bluuebunny/crossref_metadata_2025_split huggingface dataset:
Brain‐derived neurotrophic factor induces long‐lasting Ca2+‐activated K+ currents in rat visual cortex neurons
Authors: Mizoguchi Yoshito , Monji Akira , Nabekura Junichi 
Published: March 2003

AbstractBrain‐derived neurotrophic factor (BDNF) increases postsynaptic intracellular Ca2+ and modulates synaptic transmission in various types of neurons. Ca2+‐activated K+ currents, opened mainly by intracellular Ca2+ elevation, contribute to hyperpolarization following action potentials and modulate synaptic transmission. We asked whether BDNF induces Ca2+‐activated K+ currents by postsynaptic elevation of intracellular Ca2+ in acutely dissociated visual cortex neurons of rats. Currents were analysed using the nystatin‐perforated patch clamp technique and imaging of intracellular Ca2+ mobilization with fura‐2. At a holding potential of −50 mV, BDNF application (20 ng/mL) for 1–2 min induced an outward current (IBDNF‐OUT; 80.0 ± 29.0 pA) lasting for more than 90 min without attenuation in every neuron tested. K252a (200 nm), an inhibitor of Trk receptor tyrosine kinase, and U73122 (3 μm), a specific phospholipase C (PLC)‐γ inhibitor, suppressed IBDNF‐OUT completely. IBDNF‐OUT was both charybdotoxin‐ (600 nm) and apamin‐ (300 nm) sensitive, suggesting that this current was carried by Ca2+‐activated K+ channels. BAPTA‐AM (150 μm) gradually suppressed IBDNF‐OUT. Fura‐2 imaging revealed that a brief application of BDNF elicited a long‐lasting elevation of intracellular Ca2+. These results show that BDNF induces long‐lasting Ca2+‐activated K+ currents by sustained intracellular Ca2+ elevation in rat visual cortex neurons. While BDNF, likely acting through the Trk B receptor, was necessary for the induction of long‐lasting Ca2+‐activated K+ currents via intracellular Ca2+ elevation, BDNF was not necessary for the maintenance of this current.
Astrocytes enhance lipopolysaccharide‐induced nitric oxide production by microglial cells
Authors: Solà Carme , Casal Carme , Tusell Josep M. , Serratosa Joan 
Published: March 2003

AbstractSeveral stimuli result in glial activation and induce nitric oxide (NO) production in microglial and astroglial cells. The bacterial endotoxin lipopolysaccharide (LPS) has been widely used to achieve glial activation in vitro, and several studies show that both microglial and, to a lesser extent, astroglial cell cultures produce NO after LPS treatment. However, NO production in endotoxin‐treated astrocyte cultures is controversial. We characterized NO production in microglial, astroglial and mixed glial cell cultures treated with lipopolysaccharide, measured as nitrite accumulation in the culture media. We also identified the NO‐producing cells by immunocytochemistry, using specific markers for the inducible NO synthase (iNOS) isoform, microglial and astroglial cells. Only microglial cells showed iNOS immunoreactivity. Thus, contaminating microglial cells were responsible for NO production in the secondary astrocyte cultures. We then analysed the effect of astrocytes on NO production by microglial cells using microglial–astroglial cocultures, and we observed that this production was clearly enhanced in the presence of astroglial cells. Soluble factors released by astrocytes did not appear to be directly responsible for such an effect, whereas nonsoluble factors present in the cell membrane of LPS‐treated astrocytes could account, at least in part, for this enhancement.
Expression and regulation of interleukin‐10 and interleukin‐10 receptor in rat astroglial and microglial cells
Authors: Ledeboer Annemarie , Brevé John J. P. , Wierinckx Anne , Van Der Jagt Saskia , Bristow Adrian F. , Leysen Josée E. , Tilders Fred J. H. , Van Dam Anne‐Marie 
Published: March 2003

