bluuebunny/crossref_metadata_2025_split huggingface dataset:
Properties of LTD and LTP of retinocollicular synaptic transmission in the developing rat superior colliculus
Authors: Lo Fu‐Sun , Mize R. Ranney 
Published: March 2003

AbstractThe developing retinocollicular pathway undergoes synaptic refinement in order to form the precise retinotopic pattern seen in adults. To study the mechanisms which underlie refinement, we investigated long‐term changes in retinocollicular transmission in rats aged P0–P25. Field potentials (FPs) in the superior colliculus (SC) were evoked by stimulation of optic tract fibers in an in vitro isolated brainstem preparation. High intensity stimulation induced long‐term depression (LTD) in the SC after both low (1000 stimuli at 1 Hz) and higher (1000 stimuli at 50 Hz) frequency stimulation. The induction of LTD was independent of activation of NMDA and GABAA receptors, because d‐APV (100 µM) and bicuculline (10 µM) did not block LTD. Induction of LTD was dependent upon activation of l‐type Ca2+ channels as 10 µM nitrendipine, an l‐type Ca2+ channel blocker, significantly decreased the magnitude of LTD. LTD was down‐regulated during development. LTD magnitude was greatest in rats aged P0–P9 and significantly less in rats aged P10–P25. Long‐term potentiation (LTP) was induced by low intensity stimulation and only after high frequency tetanus (1000 stimuli at 50 Hz). LTP was NMDA receptor dependent because d‐APV (100 μM) completely abolished it. LTP induction was also blocked by the l‐type Ca2+ channel blocker nitrendipine. The magnitude of LTP first increased with age, being significantly greater at P7–P13 than at P0–3 and then decreased at P23–25. In summary, both LTD and LTP are present during retinocollicular pathway refinement, but have different transmitter and ionic mechanisms and time courses of expression.
Increased vulnerability to kainate‐induced seizures in utrophin‐knockout mice
Authors: Knuesel Irene , Riban Véronique , Zuellig Richard A. , Schaub Marcus C. , Grady R. Mark , Sanes Joshua R. , Fritschy Jean‐Marc 
Published: March 2003

AbstractUtrophin, the autosomal homologue of dystrophin, the Duchenne muscular dystrophy gene product, is a cytoskeletal protein found in many tissues. In muscle fibers, the level and localization of utrophin depend on their state of differentiation and innervation. Transgenic overexpression of utrophin prevents degeneration of dystrophin‐deficient muscle fibers. In brain, in addition to its enrichment in blood vessels, utrophin is associated primarily with the plasma membrane of large sensory and motor brainstem neurons, suggesting a contribution to their structural stability. Here, we examined the role of utrophin for long‐term survival of dentate granule cells, which become markedly hypertrophic in a mouse model of temporal lobe epilepsy. This morphogenetic change is induced several weeks after a unilateral intrahippocampal injection of kainic acid (KA), while mice experience chronic focal seizures. Using in situ hybridization and immunohistochemistry, we show that dispersion and hypertrophy of granule cells in KA‐treated wildtype mice are accompanied by a strong and long‐lasting expression of utrophin in somata and proximal dendrites. Utrophin knockout mice had a normal hippocampal cytoarchitecture but were more sensitive to KA‐induced excitotoxicity, as shown by increased mortality and faster progression of the lesion. At 6 weeks post‐KA, the numerical density of granule cells and thickness of the granule cell layer were significantly reduced ipsilaterally in mutant mice, indicating a profound reduction in total cell number in the absence of utrophin. These findings suggest that utrophin contributes to protect CNS neurons against pathological insults, in particular, stimuli leading to massive neuronal hypertrophy.
PACAP protects cerebellar granule neurons against oxidative stress‐induced apoptosis
Authors: Vaudry D. , Pamantung T. F. , Basille M. , Rousselle C. , Fournier A. , Vaudry H. , Beauvillain J. C. , Gonzalez B. J. 
Published: March 2003

