bluuebunny/crossref_metadata_2025_split huggingface dataset:
Contribution of intralaminar thalamic nuclei to spike‐and‐wave‐discharges during spontaneous seizures in a genetic rat model of absence epilepsy
Authors: Seidenbecher Thomas , Pape Hans‐Christian 
Published: March 2003

AbstractIn an epileptic rat model of generalized absence epilepsies, the genetic absence epilepsy rats from Strasbourg (GAERS), simultaneous recordings of bilateral epidural electroencephalogram (EEG) of the prefrontal cortex and unit activity of neurons in the intralaminar centrolateral (CL) and paracentral thalamic nucleus (PC) were performed under neurolept‐anaesthesia (fentanyl–dehydrobenzperidol analgesia). Spike‐and‐wave (SW) seizures in these rats are characterized by generalized 7–10 Hz spike‐and‐wave discharges (SWDs) on the EEG. All neurons recorded in intralaminar thalamic nuclei during spontaneous SWDs showed high‐frequency (average 368 Hz, range 200–500 Hz), burst‐like activity, which occurred in a highly synchronized fashion with every SWD or with alternating SWD‐complexes. Burst discharges in intralaminar neurons were delayed by 13.1 ms (CL) and 12.7 ms (PC), with respect to the spike component of a given SWD on the EEG, whereas burst discharges in the ventrobasal thalamus (VB) and in the rostral nucleus reticularis thalami (rRT) preceded the spike component by 17.8 ms and 8.3 ms, respectively. The onset of SWDs on the EEG was preceded by a tonic firing pattern (20–50 Hz) in about one third of CL and PC neurons. Microiontophoretic application of the γ‐aminobutyric acid (GABA)A receptor antagonist bicuculline aggravated, whereas, the glutamate receptor antagonists DNQX and APV dampened, SWD‐related discharges in PC and CL; the GABAB receptor antagonist CGP 35347 had no measurable effect. These data indicate that intrathalamic nuclei are recruited rhythmically during SWDs, through mechanisms that seem to rely on a delayed glutamatergic excitation modulated by GABAergic influences, rather than a GABA‐mediated rebound burst activity typical of relay cells. The finding of a temporal delay of SWD‐related activity in intrathalamic, compared with ‘specific’ thalamic relay nuclei, does not support the notion of a leading or pacemaker role in SWD generation. It is, however, rather suggestive of a function of intrathalamic neurons during synchronization and maintenance of neuronal oscillations, and these intrathalamic neurons may be recruited through glutamatergic corticofugal inputs.
The cortical connections of area V6: an occipito‐parietal network processing visual information
Authors: Galletti Claudio , Gamberini Michela , Kutz Dieter F. , Fattori Patrizia , Luppino Giuseppe , Matelli Massimo 
Published: March 2003

AbstractThe aim of this work was to study the cortical connections of area V6 by injecting neuronal tracers into different retinotopic representations of this area. To this purpose, we first functionally recognized V6 by recording from neurons of the parieto‐occipital cortex in awake macaque monkeys. Penetrations with recording syringes were performed in the behaving animals in order to inject tracers exactly at the recording sites. The tracers were injected into the central or peripheral field representation of V6 in different hemispheres. Irrespective of whether injections were made in the centre or periphery, area V6 showed reciprocal connections with areas V1, V2, V3, V3A, V4T, the middle temporal area /V5 (MT/V5), the medial superior temporal area (MST), the medial intraparietal area (MIP), the ventral intraparietal area (VIP), the ventral part of the lateral intraparietal area and the ventral part of area V6A (V6AV). No labelled cells or terminals were found in the inferior temporal, mesial and frontal cortices. The connections of V6 with V1, and with all the retinotopically organized prestriate areas, were organized retinotopically. The connection of V6 with MIP suggests a visuotopic organization for this latter. Labelling in V6A and VIP after either central or peripheral V6 injections was very similar in location and extent, as expected on the basis of the nonretinotopic organization of these areas. We suggest that V6 plays a pivotal role in the dorsal visual stream, by distributing the visual information coming from the occipital lobe to the sensorimotor areas of the parietal cortex. Given the functional characteristics of the cells of this network, we suggest that it could perform the fast form and motion analyses needed for the visual guiding of arm movements as well as their coordination with the eyes and the head.
GABAA receptor subunit interactions important for benzodiazepine and zinc modulation: a patch‐clamp and single cell RT‐PCR study
Authors: Alsbo Carsten W. , Kristiansen Uffe , Møller Flemming , Hansen Suzanne L. , Johansen Flemming Fryd 
Published: March 2003

