bluuebunny/crossref_metadata_2025_split huggingface dataset:
The roles of the cerebellum and basal ganglia in timing and error prediction
Authors: Dreher Jean‐Claude , Grafman Jordan 
Published: March 2003

AbstractRecent evidence that the cerebellum and the basal ganglia are activated during the performance of cognitive and attention tasks challenges the prevailing view of their primary function in motor control. The specific roles of the basal ganglia and the cerebellum in cognition, however, have been difficult to identify. At least three functional hypotheses regarding their roles have been proposed. The first hypothesis suggests that their main function is to switch attentional set. The second hypothesis states that they provide error signals regarding stimuli or rewards. The third hypothesis is that they operate as an internal timing system, providing a precise representation of temporal information. Using functional magnetic resonance imaging, we tested these three hypotheses using a task‐switching experiment with a 2 × 2 factorial design varying timing (random relative to fixed) and task order (unpredictable relative to predictable). This design allowed us to test whether switching between tasks, timing irregularity and/or task order unpredictability activate the basal ganglia and/or the cerebellum. We show that the cerebellum is primarily activated with timing irregularity while the anterior striatum is activated with task order unpredictability, supporting their distinctive roles in two forms of readjustment. Task order unpredictability alone, independent of reward delivery, is sufficient to induce striatal activation. In addition, activation of the cerebellum and basal ganglia were not specific to switching attention because these regions were both activated during switching between tasks and during the simultaneous maintenance of two tasks without switching between them.
A novel stereocilia defect in sensory hair cells of the deaf mouse mutant Tasmanian devil
Authors: Erven Alexandra , Skynner Michael J. , Okumura Katsuzumi , Takebayashi Shin‐ichiro , Brown Steve D. M. , Steel Karen P. , Allen Nicholas D. 
Published: March 2003

AbstractStereocilia are specialized actin‐filled, finger‐like processes arrayed in rows of graded heights to form a crescent or W‐shape on the apical surface of sensory hair cells. The stereocilia are deflected by the vibration of sound, which opens transduction channels and allows an influx of ions to depolarize the hair cell, in turn triggering synaptic activity. The specialized morphology and organization of the stereocilia bundle is crucial in the process of sensory transduction in the inner ear. However, we know little about the development of stereocilia in the mouse and few molecules that are involved in stereocilia maturation are known. We describe here a new mouse mutant with abnormal stereocilia development. The Tasmanian devil (tde) mouse mutation arose by insertional mutagenesis and has been mapped to the middle of chromosome 5. Homozygotes show head‐tossing and circling and have raised thresholds for cochlear nerve responses to sound. The gross morphology of the inner ear was normal, but the stereocilia of cochlear and vestibular hair cells are abnormally thin, and they become progressively disorganized with increasing age. Ultimately, the hair cells die. This is the first report of a mutant showing thin stereocilia. The association of thin stereocilia with cochlear dysfunction emphasizes the critical role of stereocilia in auditory transduction, and the discovery of the Tasmanian devil mutant provides a resource for the identification of an essential molecule in hair cell function.
Impaired acquisition in the water maze and hippocampal long‐term potentiation after chronic prenatal ethanol exposure in the guinea‐pig
Authors: Richardson D. P. , Byrnes M. L. , Brien J. F. , Reynolds J. N. , Dringenberg H. C. 
Published: March 2003

AbstractIn the hippocampus, the CA1 region is selectively vulnerable to the effects of chronic prenatal ethanol exposure. In the guinea‐pig, the number of CA1 pyramidal cells is decreased after chronic prenatal ethanol exposure. We tested the hypotheses that chronic prenatal ethanol exposure (through maternal ethanol ingestion) results in impairments in spatial learning and short‐ and long‐term plasticity in the CA1 region of the postnatal guinea‐pig hippocampus. Timed, pregnant guinea‐pigs were treated with ethanol (4 g/kg maternal body weight/day), isocaloric sucrose/pair‐feeding, or water throughout gestation. Offspring were studied between postnatal days 40 and 80. In the Morris water maze, animals exposed to ethanol prenatally showed slower acquisition of an escape response to a hidden platform over 5 days of training. The amplitude of the field excitatory postsynaptic potential in the CA1 region in response to contralateral CA3 stimulation was decreased in offspring exposed to ethanol prenatally. Two forms of short‐term plasticity (paired‐pulse and frequency facilitation) were unaffected by chronic prenatal ethanol exposure. Long‐term potentiation (LTP) in response to high‐frequency CA3 stimulation was induced reliably and maintained over 60 min in isocaloric‐sucrose and water control animals. However, LTP failed to be induced in the CA1 area of the hippocampus in prenatal ethanol‐exposed offspring. These data show that chronic prenatal ethanol exposure, through maternal ethanol administration, impairs spatial performance and LTP in CA1 neurons. Hippocampal dysfunction could contribute importantly to the cognitive and behavioural deficits resulting from chronic prenatal ethanol exposure.
Development of two transmitter release components during the critical period for imprinting in the chick IMHV
Authors: Kiyosue Kazuyuki , Shimabayashi Eiko , Taguchi Takahisa 
Published: March 2003

