bluuebunny/crossref_metadata_2025_split huggingface dataset:
NMDA receptors and PSD‐95 are found in attachment plaques in cerebellar granular layer glomeruli
Authors: Petralia Ronald S. , Wang Ya‐Xian , Wenthold Robert J. 
Published: March 2003

AbstractN‐methyl‐d‐aspartate (NMDA) receptors mediate long‐term changes in excitatory synapses in response to glutamate release. In the cerebellar granular layer, most glutamatergic synapses are formed between mossy terminals and granule cell dendrites, which together with some other components, make up complex glomerular structures. Glomeruli contain numerous attachment plaques (or puncta adherentia), which are sites of adhesion between cells. These structures are found mainly between granule cell dendrites, and probably help maintain the integrity of glomeruli. Attachment plaques contain adhesive proteins such as cadherins. In this study, we show that NMDA receptors are common at these attachment plaques, in addition to being found at synapses. We used four different antibodies to the NMDA receptor subunit, NR1, and another to NR2A/B. In contrast, labelling for an α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionate (AMPA) glutamate receptor antibody was seen only in a few attachment plaques, although AMPA receptors were seen frequently at glomerular synapses. We also show that substantial levels of the NMDA receptor‐associated protein, PSD‐95, are found in both synapses and attachment plaques. One way that NMDA receptors mediate changes in synapses is through effects on synaptic cadherins, which change their adhesive properties in response to NMDA receptor activation and consequently may alter synaptic function. The presence of NMDA receptors in attachment plaques suggests that these receptors mediate changes in the adhesive properties of these plaques, similar to this function in synapses.
Decreased BDNF signalling in transgenic mice reduces epileptogenesis
Authors: Lähteinen Sari , Pitkänen Asla , Saarelainen Tommi , Nissinen Jari , Koponen Eija , Castrén Eero 
Published: March 2003

AbstractBrain derived neurotrophic factor (BDNF) has been suggested to be involved in epileptogenesis. Both pro‐ and antiepileptogenic effects have been reported, but the exact physiological role is still unclear. Here, we investigated the role of endogenous BDNF in epileptogenesis by using transgenic mice overexpressing truncated trkB, a dominant negative receptor of BDNF. After induction of status epilepticus (SE) by kainic acid, the development of spontaneous seizures was monitored by video‐EEG system. Hilar cell loss, and the number of neuropeptide Y immunoreactive cells were studied as markers of cellular damage, and mossy fibre sprouting was investigated as a plasticity marker. Our results show that transgenic mice had significantly less frequent interictal spiking than wild‐type mice, and the frequency of spontaneous seizures was lower. Furthermore, compared to wild‐type animals, transgenic mice had less severe seizures with later onset and mortality was lower. In contrast, no differences between genotypes were observed in any of the cellular or plasticity markers. Our results suggest that transgenic mice with decreased BDNF signalling have reduced epileptogenesis.
In vivo activation and nuclear translocation of phosphorylated glycogen synthase kinase‐3β in neuronal apoptosis: links to tau phosphorylation
Authors: Elyaman W. , Terro F. , Wong N. S. , Hugon J. 
Published: March 2003

AbstractThe roles of glycogen synthase kinase‐3β (GSK‐3β) and tau phosphorylation were examined in seven‐day‐old rats injected with the NMDA receptor antagonist (MK801) that is known to induce neuronal apoptosis. Immunoblot and immunohistochemical analysis of brain samples demonstrated a site‐specific increase in tau phosphorylation associated with the relocalization of the protein to the nuclear/perinuclear region of apoptotic neurons. In addition, a tau 32‐kDa fragment was detected, suggesting that tau was a target of intracellular proteolysis in MK801‐treated brains. The proteolytically modified form of tau has reduced ability to bind to microtubules. GSK‐3β kinase assay and immunoblottings of active (tyrosine‐216) and inactive (serine‐9) forms of GSK‐3β revealed a rapid and transient increase in the kinase activity. Lithium chloride, a GSK‐3β inhibitor, prevented tau phosphorylation suggesting that tau phosphorylation is mediated by the activation of GSK‐3β. Confocal microscopy using double labelling of tau and GSK‐‐3β revealed that the activation of GSK‐3β in neurons was associated with early (2 h) nuclear translocation of tyrosine‐216 GSK‐3β. The execution phase of neuronal apoptosis was accompanied by a selective phosphorylation of serine‐9 and dephosphorylation of tyrosine‐216 GSK‐3β. These findings demonstrate that in vivo, GSK‐3β kinase activation and nuclear translocation are early stress signals of neuronal apoptosis.
Integration of calcium signals by calmodulin in rat sensory neurons
Authors: Milikan Jacob M. , Carter Tom D. , Horne John H. , Tzortzopoulos Athanasios , Török Katalin , Bolsover Stephen R. 
Published: March 2003

