bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential participation of actin‐ and tubulin‐based vesicle transport systems during secretion in bovine chromaffin cells
Authors: Ñeco Patricia , Giner Daniel , Del Mar Francés María , Viniegra. Salvador , Gutiérrez Luis M. 
Published: August 2003

AbstractThe role of cytoskeletal elements in vesicle transport occurring during exocytosis was examined in adrenal medullary bovine chromaffin cells maintained in culture. Amperometric determination of depolarization‐dependent catecholamine release from individual intact cells treated with actin or myosin inhibitors showed alterations in the fast and slow phases of secretion when compared with untreated cells. In contrast, microtubule disassemblers or stabilizers have a moderate effect on secretion, only affecting the release of slow secretory components. In experiments using confocal dynamic microscopy we have observed the drastic effect of actin and myosin inhibitors in abolishing vesicle movement throughout the cytoplasm, and the inhibition of granule mobility in deep perinuclear regions caused by the microtubule stabilizers. Following loss of mobility, vesicles were associated with filaments of F‐actin or microtubules. In addition, the mobility of cortical vesicles was affected by actin–myosin inhibitors but not by microtubule inhibitors. The study of cortical cytoskeleton in living cells showed vesicles associated with dense tubular F‐actin structures, with microtubules appearing as low density networks. These findings suggest that the distribution and density of both cytoskeletal elements in the cortical region may influence the recruitment of vesicle pools during secretion.
High frequency stimulation of the subthalamic nucleus has beneficial antiparkinsonian effects on motor functions in rats, but less efficiency in a choice reaction time task
Authors: Darbaky Yassine , Forni Claude , Amalric Marianne , Baunez Christelle 
Published: August 2003

AbstractChronic subthalamic nucleus high frequency stimulation (STN HFS) improves motor function in Parkinson's disease. However, its efficacy on cognitive function and the mechanisms involved are less known. The aim of this study was to assess the effects of STN HFS in hemiparkinsonian awake rats performing different specific motor tests and a cognitive operant task. Unilateral STN HFS applied in unilaterally DA‐depleted rats decreased the apomorphine‐induced circling behaviour and reduced catalepsy induced by the neuroleptic haloperidol. DA‐depleted rats exhibited severe deficits in the operant task, among which the inability to perform the task was not alleviated by STN HFS. However, in a few animals showing less impairment, STN HFS significantly reduced the contralateral neglect induced by the lesion. These results are the first to demonstrate a beneficial effect of STN HFS applied in awake rats on basic motor functions. However, STN HFS appears to be less effective on impaired cognitive functions.
Adult neural progenitor cell grafts survive after acute spinal cord injury and integrate along axonal pathways
Authors: Vroemen Maurice , Aigner Ludwig , Winkler Juergen , Weidner Norbert 
Published: August 2003

AbstractThe main rationale for cell‐based therapies following spinal cord injury are: (i) replacement of degenerated spinal cord parenchyma by an axon growth supporting scaffold; (ii) remyelination of regenerating axons; and (iii), local delivery of growth promoting molecules. A potential source to meet these requirements is adult neural progenitor cells, which were examined in the present study. Fibroblast growth factor 2‐responsive adult spinal cord‐derived syngenic neural progenitor cells were either genetically modified in vitro to express green fluorescent protein (GFP) using retroviral vectors or prelabelled with bromodeoxyuridine (BrdU). Neural progenitor cells revealed antigenic properties of neurons and glial cells in vitro confirming their multipotency. This differentiation pattern was unaffected by retroviral transduction. GFP‐expressing or BrdU‐prelabelled neural progenitor cells were grafted as neurospheres directly into the acutely injured rat cervical spinal cord. Animals with lesions only served as controls. Three weeks postoperatively, grafted neural progenitor cells integrated along axonal profiles surrounding the lesion site. In contrast to observations in culture, grafted neural progenitor cells differentiated only into astro‐ and oligodendroglial lineages, supporting the notion that the adult spinal cord provides molecular cues for glial, but not for neuronal, differentiation. This study demonstrates that adult neural progenitor cells will survive after transplantation into the acutely injured spinal cord. The observed oligodendroglial and astroglial differentiation and integration along axonal pathways represent important prerequisites for potential remyelination and support of axonal regrowth.
Differential responsiveness of rat striatal nerve endings to the mitochondrial toxin 3‐nitropropionic acid: implications for Huntington's disease
Authors: Marti Matteo , Mela Flora , Ulazzi Linda , Hanau Stefania , Stocchi Sara , Paganini Francesca , Beani Lorenzo , Bianchi Clementina , Morari Michele 
Published: August 2003