AbstractOxidative stress, resulting from accumulation of reactive oxygen species, plays a critical role in neuronal cell death associated with neurodegenerative diseases and stroke. In the present study, we have investigated the potential neuroprotective effect of pituitary adenylate cyclase‐activating polypeptide (PACAP) on oxidative stress‐induced apoptosis. Incubation of cerebellar granule cells with PACAP inhibited hydrogen peroxide‐evoked cell death in a concentration‐dependent manner. The effect of PACAP on granule cell survival was not mimicked by vasoactive intestinal polypeptide and was blocked by the antagonist PACAP6‐38. The protective action of PACAP upon hydrogen peroxide‐induced neuronal cell death was abolished by the MAP‐kinase kinase (MEK) inhibitor U0126 and mimicked by the caspase‐3 inhibitor Z‐DEVD‐FMK. PACAP markedly inhibited hydrogen peroxide‐evoked caspase‐3 activation and DNA fragmentation. Taken together, these data indicate that PACAP, acting through PACAP receptor type 1, exerts a potent protective effect against neuronal degeneration induced by hydrogen peroxide. The anti‐apoptotic effect of PACAP is mediated through the MAP‐kinase pathway and can be accounted for by inhibition of caspase‐3 activation resulting from oxidative stress.
Downregulation of P2X3 receptor‐dependent sensory functions in A/J inbred mouse strain
Authors: Tsuda Makoto , Shigemoto‐Mogami Yukari , Ueno Shinya , Koizumi Schuichi , Ueda Hiroshi , Iwanaga Toshihiko , Inoue Kazuhide 
Published: March 2003

AbstractThere is large variability in the various pain responses including those to tissue injury among inbred mouse strains. However, the determinant factors for the strain‐specific differences remain unknown. The P2X3 sensory‐specific ATP‐gated channel has been implicated as a damage‐sensing molecule that evokes a pain sensation by receiving endogenous ATP from injured tissue. In this study, to clarify the contribution of the sensory P2X3 signalling to strain‐specific differences in tissue injury pain, we examined whether the P2X3‐mediated in vivo and in vitro responses in dorsal root ganglion (DRG) neurons are changed in the A/J inbred mouse strain, which is known to be resistant to tissue injury pain caused by formalin. Here we found that A/J mice exhibited a low magnitude of nocifensive behaviour induced by the P2X agonist α,β‐methylene ATP (αβmeATP) into the hindpaw compared with C57BL/6 J mice. This behaviour was blocked by P2X3 antisense oligodeoxynucleotides. The low magnitude of the in vivo pain sensation could be observed similarly in the in vitro response; the increase in the intracellular Ca2+ increase by αβmeATP in capsaicin‐sensitive DRG neurons from A/J mice was significantly lower than that from C57BL/6 J mice. In A/J DRG neurons the P2X3 protein level was significantly lower compared with C57BL/6 J DRG neurons. The change in P2X3 protein was selective because P2X2 protein was expressed equally in both strains. The present study suggests that the downregulation of sensory P2X3 could be one of the molecular predispositions to low sensitivity to tissue injury pain in the A/J inbred mouse strain.
Expression and immunohistochemical localization of heparan sulphate proteoglycan N‐syndecan in the migratory pathway from the rat olfactory placode
Authors: Toba Yoko , Horie Masao , Sango Kazunori , Tokashiki Akiko , Matsui Fumiko , Oohira Atsuhiko , Kawano Hitoshi 
Published: March 2003

