bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulation of Rat Neuronal Voltage‐dependent Calcium Channels By Endogenous p21‐ras
Authors: Fitzgerald E. M. , Dolphin A. C. 
Published: April 2006

AbstractInflux of calcium through voltage‐dependent calcium channels (VDCCs) has been implicated in the processes of cell growth and differentiation. Various signalling proteins, including nerve growth factor (NGF), p21–ras and src tyrosine kinases, have been suggested to have a role in the regulation of neuronal VDCCs. Using the whole‐cell patch‐clamp technique we have investigated the role of endogenous p21–ras in the regulation of VDCCs in primary cultured dorsal root ganglion (DRG) neurons obtained from neonatal rats. Neutralization of endogenous p21–ras by microinjection of p21–ras antibody (Y13–259) reduced the maximum peak barium current, Imax whereas microinjection of oncogenic p21–K‐ras increased the current. Thus, endogenous p21–ras is involved in the tonic regulation of calcium currents in these cells. lntracellular application of a phosphopeptide, Trk490, which prevents the binding of the adaptor protein shc to the activated NGF receptor, so blocking p21–ras activation, reduced Imax. Similarly, deprivation of NGF by overnight incubation in NGF‐free medium also reduced ImaX, Together, these results suggest that NGF receptor tyrosine kinase activation of p21–ras is likely to be involved in the tonic regulation of VDCCs in DRG neurons. Deprivation of NGF combined with microinjection of p21–ras antibody (Y13–259), however, caused an even greater reduction of Imax. Thus, NGF activation can only partially explain the regulation of these currents by endogenous p21–ras. Src tyrosine kinases have been suggested to activate p21–ras. In DRG neurons, microinjection of purified src tyrosine kinase, pp60c‐src, increased Imax in these cells. However, co‐microinjection of pp60c‐src with Y13–259 antibody prevented the increase in Imax, implying that pp60c‐src can also regulate calcium currents via the activation of endogenous p21–ras. Further support for the involvement of tyrosine kinases in VDCC regulation was provided by the application of the general tyrosine kinase inhibitor, genistein, which also reduced Imax, Thus, VDCCs in rat DRG neurons appear to be tonically up‐regulated by endogenous p21–ras. This effect appears largely to involve NGF receptor tyrosine kinase activation of p21–ras. In addition, src tyrosine kinase may also regulate VDCCs, possibly via p21–ras.
Neurotrophin‐3 Delivered Locally via Fibronectin Mats Enhances Peripheral Nerve Regeneration
Authors: Sterne G. D. , Brown R. A. , Green C. J. , Terenghi G. 
Published: April 2006

AbstractA better understanding of the mechanisms of nerve regeneration could improve the outcome of surgical nerve repair. We have previously shown that axonal regeneration is increased by nerve growth factor. Neurotrophin‐3 (NT‐3) belongs to the same family as nerve growth factor but acts on a distinct neuron subpopulation. As little is known about its role following nerve injury, we have investigated the effect of NT‐3 delivered via fibronectin mats, previously shown to support nerve regeneration comparable to nerve grafts. NT‐3 stimulation (0.1–1000 ng/ml) of neurite extension from embryonic chick dorsal root ganglia in vitro has shown that fibronectin can bind and release bioactive NT‐3. Fibronectin mats impregnated with NT‐3 (500 ng/ml) were grafted into 1 cm sciatic nerve defects in adult Lewis rats. Plain mats were used as controls. Computerized quantification of penetration distance, volume of axonal regeneration and myelinated fibre counts was undertaken using immunostaining for axonal markers (growth‐associated protein 43, calcitonin gene‐related peptide, substance P, vasoactive intestinal peptide and neuropeptide tyrosine), or S100 orthionine blue staining up to 8 months postoperatively. The maximal effect of NT‐3 occurred at day 15, when for GAP43‐immunostained axons both penetration distance (NT‐3, 6.10 ± 0.42 mm; control, 4.11 ± 0.41 mm; P <0.01) and staining area (NT‐3, 0.137 ± 0.012 mm2; control, 0.077 ± 0.018 mm2; P < 0.05) were significantly increased. Similar results were found for each neuronal subpopulation investigated. By 8 months after repair, the NT‐3 group supported a significantly greater number of myelinated axons (NT‐3, 7003 ± 402; control, 4932 ± 725; P < 0.05) of similar diameter and g‐ratio to controls. These results demonstrate the contribution of NT‐3 to the increase of nerve regeneration promoted by growth factors.
Organization and Development of Facial Motor Neurons in the Kreisler Mutant Mouse
Authors: McKay Ian J. , Lewis Julian , Lumsden Andrew 
Published: April 2006

