bluuebunny/crossref_metadata_2025_split huggingface dataset:
Light‐ and clock‐dependent regulation of ribosomal S6 kinase activity in the suprachiasmatic nucleus
Authors: Butcher Greg Q. , Lee Boyoung , Hsieh Fortune , Obrietan Karl 
Published: February 2004

AbstractRecent work has revealed that signalling via the p42/44 mitogen‐activated protein kinase (MAPK) pathway couples light to entrainment of the circadian clock located in the suprachiasmatic nucleus (SCN). Given that many effects of the MAPK pathway are mediated by intermediate kinases, it was of interest to identify kinase targets of ERK in the SCN. One potential target is the family of 90‐kDa ribosomal S6 kinases (RSKs). In this study, we examined light‐induced regulation of RSK‐1 in the SCN. Immunohistochemical and Western analysis were used to show that photic stimulation during the early and late night triggered the phosphorylation of RSK‐1 at two sites that are targeted by ERK. This increase in the phosphorylation state of RSK‐1 corresponded with an approximate fourfold increase in kinase activity. Light exposure during the subjective day did not increase the phosphorylated form of RSK‐1, indicating that the capacity of light to stimulate RSK‐1 activation is phase‐restricted. Double immunofluorescent labelling of SCN tissue revealed the colocalized expression of the activated form of ERK with the phosphorylated form of RSK‐1 following a light pulse. In vivo pharmacological inhibition of light‐induced MAPK pathway activation blocked RSK‐1 phosphorylation, indicating that RSK‐1 activity is regulated by the MAPK pathway. PDK‐1, a coregulator of RSK‐1, is also expressed in the SCN and is likely to contribute to RSK‐1 activity. RSK‐1 phosphorylation was also rhythmically regulated within a subset of phospho‐ERK‐expressing cells. Together these results identify RSK‐1 as a light‐ and clock‐regulated kinase and raise the possibility that it contributes to entrainment and timing of the circadian pacemaker.
Neuron–glial trafficking of NH4+ and K+: separate routes of uptake into glial cells of bee retina
Authors: Marcaggi Païkan , Jeanne Marion , Coles Jonathan A. 
Published: February 2004

AbstractAmmonium (NH4+ and/or NH3) and K+ are released from active neurons and taken up by glial cells, and can modify glial cell behaviour. Study of these fluxes is most advanced in the retina of the honeybee drone, which consists essentially of identical neurons (photoreceptors) and identical glial cells (outer pigment cells). In isolated bee retinal glial cells, ammonium crosses the membrane as NH4+ on a Cl− cotransporter. We have now investigated, in the more physiological conditions of a retinal slice, whether the NH4+‐Cl− cotransporter can transport K+ and whether the major K+ conductance can transport NH4+. We increased [NH4+] or [K+] in the superfusate and monitored uptake by recording from the glial cell syncytium or from interstitial space with microelectrodes selective for H+ or K+. In normal superfusate solution, ammonium acidified the glial cells but, after 6 min superfusion in low [Cl−] solution, ammonium alkalinized them. In the same low [Cl−] conditions, the rise in intraglial [K+] induced by an increase in superfusate [K+] was unchanged, i.e. no K+ flux on the Cl− cotransporter was detected. Ba2+ (5 mm) abolished the glial depolarization induced by K+ released from photoreceptors but did not reduce NH4+uptake. We estimate that when extracellular [NH4+] is increased, 62–100% is taken up by the NH4+‐Cl− cotransporter and that when K+ is increased, 77–100% is taken up by routes selective for K+. This separation makes it possible that the glial uptake of NH4+ and of K+, and hence their signalling roles, might be regulated separately.
Bombesin/gastrin‐releasing peptide receptors in the basolateral amygdala regulate memory consolidation
Authors: Roesler Rafael , Lessa Daniela , Venturella Roberta , Vianna Mônica R. M. , Luft Tatiana , Henriques João Antônio Pegas , Izquierdo Ivan , Schwartsmann Gilberto 
Published: February 2004