AbstractN‐syndecan, a membrane‐bound heparan sulphate proteoglycan, is abundantly present in the developing nervous system and thought to play important roles in the neurite outgrowth. In the present study, we examined the distribution of N‐syndecan in the migratory route from the rat olfactory placode using immunohistochemistry and in situ hybridization. At embryonic day 15, both heparan sulphate and N‐syndecan immunoreactivities were localized in and around the migrating cell clusters, which contained luteinizing hormone‐releasing hormone (LHRH) and calbindin D‐28k. Immunoreactivity for other glycosaminoglycan chains, such as chondroitin and keratan sulphate, and core proteins of the chondroitin sulphate proteoglycan, neurocan and phosphacan, were barely detected in the migratory pathway from the olfactory placode. By in situ hybridization histochemistry, N‐syndecan mRNA was localized in virtually all of migrating neurons as well as in cells of the olfactory epithelium and the vomeronasal organ. N‐syndecan immunoreactivity surrounded cells migrating along the vomeronasal nerves that were immunoreactive for neural cell adhesion molecules, NCAM, L1 and TAG‐1. Considering that NCAM is implicated in the migratory process of LHRH neurons and specifically binds to heparan sulphate, it is likely that a heterophilic interaction between NCAM and N‐syndecan participates in the neuronal migration from the rat olfactory placode.
Second phase of formalin‐induced excitation of spinal dorsal horn neurons in spinalized rats is reversed by sciatic nerve block
Authors: Pitcher Graham M. , Henry James L. 
Published: March 2003

AbstractConsiderable debate persists concerning peripheral vs. central mechanisms underlying the second phase of the nociceptive response in the formalin test in the rat. To gain insight into the neurophysiological basis of this pain, we investigated the effects of block of afferent nerve conduction during the second phase of formalin‐evoked excitation of single nociceptive neurons recorded extracellularly from rat spinal dorsal horn segments (L3−4) in pentobarbital‐anaesthetized, male Sprague–Dawley rats. Rats were spinally transected (T9) to examine exclusively peripheral and spinal nociceptive processing. In six control rats, hind paw intraplantar formalin injection (50 µL, 2.5%) induced the typical biphasic increase in the discharge rate of the six wide dynamic range neurons tested. This response consisted of a relatively brief immediate phase (approximately 5 min), followed by decreased firing. An ensuing second phase of elevated discharge began approximately 35 min after injection and persisted to at least 80 min. In this control group, 0.9% saline was applied to the exposed ipsilateral sciatic nerve after onset of the second phase (40 min after formalin injection). In a group of six test rats, application of 2% lidocaine instead of saline reversed the second phase of excitation in all six wide dynamic range neurons examined. When the firing rate was normalized to that at 40 min (100%), the time of saline or lidocaine administration, the rate at 50 min was 120 ± 7.5% in the saline‐treated group and 31 ± 7.4% in the lidocaine‐treated group; following lidocaine treatment firing rate remained markedly less than that before administration throughout the remainder of the recording. It is concluded that: (i) spinal mechanisms alone are not sufficient for induction and maintenance of second phase increased discharge of spinal nociceptive dorsal horn neurons; (ii) descending influences via supraspinal inputs are not causal in the development and maintenance of second phase increased discharge and (iii) tonic input from afferent neurons during the second phase plays a primary and essential role in generating and sustaining the second phase of elevated discharge of dorsal horn neurons and, thus, presumably the second phase of nociceptive scores in the formalin test. The data in this study reveal how much of an altered synaptically elicited response in the spinal dorsal horn can be attributed to postsynaptic plastic changes vs. how much can be simply due to increased synaptic input. The present results are important not only in the context of the formalin test but also in the context of other models related to inflammatory pain and neuropathic pain.
Epileptic fast activity can be explained by a model of impaired GABAergic dendritic inhibition
Authors: Wendling F. , Bartolomei F. , Bellanger J. J. , Chauvel P. 
Published: March 2003