AbstractActivated glial cells crucially contribute to brain inflammatory responses. Interleukin‐10 (IL‐10) is an important modulator of glial cell responses in the brain. In the present study we describe the expression of IL‐10 and the IL‐10 receptor (IL‐10R1) in primary cocultures of rat microglial and astroglial cells. Using quantitative RT‐PCR and ELISA, we show that IL‐10 mRNA expression and subsequent IL‐10 secretion is time‐dependently induced by lipopolysaccharide (LPS). IL‐10R1, however, is constitutively expressed in glial cell cocultures, as shown by RT‐PCR and immunocytochemistry. Radioligand binding studies using 125I‐IL‐10 reveal that rat glial cells express a single binding site with an apparent affinity of approximately 600 pm for human IL‐10. Observations in enriched cultures of either microglial or astroglial cells indicate that both cell types express IL‐10 mRNA and are capable of secreting IL‐10. Both cell types also express IL‐10R1 mRNA and protein. However, in glial cell cocultures immunoreactive IL‐10R1 protein is predominantly observed in astrocytes, suggesting that microglial expression of IL‐10R1 in cocultures is suppressed by astrocytes. In addition, exogenous IL‐10 is highly potent in down‐regulating LPS‐induced IL‐1β and IL‐10 mRNA, and, at a higher dose, IL‐10R1 mRNA in untreated and LPS‐treated cultures, suggesting that IL‐10 autoregulates its expression and inhibits that of IL‐1β at the transcriptional level. Together the findings support the concept that IL‐10, produced by activated microglial and astroglial cells, modulates glia‐mediated inflammatory responses through high‐affinity IL‐10 receptors via paracrine and autocrine interactions.
Stimulation of cortical acetylcholine release following blockade of ionotropic glutamate receptors in nucleus accumbens
Authors: Neigh‐McCandless Gretchen , Kravitz B. Adar , Sarter Martin , Bruno John P. 
Published: March 2003

AbstractIn vivo microdialysis techniques were used to determine the ability of glutamate receptors within the nucleus accumbens to trans‐synaptically modulate the basal forebrain cortical cholinergic system. Rats were implanted with a dialysis probe in the medial prefrontal cortex to measure changes in cortical acetylcholine efflux and in the ipsilateral nucleus accumbens to locally manipulate glutamate receptor activity. Intra‐accumbens perfusion of the broad spectrum ionotropic glutamate receptor antagonist kynurentate (1.0, 5.0 mm) led to a dose‐dependent increase (maximum of 200%) in cortical acetylcholine efflux. This stimulated efflux was reproduced with the intra‐accumbens perfusion of the AMPA/kainate antagonist DNQX (0.1, 0.25, 2.5 mm; maximum increase of 200%) or the NMDA antagonist D‐CPP (10.0, 100.0, 200 µM; maximum increase of 400%). These results reveal a significant glutamatergic tone within the accumbens of awake rats and support the hypothesis that accumbens efferents to basal forebrain modulate the excitability of the basal forebrain cortical cholinergic system.
Caspase‐mediated death of newly formed neurons in the adult rat dentate gyrus following status epilepticus
Authors: Ekdahl Christine T. , Mohapel Paul , Weber Ekkehard , Bahr Ben , Blomgren Klas , Lindvall Olle 
Published: March 2003

AbstractA large proportion of cells that proliferate in the adult dentate gyrus under normal conditions or in response to brain insults exhibit only short‐term survival. Here, we sought to determine which cell death pathways are involved in the degeneration of newly formed neurons in the rat dentate gyrus following 2 h of electrically induced status epilepticus. We investigated the role of three families of cysteine proteases, caspases, calpains, and cathepsins, which can all participate in apoptotic cell death. Status epilepticus increased the number of bromodeoxyuridine (BrdU)‐positive proliferated cells in the subgranular zone of the dentate gyrus. At the time of maximum cell proliferation, immunohistochemical analyses revealed protein expression of active caspase‐cleaved poly (ADP‐ribose) polymerase (PARP) in ≈ 66% of the BrdU‐positive cells, while none of them expressed cathepsin B or the 150‐kDa calpain‐produced fodrin breakdown product. To evaluate the importance of cysteine proteases in regulating survival of the newly formed neurons, we administered intracerebroventricular infusions of a caspase inhibitor cocktail (zVAD‐fmk, zDEVD‐fmk and zLEHD‐fmk) over a 2‐week period, sufficient to allow for neuronal differentiation, starting 1 week after the epileptic insult. Increased numbers of cells double‐labelled with BrdU and neuron‐specific nuclear protein (NeuN) marker were detected in the subgranular zone and granule cell layer of the caspase inhibitor‐treated rats. Our data indicate that caspase‐mediated cell death pathways are active in progenitor cell progeny generated by status epilepticus and compromise survival during neuronal differentiation.
Descending pathways controlling visually guided updating of reaching in cats
Authors: Pettersson L.‐G. , Perfiliev S. 
Published: March 2003