AbstractTransmitter release at an excitatory synapse has two components, fast synchronous and slow asynchronous transmitter release. Using the whole cell recording technique, we investigated the developmental properties of neurotransmitter release, which is composed of the two components in the intermediate and medial part of the hyperstriatum ventral (IMHV) of chicks during the critical period for imprinting. Analysis of the paired‐pulse responses revealed that the depression of the excitatory postsynaptic currents (EPSCs), driven mainly by fast synchronous release, was frequently observed in P0–1 chicks but not in those at P5–8. The spontaneous excitatory postsynaptic currents (sEPSCs) after the paired‐pulse stimulation, which were thought to be driven by asynchronous transmitter releases, were observed more frequently in P0–1 chicks than P5–8 chicks. Furthermore, examination of Ca2+ dependency in the evoked EPSCs showed that the amplitudes in P5–8 chicks were more sensitive to reduction of the extracellular Ca2+ concentration than younger chicks. Considering that the Ca2+ dependency of EPSCs is defined by both Ca2+ sensitivity and the proportion of each type of release machineries at the release site, these results indicate that the ratio of fast synchronous to slow asynchronous transmitter release machinery changed during the critical period. These changes may play critical roles in the capacity of the avian brain to consolidate novel experience in the immediate period after hatching.
Microarray analysis suggests the involvement of proteasomes, lysosomes, and matrix metalloproteinases in the response of motor neurons to root avulsion
Authors: Hu Jian , Fink David , Mata Marina 
Published: March 2003

AbstractWe used microarray analysis of RNA expression from punch samples from ventral horn of spinal cord to identify alterations in gene expression in motor neurons 3 days after proximal spinal root avulsion, a traumatic injury that results in the death of 80% of the motor neurons. This analysis identified the anticipated increases in expression of genes coding for proteins involved in the apoptosis cascades and abortive cell cycle re‐entry, as well as decreases in expression of genes coding for proteins related to neuronal functional activity, including groups of genes related to energy metabolism, transporter proteins, ion channels, and receptors. It was also found that cathepsins, metalloproteinases, and proteasome‐related protein products were highly up‐regulated in motor neurons following axotomy. Each of these products represent pathways that have been implicated in other models of neuronal damage, but which have not previously been described as a response to axotomy.
Mutation in hotfoot‐4J mice results in retention of δ2 glutamate receptors in ER
Authors: Matsuda Shinji , Yuzaki Michisuke 
Published: March 2003

