bluuebunny/crossref_metadata_2025_split huggingface dataset:
Small sensory neurons in the rat dorsal root ganglia express functional NK‐1 tachykinin receptor
Authors: Li Hong‐Sheng , Zhao Zhi‐Qi 
Published: March 2003

AbstractThe tachykinins substance P (SP) and neurokinin A, released by the C‐type primary afferent fibre terminals of the small dorsal root ganglion (DRG) neurons, play important roles in spinal nociception. By means of non‐radioactive in situ hybridization and whole‐cell recording, we showed that the small rat DRG neurons also express the NK‐1 tachykinin receptor. In situ hybridization demonstrated that the positive neurons in rat DRG sections were mainly small cells (85.9%) with diameters less than 25 μm. The remaining positive neurons (14.1%) were cells with medium diameters between 26 and 40 μm. No positive large neurons (diameters > 40 μm) were observed. Expression in small DRG neurons (diameter < 21 μm) was confirmed by in situ hybridization of isolated cells, which were demonstrated to express NK‐1 receptor mRNA at a very high frequency (> 90% of small DRG neurons) and therefore were subjected to whole‐cell recording. In 57 of 61 cells recorded, SP or the selective NK‐1 receptor agonist [Sar9, Met(O2)11]SP (Sar‐SP, 1 or 2 μm) produced a delayed vibrating inward current (50–300 nA) with a long duration of 0.5–2 h. These currents were blocked by co‐application of the NK‐1 receptor antagonist L‐668, 169 (1 μm), but were not affected by the NK‐2 antagonistL‐659, 877 (2 μm). Both current‐clamp recording and cell‐attached single‐channel recording demonstrated that the long‐lasting response was due to the opening of a channel with an inward current. Employment of non‐Ca2+ and Ca2+ + choline solutions revealed that this channel might be a Ca2+‐permeable, non‐selective cation channel. The prolonged NK‐1 tachykinin response exhibited extreme desensitization. This work suggests that presynaptic NK‐1 autoreceptors may be present on the primary afferent terminals in the spinal cord, where they could contribute to the chronic pain and hyperalgesia.
Chemosensitivity of nociceptive, mechanosensitive afferent nerve fibres in the guinea‐pig ureter
Authors: Sann Holger 
Published: March 2003

AbstractThe mechanosensitivity and chemosensitivity of afferent fibres were investigated in an in vitro preparation of the guinea‐pig ureter. Electrophysiological recordings were obtained from 5 U‐1 (low mechanical threshold, contraction‐sensitive) and 74 U‐2 units (high threshold). U‐2 units had significant higher levels of spontaneous activity, lower conduction velocities, higher mechanical thresholds (U‐1: 7 mmHg; U‐2: 39 mmHg), less pronounced phasic responses and longer latencies in the response to distensions than the U‐1 units. For chemical stimulation, guinea‐pig urine (> 800 mosmol/L), bradykinin and capsaicin were applied intraluminally. The responses of U‐1 units mainly corresponded to the contractions induced by the chemical stimulation. The vast majority of the U‐2 units were excited by urine, bradykinin (threshold: 0.1–1 μm) and capsaicin (threshold: 0.03–0.3 μm). The responses to urine could be mimicked by high concentrations of potassium ions (> 200 mm), but not by an equiosmolar solution of NaCl, urea and mannitol. Chemical stimulation could also result in a transient sensitization of the U‐2 units to mechanical stimuli. In the anaesthetized guinea‐pig, pseudo‐affective responses could be evoked by ureteric distension (threshold: 30–60 mmHg) and serosal application of capsaicin. Intraluminal application of urine in vivo did not evoke any reactions, suggesting that the responses of the U‐2 units to urine might be due to an impaired barrier function of the urothelium in vitro. The data are in agreement with the hypothesis that U‐2 units are visceral polymodal nociceptors. Since the U‐1 units were also able to encode at least noxious mechanical stimuli, their involvement in visceral nociception cannot be excluded.
Modulation of the voltage‐gated sodium current in rat striatal neurons by DARPP‐32, an inhibitor of protein phosphatase
Authors: Schiffmann  , Desdouits  , Menu  , Greengard  , Vincent J‐D. , Vanderhaeghen J‐J. , Girault J‐A. 
Published: March 2003

