bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional glycine receptors are expressed by postnatal nestin‐positive neural stem/progenitor cells
Authors: Nguyen Laurent , Malgrange Brigitte , Belachew Shibeshih , Rogister Bernard , Rocher Véronique , Moonen Gustave , Rigo Jean‐Michel 
Published: March 2003

AbstractMultipotent neural stem and progenitor cells (NS/PCs) are well‐established cell subpopulations occurring in the developing, and also in the mature mammalian nervous systems. Trophic and transcription factors are currently the main signals known to influence the development and the commitment of NS/PCs and their progeny. However, recent studies suggest that neurotransmitters could also contribute to neural development. In that respect, rodent‐cultured embryonic NS/PCs have been reported to express functional neurotransmitter receptors. No similar investigation has, however, been made in postnatal and/or in adult rodent brain stem cells. In this study, using RT‐PCR and immunocytochemical methods, we show that α1‐, α2‐ and β‐subunit mRNAs and α‐subunit proteins of the glycine ionotropic receptor are expressed by 80.5 ± 0.9% of postnatal rat striatum‐derived, nestin‐positive cells within cultured neurospheres. Whole‐cell patch‐clamp experiments further demonstrated that glycine triggers in 33.5% of these cells currents that can be reversibly blocked by strychnine and picrotoxin. This demonstrates that NS/PCs express functional glycine receptors, the consequence(s) of their activation remaining unknown.
Quantification and localization of PEGylated polycyanoacrylate nanoparticles in brain and spinal cord during experimental allergic encephalomyelitis in the rat
Authors: Calvo Pilar , Gouritin Bruno , Villarroya Henri , Eclancher Françoise , Giannavola Claudia , Klein Christophe , Andreux Jean P. , Couvreur Patrick 
Published: March 2003

AbstractUnder healthy conditions, the blood–brain barrier (BBB) limits the passage of solutes and cells from the blood to the CNS. During neurological diseases, BBB permeability increases dramatically and it has been hypothesized that drug carrier systems such as polymeric nanoparticles could cross the BBB and penetrate into the CNS. PEGylated polyalkylcyanoacrylate nanoparticles (long‐circulating carrier) are one such system and have been investigated during experimental allergic encephalomyelitis (EAE). Brain and spinal cord concentrations of [14C]‐radiolabelled PEGylated polyalkylcyanoacrylate nanoparticles were compared with another blood long‐circulating carrier (poloxamine 908‐coated polyalkylcyanoacrylate nanoparticles) and with conventional non‐long‐circulating polyalkylcyanoacrylate nanoparticles. The microscopic localization of fluorescent nanoparticles in the CNS was also investigated in order to further understand the mechanism by which the particles penetrate the BBB. The results demonstrate that the concentration of PEGylated nanoparticles in the CNS, especially in white matter, is greatly increased in comparison to conventional non‐PEGylated nanoparticles. In addition, this increase was significantly higher in pathological situations where BBB permeability is augmented and/or macrophages have infiltrated. Passive diffusion and macrophage uptake in inflammatory lesions seems to be the mechanism underlying such particles' brain penetration. Based on their long‐circulating properties in blood and on their surface characteristics that allow cell interactions, PEGylated nanoparticles penetrated into CNS to a larger extent than all the other formulations tested. Thus, PEGylated polycyanoacrylate nanoparticles are proposed here as a new brain delivery system for neuroinflammatory diseases.
Neuronal populations in primary motor cortex encode bimanual arm movements
Authors: Steinberg O. , Donchin O. , Gribova A. , De Oliveira S. Cardoso , Bergman H. , Vaadia E. 
Published: March 2003