AbstractThis study uses a previously described paradigm (Pettersson et al., 1997) to investigate the ability of cats to change the direction of ongoing reaching when the target is shifted sideways; the effect on the switching latency of spinal cord lesions was investigated. Large ventral lesions transecting the ventral funicle and the ventral half of the lateral funicle gave a 20–30 ms latency prolongation of switching in the medial (right) direction, but less prolongation of switching directed laterally (left), and in one cat the latencies of switching directed laterally were unchanged. It may be inferred that the command for switching in the lateral direction can be mediated by the dorsally located cortico‐ and rubrospinal tracts whereas the command for short‐latency switching in the medial direction is mediated by ventral pathways. A restricted ventral lesion transecting the tectospinal pathway did not change the switching latency. Comparison of different ventral lesions revealed prolongation of the latency if the lesion included a region extending dorsally along the ventral horn and from there ventrally as a vertical strip, so it may be postulated that the command for fast switching, directed medially, is mediated by a reticulospinal pathway within this location. A hypothesis is forwarded suggesting that the visual control is exerted via ponto‐cerebellar pathways.
Inhibition of tonic spinal glutamatergic activity induces antinociception in the rat
Authors: Tambeli Claudia H. , Parada Carlos A. , Levine Jon D. , Gear Robert W. 
Published: March 2003

SummaryInhibition of tonic activity in spino‐supraspinal projection neurons induces heterosegmental antinociception that is mediated by opioid receptors in nucleus accumbens. To investigate the origin of this tonic activity, we evaluated the ability of inhibiting neurotransmission in the spinal cord to produce heterosegmental antinociception in the trigeminal nociceptive jaw‐opening reflex (JOR) in the rat. Spinal intrathecal administration of calcium channel blockers attenuated the JOR, suggesting that the tonic spinal activity depends on synaptic input. To identify the excitatory neurotransmitter receptors involved, selective antagonists for AMPA/kainate, mGluR1, NMDA or NK1 receptors were administered intrathecally to the spinal cord. The AMPA/kainate and mGluR1 receptor antagonists, but not the NMDA or NK1 receptor antagonists, induced antinociception, which was antagonized by intra‐accumbens administration of the selective µ‐opioid receptor antagonist CTOP. Thus, inhibition of tonic spinal glutamatergic activity resulted in supraspinally mediated antinociception. As this antinociception occurred in the absence of interventions that would produce a facilitated nociceptive state, this tonic glutamatergic activity is important in setting nociceptive threshold.
Dynamic patterns of BDNF expression in injured sensory neurons: differential modulation by NGF and NT‐3
Authors: Karchewski L. A. , Gratto K. A. , Wetmore C. , Verge V. M. K. 
Published: March 2003

AbstractIt has been suggested that altered retrograde neurotrophin support contributes to the phenotypic switch observed in BDNF expression in injured sensory neurons. Thus, modulatory influences of NGF and NT‐3 on BDNF expression in injured adult rat DRG neurons were examined using in situ hybridization and immunohistochemical approaches. Quantitative analysis reveals a biphasic response to sciatic nerve injury, whereby in the first day following injury, BDNF expression is up‐regulated in ≈83% of injured neurons including all small neurons, and a larger pool of trkB expressing neurons than in intact. By 1 week and up to 3 weeks later expression is still seen in ≈66% of injured neurons, but the characteristic phenotypic switch in the subpopulations expressing BDNF occurs, whereby expression in the trkA population is reduced and expression in trkB‐ and in trkC‐positive neurons is elevated. NGF infusion results in elevated levels of BDNF expression in both intact and injured trkA‐positive neurons, accompanied by reduced trkB expression. NT‐3 acts in an opposite fashion effecting a down‐regulation in BDNF expression in intact neurons and preventing/reducing the injury‐associated increases in BDNF expression in both trkC‐ and nontrkC‐expressing subpopulations of injured neurons. These effects suggest NGF can regulate BDNF expression in trkA‐expressing neurons regardless of the axonal state and that elevated levels of BDNF may contribute to the down‐regulation in trkB expression associated with these states. Furthermore, the findings demonstrate that NT‐3 can act in an antagonistic fashion to NGF in the regulation of BDNF expression in intact neurons, and mitigate BDNF's expression in injured neurons.
Visual–vestibular interactive responses in the macaque ventral intraparietal area (VIP)
Authors: Bremmer Frank , Klam François , Duhamel Jean‐René , Ben Hamed Suliann , Graf Werner 
Published: March 2003

