bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transient Ca2+‐permeable AMPA receptors in postnatal rat primary auditory neurons
Authors: Eybalin Michel , Caicedo Alejandro , Renard Nicole , Ruel Jérôme , Puel Jean‐Luc 
Published: December 2004

AbstractFast excitatory transmission in the nervous system is mostly mediated by α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionic acid (AMPA) receptors whose subunit composition governs physiological characteristics such as ligand affinity and ion conductance properties. Here, we report that AMPA receptors at inner hair cell (IHC) synapses lack the GluR2 subunit and are transiently Ca2+‐permeable before hearing onset as evidenced using agonist‐induced Co2+ accumulation, Western blots and GluR2 confocal microscopy in the rat cochlea. AMPA (100 µm) induced Co2+ accumulation in primary auditory neurons until postnatal day (PND) 10. This accumulation was concentration‐dependent, strengthened by cyclothiazide (50 µm) and blocked by GYKI 52466 (80 µm) and Joro spider toxin (1 µm). It was unaffected by D‐AP5 (50 µm), and it could not be elicited by 56 mm K+ or 1 mm NMDA + 10 µm glycine. Western blots showed that GluR1 immunoreactivity, present in homogenates of immature cochleas, had disappeared by PND12. GluR2 immunoreactivity was not detected until PND10 and GluR3 and GluR4 immunoreactivities were detected at all the ages examined. Confocal microscopy confirmed that the GluR2 immunofluorescence was not located postsynatically to IHCs before PND10. In conclusion, AMPA receptors on maturing primary auditory neurons differ from those on adult neurons. They are probably composed of GluR1, GluR3 and GluR4 subunits and have a high Ca2+ permeability. The postsynaptic expression of GluR2 subunits may be continuously regulated by the presynaptic activity allowing for variations in the Ca2+ permeability and physiological properties of the receptor.
Estrogen attenuates antinociception produced by stimulation of Kölliker–Fuse nucleus in the rat
Authors: Nag S. , Mokha S. S. 
Published: December 2004

AbstractThis is the first demonstration of sex‐related differences in the α2‐adrenoceptor‐mediated antinociceptive effects produced by stimulation of an endogenous noradrenergic pathway. Electrical or chemical (substance P) stimulation of Kölliker–Fuse nucleus (KF, A7) is known to produce antinociception mediated by α2‐adrenoceptors in the spinal cord. KF stimulation has also been shown to inhibit the responses of nociceptive neurons in the dorsal horn of the medulla and the spinal cord. We investigated whether KF stimulation produces sex‐specific modulation of trigeminal nociception. The N‐methyl‐d‐aspartic acid (NMDA)‐induced nociceptive behavior was employed as an index of nociception. Microinjection of NMDA (2 nmol/10 µL) in the trigeminal region produced nociceptive scratching behavior that was confined to the orofacial region. Male and ovariectomized (OVX) Sprague–Dawley rats were implanted with a guide cannula dorsal to the KF nucleus and a PE‐10 cannula in the trigeminal region dorsal to obex. Nociceptive testing was conducted after 5–7 days of recovery. A group of ovariectomized rats (OVX+E) was treated with estradiol benzoate 48 h prior to nociceptive testing. There were no significant differences in the number of NMDA‐induced scratches or duration between the male, OVX and OVX+E groups. Microinjection of substance P (3.7 pmol/0.5 µL) in the KF significantly reduced the number of NMDA‐induced scratches and their duration in male and OVX groups; these were restored to control levels by yohimbine (30 µg/15 µL), an α2‐adrenoceptor antagonist. However, KF stimulation failed to inhibit the NMDA‐induced scratching behavior in the OVX+E group. We conclude that stimulation of KF produces estrogen‐dependent modulation of nociception.
Entorhinal cortex contributes to object‐in‐place scene memory
Authors: Charles David P. , Browning Philip G. F. , Gaffan David 
Published: December 2004

AbstractFour rhesus monkeys (Macaca mulatta) were trained preoperatively in a test of object‐in‐place scene memory. They were presented daily with lists of unique computer‐generated scenes each containing a spatial array of multiple individual objects. Within each scene, objects to be discriminated appeared in the foreground, each occupying a unique location, and monkeys were required to correctly discriminate the rewarded object to receive a food reward. Once this preoperative criterion was attained, the monkeys received bilateral entorhinal cortex ablation performed as either one or two surgical operations with a period of testing following each. Postoperatively, they were significantly impaired in learning new object‐in‐place scene problems. These results show that the entorhinal cortex, like anatomically related structures including the perirhinal cortex and the fornix, contributes to object‐in‐place scene learning.
The clock in the dorsal suprachiasmatic nucleus runs faster than that in the ventral
Authors: Noguchi Takako , Watanabe Kazuto , Ogura Akihiko , Yamaoka Sadao 
Published: December 2004