AbstractDARPP‐32 is a cyclic adenosine monophosphate‐regulated inhibitor of protein phosphatase 1, highly enriched in striatonigral neurons. Stimulation of dopamine D1 receptors increases phosphorylation of DARPP‐32, whereas glutamate acting on N‐methyl‐d‐aspartate receptors induces its dephosphorylation. Yet, to date, there is little direct evidence for the function of DARPP‐32 in striatal neurons. Using a whole cell patch‐clamp technique, we have studied the role of DARPP‐32 in the regulation of voltage‐gated sodium channels in rat striatal neurons maintained in primary culture. Injection of phospho‐DARPP‐32, but not of the unphosphorylated form, reduced the sodium current amplitude. This effect was similar to those induced by okadaic acid, with which there was no additivity and by tautomycin. Our results indicate that, in striatal neurons, sodium channels are under dynamic control by phosphorylation/dephosphorylation, and that phospho‐DARPP‐32 reduces sodium current by stabilizing a phosphorylated state of the channel or an associated regulatory protein. We propose that the DARPP‐32‐mediated modulation of sodium channels, via inhibition of phosphatase 1, contributes to the regulation of these channels by D1 receptors and other neurotransmitters which influence the state of phosphorylation of DARPP‐32.
Cytoskeletal and nuclear localization of myelin oligodendrocytic basic protein isoforms
Authors: Montague  , Barrie  , Thomson  , Kirkham  , McCallion  , Davies  , Kennedy  , Griffths>  
Published: March 2003

AbstractThe recently described single copy Myelin‐associated Oligodendrocytic Basic Protein (Mobp) gene is expressed exclusively in the central nervous system (CNS). The gene encodes a family of small highly basic polypeptides with predicted amino acid lengths of 69, 71, 81, 99 and 170, all of which share a 68 residue amino terminal. Here we report on the subcellular distribution of two of these polypeptides termed MOBP81 and MOBP170 in transiently transfected Cos7 cells using an antibody raised against a region common to all isoforms of MOBP. Additionally, we describe MOBP trafficking in cultured mouse spinal cord oligodendrocytes. Immunostaining for MOBP81 is intense in the perinuclear region and extends throughout the cytoplasm colocalizing with the microtubular cytoskeletal network. Consistent with this we demonstrate that MOBP partitions with the cytoskeletal fraction prepared from myelin. In contrast, although MOBP170 is present in the cytoplasm it does not colocalize with the cytoskeleton and displays a greater variation in distribution. In the majority of transfectants immunostaining is present throughout the karyoplasm but with increased intensity around the nucleolus. Within mouse primary oligodendrocytes endogenous MOBP is present in the cell body and processes colocalizing with the microtubular network. Immunoreactivity is not detectable in the nucleus in these mature oligodendrocytes. These significant differences in MOBP81 and MOBP170 protein kinesis coupled to different expression profiles of their respective message populations may be indicative of both myelin structural and cellular/regulatory functions, respectively, for these polypeptides.
A role for slow NMDA receptor‐mediated, intrinsic neuronal oscillations in the control of fast fictive swimming in Xenopus laevis larvae
Authors: Reith Carolyn A. , Sillar Keith T. 
Published: March 2003

AbstractIn larvae of the amphibian, Xenopus laevis, spinal neurons which are active during fictive swimming also display tetrodotoxin‐resistant membrane potential oscillations following the coactivation of N‐methyl‐dl‐aspartate (NMDA) and 5‐hydroxytryptamine (serotonin or 5‐HT) receptors (Scrymgeour‐Wedderburn et al. 1997;Eur. J. Neurosci., 9, 1473–1482). The oscillations are slow (≈0.5 Hz) compared with swimming (≈7–35 Hz) raising doubt over their contribution to the cycle by cycle depolarizations occurring during swimming. We investigated an alternative: that the intrinsic oscillations modulate swimming activity over many consecutive cycles. Bath application of NMDA induced continuous fictive swimming that differed between embryonic and larval preparations. In 81% of larval preparations (n = 36), there was a slow (approximately every 2 s) rhythmic modulation of ventral root activity in which burst durations and intensities increased as cycle periods decreased. This pattern of activity was enhanced rather than abolished following blockade of glycine and γ‐aminobutyric acid (GABA) A receptors and presumably therefore resulted from a periodic increase in the excitation of motor neurons. To determine whether this slow rhythm resulted from intrinsic, 5‐HT‐dependent membrane potential oscillations, larvae were spinalized to prevent the release of 5‐HT from brainstem raphe neurons. The resulting pattern of NMDA‐induced activity lacked any slow modulation. The slow modulation could also be enhanced by the bath application of a 5‐HT receptor agonist (5‐carboxamidotryptamine) and abolished either by the addition of an antagonist (pindobind‐5‐HT1A) or by removal of magnesium ions, providing more direct evidence for a contribution of intrinsic oscillations. Thus, the 5‐HT‐dependent intrinsic oscillations modulate NMDA‐induced swimming activity over several consecutive cycles.
Reduction of noradrenaline impairs attention and dopamine depletion slows responses in Parkinson's disease
Authors: Riekkinen Minna , Kejonen Kosti , Jäkälä Pekka , Soininen Hilkka , Riekkinen Paavo 
Published: March 2003