AbstractRat striatal synaptosomes and slices were used to investigate the responsiveness of different populations of nerve terminals to 3‐nitropropionic acid (3‐NP), a suicide inhibitor of the mitochondrial enzyme succinate dehydrogenase, and to elucidate the ionic mechanisms involved. 3‐NP (0.3–3 mm) stimulated spontaneous γ‐aminobutyric acid (GABA), glutamate and [3H]‐dopamine efflux but left unchanged acetylcholine efflux from synaptosomes. This effect was associated with a >70% inhibition of succinate dehydrogenase, as measured in the whole synaptosomal population. The facilitation was not dependent on extracellular Ca2+ but relied on voltage‐dependent Na+ channel opening, because it was prevented by tetrodotoxin and riluzole. 3‐NP also elevated spontaneous glutamate efflux from slices but in a tetrodotoxin‐insensitive way. To investigate whether energy depletion could change the responsiveness of nerve endings to a depolarizing stimulus, synaptosomes were pretreated with 3‐NP and challenged with pulses of KCl evoking ‘quasi‐physiological’ neurotransmitter release. 3‐NP potentiated the K+‐evoked GABA, glutamate and [3H]‐dopamine release but inhibited the K+‐evoked acetylcholine release. The 3‐NP induced potentiation of GABA release was Ca2+‐dependent and prevented by tetrodotoxin and riluzole whereas the 3‐NP‐induced inhibition of acetylcholine release was tetrodotoxin‐ and riluzole‐insensitive but reversed by glipizide, an ATP‐dependent K+ channel inhibitor. We conclude that the responsiveness of striatal nerve endings to 3‐NP relies on activation of different ionic conductances, and suggest that the selective survival of striatal cholinergic interneurons following chronic 3‐NP treatment (as in models of Huntington's disease) may rely on the opening of ATP‐dependent K+ channels, which counteracts the fall in membrane potential as a result of mitochondrial impairment.
Callosal connections of dorso‐lateral premotor cortex
Authors: Marconi B. , Genovesio A. , Giannetti S. , Molinari M. , Caminiti R. 
Published: August 2003

AbstractThis study investigated the organization of the callosal connections of the two subdivisions of the monkey dorsal premotor cortex (PMd), dorso‐rostral (F7) and dorso‐caudal (F2). In one animal, Fast blue and Diamidino yellow were injected in F7 and F2, respectively; in a second animal, the pattern of injections was reversed. F7 and F2 receive a major callosal input from their homotopic counterpart. The heterotopic connections of F7 originate mainly from F2, with smaller contingent from pre‐supplementary motor area (pre‐SMA, F6), area 8 (frontal eye fields), and prefrontal cortex (area 46), while those of F2 originate from F7, with smaller contributions from ventral premotor areas (F5, F4), SMA‐proper (F3), and primary motor cortex (M1). Callosal cells projecting homotopically are mostly located in layers II–III, those projecting heterotopically occupy layers II–III and V–VI. A spectral analysis was used to characterize the spatial fluctuations of the distribution of callosal neurons, in both F7 and F2, as well as in adjacent cortical areas. The results revealed two main periodic components. The first, in the domain of the low spatial frequencies, corresponds to periodicities of cell density with peak‐to‐peak distances of approximately 10 mm, and suggests an arrangement of callosal cells in the form of 5‐mm wide bands. The second corresponds to periodicities of approximately 2 mm, and probably reflects a 1‐mm columnar‐like arrangement. Coherency and phase analyses showed that, although similar in their spatial arrangements, callosal cells projecting to dorsal premotor areas are segregated in the tangential cortical domain.
Independence of visuotopic representation and orientation map in the visual cortex of the cat
Authors: Buzás Péter , Volgushev Maxim , Eysel Ulf T. , Kisvárday Zoltán F. 
Published: August 2003