AbstractIn mammals, circadian rhythms are driven by a pacemaker located in the suprachiasmatic nuclei (SCN) of the hypothalamus. The pacemaker is composed of an ensemble of multiple, single‐cell oscillators in the SCN. We measured arginine–vasopressin (AVP) release in organotypic SCN slices. The SCN slice culture showed circadian oscillation of AVP release with a period length (± SEM) of 23.84 ± 00.03 h. This period is very similar to the one we previously reported in dispersed SCN cultures and is also close to that of behavioural rhythms. When the ventral part was removed by a surgical cut across the slice in the horizontal plane, however, the period became shorter (23.22 ± 00.08 h). On the other hand, the removal of the dorsal part did not affect period length. These results suggest that the oscillators in ventral and dorsal cells contribute differently to period length and that the dorsal oscillators are entrained by the ventral ones to form a single integrated oscillator.
Possible role of phosphatidylinositol 4,5, bisphosphate in luteinizing hormone releasing hormone‐mediated M‐current inhibition in bullfrog sympathetic neurons
Authors: Ford Christopher P. , Stemkowski Patrick L. , Smith Peter A. 
Published: December 2004

AbstractLuteinizing hormone releasing hormone (LHRH) is a physiological modulator of neuronal excitability in bullfrog sympathetic ganglia (BFSG). Actions of LHRH involve suppression of the noninactivating, voltage‐dependent M‐type K+ channel conductance (gM). We found, using whole‐cell recordings from these neurons, that LHRH‐induced suppression of gM was attenuated by the phospholipase C (PLC) inhibitor U73122 (10 µm) but not by the inactive isomer U73343 (10 µm). Buffering internal Ca2+ to 117 nm with intracellular 20 mm BAPTA + 8 mm Ca2+ or to < 10 nm with intracellular 20 mm BAPTA + 0.4 mm Ca2+ did not attenuate LHRH‐induced gM suppression. Suppression of gM by LHRH was not antagonized by the inositol 1,4,5 trisphosphate (InsP3) receptor antagonist heparin (∼ 300 µm). Preventing phosphatidylinositol‐4,5‐bisphosphate (PIP2) synthesis by blocking phosphatidylinositol‐4‐kinase with wortmannin (10 µm) or with the nonhydrolysable ATP analogue AMP‐PNP (3 mm) prolonged recovery of LHRH‐induced gM suppression. This effect was not produced by blocking phosphatidyl inositol‐3‐kinase with LY294002 (10 µm). Rundown of gM was attenuated when cells were dialysed with 240 µm di‐octanoyl PIP2 or 240 µm di‐octanoyl phosphatidylinositol‐3,4,5‐trisphosphate (PIP3) but not with 240 µm di‐octanoyl phosphatidylcholine. LHRH‐induced gM suppression was competitively antagonized by dialysis with 240 µm di‐octanoyl PIP2, but not with di‐octanoyl phosphatidylcholine. These results would be expected if LHRH‐induced gM suppression reflects a PLC‐mediated decrease in plasma membrane PIP2 levels.
Feedback control of Purkinje cell activity by the cerebello‐olivary pathway
Authors: Bengtsson F. , Svensson P. , Hesslow G. 
Published: December 2004

AbstractThe pathway from the deep cerebellar nuclei to the inferior olive, the source of the climbing fibre input to the cerebellum, inhibits olivary transmission. As climbing fibre activity can depress the background firing of the Purkinje cells, it was suggested that nucleo‐olivary (N–O) inhibition is a negative feedback mechanism for regulating Purkinje cell excitability. This suggestion was investigated, in a set‐up with decerebrate ferrets, both by blocking and by stimulating cerebellar output while recording Purkinje cell activity. Blocking the N–O pathway was followed by an increased climbing fibre activity and a dramatic reduction in simple spike firing. Stimulation of the N–O fibres depressed climbing fibre responses and caused an increase in simple spike firing. These results are taken as support for the feedback hypothesis.
Myelination triggers local loss of axonal CNR/protocadherinα family protein expression
Authors: Morishita Hirofumi , Kawaguchi Masahumi , Murata Yoji , Seiwa Chika , Hamada Shun , Asou Hiroaki , Yagi Takeshi 
Published: December 2004

