bluuebunny/crossref_metadata_2025_split huggingface dataset:
Divergence and convergence of thalamocortical projections to premotor and supplementary motor cortex: a multiple tracing study in the macaque monkey
Authors: Morel Anne , Liu Jian , Wannier Thierry , Jeanmonod Daniel , Rouiller Eric M. 
Published: March 2005

AbstractThe premotor cortex of macaque monkeys is currently subdivided into at least six different subareas on the basis of structural, hodological and physiological criteria. To determine the degree of divergence/convergence of thalamocortical projections to mesial [supplementary motor area (SMA)‐proper and pre‐SMA] and lateral (PMd‐c, PMd‐r, PMv‐c and PMv‐r) premotor (PM) subareas, quantitative analyses were performed on the distribution of retrograde labelling after multiple tracer injections in the same animal. The results demonstrate that all PM and SMA subareas receive common inputs from several thalamic nuclei, but the relative contribution of these nuclei to thalamocortical projections differs. The largest difference occurs between subareas of SMA, with much greater contribution from the mediodorsal (MD) and area X, and a smaller contribution from the ventral lateral anterior (VLa) and ventral part of the ventral lateral posterior (VLpv) to pre‐SMA than to SMA‐proper. In PM, differences between subareas are less pronounced; in particular, all receive a significant contribution from MD, the ventral anterior (VApc) and area X. However, there are clear gradients, such as increasing projections from MD to rostral, from VLa and VLpv to caudal, and from dorsal VLp (VLpd) to dorsal premotor subareas. Intralaminar nuclei provide widespread projections to all premotor subareas. The degree of overlap between thalamocortical projections varies among different PM and SMA subareas and different sectors of the thalamus. These variations, which correspond to different origin and topography of thalamocortical projections, are discussed in relation to functional organizations at thalamic and cortical levels.
Stabilizing effects of extracellular ATP on synaptic efficacy and plasticity in hippocampal pyramidal neurons
Authors: Martín Eduardo D. , Buño Washington 
Published: March 2005

AbstractThe role of adenosine triphosphate (ATP) as a neurotransmitter and extracellular diffusible messenger has recently received considerable attention because of its possible participation in the regulation of synaptic plasticity. However, the possible contribution of extracellular ATP in maintaining and regulating synaptic efficacy during intracellular ATP depletion is understudied. We tested the effects of extracellular ATP on excitatory postsynaptic currents (EPSCs) evoked in CA1 pyramidal neurons by Schaffer collateral stimulation. In the absence of intracellular ATP, EPSC rundown was neutralized when a low concentration of ATP (1 µm) was added to the extracellular solution. Adenosine and ATP analogues did not prevent the EPSC rundown. The P2 antagonists piridoxal‐5′‐phosphate‐azophenyl 2′,4′‐disulphonate (PPADS) and reactive blue‐2, and the P1 adenosine receptor antagonist 8‐cyclopentyltheophylline (CPT) had no detectable effects in cells depleted of ATP. However, the protective action of extracellular ATP on synaptic efficacy was blocked by extracellular application of the protein kinase inhibitors K252b and staurosporine. In contrast, K252b and staurosporine per se did not interfere with synaptic transmission in ATP loaded cells. Without intracellular ATP, bath‐applied caffeine induced a transient (< 35 min) EPSC potentiation that was transformed into a persistent long‐term potentiation (> 80 min) when 1 µm ATP was added extracellularly. An increased probability of transmitter release paralleled the long‐term potentiation induced by caffeine, suggesting that it originated presynaptically. Therefore, we conclude that extracellular ATP may operate to maintain and regulate synaptic efficacy and plasticity in conditions of abnormal intracellular ATP depletion by phosphorylation of a surface protein substrate via activation of ecto‐protein kinases.
Modulation of synaptic transmission in neocortex by network activities
Authors: Crochet Sylvain , Chauvette Sylvain , Boucetta Sofiane , Timofeev Igor 
Published: March 2005