AbstractThe expression of mRNAs for the GABAA receptor subunits α1, α6, β2, β3, γ2 and δ in single mouse cerebellar granule cells and cortical interneurons were analysed by RT‐PCR and correlated to their midazolam and zinc modulation of agonist‐induced receptor currents. The registration of molecular and electrophysiological data from each cell allowed us to estimate the significance of individual subunits and their two‐factor interaction for modulation. The presence of α6 decreased midazolam modulation, but statistical analysis also suggested interactions of α6 with β3 and γ2 with respect to midazolam modulation. Zinc modulation was decreased by the presence of γ2, and analysis points to an β3 effect as well as an interaction between γ2 and δ in zinc modulation. Thus, our model confirmed, in single native cells, the known effects of α6 in midazolam and γ2 in zinc modulation, and additionally pointed to significant subunit interactions that need to be further tested in recombinant receptors. The present study offers a method to identify subunit interactions in heteromeric receptor complexes.
Human brain carboxypeptidase B, which cleaves β‐amyloid peptides in vitro, is expressed in the endoplasmic reticulum of neurons
Authors: Matsumoto Akira , Itoh Kyoko , Seki Tsuneyoshi , Motozaki Kenjiro , Matsuyama Shogo 
Published: March 2003

AbstractIntracellular localization of novel human brain carboxypeptidase B (HBCPB) was investigated in human hippocampus, using immunohistochemistry by confocal laser microscopy and biochemical purification of the homogenate by density gradient ultracentrifugation. The former revealed that the majority of HBCPB was expressed in the endoplasmic reticulum, in which the HBCPB‐specific C14‐module immunoreactivity was colocalized with GRP78 immunoreactivity, a stress 70 heat shock protein specifically expressed in the endoplasmic reticulum. The latter showed that anti‐C14‐module immunoreactivity and prepro‐HBCPB immunoreactivity were both enriched in the microsome fraction, especially in that of the endoplasmic reticulum‐density fraction of normal human hippocampal homogenates from various sources. However, HBCPB prepared from human hippocampus showed exopeptidase activity for synthetic β‐amyloid 1–42 peptide, in which Aβ X‐42 C‐terminus immunoreactivity was decreased in a fashion dose‐dependent of the amount of the protease added. These findings indicate that HBCPB, which is expressed in the endoplasmic reticulum of a group of neuronal perikarya, may play an important physiological role in degradation of β‐amyloid 1–42, which is specifically generated in the endoplasmic reticulum of human and rodent neurons and is also regarded as the most pathogenic and aggregatable species among all β‐amyloid peptides.
An activity‐dependent switch from facilitation to inhibition in the control of excitotoxicity by group I metabotropic glutamate receptors
Authors: Bruno Valeria , Battaglia Giuseppe , Copani Agata , Cespédes Virtudes M. , Galindo María F. , Ceña Valentín , Sánchez‐Prieto Jose , Gasparini Fabrizio , Kuhn Rainer , Flor Peter J. , Nicoletti Ferdinando 
Published: March 2003

AbstractActivation of group I metabotropic glutamate receptors (mGlu1 or ‐5 receptors) is known to either enhance or attenuate excitotoxic neuronal death depending on the experimental conditions. We have examined the possibility that these receptors may switch between two different functional modes in regulating excitotoxicity. In mixed cultures of cortical cells, the selective mGlu1/5 agonist, 3,5‐dihydroxyphenylglycine (DHPG), amplified neurodegeneration induced by a toxic pulse of NMDA. This effect was observed when DHPG was either combined with NMDA or transiently applied to the cultures prior to the NMDA pulse. However, two consecutive applications of DHPG consistently produced neuroprotection. Similar effects were observed with DHPG or quisqualate (a potent agonist of mGlu1/5 receptors) in pure cultures of cortical neurons virtually devoid of astrocytes. In cultures of hippocampal pyramidal neurons, however, only protective effects of DHPG were seen suggesting that, in these particular cultures, group I mGlu receptors were endogenously switched into a ‘neuroprotective mode’. The characteristics of the activity‐dependent switch from facilitation to inhibition were examined in mixed cultures of cortical cells. The switch in the response to DHPG was observed when the two applications of the drug were separated by an interval ranging from 1–45 min, but was lost when the interval was extended to 90 min. In addition, this phenomenon required the initial activation of mGlu5 receptors (as indicated by the use of subtype‐selective antagonists) and was mediated by the activation of protein kinase C. We conclude that group I mGlu receptors are subjected to an activity‐dependent switch in regulating excitotoxic neuronal death and, therefore, the recent ‘history’ of these receptors is critical for the response to agonists or antagonists.
Neuroimmunophilin ligands exert neuroregeneration and neuroprotection in midbrain dopaminergic neurons
Authors: Guo Xin , Dawson Valina L. , Dawson Ted M. 
Published: March 2003