AbstractThe cadherin‐related neuronal receptor (CNR)/protocadherin (Pcdh) α family is one of the diverse protocadherin families expressed in developing axons. We observed a strong axonal expression of these proteins at late embryonic and early postnatal stages corresponding to regions where fibers had not yet been myelinated. We therefore followed the postnatal localization of CNR/Pcdhα protein in major axonal tracts, such as the internal capsule, lateral olfactory tract, and optic nerve, and found that its axonal localization was dramatically lost in parallel with the increased expression of myelin markers. Moreover, the hypomyelinated optic nerve tracts of the myelin‐deficient Shiverer mouse exhibited elevated levels of CNR/Pcdhα expression. These axonal expression patterns of CNR/Pcdhα in wild‐type and Shiverer mice were similar to those of growth associated protein 43 (GAP‐43) and L1, both of which are associated with axonal maturation. Thus, myelination may be a trigger for the local loss of axonal CNR/Pcdhα protein, and this process may be important in the maturation of neural circuits.
5‐HT2A and α1b‐adrenergic receptors entirely mediate dopamine release, locomotor response and behavioural sensitization to opiates and psychostimulants
Authors: Auclair Agnès , Drouin Candice , Cotecchia Susanna , Glowinski Jacques , Tassin Jean‐Pol 
Published: December 2004

AbstractAddictive properties of drugs of misuse are generally considered to be mediated by an increased release of dopamine (DA) in the ventral striatum. However, recent experiments indicated an implication of α1b‐adrenergic receptors in behavioural responses to psychostimulants and opiates. We show now that DA release induced in the ventral striatum by morphine (20 mg/kg) is completely blocked by prazosin (1 mg/kg), an α1‐adrenergic antagonist. However, morphine‐induced increases in DA release in the ventral striatum were found to be similar in mice deleted for the α1b‐adrenergic receptor (α1b‐AR KO) and in wild‐type (WT) mice, suggesting the presence of a compensatory mechanism. This acute morphine‐evoked DA release was completely blocked in α1b‐AR KO mice by SR46349B (1 mg/kg), a 5‐HT2A antagonist. SR46349B also completely blocked, in α1b‐AR KO mice, the locomotor response and the development of behavioural sensitization to morphine (20 mg/kg) and d‐amphetamine (2 mg/kg). Accordingly, the concomitant blockade of 5‐HT2A and α1b‐adrenergic receptors in WT mice entirely blocked acute locomotor responses but also the development of behavioural sensitization to morphine, d‐amphetamine or cocaine (10 mg/kg). We observed, nevertheless, that inhibitory effects of each antagonist on locomotor responses to morphine or d‐amphetamine were more than additive (160%) in naïve WT mice but not in those sensitized to either drug. Because of these latter data and the possible compensation by 5‐HT2A receptors for the genetic deletion of α1b‐adrenergic receptors, we postulate the existence of a functional link between these receptors, which vanishes during the development of behavioural sensitization.
Long‐term sensorineural hearing loss induces functional changes in the rat auditory nerve
Authors: Shepherd Robert K. , Roberts Lloyd A. , Paolini Antonio G. 
Published: December 2004

AbstractLoss of cochlear hair cells in the rat initiates degenerative change within the primary auditory neurons (ANs) of the cochlea. These degenerative changes include loss of peripheral processes, demyelination and ultimately cell death. This pathology will affect the biophysical processes involved in action potential generation and propagation to an electrical stimulus via a cochlear implant. We measured the response properties of ANs, with particular reference to their refractory behaviour, in normal, short‐ (9 weeks) and long‐term (> 52 weeks) deafened rats. AN loss was moderate in the short‐term and severe in the long‐term deafened animals. AN activity was elicited using a brief electrical stimulus delivered via a bipolar electrode array implanted into the cochlea. The general response properties of ANs recorded from deafened cochleae were similar to those observed in normal cochleae, i.e. a monotonic increase in the probability of firing and a decrease in response latency and temporal jitter with increasing stimulus intensity. However, the absolute refractory period was significantly prolonged in animals deaf for > 12 months (P = 0.0026). Deafened animals also exhibited a highly significant increase in threshold compared with normal controls (P < 0.001). These functional changes have implications for recipients of cochlear implants and potential therapies directed toward halting or reversing AN pathology.
Attitudes and confidence towards computers and books as learning tools: a cross‐sectional study of student cohorts
Authors: Garland Kate , Noyes Jan 
Published: December 2004