AbstractWe have used the fluorescently labelled calmodulin TA‐CaM to follow calmodulin activation during depolarization of adult rat sensory neurons. Calcium concentration was measured simultaneously using the low affinity indicator Oregon Green BAPTA 5N. TA‐CaM fluorescence increased during a 200‐ms depolarization but then continued to increase during the subsequent 500 ms, even though total cell calcium was falling at this time. In the next few seconds TA‐CaM fluorescence fell, but to a new elevated level that was then maintained for several tens of seconds. During a train of depolarizations that evoked a series of largely independent calcium changes TA‐CaM fluorescence was in contrast raised for the duration of the train and for many tens of seconds afterwards. The presence of a peptide corresponding to the calmodulin binding domain of myosin light chain kinase significantly increased the depolarization‐induced TA‐CaM fluorescence increase and slowed the subsequent fall of fluorescence. We interpret the slow recovery component of the TA‐CaM signal as reflecting the slow dissociation of calcium–calmodulin–calmodulin binding protein complexes. Our results show that after brief electrical activity calmodulin's interaction with calmodulin binding proteins persists for approximately one minute.
Activation of extracellular signal‐regulated kinases 1 and 2 by depolarization stimulates tyrosine hydroxylase phosphorylation and dopamine synthesis in rat brain
Authors: Lindgren Niklas , Goiny Michel , Herrera‐Marschitz Mario , Haycock John W. , Hökfelt Tomas , Fisone Gilberto 
Published: March 2003

AbstractProduction of dopamine is regulated via phosphorylation of tyrosine hydroxylase (TH), the rate‐limiting enzyme in the synthesis of catecholamines. Here we have used a preparation of rat striatal slices to examine the involvement of two mitogen‐activated protein kinases (MAPKs), extracellular signal‐regulated protein kinases 1 and 2 (ERK1/2), in the depolarization‐dependent regulation of TH phosphorylation and dopamine synthesis. Depolarization with elevated KCl (45 mm) caused an increase in the phosphorylation state and, thereby, activation of ERK1/2. The same stimulus also increased TH phosphorylation at Ser19, Ser31 and Ser40 (measured using site‐ and phospho‐specific antibodies) and TH activity [measured as 3,4‐dihydroxyphenylalanine (DOPA) accumulation]. A MAPK/ERK kinase inhibitor, PD098059, decreased the basal levels of phospho‐ERK1/2 and prevented the increase in ERK1/2 phosphorylation induced by depolarization. PD098059 also decreased both basal and depolarization‐induced phosphorylation of TH at Ser31 and reduced the increase in Ser40 phosphorylation induced by high potassium, but did not affect Ser19 phosphorylation. PD098059 alone inhibited basal TH activity and decreased the accumulation of DOPA induced by depolarization. These data provide evidence for the involvement of ERK1/2 in the regulation of the state of phosphorylation of TH at Ser31 and Ser40 and a correlation between ERK1/2‐dependent phosphorylation of TH and stimulation of dopamine synthesis in the brain.
Cross‐modal neuroplasticity in neonatally enucleated hamsters: structure, electrophysiology and behaviour
Authors: Izraeli Ruth , Koay Gimseong , Lamish Meyrav , Heicklen‐Klein Alice J. , Heffner Henry E. , Heffner Rickye S. , Wollberg Zvi 
Published: March 2003