AbstractNeocortical neurons integrate inputs from thousands of presynaptic neurons that fire in vivo with frequencies that can reach 20 Hz. An important issue in understanding cortical integration is to determine the actual impact of presynaptic firing on postsynaptic neuron in the context of an active network. We used dual intracellular recordings from synaptically connected neurons or microstimulation to study the properties of spontaneous and evoked single‐axon excitatory postsynaptic potentials (EPSPs) in vivo, in barbiturate or ketamine−xylazine anaesthetized cats. We found that active states of the cortical network were associated with higher variability and decrease in amplitude and duration of the EPSPs owing to a shunting effect. Moreover, the number of apparent failures markedly increased during active states as compared with silent states. Single‐axon EPSPs in vivo showed mainly paired‐pulse facilitation, and the paired‐pulse ratio increased during active states as compare to silent states, suggesting a decrease in release probability during active states. Raising extracellular Ca2+ concentration to 2.5–3.0 mm by reverse microdialysis reduced the number of apparent failures and significantly increased the mean amplitude of individual synaptic potentials. Quantitative analysis of spontaneous synaptic activity suggested that the proportion of presynaptic activity that impact at the soma of a cortical neuron in vivo was low because of a high failure rate, a shunting effect and probably dendritic filtering. We conclude that during active states of cortical network, the efficacy of synaptic transmission in individual synapses is low, thus safe transmission of information requires synchronized activity of a large population of presynaptic neurons.
Brief exposure to NMDA produces long‐term protection of cerebellar granule cells from apoptosis
Authors: Xifro Xavier , Malagelada Cristina , Miñano Alfredo , Rodríguez‐Álvarez José 
Published: March 2005

AbstractCerebellar granule cells (CGCs) require excitatory inputs to survive during their postnatal migration from the external to the internal granule cell layers. The lack of innervation of mossy fibres induces CGC death by apoptosis. In vitro, CGCs die by apoptosis in the presence of physiological concentrations of KCl (5 mm or K5) but they survive in the presence of depolarizing concentrations of KCl (25 mm or K25) or N‐methyl‐d‐aspartate (NMDA) by a mechanism dependent on calcium influx. The addition of NMDA or K25, for only 24 h, to immature CGCs cultures [2 days in vitro (DIV)] was able to produce a remarkable and long‐term protection until 8 DIV. Moreover, our data show that NMDA and K25‐mediated long‐lasting protection was related to an inhibition of caspase‐3 activity. By using different protein kinase inhibitors, we have shown that the inhibition of caspase‐3 activation by NMDA was dependent on the activation of tyrosine kinases and phosphatidylinositol 3‐kinase (PI3‐kinase). Moreover, an impairment in NMDA‐mediated neuroprotection and caspase‐3 inhibition was observed when the action of brain‐derived neurotrophic factor (BDNF) was blocked. By contrast, K25‐mediated neuroprotection was BDNF‐independent and was mediated by a mitogen‐activated protein kinase‐ and PI3‐kinase‐dependent inhibition of caspase‐3.
PDE10A inhibition reverses subchronic PCP‐induced deficits in attentional set‐shifting in rats
Authors: Rodefer Joshua S. , Murphy Emily R. , Baxter Mark G. 
Published: March 2005

AbstractPersistent suppression of N‐methyl‐d‐aspartate (NMDA) receptor function produces enduring structural changes in neocortical and limbic regions in a pattern similar to changes reported in schizophrenia. This similarity suggests that chronic NMDA receptor antagonism in animals may represent a useful model of neurobiological and related cognitive deficits in schizophrenia. Schizophrenia is associated with impairments in frontal lobe‐dependent cognitive functions, including working memory and attentional shifting. Deficits in attention and executive function have not been well characterized in animal models of schizophrenia using chronic NMDA receptor antagonist administration. We investigated whether subchronic systemic administration of the NMDA receptor antagonist phencyclidine (PCP) to rats followed by a drug washout period would produce enduring cognitive deficits on an attentional set‐shifting task. The task is functionally analogous to a sensitive test of frontal function in humans and non‐human primates. Subchronic PCP administration selectively impaired extradimensional shift learning without affecting other discrimination or reversal tasks. Moreover, acute treatment with the PDE10A inhibitor papaverine immediately prior to testing attenuated the PCP‐induced deficits in extradimensional shift learning across a range of doses. These data suggest that subchronic PCP administration may model effectively some of the cognitive deficits that are observed in schizophrenia, and that PDE10A inhibition may be an effective therapeutic route to improve executive function deficits associated with schizophrenia.
SHORT COMMUNICATIONS: Increases in extracellular levels of 5‐HT and dopamine in the basolateral, but not in the central, nucleus of amygdala induced by aversive stimulation of the inferior colliculus
Authors: Macedo Carlos Eduardo , Martinez Raquel Chacon Ruiz , De Souza Silva Maria Angélica , Brandão Marcus Lira 
Published: March 2005