AbstractStudents today comprise a very diverse group, and this will be reflected in their attitudes towards learning. This study set out to examine four different cohorts of UK students during the same time period. Contrary to expectations, it was found that attitudes towards books and computers, as measured by separate but matched scales, were equal, even though experience of the two media varied considerably. A key predictor for computer attitude was found to be confidence for learning from computers rather than general computer confidence. Further, attitudes and confidence towards books and computers as learning tools varied significantly across the four cohorts.
How to structure online discussions for meaningful discourse: a case study
Authors: Gilbert Patricia K. , Dabbagh Nada 
Published: December 2004

AbstractThis study examined the impact of structuredness of asynchronous online discussion protocols and evaluation rubrics on meaningful discourse. Transcripts of twelve online discussions involving 87 participants from four sections of a graduate course entitled Instructional Technology Foundations and Learning Theory were analysed across four semesters. Protocols and evaluation rubrics guiding online discussions in this course ranged from minimal structure or loosely defined protocols in the first section, to high sructure or well defined and comprehensive protocols and evaluation criteria in the fourth section. The analyses revealed that some elements of structure had a significant impact on meaningful discourse. Particularly, guidelines that assisted the facilitation and evaluation of online discussions increased the cognitive quality of student postings promoting a deeper and more meaningful understanding of course content.
Identification of learning styles online by observing learners’ browsing behaviour through a neural network
Authors: Lo Jia‐Jiunn , Shu Pai‐Chuan 
Published: December 2004

AbstractIdentification of individual learning style is important when developing adaptive educational hypermedia systems. Current systems ask learners to complete questionnaires to identify their learning styles, which might not be appropriate in some contexts. The goal of this research is to identify the learner's learning style by simply observing his/her browsing behaviour without asking the learner to answer any questions or filling out any form. It is implemented through a multi‐layer feed forward neural network (MLFF). Browsing behaviour, in this research, includes three factors, the use of embedded support devices (ESDs), the selection of link types, and the navigation between visited/unvisited nodes. The experiment results showed the proposed model performed well in identifying learning styles. Link type is the dominant factor and Time shift may not be a major factor in the identification of learning styles. Because of the fast execution property of neural networks and identification of learning styles online, it is possible to incorporate learning styles into online adaptive educational web‐based systems.
Early calpain‐mediated proteolysis following AMPA receptor activation compromises neuronal survival in cultured hippocampal neurons
Authors: Araújo Inês M. , Verdasca Maria J. , Leal Ermelindo C. , Bahr Ben A. , Ambrósio António F. , Carvalho Arsélio P. , Carvalho Caetana M. 
Published: December 2004

AbstractIn this work, we investigated the involvement of calpains in the neurotoxicity induced by short‐term exposure to kainate (KA) in non‐desensitizing conditions of AMPA receptor activation (cyclothiazide present, CTZ), in cultured rat hippocampal neurons. The calpain inhibitor MDL28170 had a protective effect in cultures treated with KA plus CTZ (p < 0.01), preventing the decrease in MTT reduction caused by exposure to KA (p < 0.001). Caspase inhibition by ZVAD‐fmk was not neuroprotective against the toxic effect of KA. At 1 h after treatment, we could already observe significantly increased calpain activity, which was prevented by MDL 28170 and NBQX. Western blot analysis of calpain substrates, GluR1, neuronal nitric oxide synthase (nNOS) and nonerythroid spectrin (fodrin), showed a time‐dependent and MDL 28170‐sensitive proteolysis of these proteins. This effect was due to calpains, but not caspases, since ZVAD‐fmk was ineffective in preventing proteolytic events. Breakdown products of fodrin (BDPs) were detected as early as 15 min after exposure to KA. Overall, these results show early activation of calpains following activation of AMPA receptors as well as compromise of neuronal survival, likely due to proteolytic events that affect proteins involved in neuronal signaling.
Expression profiling upon Nex1/MATH‐2‐mediated neuritogenesis in PC12 cells and its implication in regeneration
Authors: Uittenbogaard Martine , Chiaramello Anne 
Published: December 2004