AbstractThe adult facial nerve contains the axons from two populations of efferent neurons. First, the branchiomotor efferent neurons that innervate the muscles of the second arch. These neurons project out of the hindbrain in the motor root and form the facial motor nuclei. Second, the preganglionic efferent neurons that innervate the submandibular and pterygopalatine ganglia. These neurons project from the hindbrain via the intermediate nerve and form the superior salivatory nucleus. The motor neurons of the facial nerve are known to originate within rhombomeres 4 and 5. In the kreisler mouse mutant there is a specific disruption of the hindbrain ‐rhombomeres 5 and 6 appear to be absent. To investigate changes in the organization of the facial motor neurons in this mutant, we have used lipophilic dyes to trace the facial motor components both retrogradely and anterogradely. As expected, facial motor neurons are missing from rhombomere 5 in this mutant. In addition, the loss of these neurons correlates with the specific loss of the superior salivatory nucleus. In contrast, the branchiomeric neurons, that originate in rhombomere 4, appear to develop normally. This includes the caudal migration of their cell bodies forming the genu of the facial nerve. Our studies confirm that rhombomeres are critical to hindbrain development and that they are the fundamental unit at which motor neurons are specified.
Temporo‐frontal Disconnection Impairs Visual‐visual Paired Association Learning but not Configural Learning in Macaca Monkeys
Authors: Gutnikov Sergei A. , Ma Yuan‐Ye , Gaffan David 
Published: April 2006

AbstractCynomolgus monkeys were tested in two computer‐controlled visual associative memory tasks. The monkeys chose between visual objects on a screen by touching one. In the configural learning task one correct object and one wrong object were presented in each trial. Each of these two objects was composed of two coloured alphanumeric characters abutted together. The designation of the objects as ‘correct’ or ‘wrong’ followed a configural rule: e.g. if AB and CD are correct objects then AD and CB are wrong. In the paired association learning task in each trial three spatially separate objects (single alphanumeric characters) were presented. The central object was an instruction cue and the designation of the side objects as ‘correct’ or ‘wrong’ choices followed a paired association rule: e.g. if A, C and B are presented (C in the centre) then A is correct and B is wrong: however, if A, D and C are presented then C is correct and A is wrong. Disrupting the direct cortico‐cortical interaction between the inferior temporal cortex and the prefrontal cortex by uncinate fascicle transection led to a learning deficit in the paired association task but not in the configural task. These results suggest that the uncinate fascicle facilitates visual‐visual associative learning only in the specific case where a visual object acts as an instruction cue to guide the conditional choice of another, spatially separate object, and they support the evidence for a specific role of the uncinate fascicle in the learning of conditional tasks with visual instruction cues.
Differential Display Reveals Transcriptional Up‐regulation of the Motor Molecules for Both Anteroarade and Retrograde Axonal Transport During Nerve Regeneration
Authors: Su Q. N. , Namikawa K. , Toki H. , Kiyama H. 
Published: April 2006

AbstractRNA fingerprinting using an arbitrary primed polymerase chain reaction was carried out to compare differences in expression of mRNAs between axotomized and normal hypoglossal motoneurons in the mouse. In this survey, the kinesin light chain (KLC) was identified as a nerve injury‐associated molecule. This was also confirmed by in situ hybridization using hemihypoglossal nerve‐transected brain sections. In order to identify the exact species of molecules belonging to the KLC family, in situ hybridization was carried out with oligonucleotide probes specific to rat KLC A, KLC B and KLC C, using the rat hypoglossal nerve injury model. In addition, expression of both ubiquitous and neuron‐specific kinesin heavy chain and cytoplasmic dynein which is a retrograde motor, was also examined. Expression of all the members of the KLC (A‐C) family and dynein was up‐regulated during nerve regeneration, whereas the abundant expression of the neuron‐specific KHC mRNA was not changed. The present results indicate that the molecules associated with both anterograde and retrograde axonal transport are up‐regulated in their expression during efferent motor nerve regeneration, suggesting that the retrograde transport of growth factors and anterograde transport of vesicles, providing membrane material, could be increased during motor nerve regeneration.
The Copper Chelator d‐Penicillamine Delays Onset of Disease and Extends Survival in a Transgenic Mouse Model of Familial Amyotrophic Lateral Sclerosis
Authors: Hottinger Andreas F. , Fine Eric G. , Gurney Mark E. , Zurn Anne D. , Aebischer Patrick 
Published: April 2006