AbstractImmunosuppressant drugs, like FK506, and nonimmunosuppressant compounds like, GPI1046 and L685818, are immunophilin ligands that specifically bind to immunophilins, like FK506 binding protein 12 (FKBP12). Several lines of evidence show that these ligands exert neurotrophic properties in neural injury models and in PC12 cells. However, the mechanism of the neurotrophic function of the immunophilin ligands is poorly known. In the present study, we use MPP+ and 6‐OHDA toxicity models to examine both neuroprotective and neuroregenerative effects of immunophilin ligands on primary cultures of midbrain dopaminergic neurons. We find that FK506, GPI1046 and L685818 at concentrations from 0.01 to 1 μm partially, but significantly, protect dopaminergic neurons against both MPP+ and 6‐OHDA toxicity. By Western blot analysis, we also find that all three compounds prevent tyrosine hydroxylase (TH) loss induced by MPP+ and 6‐OHDA treatments. Morphologic analysis of dopaminergic neurons, by immunocytochemistry, shows that MPP+ and 6‐OHDA cause the retraction and loss of neuronal processes, while FK506, GPI1046 and L685818 promote regeneration of these processes as indicated by increases in process number and length. To examine if FKBP12 is required for neurotrophic effects of immunophilin ligands, we cultured dopaminergic neurons from FKBP12 knockout mice and find that FK506 still protects dopaminergic neurons against MPP+ toxicity. These results suggest that FKBP12 is not essential for the neurotrophic properties of immunophilin ligands, and immunophilin ligands are a new class of neuroprotective and neuroregenerative agents that may have therapeutic potential in a variety of neurological disorders.
Gene expression profiles during long‐term memory consolidation
Authors: Cavallaro Sebastiano , Schreurs Bernard G. , Zhao Weiqin , D'Agata Velia , Alkon Daniel L. 
Published: March 2003

AbstractChanges in gene expression have been postulated to occur during long‐term memory (LTM). We used high‐density cDNA microarrays to assess changes in gene expression 24 h after rabbit eye blink conditioning. Paired animals were presented with a 400 ms, 1000 Hz, 82 dB tone conditioned stimulus that coterminated with a 100 ms, 60 Hz, 2 mA electrical pulse unconditioned stimulus. Unpaired animals received the same conditioned and unconditioned stimuli but presented in an explicitly unpaired manner. Differences in expression levels between paired and unpaired animals in the hippocampus and cerebellar lobule HVI, two regions activated during eye blink conditioning, indicated the involvement of novel genes as well as the participation of previously implicated genes. Patterns of gene expression were validated by in situ hybridization. Surprisingly, the data suggest that an underlying mechanism of LTM involves widespread decreased, rather than increased, gene expression. These results demonstrate the feasibility and utility of a cDNA microarray system as a tool for dissecting the molecular mechanisms of associative memory.
Electroencephalographic activity during perception of motion in childhood
Authors: Cochin S. , Barthelemy C. , Roux S. , Martineau J. 
Published: March 2003

AbstractThe purpose of the present study was to relate observations of biological motion to cortical activity by evaluation of the association of quantified electroencephalogram (qEEG) parameters with a video film projection. Thirty right‐handed healthy children (2–8‐year‐olds) viewed a video film showing still shots and moving shots with human movement or object movement. The EEG was recorded while children watched the video movie and was then subjected to spectral analysis; the spectral powers for theta, alpha and beta bands were matched with corresponding sequences of video film. The power values of each frequency band were analysed in a four‐way repeated‐measuresanova(Age × Hemisphere × Electrode × Sequence). Three main results were obtained: (i) younger children (2–4‐year‐olds) had higher power spectral values than older children (5–8‐year‐olds); (ii) greater EEG desynchronization of the left hemisphere was observed; (iii) observation of biological movement was related to a significant decrease in theta 1 and theta 2 power values of EEG in fronto‐temporal and central regions of the left hemisphere compared with visual perception of still shots or nonhuman movement. These results indicated some support for the theory that the sensori‐motor cortex and Broca's area are activated during visual observation of human motion.
Dissociable contributions of the orbitofrontal and lateral prefrontal cortex of the marmoset to performance on a detour reaching task
Authors: Wallis J. D. , Dias R. , Robbins T. W. , Roberts A. C. 
Published: March 2003