AbstractSelf‐motion detection requires the interaction of a number of sensory systems for correct perceptual interpretation of a given movement and an eventual motor response. Parietal cortical areas are thought to play an important role in this function, and we have thus studied the encoding of multimodal signals and their spatiotemporal interactions in the ventral intraparietal area of macaque monkeys. Thereby, we have identified for the first time the presence of vestibular sensory input to this area and described its interaction with somatosensory and visual signals, via extracellular single‐cell recordings in awake head‐fixed animals. Visual responses were driven by large field stimuli that simulated either backward or forward self‐motion (contraction or expansion stimuli, respectively), or movement in the frontoparallel plane (visual increments moving simultaneously in the same direction). While the dominant sensory modality in most neurons was visual, about one third of all recorded neurons responded to horizontal rotation. These vestibular responses were typically in phase with head velocity, but in some cases they could signal acceleration or even showed integration to position. The associated visual responses were always codirectional with the vestibular on‐direction, i.e. noncomplementary. Somatosensory responses were in register with the visual preferred direction, either in the same or in the opposite direction, thus signalling translation or rotation in the horizontal plane. These results, taken together with data on responses to optic flow stimuli obtained in a parallel study, strongly suggest an involvement of area VIP in the analysis and the encoding of self‐motion.
Heading encoding in the macaque ventral intraparietal area (VIP)
Authors: Bremmer Frank , Duhamel Jean‐René , Ben Hamed Suliann , Graf Werner 
Published: March 2003

AbstractWe recorded neuronal responses to optic flow stimuli in the ventral intraparietal area (VIP) of two awake macaque monkeys. According to previous studies on optic flow responses in monkey extrastriate cortex we used different stimulus classes: frontoparallel motion, radial stimuli (expansion and contraction) and rotational stimuli (clockwise and counter‐clockwise). Seventy‐five percent of the cells showed statistically significant responses to one or more of these optic flow stimuli. Shifting the location of the singularity of the optic flow stimuli within the visual field led to a response modulation in almost all cases. For the majority of neurons, this modulatory influence could be approximated in a statistically significant manner by a two‐dimensional linear regression. Gradient directions, derived from the regression parameters and indicating the direction of the steepest increase in the responses, were uniformly distributed. At the population level, an unbiased average response for the stimuli with different focus locations was observed. By applying a population code, termed ‘isofrequency encoding’, we demonstrate the capability of the recorded neuronal ensemble to retrieve the focus location from its population discharge. Responses to expansion and contraction stimuli cannot be predicted based on quantitative data on a neuron's frontoparallel preferred stimulus direction and the location and size of its receptive field. These results, taken together with data on polymodal motion responses in this area, suggest an involvement of area VIP in the analysis and the encoding of heading.
Calcium‐dependent acetylcholine release from Xenopus oocytes: simultaneous ionic currents and acetylcholine release recordings
Authors: Aleu Jordi , Blasi Joan , Solsona Carles , Marsal Jordi 
Published: March 2003

AbstractThe fusion of synaptic vesicles with presynaptic membranes is controlled by a complex network of protein–protein and protein–lipid interactions. SNAP‐25, syntaxin and synaptobrevin (SNARE complex) are thought to participate in the formation of the core of the membrane fusion machine but the molecular basis of SNARE interactions is not completely understood. Thus, it would be interesting to design experiments to test those relationships in a new model. Xenopus laevis oocytes are valuable tools for studying the molecular structure and function of ionic channels and neurotransmitter receptors. Here we show that SNARE proteins are present in native Xenopus oocytes and that those oocytes injected with acetylcholine and presynaptic plasma membranes extracted from the electric organ of Torpedo marmorata assume some of the functions of a cholinergic nerve terminal. Neurotransmitter release and macroscopic currents were recorded and analysed simultaneously in a single oocyte electrically depolarized: acetylcholine release was detected using a chemiluminiscent method and calcium entry was measured by exploiting the endogenous Ca2+‐activated chloride current of the oocyte with a two‐electrode voltage‐clamp system. Neurotransmitter release was calcium‐ and voltage‐dependent and partially reduced in the presence of several calcium channel blockers. Clostridial neurotoxins, both holotoxin and injected light‐chain forms, also inhibited acetylcholine release. We also studied the role of the SNARE complex in synaptic transmission and membrane currents by using monoclonal antibodies against SNAP‐25, syntaxin or VAMP/synaptobrevin. The use of antibodies against VAMP/synaptobrevin, SNAP‐25 and syntaxin inhibited acetylcholine release, as did clostridial toxins. However, macroscopic currents were only modified either by syntaxin antibody or by Botulinium‐C1 neurotoxin. This model constitutes a new approach for understanding the vesicle exocytosis processes.
Bilateral parieto‐frontal network for verbal working memory: an interference approach using repetitive transcranial magnetic stimulation (rTMS)
Authors: Mottaghy Felix M. , Döring Tobias , Müller‐Gärtner Hans‐Wilhelm , Töpper Rudolf , Krause Bernd J. 
Published: March 2003