AbstractA subpopulation of familial cases of amyotrophic lateral sclerosis has been linked to mutations in the gene encoding Cu/Zn superoxide dismutase (SOD1). There is in vitro evidence that certain SOD1 mutants, in addition to their normal dismutation function, show increased ability of the enzyme to act as a peroxidase. This reaction is sensitive to inhibition by copper chelators. To test this hypothesis in vivo, we administered the copper chelator d‐penicillamine to a transgenic mouse model of familial amyotrophic lateral sclerosis overexpressing a mutated form of human SOD1. We demonstrate that oral administration of d‐penicillamine is able to delay the onset of the disease and extend the survival of these mice. Histological studies also showed a decreased loss of facial motor neurons in d‐penicillamine‐treated transgenic mice, corroborating the slower evolution of the disease in these animals. These results suggest that copper chelators may benefit patients with familial amyotrophic lateral sclerosis linked to mutations in the SOD1 gene.
Overexpression of Nerve Growth Factor in Skin Increases Sensory Neuron Size and Modulates Trk Receptor Expression
Authors: Goodness Thomas P. , Albers Kathryn M. , Davis Frankie E. , Davis Brian M. 
Published: April 2006

AbstractSensory neuron development and differentiation is dependent on a family of growth factors known as neurotrophins. Neurotrophins modulate neuron development via trk tyrosine kinase receptor proteins trkA, trkB and trkC. To determine how elevated levels of a target‐derived neurotrophin might affect neuronal differentiation, we analysed trk expression in the trigeminal ganglion of transgenic mice that overexpressed nerve growth factor (NGF) in the skin. increased levels of NGF caused a five‐fold increase in neurons expressing trkA mRNA and a two‐fold increase in neurons expressing trkC. In control mice, cell size distributions of neuronal subpopulations expressing each trk mRNA showed the three subpopulations distributed over a narrow, overlapping range. In contrast, cell size distribution in NGF‐transgenic mice was significantly divergent due in large part to hypertrophy of trkA neurons and, to a lesser extent, trkC neurons. In addition, we examined neurons that bound the isolectin B4 from Bandeiraea simplicifolia (BS‐IB4) because most of these neurons do not express any trk receptor in the adult. There was a significant increase in the size of BS‐IB4–positive neurons in transgenic mice; however, there was no increase in their number. These studies indicate that an increased level of target‐derived NGF affects the development of sensory neurons that in the adult express trkA or trkC, as well as neurons that do not express trk receptors.
Postnatal Changes in Electrophysiological Properties of Rat Nucleus Tractus Solitarii Neurons
Authors: Vincent Anne , Tell Fabien 
Published: April 2006

AbstractWhole‐cell recordings in brainstem slices revealed postnatal changes in passive and firing properties in the rat caudal nucleus tractus solitarii (cNTS) neurons. Membrane potential, threshold for Na+ spike and degree of sag were unchanged during development. In the adult, the rheobase was twice that found at birth. The input resistance decreased over the period studied, while time constants declined markedly after the third postnatal week. At all postnatal ages, Na+‐dependent action potentials (APs) were elicited in response to depolarization. Nevertheless, AP duration gradually decreased by 40% over the developmental period studied. Spike amplitude was smaller at birth than at any other ages and reached a peak two weeks after birth. At all ages, Na+‐dependent APs were blocked by application of tetrodotoxin. Full APs were replaced by an initial slow oscillation in young cells and by oscillations in older cells. The TTX‐resistant oscillations were altered by cobalt (2 mM) and cadmium (100 μM). The spike afterhyperpolarization (AHP) was not altered during development, but was observed in less neurons in adult cells when measured at a holding potential of ‐60 mV. Neurons were subdivided into one of three classes based on their responses to a hyperpolarizing prepulse: 1) post‐inhibitory rebound (PIR) cells, 2) delayed excitation (DE) cells and 3) NON cells expressing neither PIR nor DE. The relative proportions of different cell types varied with age. The mean maximum duration of DE increased three times. Voltage‐clamp experiments revealed that the DE was due to the activation of an A‐current. In addition, a three‐fold increase in its inactivation rate was observed postnatally. The physiological significance of these results is discussed.
Relations Between Long‐term Synaptic Modifications and Paired‐pulse Interactions in the Rat Neocortex
Authors: Volgushe Maxim , Voronin Leon L. , Chistiakova Marina , Singer Wolf 
Published: April 2006