AbstractPrevious studies have shown that activity of neuronal populations in the primary motor cortex (MI), processed by the population vector method, faithfully predicts upcoming movements. In our previous studies we found that single neurons responded differently during movements of one arm vs. combined movements of the two arms. It was, therefore, not clear whether the population vector approach could produce reliable movement predictions also for bimanual movements. This study tests this question by comparing the predictive quality of population vectors for unimanual and bimanual arm movements. We designed a bimanual motor task that requires coordinated movements of the two arms, in which each arm may move in eight directions, and recorded single unit activity in the MI of two rhesus (Macaca mulatta) monkeys during the performance of unimanual and bimanual arm movements. We analysed the activity of 212 MI cells from both hemispheres and found that, despite bimanual related activity, the directional tuning and preferred directions of most cells were preserved in unimanual and bimanual movements. We demonstrate that population vectors, constructed from the activity of MI cells, predict accurately the direction of movement both for unimanual and for bimanual movements even when the two arms move simultaneously in different directions.
MOR‐1‐immunoreactive neurons in the dorsal horn of the rat spinal cord: evidence for nonsynaptic innervation by substance P‐containing primary afferents and for selective activation by noxious thermal stimuli
Authors: Spike R. C. , Puskár Z. , Sakamoto H. , Stewart W. , Watt C. , Todd A. J. 
Published: March 2003

AbstractA direct action of μ‐opioid agonists on neurons in the spinal dorsal horn is thought to contribute to opiate‐induced analgesia. In this study we have investigated neurons that express the μ‐opioid receptor MOR‐1 in rat spinal cord to provide further evidence about their role in nociceptive processing. MOR‐1‐immunoreactive cells were largely restricted to lamina II, where they comprised approximately 10% of the neuronal population. The cells received few contacts from nonpeptidergic unmyelinated afferents, but many from substance P‐containing afferents. However, electron microscopy revealed that most of these contacts were not associated with synapses. None of the MOR‐1 cells in lamina II expressed the neurokinin 1 receptor; however, the μ‐selective opioid peptide endomorphin‐2 was present in the majority (62–82%) of substance P axons that contacted them.    Noxious thermal stimulation of the foot induced c‐Fos expression in approximately 15% of MOR‐1 cells in the medial third of the ipsilateral dorsal horn at mid‐lumbar level. However, following pinching of the foot or intraplantar injection of formalin very few MOR‐1 cells expressed c‐Fos, and for intraplantar formalin injection this result was not altered significantly by pretreatment with systemic naloxone.    Although these findings indicate that at least some of the neurons in lamina II with MOR‐1 are activated by noxious thermal stimulation, the results do not support the hypothesis that the cells have a role in transmitting nociceptive information following acute mechanical or chemical noxious stimuli.
Response properties of neurons in the core of the central nucleus of the inferior colliculus of the barn owl
Authors: Wagner Hermann , Mazer James A. , Von Campenhausen Mark 
Published: March 2003

AbstractThe central nucleus of the inferior colliculus (ICC) is particularly important for the processing of interaural time differences (ITDs). In the barn owl, neuronal best frequencies in a subnucleus of the ICC, the ICCcore, span the animal's entire hearing range (≈ 200–10 000 Hz). This means that low‐frequency ITD‐sensitive ICCcore neurons in the owl can be directly compared to ITD‐sensitive mammalian ICC neurons with similar best frequencies as well as to the high‐frequency ITD‐sensitive neurons usually studied in owls. This report represents a first attempt to systematically describe important physiological properties of ICCcore neurons in the barn owl, with particular attention to the low‐frequency region (< 2 kHz). Responses were obtained from 133 neurons or small clusters of neurons; recording sites were confirmed by histological reconstruction of electrode tracks based on electrolytic lesions. Iso‐intensity frequency response functions were typically ≈ 1 octave wide in the low‐frequency range and ≈ 1/3 octave wide in the high‐frequency range. Most neurons were ITD‐tuned; both noise and pure tone stimuli yielded periodic ITD tuning curves with several equivalent response maxima. In most cases ITD tuning curves had a response peak within the barn owl's physiological ITD range. ITD tuning widths were inversely correlated with neuronal best frequency. None of the ICCcore neurons studied were sensitive to interaural level differences. Monaural inputs to ICCcore cells were typically binaurally balanced, i.e. they exhibited similar response thresholds, dynamic ranges, slopes and saturation levels, for both left and right ear monaural stimulation.
Focal application of neutralizing antibodies to soluble neurotrophic factors reduces collateral axonal branching after peripheral nerve lesion
Authors: Streppel M. , Azzolin N. , Dohm S. , Guntinas‐Lichius O. , Haas C. , Grothe C. , Wevers A. , Neiss W. F. , Angelov D. N. 
Published: March 2003