AbstractTo gain insight into the nature and neural specificity of the relationship between simple problem solving, inhibitory control and prefrontal cortex, comparison of the effects of excitotoxic lesions of the orbitofrontal and lateral prefrontal cortex were examined on the performance of common marmosets on a detour reaching task. Monkeys were required to inhibit reaching directly for food reward in a transparent box and instead make a detour reach around to the side of the box either having had (i) no prior experience on the task (experiment 1) or (ii) previous experience in reaching around the sides of an opaque box (experiment 2). Whilst monkeys with orbitofrontal lesions had difficulty in inhibiting direct reaches to visible food reward (experiment 1), they could resist this prepotent response tendency following extensive prior experience of detour reaching with an opaque box (experiment 2). In marked contrast, monkeys with lateral prefrontal lesions exhibited no difficulty in inhibiting reaching to visible food reward or acquiring detour reachingper se(experiment 1). However, having been given the opportunity to acquire an efficient detour reaching strategy to hidden food reward these lateral prefrontal lesioned monkeys were impaired at transferring this strategy to the new context in which the food reward was made visible (experiment 2). This double dissociation between the effects of orbitofrontal and lateral prefrontal lesions on detour reaching provides evidence for a clear distinction in the level of control over responding exerted by the orbitofrontal and lateral prefrontal cortex, consistent with hierarchical ordering of response control processes within prefrontal cortex.
Respiratory function in adult mice lacking the µ‐opioid receptor: role of δ‐receptors
Authors: Morin‐Surun Marie‐Pierre , Boudinot Eliane , Dubois Christelle , Matthes Hans W. , Kieffer Brigitte L. , Denavit‐Saubié Monique , Champagnat Jean , Foutz Arthur S. 
Published: March 2003

AbstractMice lacking the µ‐opioid receptor (MOR) provide a unique model to determine whether opioid receptors are functionally interactive. Recent results have shown that respiratory depression produced by δ‐opioid receptor agonists is suppressed in mice lacking the µ‐opioid receptor. Here we investigated the involvement of µ‐ and δ‐opioid receptors in the control of ventilation and µ/δ receptor interactions in brainstem rhythm‐generating structures. Unrestrained MOR–/– and wild‐type mice showed similar ventilatory patterns at rest and similar chemosensory responses to hyperoxia (100% O2), hypoxia (10% O2) or hypercapnia (5%CO2−95%O2). Blockade of δ‐opioid receptors with naltrindole affected neither the ventilatory patterns nor the ventilatory responses to hypoxia in MOR–/– and wild‐type mice. In‐vitro, respiratory neurons were recorded in the pre‐Bötzinger complex of thick brainstem slices of MOR–/– and wild‐type young adult mice. Respiratory frequency was not significantly different between these two groups. The δ2 receptor agonist deltorphin II (0.1–1.0 µm) decreased respiratory frequency in both groups whereas doses of the δ1 receptor agonist enkephalin[D‐Pen2,5] (0.1–1.0 µm) which were ineffective in wild‐type mice significantly decreased respiratory frequency in MOR–/– mice. We conclude that deletion of the µ‐opioid receptor gene has no significant effect on ensuing respiratory rhythm generation, ventilatory pattern, or chemosensory control. In MOR–/– mice, the loss of respiratory‐depressant effects of δ2‐opioid receptor agonists previously observed in vivo does not result from a blunted response of δ receptors in brainstem rhythm‐generating structures. These structures show an unaltered response to δ2‐receptor agonists and an augmented response to δ1‐receptor agonists.
Bimanual organization of manipulative forces: evidence from erroneous feedforward programming of precision grip
Authors: Serrien Deborah J. , Wiesendanger Mario 
Published: March 2003