AbstractSeveral receptor and intracellular signalling systems in the basolateral amygdala (BLA) regulate memory formation. In the present study, we show that bombesin/gastrin‐releasing peptide (GRP) receptors in the BLA are involved in the consolidation of affectively motivated memory. Adult male rats were trained in a single‐trial step‐down inhibitory avoidance task and tested for retention 24 h later. Post‐training systemic injection of the bombesin/GRP receptor antagonist (D‐Tpi6, Leu13 psi[CH2NH]‐Leu14) bombesin (6–14) (RC‐3095) impaired memory retention. In rats implanted under thionembutal anaesthesia with guide cannulae aimed at the BLA, post‐training bilateral infusion of RC‐3095 into the BLA dose‐dependently impaired retention. Pre‐training unilateral muscimol inactivation of the BLA blocked the memory‐impairing effect of post‐training systemic administration of RC‐3095. The results suggest that bombesin/GRP receptors in the BLA are involved in the consolidation of aversive memory, and the BLA mediates the memory‐impairing effect of systemic bombesin/GRP receptor blockade.
Modulation of oscillatory brain activity and evoked potentials in a repetition priming task in the human EEG
Authors: Gruber Thomas , Malinowski Peter , Müller Matthias M. 
Published: February 2004

AbstractCortical object representations seem to require the formation of neural cell assemblies. The physiological correlate of cell assembly activity may be seen in synchronized neural activity in the gamma band range. The improvement in perceiving and identifying an object by experience is commonly referred to as repetition priming. One possible neural mechanism for repetition priming is ‘repetition suppression’ within a cell assembly coding the stimulus. The present electroencephalogram study was designed to investigate oscillatory brain activity when line drawings of concrete objects were repeated either immediately after a first presentation or after intervening a number of different stimuli. Results showed a broad posterior distribution of induced gamma band responses (GBRs) after the initial picture presentation. Repeated presentations of the same picture led to a significant decrease of induced gamma power. Furthermore, repeated presentations of the same object resulted in a decrease in phase synchrony between distant electrode sites. No significant repetition effects were found in the alpha or beta frequency range. The event‐related potential (ERP), which was also modulated by priming, showed a different scalp distribution compared with induced GBRs. In addition, ERP repetition effects decayed at larger intervals between initial and repeated presentations, whereas induced GBRs were not modulated as a function of stimulus lag. We concluded that the decrease in amplitude of induced GBRs and the reduction of gamma phase synchrony between pairs of electrodes after repeated picture presentations might be linked to a ‘sharpening’ mechanism within a cell assembly representing an object.
Nitric oxide acts as a slow‐down and search signal in developing neurites
Authors: Trimm Kevin R. , Rehder Vincent 
Published: February 2004

AbstractNitric oxide (NO) has been demonstrated to act as a signaling molecule during neuronal development, but its precise function is unclear. Here we investigate whether NO might function at the neuronal growth cone to affect growth cone motility. We have previously demonstrated that growth cones of identified neurons from the snail Helisoma trivolvis show a rapid and transient increase in filopodial length in response to NO, which was regulated by soluble guanylyl cyclase (sGC) [S. Van Wagenen and V. Rehder (1999) J. Neurobiol., 39, 168–185]. Because in vivo studies have demonstrated that growth cones have longer filopodia and advance more slowly in regions where pathfinding decisions are being made, this study aimed to establish whether NO could function as a combined ‘slow‐down and search signal’ for growth cones by decreasing neurite outgrowth. In the presence of the NO donor NOC‐7, neurites of B5 neurons showed a concentration‐dependent effect on neurite outgrowth, ranging from slowing at low, stopping at intermediate and collapsing at high concentrations. The effects of the NO donor were mimicked by directly activating sGC with YC‐1, or by increasing its product with 8‐bromo‐cGMP. In addition, blocking sGC in the presence of NO with NS2028 blocked the effect of NO, suggesting that NO affected outgrowth via sGC. Ca2+ imaging of growth cones with Fura‐2 indicated that [Ca2+]i increased transiently in the presence of NOC‐7. These results support the hypothesis that NO can function as a potent slow/stop signal for developing neurites. When coupled with transient filopodia elongation, this phenomenon emulates growth cone searching behavior.
Left and right superior parietal lobule in tactile object discrimination
Authors: Stoeckel M. C. , Weder B. , Binkofski F. , Choi H.‐J. , Amunts K. , Pieperhoff P. , Shah N. J. , Seitz R. J. 
Published: February 2004

AbstractTactile object discrimination is one of the major manual skills of humans. While the exploring finger movements are not perceived explicitly, attention to the movement‐evoked kinaesthetic information gates the tactile perception of object form. Using event‐related functional magnetic resonance imaging in seven healthy subjects we found one area in the right superior parietal cortex, which was specifically activated by kinaesthetic attention during tactile object discrimination. Another area with similar location in the left hemisphere was related to the maintenance of tactile information for subsequent object discrimination. We conclude that kinaesthetic information is processed in the anterior portion of the superior parietal cortex (aSPL) with a right hemispheric predominance for discrimination and a left hemispheric predominance for information maintenance.
Cocaine‐induced vs. behaviour‐related alterations of spontaneous and evoked discharge of somatosensory cortical neurons
Authors: Drouin Candice , Waterhouse Barry D. 
Published: February 2004