AbstractPotential auditory compensation in neonatally bilaterally enucleated Syrian hamsters was explored anatomically, electrophysiologically and behaviourally. Gross morphology of the visual cortex appeared normal and no obvious cytoarchitectural malformation was discerned. However, enucleation induced a significant increase in the spontaneous firing rate of visual cortex cells. Further, auditory stimuli elicited field potentials and single unit responses in the visual cortex of enucleated, but not normal, animals. About 63% of the cells isolated in the visual cortex of 16 enucleated hamsters responded to at least one type of auditory stimulus. Most of the responses were less vigorous and less time‐locked than those of auditory cortex cells, and thresholds were typically higher. Projection tracing with WGA–HRP disclosed reciprocal connections between the visual cortex and the dorsal lateral geniculate nucleus in both intact and enucleated animals. However, in the enucleated animals retrogradely labelled cells were also found in the inferior colliculus, the major midbrain auditory nucleus. Behaviourally determined auditory sensitivity across the hearing range did not differ between enucleated and intact hamsters. Minimum audible angle, as determined by a conditioned suppression task, ranged from around 17 to 22°, with no significant difference between normal and enucleated animals. The two groups also did not differ with regard to the direction of their unconditioned head orientating response to intermittent noise. However, the enucleated animals showed a more vigorous response and were slower to habituate to the noise. These results show that bilateral enucleation of newborn hamsters results in auditory activation of visual targets, in addition to the typical activation of the intact auditory pathway. Behaviourally it appears that enucleated hamsters, compared with their normal littermates, are slower to habituate in their response to an unexpected source of sound.
Differential effects of typical and atypical antipsychotic drugs on striosome and matrix compartments of the striatum
Authors: Bubser Michael , Deutch Ariel Y. 
Published: March 2003

AbstractAdministration of typical antipsychotic drugs (APDs) is often accompanied by extrapyramidal side‐effects (EPS). Treatment with atypical APDs has a lower incidence of motor side‐effects and atypical APDs are superior to typical APDs in treating the negative symptoms of schizophrenia. Although typical APDs strongly induce the immediate‐early gene c‐fos in the striatum while atypical APDs do so only weakly, it is possible that the effects of atypical APDs are more pronounced within certain regions of the striatum. The striatum contains two histochemically defined compartments, the striosome (patch) and the matrix. These compartments have been well characterized anatomically but their functional attributes are unclear. We therefore examined the effects of typical and atypical APDs on Fos expression in the striosome and matrix of the rat. Typical and atypical APDs were distinguished by the pattern of striatal compartmental activation they induced: the striosome : matrix ratio of Fos‐li neurons was greater in rats treated with atypical APDs. Pretreating animals with selective antagonists of receptors that atypical APDs target with high affinity did not increase the striosome : matrix Fos ratio of typical APD‐treated rats and thus did not mimic the ratio seen in response to atypical APDs. However, pretreatment with the atypical APD clozapine did recapitulate the characteristic compartmental Fos pattern seen in response to typical APDs. These data suggest that some characteristics of atypical APDs, such as the lower EPS liability and greater reduction of negative symptoms, may be linked to the coordinate regulation of the striatal striosome and matrix.
Mechanisms controlling bursting activity induced by disinhibition in spinal cord networks
Authors: Darbon Pascal , Scicluna Luke , Tscherter Anne , Streit Jürg 
Published: March 2003

AbstractDisinhibition reliably induces regular synchronous bursting in networks of spinal interneurons in culture as well as in the intact spinal cord. We have combined extracellular multisite recording using multielectrode arrays with whole cell recordings to investigate the mechanisms involved in bursting in organotypic and dissociated cultures from the spinal cords of embryonic rats. Network bursts induced depolarization and spikes in single neurons, which were mediated by recurrent excitation through glutamatergic synaptic transmission. When such transmission was blocked, bursting ceased. However, tonic spiking persisted in some of the neurons. In such neurons intrinsic spiking was suppressed following the bursts and reappeared in the intervals after several seconds. The suppression of intrinsic spiking could be reproduced when, in the absence of fast synaptic transmission, bursts were mimicked by the injection of current pulses. Intrinsic spiking was also suppressed by a slight hyperpolarization. An afterhyperpolarization following the bursts was found in roughly half of the neurons. These afterhyperpolarizations were combined with a decrease in excitability. No evidence for the involvement of synaptic depletion or receptor desensitization in bursting was found, because neither the rate nor the size of spontaneous excitatory postsynaptic currents were decreased following the bursts. Extracellular stimuli paced bursts at low frequencies, but failed to induce bursts when applied too soon after the last burst. Altogether these results suggest that bursting in spinal cultures is mainly based on intrinsic spiking in some neurons, recurrent excitation of the network and auto‐regulation of neuronal excitability.
Task‐dependent and cell‐type‐specific Fos enhancement in rat sensory cortices during audio‐visual discrimination
Authors: Sakata Shuzo , Kitsukawa Takashi , Kaneko Takeshi , Yamamori Tetsuo , Sakurai Yoshio 
Published: March 2003