AbstractThe objective of the present study was to investigate grip–load force regulation during a bimanual lifting task with two hand‐held objects. Various conditions were included during which the weight of one or both objects was changed in an unpredictable order every fourth trial. Results showed that force control of heavy weight movements preceded by light weight movements was not strongly influenced across trials. Conversely, force responses of light weight movements preceded by heavy weight movements were overestimated due to an augmented degree of grip force. However, successful updating of force output occurred after one trial. Furthermore, bimanual interactions between the grasping forces were observed, suggestive of a coordinative command that assimilated the individual response specifications. The latter also became apparent from a similar grip–load force ratio for both hands when the objects' physical properties had become predictable, independent of the forces that were produced according to the individual weight requirements. These data indicate that the grip–load force ratio is the controlled variable for bimanual manipulative behaviour.
Dendritic attenuation of synaptic potentials in the CA1 region of rat hippocampal slices detected with an optical method
Authors: Inoue Masashi , Hashimoto Yoshinori , Kudo Yoshihisa , Miyakawa Hiroyoshi 
Published: March 2003

AbstractWe directly measured fast excitatory postsynaptic potentials (EPSPs) along the dendrites of hippocampal CA1 pyramidal neurons by employing an optical method to study how synaptic potentials spread along the dendrites. Rat hippocampal slices were stained with a fluorescent voltage‐sensitive dye JPW1114 and optical signals were monitored with a 16 × 16 photodiode array system. A stimulating electrode was placed either at stratum lacunosum moleculare to activate perforant fibers that make synaptic contacts to the distal apical dendrites or at stratum oriens to induce EPSPs at the basal dendrites of CA1 pyramidal cells. CNQX‐sensitive components of the optical signals, which were assumed to be population EPSPs, were isolated. Propagation and attenuation of the CNQX components were successfully observed with the optical method. At the cell body layer, the peak of the CNQX‐sensitive component was delayed by 17.08 ± 1.64 ms from the input sites. Additionally we performed a simulation study to estimate the passive membrane parameters of the apical dendrites. Estimated apparent specific internal axial resistance (Ri) following stratum lacunosum moleculare stimulation was 76.0 ± 4.2 Ω·cm and apparent specific membrane resistance (Rm) was 27.8 ± 2.1 kΩ·cm2 (assuming the specific membrane capacitance of dendrites Cm = 1.6 µF/cm2). These values are comparable to those previously reported. When synaptic inputs were applied at stratum oriens, these apparent passive membrane parameters were different (high Ri and low Rm), suggesting that nonuniform dendritic membrane conductance or voltage‐dependent conductances which are active near the resting potential may contribute to the measured passive membrane properties.
Pyrogenic cytokines injected into the rat cerebral ventricle induce cyclooxygenase‐2 in brain endothelial cells and also upregulate their receptors
Authors: Cao Chunyu , Matsumura Kiyoshi , Shirakawa Noriyuki , Maeda Mitsuyo , Jikihara Ikuyo , Kobayashi Shigeo , Watanabe Yasuyoshi 
Published: March 2003

AbstractPeripheral immunological insults induce interleukin (IL)‐1β and IL‐6 in the brain. To elucidate the mechanism(s) of fever evoked by these brain‐derived cytokines, and possible interactions between them, we examined in rats: (i) whether cyclooxygenase‐2 is responsible for fever evoked by central injection of these cytokines; (ii) if so, where in the brain cyclooxygenase‐2 is induced; (iii) where the receptors for these cytokines are located; and (iv) how the expression of these receptors is influenced by the cytokines. Intracerebroventricular injection of these cytokines evoked fever that was suppressed by a cyclooxygenase‐2 inhibitor. Brain endothelium was the site of cyclooxygenase‐2 induction by these cytokines. IL‐1 receptor (IL‐1R) was constitutively expressed in brain endothelium, and its mRNA was further upregulated by either cytokine. IL‐6R mRNA was constitutively expressed in the cerebral cortex, and was newly induced in as yet unidentified cells in brain blood vessels by either cytokine. Messenger RNAs for cyclooxygenase‐2, IL‐1R, and IL‐6R were often observed in the same blood vessels. These results suggest that COX‐2 induced in brain endothelium is, at least in part, involved in the fever evoked by these cytokines, and that one possible interaction between these two cytokines is mutual upregulation of their receptors in the endothelium or perivascular cells, resulting in augmentation of their actions.