts of visuospatial attention, other than those associated with the executions of saccadic eye movements, which are driven by a parallel feature analysis of the visual scene, in both types of search tasks. A time‐limited competitive model for attentive target identification, in which both parallel (competitive) and serial (attentive) processing mechanisms are integrated, can account for these findings, providing a unified conceptual framework for all kinds of visual search.
Action observation activates premotor and parietal areas in a somatotopic manner: an fMRI study
Authors: Buccino G. , Binkofski F. , Fink G. R. , Fadiga L. , Fogassi L. , Gallese V. , Seitz R. J. , Zilles K. , Rizzolatti G. , Freund H.‐J. 
Published: July 2009

AbstractFunctional magnetic resonance imaging (fMRI) was used to localize brain areas that were active during the observation of actions made by another individual. Object‐ and non‐object‐related actions made with different effectors (mouth, hand and foot) were presented. Observation of both object‐ and non‐object‐related actions determined a somatotopically organized activation of premotor cortex. The somatotopic pattern was similar to that of the classical motor cortex homunculus. During the observation of object‐related actions, an activation, also somatotopically organized, was additionally found in the posterior parietal lobe. Thus, when individuals observe an action, an internal replica of that action is automatically generated in their premotor cortex. In the case of object‐related actions, a further object‐related analysis is performed in the parietal lobe, as if the subjects were indeed using those objects. These results bring the previous concept of an action observation/execution matching system (mirror system) into a broader perspective: this system is not restricted to the ventral premotor cortex, but involves several somatotopically organized motor circuits.
NAAG inhibits KCl‐induced [3H]‐GABA release via mGluR3, cAMP, PKA and L‐type calcium conductance
Authors: Zhao Jing , Ramadan Epolia , Cappiello Marisa , Wroblewska Barbara , Bzdega Tomasz , Neale Joseph H. 
Published: July 2009

AbstractThe peptide neurotransmitter,N‐acetylaspartylglutamate (NAAG), is a selective agonist at the type 3 metabotropic glutamate receptor (mGluR3) where it acts to decrease cAMP levels. Rat cortical interneurons express both NAAG and glutamic acid decarboxylase, as well as mGluR3 mRNA. In the presence of ionotropic glutamate receptor antagonists, both NAAG and the group II metabotropic glutamate receptor agonist, DCG‐IV, reduced the calcium‐dependent, KCl‐induced [3H]‐GABA release from rat cortical neurons by 35%. This release process was unaffected by tetrodotoxin. The group II antagonist, ethyl glutamate, reversed the effects of DCG‐IV and NAAG. The mGluR3‐selective antagonist, β‐N‐acetylaspartylglutamate, reversed the effect of NAAG. While pretreatment of cortical neurons with forskolin alone did not significantly affect KCl‐stimulated [3H]‐GABA‐release, forskolin abolished the inhibition of release produced by NAAG. The protein kinase A inhibitor, H‐89, decreased [3H]‐GABA release while NAAG produced no additional inhibition in the presence of H‐89. In contrast, the protein kinase C inhibitor, Ro 31–8220, had no effect on KCl‐stimulated release, nor did it affect the inhibition of release produced by NAAG. The L‐type calcium channel blocker, nifedipine, also inhibited the release of [3H]‐GABA and coapplication with NAAG resulted in no significant additional inhibition of release. These data support the hypothesis that the inhibition of KCl‐stimulated [3H]‐GABA release by NAAG is mediated via presynaptic mGluR3 on GABAergic cortical neurons and that this effect is obtained by decreasing cAMP with a consequent decrease in protein kinase A activity and L‐type calcium channel conductance.