AbstractWhile the abuse potential of cocaine stems mainly from its ability to increase dopaminergic transmission in limbic regions, drug actions on other monoamine‐innervated circuits may contribute to the development and maintenance of cocaine addiction. Previous extracellular recordings in anaesthetized rats revealed a facilitatory influence of cocaine on primary sensory pathways, which could influence the processing of drug‐related stimuli during the development of cocaine addiction. We further analysed these sensory effects of cocaine in freely behaving rats (n = 9). Using an array of eight microelectrodes chronically implanted in infragranular layers of primary somatosensory cortex, we recorded the basal activity of 40 single‐ and 64 multiunits and their response to electrical stimulation of the whisker pad before and after incremental doses of cocaine (0.25–2 mg/kg i.v.). Both spontaneous and cocaine‐induced explorations were associated with elevated basal firing of the cortical neurons and suppression of their short‐latency excitation and postexcitatory inhibition in response to the whisker‐pad stimulation. In addition to exploration‐related alterations, the administration of cocaine enhanced the long‐latency rebound excitation induced by the whisker‐pad stimulation. This component of the sensory response, which is more labile and does not seem to convey information about the physical characteristics of the stimulus, may participate in the processing of drug‐related sensory stimuli.
GAP‐43 overexpression in adult mouse Purkinje cells overrides myelin‐derived inhibition of neurite growth
Authors: Gianola Sara , Rossi Ferdinando 
Published: February 2004

AbstractUp‐regulation of growth‐associated proteins in adult neurons promotes axon regeneration and neuritic elongation onto nonpermissive substrates. To investigate the interaction between these molecules and myelin‐related inhibitory factors, we examined transgenic mice in which overexpression of the growth‐associated protein GAP‐43 is driven by the Purkinje cell‐specific promoter L7. Contrary to their wild‐type counterparts, which have extremely poor regenerative capabilities, axotomized transgenic Purkinje cells exhibit profuse sprouting along the intracortical neurite and at the severed stump [Buffo et al. (1997) J. Neurosci., 17, 8778–8791]. Here, we investigated the relationship between such sprouting axons and oligodendroglia to ask whether GAP‐43 overexpression enables Purkinje neurites to overcome myelin‐derived inhibition. Intact transgenic Purkinje axons display normal morphology and myelination. Following injury, however, many GAP‐43‐overexpressing neurite stumps are devoid of myelin cover and sprout into white matter regions containing densely packed myelin and Nogo‐A‐ or MAG‐immunopositive oligodendrocytes. The intracortical segments of these neurites show focal accumulations of GAP‐43, which are associated with disrupted or retracted myelin sheaths. Numerous sprouts originate from such demyelinated segments and spread into the granular layer. Some myelin loss, though not axon sprouting, is also evident in wild‐type mice, but this phenomenon is definitely more rapid and extensive in transgenic cerebella. Thus, GAP‐43‐overexpressing Purkinje axons are endowed with enhanced capabilities for growing into nonpermissive territories and show a pronounced tendency to lose myelin. Our observations suggest that accumulation of GAP‐43 along precise axon segments disrupts the normal axon–glia interaction and enhances the retraction of oligodendrocytic processes to facilitate the outgrowth of neuritic sprouts.
Enhancement of steady‐state auditory evoked magnetic fields in tinnitus
Authors: Diesch Eugen , Struve Maren , Rupp Andre , Ritter Steffen , Hülse Manfred , Flor Herta 
Published: February 2004

AbstractThe steady‐state auditory evoked magnetic field and the Pbm, the magnetic counterpart of the second frontocentrally positive middle latency component of the transitory auditory evoked potential, were measured in ten tinnitus patients using a 122‐channel gradiometer system. The patients had varying degrees of hearing loss. In all patients, the tinnitus frequency was located above the frequency of the audiometric edge, i.e. the location on the frequency axis above which hearing loss increases more rapidly. Stimuli were amplitude‐modulated sinusoids with carrier frequencies at the tinnitus frequency, the audiometric edge, two frequencies below the audiometric edge, and two frequencies between the audiometric edge and the tinnitus frequency. Below the audiometric edge, the root‐mean‐square field amplitude of the steady‐state response computed across the whole head as well as the contralateral and the ipsilateral dipole moment decreased as a function of carrier frequency. With carrier frequency above the audiometric edge, the steady‐state response increased again. The amplitudes of the transitory Pbm component were patterned in a qualitatively similar way, but without the differences being significant. For the steady‐state response, both whole‐head root‐mean‐square field amplitude and the dipole moment of the sources at the tinnitus frequency showed significant positive correlations with subjective ratings of tinnitus intensity and intrusiveness. These correlations remained significant when the influence of hearing loss was partialled out. The observed steady‐state response amplitude pattern likely reflects an enhanced state of excitability of the frequency region in primary auditory cortex above the audiometric edge. The relationship of tinnitus to auditory cortex hyperexcitability and its independence of hearing loss is discussed with reference to loss of surround inhibition in and map reorganization of primary auditory cortex.
Second messenger cascade of glial responses evoked by interneuron activity and by a myomodulin peptide in the leech central nervous system
Authors: Britz Frank C. , Hirth Ingolf C. , Deitmer Joachim W. 
Published: February 2004