AbstractAttention modulates neural activities in sensory cortices. Because cortical neurons are composed of many types of neurons, the activities of these different types of cells can exhibit different modifications depending on whether an animal pays attention to a particular sensory stimulus or not. In the present study, we examined which types of cortical neurons change their activities in rats during one of two types of audio‐visual discrimination (AVD) tasks by using Fos immunohistochemistry. In the tasks, both auditory and visual stimuli were simultaneously presented but only one of the two modalities was task‐relevant. Once the rats had learned one of the AVD tasks, presenting only relevant sensory stimuli was sufficient for them to perform the task correctly. These results suggest that the rats indeed attended to the relevant stimuli during the performance of the tasks. We found that Fos expression in the primary auditory and visual cortices was enhanced in a task‐dependent manner during the performance of the AVD tasks. The enhancement of Fos expression depended on the behavioural significance of the stimulus in the tasks. Moreover, using double immunohistochemistry of Fos and a cell type‐specific marker protein (phosphate‐activated glutaminase, nonphosphorylated neurofilament protein, parvalbumin, calretinin or somatostatin), the task‐dependent Fos expression was observed preferentially in excitatory neurons but not in inhibitory interneurons. These results suggest that modulation in cortical excitatory neurons might have critical roles in selecting and processing behaviourally relevant sensory stimuli.
c‐Fos expression in dopaminergic and GABAergic neurons of the ventral mesencephalic tegmentum after paradoxical sleep deprivation and recovery
Authors: Maloney Karen J. , Mainville Lynda , Jones Barbara E. 
Published: March 2003

AbstractEvidence suggests that dopaminergic neurons of the ventral mesencephalic tegmentum (VMT) could be important for paradoxical sleep (PS). Here, we examined whether dopamine (DA) and adjacent γ‐aminobutyric acid (GABA)‐synthesizing neurons are active in association with PS recovery as compared to PS deprivation or control conditions in different groups of rats by using c‐Fos expression as a reflection of neural activity, combined with dual immunostaining for tyrosine hydroxylase (TH) or glutamic acid decarboxylase (GAD). Numbers of TH+/c‐Fos+ neurons in the substantia nigra (SN) were not significantly different across groups, whereas those in the ventral tegmental area (VTA) were significantly different and greatest in PS recovery. Numbers of GAD+/c‐Fos+ neurons in both VTA and SN were greatest in PS recovery. Thus, DA neuronal activity does not appear to be suppressed by local GABAergic neuronal activity during PS but might be altered in pattern by this inhibitory as well as other excitatory, particularly cholinergic, inputs such as to allow DA VTA neurons to become maximally active during PS and thereby contribute to the unique physiological and cognitive aspects of that state.
Transient forebrain ischemia induces persistent hyperactivity of large conductance Ca2+‐activated potassium channels via oxidation modulation in rat hippocampal CA1 pyramidal neurons
Authors: Gong Liang‐Wei , Gao Tian M. , Huang Hao , Zhuang Zhi‐Ye , Tong Zhenqing 
Published: March 2003

AbstractThe present study examined temporal changes in activity of large conductance, Ca2+‐activated potassium (BKCa) channels in postischemic CA1 pyramidal neurons at 2, 6, 24 and 48 h after reperfusion. These changes in activity and possible cellular mechanisms were examined using the inside–out configuration of patch clamp. The unitary conductance of postischemic BKCa channels increased transiently to 119% of the control at 2 h after reperfusion, and recovered to the control level thereafter. A persistent increase in [Ca2+]i sensitivity of BKCa channels was observed in postischemic CA1 neurons with the maximal sensitivity to [Ca2+]i at 6 h after reperfusion while channel voltage‐ dependence showed no obvious changes. Kinetic analyses showed that the postischemic enhancement of BKCa channel activity was due to longer open times and shorter closed times as there was no significant changes in opening frequency after ischemia. Glutathione disulphide markedly increased BKCa channel activity in normal CA1 neurons, while reducing glutathione caused a decrease in BKCa channel activity by reducing the sensitivity of this channel to [Ca2+]i in postischemic CA1 neurons. Similar modulatory effects on postischemic BKCa channels were also observed with another redox couple, DTNB and DTT, suggesting an oxidation modulation of BKCa channel function after ischemia. The present results indicate that a persistent enhancement in activity of BKCa channels, probably via oxidation of channels, in postischemic CA1 pyramidal neurons may account for the decrease in neuronal excitability and increase in fAHP after ischemia. The ischemia‐induced augmentation in BKCa channel activity may be also associated with the postischemic neuronal injury.
Different respiratory control systems are affected in homozygous and heterozygous kreisler mutant mice
Authors: Chatonnet Fabrice , Del Toro Eduardo Domínguez , Voiculescu Octavian , Charnay Patrick , Champagnat Jean 
Published: March 2003