AbstractA major reason for the insufficient recovery of function after motor nerve injury are the numerous axonal branches which often re‐innervate muscles with completely different functions. We hypothesized that a neutralization of diffusable neurotrophic factors at the lesion site in rats could reduce the branching of transected axons. Following analysis of local protein expression by immunocytochemistry and by in situ hybridization, we transected the facial nerve trunk of adult rats and inserted both ends into a silicon tube containing (i) collagen gel with neutralizing concentrations of antibodies to NGF, BDNF, bFGF, IGF‐I, CNTF and GDNF; (ii) five‐fold higher concentrations of the antibodies and (iii) combination of antibodies. Two months later, retrograde labelling was used to estimate the portion of motoneurons the axons of which had branched and projected into three major branches of the facial trunk. After control entubulation in collagen gel containing non‐immune mouse IgG 85% of all motoneurons projecting along the zygomatic branch sprouted and sent at least one twin axon to the buccal and/or marginal‐mandibular branches of the facial nerve. Neutralizing concentrations of anti‐NGF, anti‐BDNF and anti‐IGF‐I significantly reduced sprouting. The most pronounced effect was achieved after application of anti‐BDNF, which reduced the portion of branched neurons to 18%. All effects after a single application of antibodies were concentration‐dependent and superior to those observed after combined treatment. This first report on improved quality of reinnervation by antibody‐therapy implies that, in rats, the post‐transectional collateral axonal branching can be reduced without obvious harmful effects on neuronal survival and axonal elongation.
Protein kinase C‐mediated translocation of secretory vesicles to plasma membrane and enhancement of neurotransmitter release from PC12 cells
Authors: Shoji‐Kasai Yoko , Itakura Makoto , Kataoka Masakazu , Yamamori Saori , Takahashi Masami 
Published: March 2003

AbstractIn order to elucidate the molecular mechanism of phorbol ester‐induced potentiation of neurotransmitter release, changes in the subcellular distribution of secretory vesicles were studied in PC12 cells. Dopamine (DA) and acetylcholine containing vesicles were selectively labelled by expressing green fluorescent protein‐conjugated vesicular monoamine transporter and vesicular acetylcholine transporter, respectively. In the resting state, these vesicles were distributed throughout the cytoplasm. Phorbol‐12‐myristate‐13‐acetate (PMA), but not the inactive analogue 4α‐PMA, induced a redistribution of both types of secretory vesicles near the plasma membrane, and this change was abolished by a protein kinase C (PKC) inhibitor, bisindolylmaleimide I (BIS). PMA also induced a marked enhancement of depolarization‐induced DA release and phosphorylation of SNAP‐25 at Ser187. BIS completely inhibited PMA‐induced SNAP‐25 phosphorylation but suppressed PMA‐induced enhancement of DA release only partially. These results suggest that PMA enhances neurotransmitter release from PC12 cells by both PKC‐dependent and PKC‐independent mechanisms, and PKC enhances neurotransmitter release by recruiting secretory vesicles to the plasma membrane.
Projections from the parahippocampal region to the prefrontal cortex in the rat: evidence of multiple pathways
Authors: Delatour B. , Witter M. P. 
Published: March 2003