AbstractWe investigated the role dopamine and noradrenaline in the modulation of attention in Parkinson's disease (PD) patients. We observed that PD patients with mild and moderate motor disability did not differ in their attentional accuracy in easy tests, but the severe PD group was slightly disrupted in a more arduous test of attention. Attentional accuracy was not affected by withdrawal of dopaminergic drugs in mild or severe PD patients. The movements of severe PD patients were slower, and withdrawal of dopaminergic drugs aggravated motor slowing more in severe PD patients. Clonidine (0.5 and 2 μg/kg) retarded accuracy of performance in the most difficult attention test in mild PD patients, but had no effect in the severe PD group. Clonidine had no effect on movement times. These data suggest that a defect in noradrenaline release may contribute to the impaired accuracy of attention in severe PD patients and that dopamine may be important for maintaining rapid motor responding.
Visual activity is required to maintain the phenotype of supragranular NPY neurons in rat area 17
Authors: Obst Kirstin , Bronzel Margit , Wahle Petra 
Published: March 2003

AbstractVisual activity governs the functional maturation of the mammalian visual cortex. We report here, that visual experience is required for stabilizing the phenotype of a subset of cortical interneurons. Neurons expressing neuropeptide Y mRNA (NPY neurons) display a transiently higher expression in the early postnatal visual areas 18a and 17 that is followed by a phenotype restriction during the second postnatal month: about 50% of the NPY neurons in supragranular and infragranular layers of area 18a, and in infragranular layers of area 17 gradually stop the NPY expression. In contrast, the expression remains unchanged in supragranular layers of area 17. Dark rearing rats from birth to up to 100 days does neither prevent the developmental onset of NPY mRNA expression, nor does it prevent the phenotype restriction from occurring. In contrast, in dark reared animals NPY neurons in supragranular layers of area 17 now also undergo a phenotype restriction. Returning animals to light after variable periods of darkness results in an upregulation of NPY mRNA expression selectively in neurons in supragranular layers of area 17. These neurons acquire a constitutive expression during the second postnatal month. This suggests that the phenotypic specification of a distinct subset of cortical interneurons is regulated by visual experience which thus influences on the maturation of the neurochemical architecture of area 17.
Basic fibroblast growth factor promotes the generation and differentiation of calretinin neurons in the rat cerebral cortex in vitro
Authors: Pappas Ioannis S. , Parnavelas John G. 
Published: March 2003

AbstractCalretinin‐expressing neurons are some of the earliest postmitotic cells to appear in the developing cerebral cortex. Lineage studies have shown that the expression of this calcium‐binding protein in cortical neurons is not genetically programmed and is likely to be induced by external factors. A number of studies have clearly shown that basic fibroblast growth factor (bFGF) and a number of neurotrophins promote the proliferation and differentiation of cortical progenitor cells to a particular lineage. Here, using a culture system of dissociated rat cortical cells, we found that brain‐derived neurotrophic factor and neurotrophin‐3 promoted the morphological differentiation of one of the calretinin‐containing neuronal subpopulations, the Cajal–Retzius cells. Another subpopulation of calretinin‐expressing cells of smaller size and bipolar form was generated when cultures were treated with bFGF. The progenitors of these neurons were stimulated by bFGF to divide a number of times before initiating their differentiation programme. The number of calretinin‐expressing neurons increased further when cultures were treated with a combination of bFGF and retinoic acid.
Death‐signalling cascade in mouse cerebellar granule neurons
Authors: Tanabe Hiroki , Eguchi Yutaka , Shimizu Shigeomi , Martinou Jean‐Claude , Tsujimoto Yoshihide 
Published: March 2003