AbstractConsistent evidence has shown that dopamine release in the prefrontal cortex is increased by electrical stimulation of the inferior colliculus (IC) as unconditioned stimulus. Recent reports have also demonstrated that inactivation of the basolateral nucleus of the amygdala (BLA) with muscimol enhances the behavioural consequences of the aversive stimulation of the IC and reduces the dopamine release in the prefrontal cortex. Moreover, neurotoxic lesions of the BLA enhance whereas those of the central nucleus of the amygdala (CeA) reduce the aversiveness of the electrical stimulation of the IC. Based on these findings the present study examined the effects of the electrical stimulation of the IC on the extracellular levels of serotonin and dopamine in the BLA and CeA. To this end, rats implanted with a stimulation electrode in the IC also bore a microdialysis probe in the BLA or CeA for determination of the release of dopamine and serotonin. IC electrical stimulation at the freezing and escape thresholds increased the levels of serotonin (≈ 70%) and dopamine (≈ 60%) in the BLA related to the basal values. Similarly, the metabolites DOPAC and 5‐HIAA increased in a parallel fashion in BLA. No significant changes could be detected in these biogenic amines and metabolites in CeA following IC aversive stimulation. These findings point to a differential role of serotonergic and dopaminergic mechanisms of the BLA and CeA in the setting up of adaptive responses to fear states generated at the inferior colliculus level.
Purkinje cell loss affects differentially the execution, acquisition and prepulse inhibition of skeletal and facial motor responses in Lurcher mice
Authors: Porras‐García Elena , Cendelin Jan , Domínguez‐del‐Toro Eduardo , Vožeh František , Delgado‐García José M. 
Published: March 2005

AbstractAdult heterozygous Lurcher mice show a degeneration of almost all Purkinje cells and 90% of the granular cells of the cerebellum, resulting in ataxia or general deficits in motor coordination. These mice are therefore an excellent model for studying the role of the cerebellar cortex in motor performance, including the acquisition of new motor abilities. The performance of 3‐month‐old Lurcher mice was studied in various behavioural (fall, horizontal bar, rotating cylinder, and ladder), spatial orientation (water maze) and associative learning (eyelid classical conditioning) tasks and compared with that of wild‐type mice. Behavioural tasks indicated a deficit for motor abilities in Lurcher mice but with some adaptation to the tests and improvement in performance. Wild‐type and Lurcher mice performed swimming equally, but the latter learned the task significantly more slowly than the former. The late component of reflex blinks was smaller in amplitude and had a longer latency in Lurcher mice than in controls. Learning curves for Lurcher mice during classical conditioning of eyelid responses were similar to controls, but the amplitude of the learned response in Lurcher mice was significantly lower. The startle response to a severe tone was similar in both control and Lurcher mice but the latter were unable to produce prepulse inhibition. These results suggest that the cerebellar cortex is not indispensable for the performance of this complete set of skeletal and facial tasks, or for the acquisition of new motor abilities, but it is for the appropriate execution and adjustment of any of these motor activities.
Ascent-Based Monte Carlo Expectation– Maximization
Authors: Caffo Brian S. , Jank Wolfgang , Jones Galin L. 
Published: March 2005

SummaryThe expectation–maximization (EM) algorithm is a popular tool for maximizing likelihood functions in the presence of missing data. Unfortunately, EM often requires the evaluation of analytically intractable and high dimensional integrals. The Monte Carlo EM (MCEM) algorithm is the natural extension of EM that employs Monte Carlo methods to estimate the relevant integrals. Typically, a very large Monte Carlo sample size is required to estimate these integrals within an acceptable tolerance when the algorithm is near convergence. Even if this sample size were known at the onset of implementation of MCEM, its use throughout all iterations is wasteful, especially when accurate starting values are not available. We propose a data-driven strategy for controlling Monte Carlo resources in MCEM. The algorithm proposed improves on similar existing methods by recovering EM's ascent (i.e. likelihood increasing) property with high probability, being more robust to the effect of user-defined inputs and handling classical Monte Carlo and Markov chain Monte Carlo methods within a common framework. Because of the first of these properties we refer to the algorithm as ‘ascent-based MCEM’. We apply ascent-based MCEM to a variety of examples, including one where it is used to accelerate the convergence of deterministic EM dramatically.
Scaling Limits for the Transient Phase of Local Metropolis–Hastings Algorithms
Authors: Christensen Ole F. , Roberts Gareth O. , Rosenthal Jeffrey S. 
Published: March 2005