AbstractThe purpose of the present study was to investigate, by means of anterograde tracing methods, the detailed organization of the parahippocampal–prefrontal projections in the rat brain. Efferents from the perirhinal cortex were found to terminate principally in both the ventromedial (prelimbic and infralimbic cortices) and lateral (agranular insular cortex) regions of the prefrontal cortex. Terminal fields were observed mainly in the superficial layers of the prefrontal cortex. Projections arising from the dorsolateral entorhinal cortex, which borders the perirhinal cortex along its ventral extent, were similarly directed to the ventromedial and lateral prefrontal cortices but also encompassed other frontal areas (dorsomedial and orbital prefrontal regions). Terminal fields of entorhinal projections were also found in the superficial layers of the prefrontal cortex. A third pathway, taking its source in the post‐rhinal cortex, presented striking topographical differences with the two other output systems. Hence, post‐rhinal efferences terminated only in the ventrolateral orbital area. The results indicate that two main routes originate from the parahippocampal region to reach the prefrontal cortex. One pathway involves the rostral and lateral portions of the parahippocampal region (perirhinal and dorsolateral entorhinal cortices), and the other relies on its most caudal region, the post‐rhinal cortex. The presence of such different multiple parahippocampal–prefrontal pathways may have functional relevance for learning and memory processes.
Influence of cue‐conditioning on acquisition, maintenance and relapse of cocaine intravenous self‐administration
Authors: Deroche‐Gamonet Véronique , Piat Frédéric , Le Moal Michel , Piazza Pier Vincenzo 
Published: March 2003

AbstractConditioning theories propose that, through a Pavlovian associative process, discrete stimuli acquire the ability to elicit neural states involved in the maintenance and relapse of a drug‐taking behaviour. Experimental evidence indicates that drug‐related cues play a role in relapse, however, their influence on the development and maintenance of drug self‐administration has been poorly investigated. In this report, we analysed the effects of a drug‐associated cue light on acquisition, maintenance and reinstatement of intravenous cocaine self‐administration. The results show that a cocaine‐associated cue light can act as an incentive in absence of the drug, but does not directly modify drug‐reinforcing effects. Contingent and non‐contingent presentations of a cocaine‐associated cue light reinstated an extinguished self‐administration behaviour. However, regardless of whether or not a cue light was associated with cocaine infusions, rats acquire cocaine intravenous self‐administration reaching the same levels of intake. Furthermore, after self‐administration has been acquired in presence of the cue light, the omission of the cue light or its non‐contingent presentation did not modify rat behaviour. In conclusion, our work shows that cocaine‐associated explicit cues do not directly interfere with the reinforcing effects of the drug.
Frontal theta activity in humans increases with memory load in a working memory task
Authors: Jensen Ole , Tesche Claudia D. 
Published: March 2003

AbstractRecent theoretical work has suggested that brain oscillations in the theta band are involved in active maintenance and recall of working memory representations. To test this theoretical framework we recorded neuromagnetic responses from 10 subjects performing the Sternberg task. Subjects were required to retain a list of 1, 3, 5 or 7 visually presented digits during a 3‐s retention period. During the retention period we observed ongoing frontal theta activity in the 7–8.5‐Hz band recorded by sensors over frontal brain areas. The activity in the theta band increased parametrically with the number of items retained in working memory. A time–frequency analysis revealed that the task‐dependent theta was present during the retention period and during memory scanning. Following the memory task the theta activity was reduced. These results suggest that theta oscillations generated in frontal brain regions play an active role in memory maintenance.
Enhanced motivation to self‐administer cocaine is predicted by self‐grooming behaviour and relates to dopamine release in the rat medial prefrontal cortex and amygdala
Authors: Homberg Judith R. , Van Den Akker Margot , Raasø Halfdan S. , Wardeh George , Binnekade Rob , Schoffelmeer Anton N. M. , De Vries Taco J. 
Published: March 2003