AbstractThe representations of visual space and stimulus orientation were mapped in the cat primary visual cortex using electrophysiological recordings supplemented with intrinsic signal optical imaging. The majority of units displaced up to 600 µm laterally had overlapping RFs both in orientation domains and around singularities of the orientation map. Quantitative comparison of these units revealed only a weak, positive correlation between the difference in their preferred orientations and RF separations (area 17: r = 0.09; area 18: r = 0.15). The occurrence of nonoverlapping RFs could be accounted for by random RF position scatter rather than by orientation difference between the units. Monte Carlo analysis showed that our findings are compatible with a locally smooth and linear representation of visual space that is not coupled to the representation of stimulus orientation. An important functional implication of the above map relationships is that positional information captured by the retina is faithfully transmitted into the cortex.
Corticospinal neurons up‐regulate a range of growth‐associated genes following intracortical, but not spinal, axotomy
Authors: Mason M. R. J. , Lieberman A. R. , Anderson P. N. 
Published: August 2003

AbstractThe failure of some CNS neurons to up‐regulate growth‐associated genes following axotomy may contribute to their failure to regenerate axons. We have studied gene expression in rat corticospinal neurons following either proximal (intracortical) or distal (spinal) axotomy. Corticospinal neurons were retrogradely labelled with cholera toxin subunit B prior to intracortical lesions or concomitantly with spinal lesions. Alternate sections of forebrain were immunoreacted for cholera toxin subunit B or processed for mRNA in situ hybridization for ATF3, c‐jun, GAP‐43, CAP‐23, SCG10, L1, CHL1 or krox‐24, each of which has been associated with axotomy or axon regeneration in other neurons. Seven days after intracortical axotomy, ATF3, c‐jun, GAP‐43, SCG10, L1 and CHL1, but not CAP‐23 or krox‐24, were up‐regulated by layer V pyramidal neurons, including identified corticospinal neurons. The maximum distance between the lesion and the neuronal cell bodies that up‐regulated genes varied between 300 and 500 µm. However, distal axotomy failed to elicit changes in gene expression in corticospinal neurons. No change in expression of any molecule was seen in the neocortex 1 or 7 days after corticospinal axotomy in the cervical spinal cord. The expression of GAP‐43, CAP‐23, L1, CHL1 and SCG10 was confirmed to be unaltered after this type of injury in identified retrogradely labelled corticospinal neurons. Thus, while corticospinal neuronal cell bodies fail to respond to spinal axotomy, these cells behave like regeneration‐competent neurons, up‐regulating a wide range of growth‐associated molecules if axotomized within the cerebral cortex.
Induced down‐regulation of neuropeptide Y‐Y1 receptors delays initiation of kindling
Authors: Benmaamar Ramla , Pham‐Lê Bich‐Thuy , Marescaux Christian , Pedrazzini Thierry , Depaulis Antoine 
Published: August 2003

AbstractNeuropeptide Y appears to modulate epileptic seizures differentially according to the receptor subtypes involved. In the hippocampus, neuropeptide Y expression and release are enhanced in different models of epileptogenesis. On the contrary, the expression of Y1 receptors is decreased and it has been shown that activation of these receptors has pro‐convulsant effects. The aim of our study was to investigate the role of Y1 receptors during hippocampal kindling epileptogenesis using (i) knock‐out mice lacking Y1 receptors and (ii) intrahippocampal infusion of Y1 antisense oligodeoxynucleotide in rats. Y1 knock‐out mice showed similar susceptibility to seizure induction and presented no difference in kindling development as compared with their control littermates. Conversely, local hippocampal down‐regulation of Y1 receptors during the first week of hippocampal kindling, induced by a local infusion of a Y1 antisense oligodeoxynucleotide, significantly increased seizure threshold intensity and decreased afterdischarge duration. A reverse effect was observed during the week following the infusion period, which was confirmed by a significant decrease in the number of hippocampal stimulations necessary to evoke generalized seizures. At the end of this second week, an up‐regulation of Y1 receptors was observed in kindled rats infused with the antisense as compared with the mismatch‐treated controls. Our results in the rat suggest that the down‐regulation of Y1 receptors in the hippocampus participates in the control of the initiation of epileptogenesis. The lack of an effect of the deficiency of Y1 receptors in the control of kindling development in Y1 knock‐out mice could be due to compensatory mechanisms.
Proton‐induced calcitonin gene‐related peptide release from rat sciatic nerve axons, in vitro, involving TRPV1
Authors: Fischer Michael J. M. , Reeh Peter W. , Sauer Susanne K. 
Published: August 2003