SummaryThe paper considers high dimensional Metropolis and Langevin algorithms in their initial transient phase. In stationarity, these algorithms are well understood and it is now well known how to scale their proposal distribution variances. For the random-walk Metropolis algorithm, convergence during the transient phase is extremely regular—to the extent that the algo-rithm's sample path actually resembles a deterministic trajectory. In contrast, the Langevin algorithm with variance scaled to be optimal for stationarity performs rather erratically. We give weak convergence results which explain both of these types of behaviour and practical guidance on implementation based on our theory.
Model Determination for Categorical Data With Factor Level Merging
Authors: Dellaportas Petros , Tarantola Claudia 
Published: March 2005

SummaryWe deal with contingency table data that are used to examine the relationships between a set of categorical variables or factors. We assume that such relationships can be adequately described by the cond‘itional independence structure that is imposed by an undirected graphical model. If the contingency table is large, a desirable simplified interpretation can be achieved by combining some categories, or levels, of the factors. We introduce conditions under which such an operation does not alter the Markov properties of the graph. Implementation of these conditions leads to Bayesian model uncertainty procedures based on reversible jump Markov chain Monte Carlo methods. The methodology is illustrated on a 2×3×4 and up to a 4×5×5×2×2 contingency table.
Regularization and Variable Selection Via the Elastic Net
Authors: Zou Hui , Hastie Trevor 
Published: March 2005

SummaryWe propose the elastic net, a new regularization and variable selection method. Real world data and a simulation study show that the elastic net often outperforms the lasso, while enjoying a similar sparsity of representation. In addition, the elastic net encourages a grouping effect, where strongly correlated predictors tend to be in or out of the model together. The elastic net is particularly useful when the number of predictors (p) is much bigger than the number of observations (n). By contrast, the lasso is not a very satisfactory variable selection method in the p≫n case. An algorithm called LARS-EN is proposed for computing elastic net regularization paths efficiently, much like algorithm LARS does for the lasso.
14‐3‐3 epsilon modulates the stimulated secretion of endopeptidase 24.15
Authors: Carreño Flávia R. , Goñi Camila N. , Castro Leandro M. , Ferro Emer S. 
Published: March 2005

AbstractEndopeptidase 24.15 (ep24.15: EC3.4.24.15), a secreted protein involved in peptide metabolism, is unusual in that it does not contain a signal peptide sequence. In this work, we describe the physical interaction between ep24.15 and 14‐3‐3 epsilon, one isoform of a family of ubiquitous phosphoserine/threonine‐scaffold proteins that organizes cell signaling and is involved in exocytosis. The interaction between ep24.15 and 14‐3‐3 epsilon increased following phosphorylation of ep24.15 at Ser644 by protein kinase A (PKA). The co‐localization of ep24.15 and 14‐3‐3 epsilon was increased by exposure of HEK293 cells (human embryonic kidney cells) to forskolin (10 µm). Overexpression of 14‐3‐3 epsilon in HEK293 cells almost doubled the secretion of ep24.15 stimulated by A23187 (7.5 µm) from 10%[1.4 ± 0.24 AFU/(min 106 cells)] to 19%[2.54 ± 0.24 AFU/(min 106 cells)] (p < 0.001) of the total intracellular enzyme activity. Treatment with forskolin had a synergistic effect on the A23187‐stimulated secretion of ep24.15 that was totally blocked by the PKA inhibitor KT5720. The ep24.15 point mutation S644A reduced the co‐localization of ep24.15 and 14‐3‐3 in stably transfected HEK293 cells. Indeed, secretion of the ep24.15 S644A mutant from these cells was only slightly stimulated by A23187 and insensitive to forskolin, in contrast to that of the wild type enzyme. Together, these data suggest that prior interaction with 14‐3‐3 is an important step in the unconventional stimulated secretion of ep24.15.
Dopamine D1 receptor interaction with arrestin3 in neostriatal neurons
Authors: Macey Tara A. , Liu Yong , Gurevich Vsevolod V. , Neve Kim A. 
Published: March 2005