AbstractThe orphan glutamate receptor δ2 is selectively expressed in Purkinje cells and plays a critical role in cerebellar function. Recently, the ataxia of hotfoot‐4J (ho‐4J) mice was shown to be caused by a 170–amino acid deletion in the N‐terminal region of δ2 receptors. To understand δ2 receptor function, we characterized these mutant receptors (δ2ho) in Purkinje cells. Immunohistochemical staining showed that δ2ho receptors of the ho‐4J homozygotes were abundantly expressed but localized to the Purkinje cell soma; in wild‐type mice, δ2 receptors were predominantly present at distal dendrites of Purkinje cells. In addition, δ2ho receptors of the ho‐4J mice were sensitive to endoglycosidase H, a finding suggesting that δ2ho receptors were not transported beyond the endoplasmic reticulum (ER) or cis‐Golgi apparatus. To gain further insights into the mechanisms of this phenomenon, we characterized δ2ho receptors in transfected HEK293 cells. δ2ho receptors expressed in HEK293 cells were also sensitive to endoglycosidase H. Immunohistochemical staining showed that δ2ho receptors colocalized with proteins retained in the ER. Furthermore, δ2ho receptors were not labelled by membrane‐impermeable biotinylation reagents. Coimmunoprecipitation assays showed that the intermolecular interaction of δ2ho receptors was significantly weaker than those of wild‐type δ2 receptors, a finding suggesting that the ho‐4J region is involved in oligomerization of δ2 receptors. Thus, δ2ho receptors were retained in the ER, probably by the quality control mechanism that detects unstable oligomers. We conclude that the absence of δ2 receptors on the cell surface by failed transport from the ER of Purkinje cells causes ataxia.
Upregulation of [3H]methyllycaconitine binding sites following continuous infusion of nicotine, without changes of α7 or α6 subunit mRNA: an autoradiography andin situhybridization study in rat brain
Authors: Mugnaini Manolo , Tessari Michela , Tarter Giorgio , Merlo Pich Emilio , Chiamulera Cristiano , Bunnemann Bernd 
Published: March 2003

AbstractIt is well established that exposure of experimental animals to nicotine results in upregulation of the α4β2‐subtype of neuronal nicotinic acetylcholine receptors (nAChRs). The aim of this study was to determine the effect of nicotine on the levels of α7‐nAChRs in rat brain, for which only partial information is available. Rats were infused with nicotine (3 mg/kg/day) or saline for 2 weeks and their brains processed for receptor autoradiography with [3H]methyllycaconitine (MLA), a radioligand with nanomolar affinity for α7‐nAChRs. In control rats binding was high in hippocampus, intermediate in cerebral cortex and hypothalamus, and low in striatum, thalamus and cerebellum. There was high correlation between the distribution of [3H]MLA binding sites and α7 subunit mRNA (r = 0.816). With respect to saline‐treated controls, nicotine‐treated rats presented higher [3H]nicotine binding in 11 out of 15 brain regions analysed (average increase 46 ± 6%). In contrast, only four regions showed greater [3H]MLA binding, among which the ventral tegmental area (VTA) and cingulate cortex (mean increase 32 ± 3%). No changes in α7 mRNA levels were observed after nicotine treatment. Similarly, there was no variation of α6 subunit transcript in the VTA, a region which may contain MLA‐sensitive (non‐α7)‐α6*‐nAChRs (Klinket al., 2001). In conclusion, nicotine increased [3H]MLA binding, although to a smaller extent and in a more restricted regional pattern than [3H]nicotine. The enhancement of binding was not paralleled by a significant change of α7 and α6 subunit transcription. Finally, the present results provide the first anatomical description of the distribution of [3H]MLA binding sites in rat brain.
GABAA receptor heterogeneity in histaminergic neurons
Authors: Sergeeva Olga A. , Eriksson Krister S. , Sharonova Irina N. , Vorobjev Vladimir S. , Haas Helmut L. 
Published: March 2003

AbstractHistaminergic neurons of the tuberomamillary nucleus display pacemaker properties; their firing rate is regulated according to behavioural state by gabaergic inhibition. Whole‐cell recordings and single‐cell RT‐PCR from acutely isolated rat tuberomamillary neurons were used to characterize GABA ‐evoked currents and to correlate them with the expression pattern of 12 GABAA receptor subunits. We report differences in sensitivity to GABA and zinc as well as in the modulation of IPSC‐decay times by zolpidem in histaminergic neurons expressing γ‐subunits at different levels. Immunocytochemistry and pharmacological analysis of whole‐cell GABA‐currents in these neurons revealed that all carry the γ2‐subunit protein and that all receptors contain at least one γ‐subunit. Neurons with different expression levels of γ‐subunits displayed a difference in cooperativity of GABA and zolpidem binding which we explain by the presence of one vs. two γ‐subunits in one receptor. Thus, we describe here native GABAA receptor function in relation to its stoichiometry.
Effect of melatonin administration on qPer2, qPer3, and qClock gene expression in the suprachiasmatic nucleus of Japanese quail
Authors: Yasuo Shinobu , Yoshimura Takashi , Bartell Paul A. , Iigo Masayuki , Makino Eri , Okabayashi Naritoshi , Ebihara Shizufumi 
Published: March 2003