AbstractThe giant glial cell in the neuropil of segmental ganglia of the leech Hirudo medicinalis responds to the activity of the Leydig interneuron and to a peptide of the myomodulin family, the presumed transmitter mediating the Leydig neuron‐to‐giant glial cell transmission, with a membrane hyperpolarization due to an increased membrane K+ conductance [Britz et al. (2002) Glia, 38, 215–227]. We have now studied the second messenger cascade initiated by Leydig neuron stimulation and by the endogenous myomodulin (MMHir) in the voltage‐clamped giant glial cell. Glial responses to both stimuli are mediated by a G‐protein‐coupled receptor linked to adenylyl cyclase by the following criteria: (i) injection of GDP‐β‐S, but not GDP, resulted in an irreversible decrease of the glial responses to both stimuli; (ii) the responses to both stimuli were reversibly inhibited by the adenylyl cyclase inhibitor SQ22,536; and (3) bath‐applied di‐butyryl‐cyclic AMP, but not di‐butyryl‐cyclic GMP, elicited an outward current, which reduced the responses elicited by neuronal stimulation or myomodulin. A cocktail of protein kinase (PK) inhibitors (H‐8, KT5720), the PKA antagonist Rp‐cAMPS, or presumed inhibitors of cyclic nucleotide channels, LY83583 and l‐cis‐diltiazem, had no effect on the glial responses. Our results suggest that Leydig neuron stimulation and MMHir activate a cAMP‐mediated K+ conductance in the glial cell, which appeared neither to be due to the activation of PKA nor of known cyclic nucleotide‐gated channels directly.
Adaption of the serotoninergic neuronal phenotype in the absence of 5‐HT autoreceptors or the 5‐HT transporter: involvement of BDNF and cAMP
Authors: Rumajogee Prakasham , Vergé Daniel , Hanoun Naïma , Brisorgueil Marie‐Jeanne , Hen René , Lesch Klaus‐Peter , Hamon Michel , Miquel Marie‐Christine 
Published: February 2004

AbstractSerotonin 5‐HT1A and 5‐HT1B receptors and the 5‐HT transporter are key regulators of the serotoninergic neuronal phenotype. We show here that genetic deletion of any of these elements differentially regulates 5‐HT neuronal number in rostral raphe cultures from E14 mice. Serotonin neuronal number was increased by almost four‐fold and 1.8‐fold in cultures from 5‐HT1AR−/− and 5‐HT1BR−/− mice, respectively. In contrast, the lack of serotonin transporter expression was associated with a 50% decrease in 5‐HT neuronal number. In raphe cultures from the rat, BDNF and cAMP have been shown to up‐regulate the neuronal serotoninergic phenotype through TrkB‐dependent mechanisms [Rumajogee et al. (2002) J. Neurochem., 83, 1525–1528]. Similar tyrosine kinase‐dependent up‐regulating effects, in the absence of serotoninergic key‐elements are reported here, on both 5‐HT neuronal number and neurites length. However, the extents of BDNF‐triggered and cAMP‐triggered effects on serotoninergic neuritic length were approximately 1.5‐fold higher in 5‐HT1AR−/− mutants. These findings show that the up‐regulatory mechanisms triggered by BDNF on serotoninergic neuronal number and neurite extension are different and that the latter are partially linked to 5‐HT, probably through 5‐HT1A autoreceptors. Together, these data suggest that serotonin autoreceptors, mainly 5‐HT1A but also 5‐HT1B, may be responsible for a tonic auto‐inhibitory effect of 5‐HT itself on the serotoninergic neuronal phenotype during embryonic development, particularly marked in the absence of the 5‐HT transporter.
Somatodendritic localization of the mRNA for EFA6A, a guanine nucleotide exchange protein for ARF6, in rat hippocampus and its involvement in dendritic formation
Authors: Sakagami Hiroyuki , Matsuya Shigetsune , Nishimura Hideki , Suzuki Ryoji , Kondo Hisatake 
Published: February 2004