AbstractDopamine D1 receptor interactions with arrestins have been characterized using heterologously expressed D1 receptor and arrestins. The purpose of this study was to investigate the interaction of the endogenous D1 receptor with endogenous arrestin2 and 3 in neostriatal neurons. Endogenous arrestin2 and 3 in striatal homogenates bound to the C‐terminus of the D1 receptor in a glutathione‐S‐transferase (GST) pulldown assay, with arrestin3 binding more strongly. The D1 C‐terminus and, to a lesser extent, the third cytoplasmic loop also bound purified arrestin2 and 3. In neostriatal neurons, 2, 5, and 20 min agonist treatment increased the colocalization of the D1 receptor and arrestin3 immunoreactivity without altering the colocalization of the D1 receptor and arrestin2. Further, agonist treatment for 5 and 20 min caused translocation of arrestin3, but not arrestin2, to the membrane. The binding of arrestin3, but not arrestin2, to the D1 receptor was increased as assessed by coimmunoprecipitation after agonist treatment for 5 and 20 min. Agonist treatment of neurons induced D1 receptor internalization (35–45%) that was maximal within 2–5 min, a time‐course similar to that of the increase in colocalization of the D1 receptor with arrestin3. These data indicate that the D1 receptor preferentially interacts with arrestin3 in neostriatal neurons.
Up‐regulation of neuropeptide Y levels and modulation of glutamate release through neuropeptide Y receptors in the hippocampus of kainate‐induced epileptic rats
Authors: Silva Ana P. , Xapelli Sara , Pinheiro Paulo S. , Ferreira Raquel , Lourenço Joana , Cristóvão Armando , Grouzmann Eric , Cavadas Cláudia , Oliveira Catarina R. , Malva João O. 
Published: March 2005

AbstractKainate‐induced epilepsy has been shown to be associated with increased levels of neuropeptide Y (NPY) in the rat hippocampus. However, there is no information on how increased levels of this peptide might modulate excitation in kainate‐induced epilepsy. In this work, we investigated the modulation of glutamate release by NPY receptors in hippocampal synaptosomes isolated from epileptic rats. In the acute phase of epilepsy, a transient decrease in the efficiency of NPY and selective NPY receptor agonists in inhibiting glutamate release was observed. Moreover, in the chronic epileptic hippocampus, a decrease in the efficiency of NPY and the Y2 receptor agonist, NPY13‐36, was also found. Simultaneously, we observed that the epileptic hippocampus expresses higher levels of NPY, which may account for an increased basal inhibition of glutamate release. Consistently, the blockade of Y2 receptors increased KCl‐evoked glutamate release, and there was an increase in Y2 receptor mRNA levels 30 days after kainic acid injection, suggesting a basal effect of NPY through Y2 receptors. Taken together, these results indicate that an increased function of the NPY modulatory system in the epileptic hippocampus may contribute to basal inhibition of glutamate release and control hyperexcitability.
Multiple pathways of apolipoprotein E signaling in primary neurons
Authors: Hoe Hyang‐Sook , Harris D. Christopher , Rebeck G. William 
Published: March 2005

AbstractApolipoprotein E is a genetic risk factor for Alzheimer's disease, and the apoE protein is associated with β‐amyloid deposits in Alzheimer's disease brain. We examined signaling pathways stimulated by apoE in primary neurons in culture. ApoE and an apoE‐derived peptide activated several intracellular kinases, including prominently extracellular signal‐regulated kinase 1/2 (ERK1/2). ERK1/2 activation by apoE was blocked by an inhibitor of the low‐density lipoprotein receptor family, the specific NMDA glutamate receptor antagonist MK 801 and other calcium channel blockers. Activation of apoE receptors also induced tyrosine phosphorylation of Dab1, an adaptor protein of apoE receptors, but experiments in Dab1 knockout neurons demonstrated that Dab1 was not necessary for ERK activation. In contrast, apoE treatment of primary neurons decreased activation of c‐Jun N‐terminal kinase, a kinase that interacts with another apoE receptor adaptor protein, c‐Jun N‐terminal kinase‐interacting protein. This change also depended on interactions with the low‐density lipoprotein receptor family but was independent of calcium channels. c‐Jun N‐terminal kinase deactivation by apoE was blocked by γ‐secretase inhibitors and pertussis toxin. These results demonstrate that apoE affects several signaling cascades in neurons: increased disabled phosphorylation, activation of the ERK1/2 pathway (dependent on calcium influx via the NMDA receptor) and inhibition of the c‐Jun N‐terminal kinase 1/2 pathway (dependent on γ‐secretase and G proteins).