AbstractThis paper focuses on high‐frequency (gamma band) EEG activity, the most characteristic electrophysiological pattern in focal seizures of human epilepsy. It starts with recent hypotheses about: (i) the behaviour of inhibitory interneurons in hippocampal or neocortical networks in the generation of gamma frequency oscillations; (ii) the nonuniform alteration of GABAergic inhibition in experimental epilepsy (reduced dendritic inhibition and increased somatic inhibition); and (iii) the possible depression of GABAA,fast circuit activity by GABAA,slow inhibitory postsynaptic currents. In particular, these hypotheses are introduced in a new computational macroscopic model of EEG activity that includes a physiologically relevant fast inhibitory feedback loop. Results show that strikingly realistic activity is produced by the model when compared to real EEG signals recorded with intracerebral electrodes. They show that, in the model, the transition from interictal to fast ictal activity is explained by the impairment of dendritic inhibition.
Altered presynaptic function in monoaminergic neurons of monoamine oxidase‐A knockout mice
Authors: Owesson Catarina Å. , Hopwood Sarah E. , Callado Luis F. , Seif Isabelle , McLaughlin Daniel P. , Stamford Jonathan A. 
Published: March 2003

AbstractMonoamine oxidase‐A knockout (MAO‐A KO) mice have elevated brain serotonin (5‐HT) and noradrenaline (NA) levels, and one would therefore anticipate increased monoamine release and compensatory changes in other aspects of presynaptic monoamine function. In this study we used voltammetry in brain slices from the locus coeruleus (LC), dorsal raphe (DRN) and striatum (CPu) in 7‐week‐old MAO‐A KO and C3H control mice to measure stimulated monoamine efflux and its control by amine transporters and autoreceptors. In LC, peak NA efflux on stimulation (99 pulses, 100 Hz) was higher in MAO‐A KO than C3H mice (938 ± 58 nm cf. 511 ± 42 nm; P < 0.001). The NA uptake half time (t½) was longer in MAO‐A KO than in C3H mice (6.0 ± 0.9 s cf. 1.9 ± 0.3 s; P < 0.001) and the selective NA reuptake inhibitor desipramine (50 nm) had a smaller effect in MAO‐A KO mice. NA transporter binding was significantly lower in the LC of MAO‐A KO mice compared to C3H controls (P < 0.01) but not in the DRN. The α2 agonist dexmedetomidine (10 nm) decreased stimulated NA efflux more in C3H than in MAO‐A KO mice (73.3% cf. 29.6% inhibition, P < 0.001). In DRN, peak 5‐HT efflux on stimulation (99 pulses, 100 Hz) was greater (P < 0.01) in MAO‐A KO (262 ± 44 nm) than C3H mice (157 ± 16 nm). Moreover, 5‐HT uptake t½ was longer (P < 0.05) in MAO‐A KO than in C3H mice (8.8 ± 1.1 s cf. 4.9 ± 0.6 s, P < 0.05) and the effect of citalopram (75 nm) was attenuated in MAO‐A KOs. Serotonin transporter binding was also lower in both the DRN and LC of MAO‐A KO mice. The 5‐HT1A agonist 8‐OH‐DPAT (1 µm) decreased 5‐HT efflux more in C3H than in MAO‐A KO mice (38.3% inhibition cf. 21.6%, P < 0.001). In contrast, there were no significant differences between MAO‐A KO and C3H mice in CPu dopamine efflux and uptake and the effect of the D2/3 agonist quinpirole was similar in the two strains. In summary, MAO‐A KO mice show major dysregulation of monoaminergic presynaptic mechanisms such as autoreceptor control and transporter kinetics.
Synaptic localization of membrane‐associated guanylate kinase‐interacting protein mediated by the pleckstrin homology domain
Authors: Iida Junko , Nishimura Wataru , Yao Ikuko , Hata Yutaka 
Published: March 2003