AbstractWe have shown previously that rat sciatic nerve axons in vitro express sensitivity to capsaicin and heat and responded to these stimuli with a Ca2+‐dependent and graded immunoreactive calcitonin gene‐related peptide release. Morphological evidence for stimulated vesicular exocytosis and for the vanilloid receptor TRPV1 in the axolemma of the unmyelinated nerve fibres has also been presented. Here we used solutions of low pH, high K+ or 47 °C to stimulate isolated desheathed sciatic nerves measuring immunoreactive calcitonin gene‐related peptide release. pH 6.1 increased immunoreactive calcitonin gene‐related peptide release by 31% over baseline and pH 5.2 and 4.3 caused a log‐linear concentration‐dependent increase of 137 and 265%, respectively. The effect of pH 3.4 was out of the linear range and not reversible. Stimulation in Ca2+‐free solutions and under increased intracellular Ca2+ buffering capacity strongly reduced the proton responses. The TRPV1 antagonists capsazepine and ruthenium red substantially reduced the effects of pH 5.2 but not pH 6.1. Combining a stimulus of 60 mm K+ with the subliminal pH 6.3 reduced the axonal immunoreactive calcitonin gene‐related peptide response by 88%. The noxious heat response at pH 6.3, however, was only reduced by 39%, suggesting a hidden sensitization to heat by low pH. This was supported by an effect of capsazepine to reduce the combined response to half, indicative of an involvement of TRPV1 in the sensitization but not in the axonal heat response itself that was found to be resistant to capsazepine. Axonal calcitonin gene‐related peptide release is thought to play a physiological role in activity‐dependent autoregulation of endoneurial blood flow. Axonal sensitivity to and sensitization by protons may be a pathophysiological mechanism involved in certain peripheral neuropathies.
Homer‐1a/Vesl‐1S enhances hippocampal synaptic transmission
Authors: Hennou Sonia , Kato Akihiko , Schneider Edith M. , Lundstrom Kenneth , Gähwiler Beat H. , Inokuchi Kaoru , Gerber Urs , Ehrengruber Markus U. 
Published: August 2003

AbstractHomer/Vesl proteins are involved in regulating metabotropic glutamate receptors, synaptogenesis, dendritic spine development and axonal pathfinding. We investigated the potential modulation of glutamatergic synaptic transmission by the immediate early gene product Homer‐1a/Vesl‐1S and by the constitutively expressed long‐form Homer‐1c/Vesl‐1L in CA1 pyramidal cells from cultured rat hippocampal slices. Semliki Forest virus vector‐mediated overexpression of Homer‐1a enhanced alpha‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) receptor function, but did not detectably affect N‐methyl‐d‐aspartate (NMDA) receptor function and presynaptic glutamate release. Overexpression of Homer‐1c, by contrast, did not alter synaptic transmission. To corroborate our electrophysiological results obtained in slice cultures, we performed quantitative immunocytochemistry in cultures of dissociated hippocampal neurons. Homer‐1a also increased synaptic clustering of AMPA but not NMDA receptors, whereas Homer‐1c had no detectable effect. Our results show that Homer‐1a potentiates synaptic AMPA receptor function, supporting a critical role for Homer‐1a in hippocampal synaptic plasticity.
Vestibular response kinematics in posterior parietal cortex neurons of macaque monkeys
Authors: Klam François , Graf Werner 
Published: August 2003