AbstractMolecular mechanisms of neuronal cell death are still largely unknown. In the present study, the signal transduction pathway of cell death in cerebellar granule neurons was examined by employing various death‐preventative agents. When death was induced by the depletion of serum and a depolarizing level of potassium, transient increase in active c‐Jun, mitochondrial membrane potential (Δψ) loss, activation of caspase‐3 (‐like) proteases, and nuclear condensation and fragmentation were observed. The protein synthesis inhibitor cycloheximide blocked all these phenomena, whereas RNA synthesis inhibitor actinomycin‐D, survival factor such as insulin‐like growth factor‐1, brain‐derived neurotrophic factor, high K+(25 mm) and overproduced antiapoptotic protein Bcl‐2, prevented Δψ loss, caspase activation, and nuclear change, but not an increase in active c‐Jun. The caspase inhibitor z‐Asp‐CH2‐DCB (carbobenzoxy‐l‐aspartyl‐α‐[(2,6‐dichlorobenzoyl) oxy]methane) only inhibited activation of caspases and nuclear change. These results suggest that the death signal in cerebellar granule neurons is sequentially transduced in the order of c‐Jun activation,de novoRNA synthesis, mitochondrial Δψ loss, activation of caspase‐3 (‐like) proteases and nuclear change.
Reduced after‐hyperpolarization in rat piriform cortex pyramidal neurons is associated with increased learning capability during operant conditioning
Authors: Saar Drorit , Grossman Yoram , Barkai Edi 
Published: March 2003

AbstractLearning‐related cellular modifications were studied in the rat piriform cortex. Water‐deprived rats were divided to three groups: ‘trained’ rats were trained in a four‐arm maze to discriminate positive cues in pairs of odours, ‘control’ rats were ‘pseudo‐trained’ by random water rewarding, and ‘naive’ rats were water‐deprived only. In one experimental paradigm, the trained group was exposed to extensive training with rats learning to discriminate between 35 and 50 pairs of odours. Piriform cortex pyramidal neurons from ‘trained’, ‘control’ and ‘naive’ rats did not differ in their passive membrane properties and single spike characteristics. However, the after‐hyperpolarizations (AHPs) that follow six‐spike trains were reduced after ‘extensive training’ by 43% and 36% compared with ‘control’ and ‘naive’, respectively. This effect was not observed in the piriform cortex of another group of rats, in which hyperexcitability was induced by chemical kindling. In another experimental paradigm rats were trained only until they demonstrated ‘rule learning’, usually after discriminating between one and two pairs of odours (‘mild training’). In this experiment, a smaller, yet significant, reduction (20%) in AHPs was observed. AHP reduction was apparent in most of the sampled neurons. AHP remained reduced up to 3 days after the last training session. 5 days or more after the last training session, AHP amplitude recovered to pre‐training value and did not differ between ‘trained’ rats and the others. Accordingly, training suspension for 5 days or more resulted in slower learning of novel odours. We suggest that increased neuronal excitability, manifested as reduced AHP, is related to the ability of the cortical network to enter a ‘learning mode’ which creates favourable conditions for enhanced learning capability.
Rewarding effects elicited by the microinjection of either AMPA or NMDA glutamatergic antagonists into the ventral tegmental area revealed by an intracranial self‐administration paradigm in mice
Authors: David Vincent , Durkin Thomas P. , Cazala Pierre 
Published: March 2003

AbstractIn order to study the functional role of the trans‐synaptic neuronal interaction between glutamatergic afferents and mesolimbic dopaminergic neurons in internal reward processes, BALB/c male mice were unilaterally implanted with a guide‐cannula, the tip of which was positioned 1.5 mm above the ventral tegmental area (VTA). On each day of the following experimental period, a stainless steel injection cannula was inserted into the VTA in order to study the eventual self‐administration behaviour of either the competitive N‐methyl‐ d‐aspartate antagonist, d(–)‐2‐amino‐7‐phosphonoheptanoic acid (AP‐7) or the α‐amino‐3‐hydroxy‐5‐methyl‐isoxazole‐4‐propionic acid antagonist, 6,7‐dinitroquinoxaline‐2,3‐dione (DNQX) (3 ng/50 nL) using a spatial discrimination task in a Y maze. Mice rapidly discriminated between the arm enabling a microinjection of either of these glutamatergic antagonists and the neutral arm of the maze, and a robust self‐administration of either of these compounds was observed from the first session of acquisition. These data provide strong evidence that the intra‐VTA microinjection of either of these subclasses of glutamatergic antagonist produces an effect which is interpreted centrally by the experimental subjects as being highly rewarding. Once the self‐administration response had been fully acquired by the experimental subjects, preinjection of the dopaminergic D2 antagonist, sulpiride (50 mg/kg i.p.), 30 min before the test, produced a rapid extinction of the self‐administration response. This latter result demonstrates the dopaminergic D2 receptor dependence of this intra‐VTA self‐administration of both of these subclasses of glutamatergic antagonist. We conclude that the different glutamatergic afferent neuronal inputs to the VTA globally exert, in vivo, via the mediation of interposed endogenous GABAergic interneurons, a tonic trans‐synaptic inhibitory regulation of neuronal activity in the mesolimbic dopaminergic pathway and that this complex neuronal interaction in the VTA plays a significant functional part in the modulation of internal reward processes.
Inositol 1,4,5‐trisphosphate activates non‐selective cation conductance via intracellular Ca2+ increase in isolated frog taste cells
Authors: Okada Yukio , Fujiyama Rie , Miyamoto Takenori , Sato Toshihide 
Published: March 2003