AbstractVerbal working memory has been attributed to a left‐dominant neuronal network, including parietal, temporal and prefrontal cortical areas. The current study was designed to evaluate the contribution of these brain regions to verbal working memory processes and to assess possible hemispheric asymmetry. The effect of repetitive transcranial stimulation (rTMS) on performance in a verbal working memory task both during, and after an rTMS train (110% of individual motor threshold, 4 Hz) over nine different scalp locations was studied [bilateral middle frontal gyrus (MFG), bilateral supramarginal gyrus (SMG), bilateral inferior parietal cortex (IP) and three different midline control sites]. Significant performance deterioration was observed during rTMS over the left and right MFG and left and right IP. There was no consistent interference effect across subjects over the left or right SMG and the three different midline control sites. The interference effect with the given stimulation parameters did not last beyond the rTMS train itself. The data provide evidence for a symmetrical, bilateral parieto‐frontal verbal working memory network. The data are discussed with respect to the competing ideas of a parieto‐frontal central executive network vs. a network that processes the inherent semantic and object features of the visually presented verbal stimuli in parallel.
Substantia nigra pars reticulata neurons code initiation of a serial pattern: implications for natural action sequences and sequential disorders
Authors: Meyer‐Luehmann Melanie , Thompson Jeffrey F. , Berridge Kent C. , Aldridge J. Wayne 
Published: March 2003

AbstractSequences of movements are initiated abnormally in neurological disorders involving basal ganglia dysfunction, such as Parkinson's disease or Tourette's syndrome. The substantia nigra pars reticulata (SNpr) is one of the two primary output structures of the basal ganglia. However, little is known about how substantia nigra mediates the initiation of normal movement sequences. We studied its role in coding initiation of a sequentially stereotyped but natural movement sequence by recording neuronal activity in SNpr during behavioural performance of ‘syntactic grooming chains’. These are rule‐governed sequences of up to 25 grooming movements emitted in four predictable (syntactic) phases, which occur spontaneously during grooming behaviour by rats and other rodents. Our results show that neuronal activation in central SNpr codes the onset of this entire rule‐governed sequential pattern of grooming actions, not elemental grooming movements. We conclude that the context of sequential pattern may be more important than the elemental motor parameters in determining SNpr neuronal activation.
Changes in Fos expression in the rat brain after unilateral lesions of the anterior thalamic nuclei
Authors: Jenkins Trisha A. , Dias Rebecca , Amin Eman , Aggleton John P. 
Published: March 2003

AbstractActivity of the immediate early gene c‐fos was compared across hemispheres in rats with unilateral anterior thalamic lesions. Fos protein was quantified after rats performed a spatial working memory test in the radial‐arm maze, a task that is sensitive to bilateral lesions of the anterior thalamic nuclei. Unilateral anterior thalamic lesions produced evidence of a widespread hippocampal hypoactivity, as there were significant reductions in Fos counts in a range of regions within the ipsilateral hippocampal formation (rostral CA1, rostral dentate gyrus, ‘dorsal’ hippocampus, presubiculum and postsubiculum). A decrease in Fos levels was also found in the rostral and caudal retrosplenial cortex but not in the parahippocampal cortices or anterior cingulate cortices. The Fos changes seem most closely linked to sites that are also required for successful task performance, supporting the notion that the anterior thalamus, retrosplenial cortex and hippocampus form key components of an interdependent neuronal network involved in spatial mnemonic processing.