AbstractPerception of extrapersonal space is a fundamental requirement for accurate interaction with the environment and moving in it. Parietal cortical areas are thought to play an important role in this function. A significant sensory input to this area arrives from the vestibular system. We quantified neuronal responses in the ventral intraparietal area and the medial intraparietal area of awake head‐fixed macaque monkeys during classical vestibular sinusoidal stimulation protocols and with a newly developed random vestibular testing paradigm. The goal was to study more specifically the signal content of perietal vestibular neurons with respect to head movement kinematics. Traditional sinusoidal stimulation analysis revealed that about one‐third of the neurons responded in phase with either head position or head acceleration, besides classical head velocity tuning. Random vestibular stimulation revealed more complex signal profiles in the majority of neurons, although quantification of the kinematic variables that drove the neurons most effectively led to similar results to phase shift analysis. Thus, a majority of cells was principally driven by head velocity, and a minority by either acceleration or position. Nevertheless, random stimulation also revealed the simultaneous presence of all three kinematic response parameters (i.e. velocity, position and acceleration) in a majority of neurons. A minority of cells coded only two kinematic variables, i.e. head velocity coupled with either acceleration or position. Neurons coding only one kinematic variable were not found. We hereby demonstrate for the first time that central vestibular neurons carry several head movement kinematic variables simultaneously.
Encoding of direction and combination of movements by primate putamen neurons
Authors: Ueda Yasumasa , Kimura Minoru 
Published: August 2003

AbstractTo perform multiple movements in a preprogrammed order, the brain needs to compute both the visuospatial and temporal organization of such multiple movements. Previous studies revealed participation of the parietal and premotor areas in visuospatial processing, and of the supplementary motor and presupplementary motor areas in temporal structuring of multiple movements. In the basal ganglia, on the other hand, relatively little has been known about how the neuronal processing of the visuospatial and temporal structuring of multiple movements occurs. In the present study, monkeys performed combinations of hand movements, either a lever turn–lever turn or lever turn–button press. Combinations of the two movements were performed under visually instructed condition first, then under remembered condition. We found that activity of 43% (30/69) and 60% (42/69) of putamen neurons was selective to the preprogrammed combination of movements and to the direction of the first movement. The neurons preferring remembered condition were mainly observed in the dorsomedial part of the putamen, where most of neurons were also selective to both direction and combination of movements, while those in the ventrolateral part of the putamen were not selective to the instructed and remembered conditions. The results supported a hypothesis that the movement direction‐selective and the movement combination‐selective neuron activities in the striatum may play an indispensable role in the visuospatial and temporal organization of movements through the cortico‐basal ganglia loop system.
Decrease of adenosine A1 receptor density and of adenosine neuromodulation in the hippocampus of kindled rats
Authors: Rebola Nelson , Coelho Joana E. , Costenla Ana Rita , Lopes Luísa V. , Parada António , Oliveira Catarina R. , Soares‐da‐Silva Patrício , De Mendonça Alexandre , Cunha Rodrigo A. 
Published: August 2003

AbstractAdenosine is a neuromodulator that has been proposed to be a major endogenous anticonvulsant acting via A1 receptors. We tested if implementation of kindling through stimulation of the amygdala affected A1 receptor‐mediated neuromodulation in hippocampal slices taken from rats 4 weeks after the last stage 5 seizure. The A1 receptor agonist, N6‐cyclopentyladenosine (CPA) (6–100 nm), inhibited field excitatory postsynaptic potential (fEPSP) slope with an EC50 of 19.1–19.5 nm in control and sham‐operated rats, but was less potent in kindled rats (EC50 = 42.7 nm). This might result from a decreased number of A1 receptors in hippocampal nerve terminal membranes, because A1 receptor immunoreactivity decreased by 28 ± 3% and the binding density of the A1 receptor agonist [3H]R‐PIA decreased from 1702 ± 64 to 962 ± 78 fmol/mg protein in kindled compared with control rats. The tonic inhibition of hippocampal synaptic transmission by endogenous adenosine was also lower in kindled rats, because A1 receptor blockade with 50 nm 1,3‐dipropyl‐8‐cyclopentyladenosine (DPCPX) enhanced fEPSP slope by 23 ± 3% and θ‐burst‐induced long‐term potentiation by 94 ± 4% in control rats but was virtually devoid of effects in kindled rats. The evoked release of adenosine from hippocampal slices or nerve terminals was 56–71% lower in kindled rats probably due to the combined decrease in the capacity of adenosine transporters and decreased release of adenosine 5′‐triphosphate (ATP), which was partially compensated by a higher extracellular catabolism of ATP into adenosine in kindled rats. These results indicate that, although adenosine might inhibit the onset of epileptogenesis, once kindling is installed, the efficiency of the adenosine inhibitory system is impaired.