AbstractMembrane‐associated guanylate kinase‐interacting protein (MAGUIN) has been identified as a protein binding postsynaptic density (PSD)‐95 and synaptic scaffolding molecule (S‐SCAM). MAGUIN has one sterile α motif, one conserved region in connector enhancer of ksr (Cnk) (CRIC), one PSD‐95/Dlg‐A/ZO‐1 (PDZ) and one pleckstrin homology (PH) domain. There are two isoforms, MAGUIN‐1 and ‐2. MAGUIN‐1 binds the PDZ domains of PSD‐95 and S‐SCAM by the C‐terminus, whereas MAGUIN‐2 does not bind to PSD‐95 or S‐SCAM. Here, we have determined that MAGUIN‐2 is also localized at synapses and that the synaptic localization of MAGUIN depends on the pleckstrin homology domain. The overexpressed C‐terminal PDZ‐binding region inhibits the synaptic targeting of PSD‐95. Furthermore, the synaptic targeting of MAGUIN does not require N‐methyl‐d‐aspartate (NMDA) receptor activity. These findings suggest that MAGUIN‐1 and ‐2 are recruited to synapses by the PH domain and that MAGUIN‐1 subsequently interacts with PSD‐95 at synapses.
Metabotropic glutamate receptors are involved in amygdaloid plasticity
Authors: Fendt Markus , Schmid Susanne 
Published: March 2003

AbstractThe amygdala plays an important role in emotional learning. Synaptic plasticity underlying the acquisition of conditioned fear occurs in the lateral nucleus of the amygdala: long‐term potentiation (LTP) of synapses in the pathway of the conditioned stimulus (CS) has shown to be a neural correlate of this kind of emotional learning. The present study is based on previous results of our laboratory showing an important role of the metabotropic glutamate receptor subtype 5 (mGluR5) in fear conditioning. Here, we explored whether mGlu5 receptors within the lateral nucleus of the amygdala are involved in the plasticity underlying fear conditioning. We used an in vivo approach investigating the acquisition, consolidation and expression of conditioned fear by the fear‐potentiated startle paradigm and by the inhibition of motor activity during CS presentation. Additionally, we used an in vitro approach inducing LTP in the lateral amygdala by patch‐clamp recordings in rat brain slices. Acquisition of conditioned fear, but not consolidation and expression, was blocked by intra‐amygdaloid injections of the specific mGluR5 antagonist 2‐methyl‐6‐(phenylethynyl) pyridine hydrochloride (MPEP) in vivo. Furthermore, induction of amygdaloid LTP but not synaptic transmission was disrupted by MPEP application in vitro. These experiments show for the first time in vivo and in vitro that mGluR5 receptors are necessary for plasticity in the amygdala.
Strain differences in σ1 receptor‐mediated behaviours are related to neurosteroid levels
Authors: Phan Vân‐Ly , Urani Alexandre , Romieu Pascal , Maurice Tangui 
Published: March 2003

AbstractThe sigma1 (σ1) receptor exerts a potent neuromodulatory role in the brain with relevant consequences in memory processes, response to stress, depression and pharmacodependence. Its precise endogenous ligand is not yet identified but the σ1 receptor appears to be one target for the nongenomic rapid effects of neuroactive steroids in the brain. The aim of the present study was to establish whether differences in σ1 receptor‐mediated behaviours could be observed among mouse strains, in relation with differences in either σ1 receptor expression or steroid levels. The σ1‐receptor immunohistochemical distribution appeared similar between Swiss and C57BL/6 strains in all the brain structures examined. The levels of in vivo[3H](+)‐SKF‐10 047 binding to σ1 receptors were lower in Swiss than in C57BL/6. Adrenalectomy/castration significantly increased [3H](+)‐SKF‐10 047 binding only in Swiss. The behavioural efficacy of the selective σ1 agonists igmesine and PRE‐084 – reversion of the scopolamine‐induced amnesia in the passive avoidance test; diminution of the immobility duration in the forced swimming test – were significantly higher in C57BL/6 than in Swiss. Steroid levels were measured in the brain in basal conditions and after stress. C57BL/6 mice presented in both conditions, the lowest progesterone levels, this steroid acting as an endogenous σ1 antagonist. Collectively, the results suggested that strain differences in neuroactive steroid and particularly, progesterone, biosynthesis and sensitivity may contribute to the differential behavioural efficacy of σ1‐receptor ligands. Noteworthy, these observations are coherent with strain differences observed in the intensity of cocaine‐induced reward properties, known to critically involve the σ1 receptor.
Caffeine stimulates Ca2+entry through store‐operated channels to activate tyrosine hydroxylase in bovine chromaffin cells
Authors: McKenzie Sacha , Marley Philip D. 
Published: March 2003