AbstractThe expression of Nex1 peaks during brain development when neurite outgrowth and synaptogenesis are highly active. We previously showed that Nex1 is a critical effector of the nerve growth factor (NGF) pathway and its overexpression results in spontaneous neuritogenesis. Furthermore, the PC12‐Nex1 cells exhibit accelerated neurite extension upon NGF exposure, and have the capacity to regenerate neurites in the absence of NGF. In this study, we identify the repertoire of genes targeted by Nex1 to unravel the molecular mechanisms by which Nex1 promotes differentiation and regeneration. Our transcriptional analysis reveals that Nex1 modulates a wide spectrum of genes with diverse functions, many of them being key downstream regulators of the NGF pathway, and critical to neuritogenesis, such as microtubules, microtubule‐associated proteins (MAPs) and intermediate filaments. We also provide the first evidence that a basic helix‐loop‐helix (bHLH) protein stimulates the expression of the cyclin‐dependent kinase (CDK) inhibitors belonging to the INK4 family, which plays a role in promoting cell‐cycle arrest. Finally, we show a dramatic synergistic effect between Nex1 and cAMP, resulting in an impressive regeneration of an elaborate and dense neurite network. Thus, Nex1 has endowed the PC12‐Nex1 cells with a distinct combination of gene products that takes part in the complex regulation of neuritogenesis and regeneration.
Intracellularly generated amyloid‐β peptide counteracts the antiapoptotic function of its precursor protein and primes proapoptotic pathways for activation by other insults in neuroblastoma cells
Authors: Esposito Luke , Gan Li , Yu Gui‐Qiu , Essrich Christian , Mucke Lennart 
Published: December 2004

AbstractMost mutations in amyloid precursor proteins (APPs) linked to early onset familial Alzheimer's disease (FAD) increase the production of amyloid‐β peptides ending at residue 42 (Aβ42), which are released from APP by β‐ and γ‐secretase cleavage. Stably transfected cells expressing wild‐type human APP (APPWT) were more resistant to apoptosis‐inducing treatments than cells expressing FAD‐mutant human APP (APPFAD). Preventing Aβ42 production with an M596I mutation (β–), which blocks β‐secretase cleavage of APP, or by treatment with a γ‐secretase inhibitor increased the resistance of APPFAD‐expressing cells to apoptosis. Exposing hAPPFAD/β– cells to exogenous Aβ42 or conditioned medium from Aβ42‐producing APPFAD cells did not diminish their resistance to apoptosis. Preventing APP from entering the distal secretory pathway, where most Aβ peptides are generated, by retaining APP in the endoplasmic reticulum (ER)/intermediate compartment (IC) increased the resistance of APPFAD‐expressing cells to apoptosis and did not alter the resistance of APPWT‐expressing cells. p53‐mediated gene transactivation after apoptosis‐inducing treatments was much stronger in APPFAD cells than in hAPPWT or hAPPFAD/β– cells. In contrast, upon induction of ER stress, cells expressing APPFAD, hAPPFAD/β–, or APPWT had comparable levels of glucose‐regulated protein‐78 mRNA, an unfolded protein response indicator. We conclude that Aβ, especially intracellular Aβ, counteracts the antiapoptotic function of its precursor protein and predisposes cells to p53‐mediated, and possibly other, proapoptotic pathways.
Apolipoprotein E isoforms and apolipoprotein AI protect from amyloid precursor protein carboxy terminal fragment‐associated cytotoxicity
Authors: Maezawa Izumi , Jin Lee‐Way , Woltjer Randall L. , Maeda Nobuyo , Martin George M. , Montine Thomas J. , Montine Kathleen S. 
Published: December 2004

AbstractInheritance of the apolipoprotein (APO) E gene ɛ4 or ɛ2 allele alters the risk of developing Alzheimer disease (AD), while increased alpha‐tocopherol (AT) intake appears to lower the risk of AD. As APOE is a major apolipoprotein in the CNS and AT in vivo is transported in lipoproteins, we tested the hypothesis that CNS lipoproteins, as modeled by relevant concentrations of high density lipoprotein (HDL), and AT would interact to suppress neurotoxicity in a cell culture model of amyloid beta (Aβ)‐ related toxicity. These cells conditionally express C99‐derived peptides, proposed to be a key step in AD pathogenesis; this expression is closely associated with subsequent cell death. We found that physiologic concentrations of lipoproteins present in the CNS protected from C99‐associated toxicity and provided evidence for two mechanisms of protection. The first was AT‐independent, APOE isoform‐dependent, and most potent for the APOE2 isoform. The second was a synergistic protection afforded by a combination of APOAI, or less so APOE, and AT. These data provide a novel explanation for the apparent AD‐protective effect of inheriting an ɛ2 APOE allele, and suggest that optimizing AT enrichment of CNS lipoproteins or devising APOAI mimetics may augment AT efficacy in treating AD.