AbstractEFA6A is a guanine nucleotide exchange protein (GEP) that can specifically activate ADP‐ribosylation factor 6 (ARF6) in vitro. A recent study has demonstrated that ARF6 is involved in the dendritic formation of developing hippocampal neurons [Hernandez‐Deviez et al. (2002) Nature Neurosci., 5, 623–624]. This study examined a potential role for EFA6A in hippocampal development in Wistar rats. Our results provided definitive evidence for somatodendritic localization of EFA6A mRNA in both cultured and in vivo hippocampal neurons by nonradioactive in situ hybridization. During postnatal development, EFA6A mRNA was dramatically increased and its dendritic localization was most evident between P7 and P14. In contrast, ARF6 mRNA was confined to the neuronal layers of the hippocampus throughout development. In addition, the overexpression of a GEP‐defective mutant of EFA6A enhanced the dendritic formation of the primary hippocampal neurons. The present findings suggest that EFA6A is intimately involved in the regulation of the dendritic development of hippocampal neurons.
Activation of P‐type calcium channel regulates a unique thapsigargin‐sensitive calcium pool in embryonic motoneurons
Authors: Scamps Frédérique , Roig Anne , Boukhaddaoui Hassan , André Sylvain , Puech Sylvie , Valmier Jean 
Published: February 2004

AbstractBy regulating voltage‐dependent Ca2+ influx and intracellular Ca2+ homeostasis, electrical activity plays a central role in motoneuron development. Dissociated cultures of purified embryonic rat motoneurons were used to explore the molecular mechanisms by which Ca2+ influx control [Ca2+]i transients in these neurons. Thapsigargin (250 nm) and cyclopiazonic acid (10 µm), which deplete Ca2+ stores in the endoplasmic reticulum, decrease by 30% the depolarization‐induced [Ca2+]i transients in motoneurons without affecting voltage‐activated calcium currents. This thapsigargin‐sensitive intracellular Ca2+ pool differs from other previous described Ca2+ stores that are sensitive to ryanodine or caffeine, inositol triphosphate, insulin and from mitochondrial Ca2+ pools. Thapsigargin affected the Cav2.1 P‐type Ca2+ channel component of the depolarization‐induced [Ca2+]i transient in motoneurons but spared [Ca2+]i transient induced by Cav1 L‐type and Cav2.2 N‐type Ca2+ channel components, suggesting a close functional relationship between Cav2.1 subunit and this unique thapsigargin‐sensitive Ca2+ store. Altogether the present results demonstrate a new pathway, used by embryonic motoneurons, to regulate Ca2+ signalling through voltage‐activated (Cav2.1) Ca2+ channels.
Endothelins regulate astrocyte gap junctions in rat hippocampal slices
Authors: Blomstrand F. , Venance L. , Sirén A.‐L. , Ezan P. , Hanse E. , Glowinski J. , Ehrenreich H. , Giaume C. 
Published: February 2004

AbstractGap junctional communication (GJC) is a typical feature of astrocytes proposed to contribute to the role played by these glial cells in brain physiology and pathology. In acutely isolated hippocampal slices from rat (P11–P19), intercellular diffusion of biocytin through gap junction channels was shown to occur between hundreds of cells immuno‐positive for astrocytic markers studied in the CA1/CA2 region. Single‐cell RT‐PCR demonstrated astrocytic mRNA expression of several connexin (Cx) subtypes, the molecular constituent of gap junction channels, whereas immunoblotting confirmed that Cx43 and Cx30 are the main gap junction proteins in hippocampal astrocytes. In the brain, astrocytes represent a major target for endothelins (Ets), a vasoactive family of peptides. Our results demonstrate that Ets decrease the expression of phosphorylated Cx43 forms and are potent inhibitors of GJC. The Et‐induced effects were investigated using specific Et receptor agonists and antagonists, including Bosentan (Tracleer™), an EtA/B receptor antagonist, and using hippocampal slices and cultures from EtB‐receptor‐deficient rats. Interestingly, the pharmacological profile of Ets effects did not follow the classical profile established in cardiovascular systems. The present study therefore identifies Ets as potent endogenous inhibitory regulators of astrocyte networks. As such, the action of these peptides on astrocyte GJC might be involved in the contribution of astrocytes to neuroprotective processes and have a therapeutic potential in neuropathological situations.