AbstractThe effect of intracellular Ca2+ increase was analysed in isolated frog taste cells under the whole‐cell patch clamp. External application of a Ca2+‐ionophore, ionomycin (3 μm) induced the sustained inward current of −200 ± 17 pA (mean ± SE, n = 23) at – 50 mV in taste cells. The ionomycin‐induced response was observed in most of the cells exposed in the drug, but not when 10 mm BAPTA (1,2‐bis (o‐aminophenoxy)ethane‐N,N,N′,N′‐tetraacetic acid) was included in the pipette (eight cells). Steady‐state I–V relationships of ionomycin‐induced currents were almost linear and reversed at – 8 ± 1 mV (n = 23). The simultaneous removal of Na+ and Ca2+ from the external solution eliminated the response completely (three cells). Intracellular dialysis with 1 mm Ca2+ or 50 μm inositol 1,4,5‐trisphosphate (IP3) in K+‐internal solution also induced an inward current in the taste cells. The Ca2+‐induced and IP3‐induced responses were observed in 82% and 36% of the cells dialysed with the drugs, respectively. The Ca2+‐induced and IP3‐induced currents were inhibited by external Cd2+ (1–2 mm). The reversal potentials of the inward currents were – 15 ± 3 mV (n = 9) in Ca2+ dialysis and – 11 ± 3 mV (n = 13) in IP3 dialysis. The half‐maximal Ca2+ concentration in the pipette to induce the inward current was ≈ 170 μm. The results suggest that IP3 can depolarize the taste cell with mediation by intracellular Ca2+.
Differential expression of voltage‐gated K+ and Ca2+ currents in bipolar cells in the zebrafish retinal slice
Authors: Connaughton  , Maguire  
Published: March 2003

AbstractWhole‐cell voltage‐gated currents were recorded from bipolar cells in the zebrafish retinal slice. Two physiological populations of bipolar cells were identified. In the first, depolarizing voltage steps elicited a rapidly activating A‐current that reached peak amplitude ≤ 5 ms of step onset. IA was antagonized by external tetraethylammonium or 4‐aminopyridine, and by intracellular caesium. The second population expressed a delayed rectifying potassium current (IK) that reached peak amplitude ≥ 10 ms after step onset and did not inactivate. IK was antagonized by internal caesium and external tetraethylammonium. Bipolar cells expressing IK also expressed a time‐dependent h‐current at membrane potentials < – 50 mV. Ih was sensitive to external caesium and barium, and was also reduced by Na+‐free Ringer. In both groups, a calcium current (ICa) and a calcium‐dependent potassium current (IK(Ca)) were identified. Depolarizing voltage steps > – 50 mV activated ICa, which reached peak amplitude between – 20 and – 10 mV. ICa was eliminated in Ca+2‐free Ringer and blocked by cadmium and cobalt, but not tetrodotoxin. In most cells, ICa was transient, activating rapidly at – 50 mV. This current was antagonized by nickel. The remaining bipolar cells expressed a nifedipine‐sensitive sustained current that activated between – 40 and – 30 mV, with both slower kinetics and smaller amplitude than transient ICa. IK(Ca) was elicited by membrane depolarizations > – 20 mV. Bipolar cells in the zebrafish retinal slice preparation express an array of voltage‐gated currents which contribute to non‐linear I–V characteristics. The zebrafish retinal slice preparation is well‐suited to patch clamp analyses of membrane mechanisms and provides a suitable model for studying genetic defects in visual system development.