AbstractThe ability of caffeine‐induced store Ca2+mobilization to activate tyrosine hydroxylase was studied in bovine adrenal chromaffin cells. Caffeine increased tyrosine hydroxylase activity over 10 min with an EC50of 3 mmand maximum effect at 20 mm. The maximum response to caffeine was substantial, being almost one third that of the strongest agonists acetylcholine and PACAP‐27, about half that for K+and similar to that for histamine. In contrast, catecholamine secretion evoked by caffeine was small, being less than 10% of the response to strong agonists. Caffeine‐induced tyrosine hydroxylase activation was not mimicked or prevented by phosphodiesterase inhibition with isobutylmethylxanthine, nor was it mimicked by an equimolar concentration of sucrose. However, the effect of caffeine was prevented by depleting intracellular Ca2+stores by thapsigargin pretreatment, and reduced substantially by removing extracellular Ca2+, by blocking Ca2+channels with Co2+or Ni2+, or by inhibiting store‐operated channels with 2‐aminoethyl diphenylborate. It was not affected by inhibiting Ca2+entry through voltage‐operated Ca2+‐channels or by tetrodotoxin. The effect of caffeine was mimicked by acute thapsigargin treatment or by depleting intracellular Ca2+stores in Ca2+‐free buffer and then reintroducing extracellular Ca2+. The results indicate that mobilizing store Ca2+with caffeine is a very effective mechanism for activating tyrosine hydroxylase and that the majority of this response depends on extracellular Ca2+entry through store‐operated channels. They also suggest that extracellular Ca2+entry through such channels regulates cellular responses differently to Ca2+entry through voltage‐operated Ca2+channels.
Molecular‐feature domains with posterodorsal–anteroventral polarity in the symmetrical sensory maps of the mouse olfactory bulb: mapping of odourant‐induced Zif268 expression
Authors: Inaki Koichiro , Takahashi Yuji K. , Nagayama Shin , Mori Kensaku 
Published: March 2003

AbstractIndividual glomeruli in the mammalian olfactory bulb presumably represent a single type of odourant receptor. Thus, the glomerular sheet provides odourant receptor maps at the surface of the olfactory bulb. To understand the basic spatial organization of the olfactory sensory maps, we first compared the spatial distribution of odourant‐induced responses measured by the optical imaging of intrinsic signals with that detected immunohistochemically by expressions of Zif268, one of the immediate early gene products in juxtaglomerular cells. In the dorsal surface of the bulb, we detected a clear correlation in the spatial pattern between these responses. In addition, the molecular‐feature domains and their polarities (spatial shifts of responses with an increase in carbon chain length) that were defined by the optical imaging method could be also detected by the Zif268 mapping method. We then mapped the Zif268 signals over the entire olfactory bulb using a homologous series of fatty acids and aliphatic alcohols as stimulus odourants. We superimposed the Zif268 signals onto the standard unrolled map with the help of cell adhesion molecule compartments. Each odourant typically elicited two pairs of clusters of dense Zif268 signals. The results showed that molecular‐feature domains and their polarities were arranged symmetrically at stereotypical positions in a mirror‐image fashion between the lateral and the medial sensory maps. The polarity of each domain was roughly in parallel with the posterodorsal–anteroventral axis that was defined by the cell adhesion molecule compartments. These results suggest that the molecular‐feature domain with its fixed polarity is one of the basic structural units in the spatial organization of the odourant receptor maps in the olfactory bulb.