AbstractRats, like humans, show strong individual differences in their response to anxiogenic and stressful stimuli. In the present study we evaluated whether differences in stress‐induced self‐grooming behaviour may predict an individual's vulnerability to engage in drug self‐administration behaviour. From a population of Wistar rats, the lower and upper quartile with respect to time spent self‐grooming on an elevated plus maze (EPM) were selected and trained to intravenously self‐administer cocaine under fixed and progressive ratio schedules of reinforcement. High grooming (HG) rats reached considerably higher breakpoints than low grooming (LG) rats but showed no differences in acquisition rate and dose–response relationships. Further, EPM exposure elicited higher anxiety levels and enhanced plasma corticosterone secretion in HG rats. In addition, HG rats did not display enhanced novelty‐seeking and still spent more time self‐grooming during an EPM re‐test following the cocaine self‐administration procedure, indicating that stress‐induced self‐grooming is a stable behavioural trait marker. Neurochemically, electrically evoked [3H]dopamine release in vitro was profoundly lower in brain slices from the substantia nigra, medial prefrontal cortex and amygdala of naive HG rats as compared to LG rats, whereas no differences were found in the nucleus accumbens shell and core, the ventral tegmental area and caudate putamen. In conclusion, stress‐induced self‐grooming specifically predicts enhanced motivation to self‐administer cocaine rather than sensitivity to its reinforcing effects. Responsiveness of dopaminergic nerve terminals in the medial prefrontal cortex and amygdala may represent pre‐existing underlying factors.
Partial regeneration and long‐term survival of rat retinal ganglion cells after optic nerve crush is accompanied by altered expression, phosphorylation and distribution of cytoskeletal proteins
Authors: Dieterich Daniela C. , Trivedi Niraj , Engelmann Ralf , Gundelfinger Eckart D. , Gordon‐Weeks Phillip R. , Kreutz Michael R. 
Published: March 2003

AbstractIn a screen to identify genes that are expressed differentially in the retina after partial optic nerve crush, we identified MAP1B as an up‐regulated transcript. Western blot analysis of inner retina protein preparations confirmed changes in the protein composition of the microtubule‐associated cytoskeleton of crushed vs. uncrushed nerve. MAP1B immunoreactivity and transcript levels were elevated for two weeks after crush. Immunostaining and Western blots with monoclonal antibodies directed against developmentally regulated phosphorylation sites on MAP1B revealed a gradient of MAP1B phosphorylation from the proximal optic nerve stump to the soma of retinal ganglion cells. Most interestingly, using antibodies directed against developmentally regulated phosphorylation sites on MAP1B, we observed that a significant number of crushed optic nerve axons develop MAP1B‐immunopositive growth cones, which cross the crush site and migrate along the distal nerve fragment. In parallel, an abnormal distribution of highly phosphorylated neurofilament protein (pNF‐H) in the cell soma and dendrites of presumably axotomized retinal ganglion cells was observed following partial nerve crush. This redistribution is present for the period between day 7 and 28 postcrush and is not seen in cells that stay connected to the superior colliculus. Axotomized ganglion cells, which contain pNF‐H in soma and dendrites appear to have been disconnected from the colliculus at an early stage but survive axonal trauma for long periods.
Cysteine‐string protein in inner hair cells of the organ of Corti: synaptic expression and upregulation at the onset of hearing
Authors: Eybalin Michel , Renard Nicole , Aure Frédérique , Safieddine Saaid 
Published: March 2003

AbstractCysteine‐string protein is a vesicle‐associated protein that plays a vital function in neurotransmitter release. We have studied its expression and regulation during cochlear maturation. Both the mRNA and the protein were found in primary auditory neurons and the sensory inner hair cells. More importantly, cysteine‐string protein was localized on synaptic vesicles associated with the synaptic ribbon in inner hair cells and with presynaptic differentiations in lateral and medial olivocochlear terminals — the cell bodies of which lie in the auditory brainstem. No cysteine‐string protein was expressed by the sensory outer hair cells suggesting that the distinct functions of the two cochlear hair cell types imply different mechanisms of neurotransmitter release. In developmental studies in the rat, we observed that cysteine‐string protein was present beneath the inner hair cells at birth and beneath outer hair cells by postnatal day 2 only. We found no expression in the inner hair cells before about postnatal day 12, which corresponds to the period during which the first cochlear action potentials could be recorded. In conclusion, the close association of cysteine‐string protein with synaptic vesicles tethered to synaptic ribbons in inner hair cells and its synchronized expression with the appearance and maturation of the cochlear potentials strongly suggest that this protein plays a fundamental role in sound‐evoked glutamate release by inner hair cells. This also suggests that this role may be common to ribbon synapses and conventional central nervous system synapses.