AbstractDuring embryonic development, restricted expression of the regulatory genes Krox20 and kreisler are involved in segmentation and antero‐posterior patterning of the hindbrain neural tube. The analysis of transgenic mice in which specific rhombomeres (r) are eliminated points to an important role of segmentation in the generation of neuronal networks controlling vital rhythmic behaviours such as respiration. Thus, elimination of r3 and r5 in Krox20–/– mice suppresses a pontine antiapneic system (Jacquin et al., 1996). We now compare Krox20–/– to kreisler heterozygous (+/kr) and homozygous (kr/kr) mutant neonates. In +/kr mutant mice, we describe hyperactivity of the antiapneic system: analysis of rhythm generation in vitro revealed a pontine modification in keeping with abnormal cell specifications previously reported in r3 (Manzanares et al., 1999b). In kr/kr mice, elimination of r5 abolished all +/kr respiratory traits, suggesting that +/kr hyperactivity of the antiapneic system is mediated through r5‐derived territories. Furthermore, collateral chemosensory pathways that normally mediate delayed responses to hypoxia and hyperoxia were not functional in kr/kr mice. We conclude that the pontine antiapneic system originates from r3r4, but not r5. A different rhythm‐promoting system originates in r5 and kreisler controls the development of antiapneic and chemosensory signal transmission at this level.
The speeding of EPSC kinetics during maturation of a central synapse
Authors: Wall Mark J. , Robert Antoine , Howe James R. , Usowicz Maria M. 
Published: March 2003

AbstractSeveral factors contribute to the shape of excitatory postsynaptic currents (EPSCs) in CNS neurons, among them the kinetics of presynaptic release, transmitter clearance, and the properties and distribution of postsynaptic receptors. The decays of AMPA receptor‐mediated EPSCs at rat cerebellar mossy fibre–granule cell (MF–gc) synapses follow a bi‐exponential time‐course. The fast component dominates the decay, accounting for 84–94% of the peak amplitude. Here we show that both components of decay, and also the risetimes, became faster during postnatal maturation. At adult, but not immature, synapses, the risetimes and decays of evoked multiquantal EPSCs were similar to those of monoquantal miniature (m)EPSCs. The faster risetimes at mature synapses reflected increased synchrony of multivesicular release, whereas the faster decays appeared to reflect changes in the properties of postsynaptic receptors. Inhibition of glutamate uptake was without effect on evoked EPSCs at both ages. Furthermore, after slowing receptor desensitization with cyclothiazide, the EPSCs at mature synapses decayed as slowly as EPSCs at immature synapses, suggesting that faster glutamate clearance does not account for the developmental speeding of EPSC decay. Our results support previous conclusions that glutamate clearance and receptor deactivation are important determinants of the fast decay component at immature synapses. Desensitization becomes increasingly important during development and plays a major role in shaping EPSC decay at mature synapses.
Genetic labelling of specific axonal pathways in the mouse central nervous system
Authors: Zubair Mohamad , Watanabe Eiji , Fukada Masahide , Noda Masaharu 
Published: March 2003

AbstractWe report on transgenic mouse lines in which several sensory systems in the brain are specifically visualized genetically. We employed GAP‐lacZ as an axon‐targeted reporter protein that was constructed by fusing the membrane‐anchoring domain of the GAP‐43 protein to lacZ. The reporter gene was introduced into the genome under the control of a promoter element of Brn3b transcription factor to establish transgenic mouse lines. The individual lines thus generated afforded clear images of specific axonal pathways of the visual, vomeronasal, pontocerebellar, and auditory systems. The reporter protein labelled the entire axonal process as well as the cell body of developing and mature neurons on staining with X‐gal. We show that these lines facilitate the developmental and anatomical study of these neural systems. This strategy should be applicable to a variety of neural systems by using various specific promoter elements.