AbstractTemporal changes of mRNA expression of three clock genes, qPer2, qPer3 and qClock, were studied in the suprachiasmatic nucleus (SCN) of Japanese quail under different light conditions, as well as under the condition of continuous melatonin. In addition, the expression of melatonin receptor genes, Mel1a and Mel1c, in the SCN were also examined. The expression of qPer2 mRNA showed robust oscillation during both light and dark (LD) 12:12 cycles and under constant dark conditions (DD), but did not exhibit circadian rhythmicity in constant light conditions (LL), instead being expressed at a consistently high level. Expression of qPer3 also showed robust oscillation under both LD and DD conditions. Unlike qPer2 however, qPer3 mRNA expression remained rhythmic under LL conditions. Contrary to the findings on the other clock genes, no remarkable rhythmicity was detectable in either light condition. Both Mel1a and Mel1c mRNAs were detected in the SCN, however, Mel1a mRNA levels were higher than Mel1c and showed daily rhythmicity. Although implantation of melatonin tubes caused constant high levels of plasma melatonin and consequently masked the endogenous daily melatonin rhythm, no significant differences in the expression pattern of any of the three clock genes were observed between birds with and without constant melatonin. In addition, a single injection of melatonin did not affect mRNA expression of these clock genes. These results suggest that melatonin does not affect transcription of clock genes, but may act on the mechanism of synchronization among SCN oscillatory cells.
Long‐lasting enhancement of corticostriatal neurotransmission by taurine
Authors: Chepkova A. N. , Doreulee N. , Yanovsky Y. , Mukhopadhyay D. , Haas H. L. , Sergeeva O. A. 
Published: March 2003

AbstractTaurine occurs at high concentrations in the forebrain and its distribution varies with (patho)physiological conditions; however, its role in neural function is poorly understood. We have now characterized its effects on corticostriatal synaptic transmission. Bath application of taurine (10 mm) to slices obtained from mice and rats exerted a biphasic action on corticostriatal field potentials. The fast and reversible inhibition by taurine was accompanied by a depolarization and conductance increase in medium spiny neurons and was sensitive to γ‐aminobutyric acid (GABA)A and glycine receptor (GlyR) antagonists. A long‐lasting enhancement (LLETAU) of field potentials was recorded after taurine withdrawal. The LLETAU was not prevented by N‐methyl‐d‐aspartate (NMDA)‐ or by GABAA receptor‐antagonists, but was sensitive to the GlyR‐antagonist strychnine and blocked by the competitive taurine uptake inhibitor guanidinoethylsulphonate (GES, 1 mm). GES at 10 mm evoked an enhancement of field potentials similar to LLETAU. LLETAU depended on protein kinase C activation as it was blocked by chelerythrine, but was unaffected by trifluoperazine, and thus independent of calmodulin. LLETAU was significantly smaller in juvenile than in mature rodents. Activation of GlyRs and the specific taurine transporter by taurine evoke a long‐lasting enhancement of corticostriatal transmission.
Differential induction and localization of mPer1 and mPer2 during advancing and delaying phase shifts
Authors: Yan Lily , Silver Rae 
Published: March 2003

AbstractThe mechanism whereby brief light exposure resets the mammalian circadian clock in a phase dependent manner is not known, but is thought to involve Per gene expression. At the behavioural level, a light pulse produces phase delays in early subjective night, phase advances in late subjective night, and no phase shifts in mid‐subjective night or subjective day. To understand the relationship between Per gene activity and behavioural phase shifts, we examined light‐induced mPer1 and mPer2 expression in the suprachiasmatic nucleus (SCN) of the mouse, in the subjective night, with a view to understanding SCN heterogeneity. In the VIP‐containing region of the SCN (termed ‘core’), light‐induced mPer1 expression occurs at all times of the subjective night, while mPer2 induction is seen only in early subjective night. In the remaining regions of the SCN (termed ‘shell’), a phase delaying light pulse produces no mPer1 but significant mPer2 expression, while a phase advancing light pulse produces no mPer2 but substantial mPer1 induction. Moreover, following a light pulse during mid‐subjective night, neither mPer1 nor mPer2 are induced in the shell. The results reveal that behavioural phase shifts occur only when light‐induced Per gene expression spreads from the core to the shell SCN, with mPer1 expression in shell corresponding to phase advances, and mPer2 corresponding to phase delays. The results indicate that the time course and the localization of light‐induced Per gene expression in SCN reveals important aspects of intra‐SCN communication.
Long‐term depression and long‐term potentiation in horizontal connections of the barrel cortex
Authors: Urban Joanna , Kossut Malgorzata , Hess Grzegorz 
Published: March 2003

AbstractSynaptic plasticity of horizontally orientated connections between barrels, in the barrel cortex of adult mice, was studied in slice preparations cut across rows of barrels. Field potentials were evoked in the middle of one barrel column (in layer IV or V) and recorded in the neighbouring barrel (in layer IV and V). In layer IV, long‐term depression (LTD) by 26.5 ± 5% was first induced by a low‐frequency stimulation (2 Hz) applied for 10 min. After 30 min, theta‐burst stimulation was delivered to previously depressed connections, resulting in long‐term potentiation (LTP) by 28.8 ± 11.8%. When theta‐burst stimulation was delivered without an earlier low‐frequency stimulation, no LTP was induced. Similar results were obtained in layer V connections (LTD: 40.6 ± 12.5%; LTP: 26.9 ± 12.5%). In layer IV, the application of 100 µm d,l‐2‐amino‐5‐phosphonovaleric acid (APV), an antagonist of NMDA receptors, blocked the induction of both LTD and LTP. These experiments show that a potential for synaptic plasticity is retained in granular and infragranular layers of adult mice.
Differential expression of c‐fos in subtypes of GABAergic cells following sensory stimulation in the cat primary visual cortex
Authors: Van der Gucht Estel , Clerens Stefan , Cromphout Kathy , Vandesande Frans , Arckens Lutgarde 
Published: March 2003

AbstractRecent immunocytochemical stainings on cat visual cortex, visually stimulated for 1 h, showed a strong induction of Fos expression in cortical neurons. We initiated immunocytochemical double staining experiments with different cytochemical markers to investigate the neurochemical and morphological character of these activated neurons showing Fos induction after sensory stimulation. Double staining with Fos and glutamic acid decarboxylase (GAD) demonstrated the presence of Fos in the nuclei of GABAergic neurons of the primary visual cortex. To further subdivide this Fos/GABAergic cell population we investigated whether Fos colocalized with parvalbumin, calbindin or calretinin. Colocalization of Fos with these calcium‐binding proteins delineated distinct neuronal subclasses of Fos‐immunoreactive neurons in supra‐ and infragranular layers of cat area 17. Quantitative analysis of the proportion of immunoreactive local circuit neurons revealed that 35% of the GABAergic neurons showed Fos induction in supragranular layers, whereas in infragranular layers a mere 10% of the GABAergic cells revealed Fos expression. Fos coexisted in about 24% of the calbindin‐immunopositive cells within supra‐ and infragranular layers, but only a minority of the parvalbumin and the calretinin neuronal subgroups were immunopositive for Fos in the corresponding layers of area 17. These findings suggest that visual stimulation induces Fos expression in distinct subsets of inhibitory neurons in cat primary visual cortex.
Visual information process in Williams syndrome: intact motion detection accompanied by typical visuospatial dysfunctions
Authors: Nakamura Miho , Kaneoke Yoshiki , Watanabe Kazuyoshi , Kakigi Ryusuke 
Published: March 2003

AbstractIt has been suggested that visuospatial cognitive disabilities seen in children with Williams syndrome (WMS) are related to a dysfunction of the dorsal stream in the visual information analysis system. We investigated whether visual motion detection is also impaired in WMS because it is one of the main functions of the dorsal stream. Using various psychophysical examinations and magnetoencephalography, we studied a child with WMS who had the typical features of the syndrome. We found profound impairments in the visuospatial cognitions, as previously reported in WMS. In contrast, he had normal ability for the direction discrimination of coherent motion on a background of randomly moving dots, and he perceived apparent motion as do normal children. Furthermore, the latencies of both responses to the coherent and incoherent motions as measured by magnetoencephalography were within the mean ± 2 SD among normal adults and the estimated origins were near the human homologue of V5/MT (visual area 5/middle temporal area). The results indicate that the visuospatial cognitive deficits in WMS can occur without impairment of the visual motion detection. We consider that the deficits are caused by a restricted dysfunction of the neural groups for position and three‐dimensional form perceptions in the dorsal stream of the visual system, though other possibilities are not excluded.