AbstractThe phenomenon of paired‐pulse facilitation (PPF) was exploited to investigate the role of presynaptic mechanisms in the induction and maintenance of long‐term synaptic plasticity in the neocortex. Long‐term potentiation (LTP) and depression (LTD) were induced without afferent activation by applying tetani of intracellular pulses. Our results show that synaptic modifications closely resembling LTP and LTD can be induced by postsynaptic activation alone. The polarity of these synaptic modifications depends on initial properties of the input, as indicated by a correlation between initial PPF ratio and post‐tetanic amplitude changes: inputs exhibiting strong PPF, which might be associated with low release probability tend to be potentiated, while inputs with small PPF are more likely to show depression. Maintenance of both LTP and LTD involve presynaptic mechanisms, as indicated by changes in PPF ratios and in failure rate after LTP or LTD induction. Presynaptic mechanisms could include changes in release probability and/or in the number of active release sites. Because induction was postsynaptic, this supports the notion of a retrograde signal. The relative contribution of pre‐ and postsynaptic mechanisms in the maintenance of long‐term synaptic modifications depends on the initial state of the synaptic input and on LTP magnitude. PPF changes were especially pronounced in inputs which had initially high PPF and underwent strong potentiation. Since LTP and LTD are associated with changes of PPF ratios these synaptic modifications do not only alter the gain but also the temporal properties of synaptic transmission. Because of the LTP associated reduction of PPF, potentiated inputs profit less from temporal summation, favouring transmission of synchronized, low frequency activity.
Glutamatergic Modulation of Cortical Acetylcholine Release in the Rat: A CombinedIn VivoMicrodialysis, Retrograde Tracing and lmmunohistochemical Study
Authors: Giovannini M. G. , Giovannelli L. , Bianchi L. , Kalfin R. , Pepeu G. 
Published: April 2006

AbstractThe microdialysis technique with one or two probes was used to investigate the modulation of cortically projecting cholinergic neurons by glutamatergic input in the ratin vivo. Male albino Wistar rats (250–300 g) were used. Under chloral hydrate anaesthesia microdialysis membranes were positioned in the parietal cortex, nucleus basalis magnocellularis (NBM) or medial septum. Acetylcholine was assayed using high‐performance liquid chromatography (HPLC) with electrochemical detection while GABA was detected using HPLC with fluorimetric detection after derivatization of the amino acid with ephthalaldehyde. Septo‐cortical neurons were retrogradely labelled with fluoro‐gold. Double labelling with choline acetyltransferase (ChAT) immunoreactivity was performed to identify these neurons. Our main findings were that: (i) icv. administration of the NMDA antagonist 3–((R)‐2‐carboxypiperazin‐4‐yl)‐propyl‐1‐phosphonic acid (CPP, 1–5 nmol) increased cortical acetylcholine outflow; (ii) local administration of CPP (100 μM) to the cortex had no effect on cortical acetylcholine outflow: (iii) local administration of CPP (100 μM) to the NBM decreased cortical acetylcholine outflow; (iv) local administration of CPP (100–200 μM) to the septum increased cortical GABA and acetylcholine outflow; (v) administration of muscimol to the septum prevented the effect of CPP on cortical acetylcholine outflow: (vi) retrograde tracing with fluoro‐gold labelled cell bodies in the medial septum; (vii) septal fluoro‐gold‐positive neurons were not ChAT‐immunoreactive. Ourin vivoneurochemical results, in combination with retrograde tracing and immunohistochemistry, indicate that the cortically projecting cholinergic system is indirectly regulated by a glutamatergic input via a polysynaptic GABAergic circuitry located in the septum.
Antidepressant Drugs Inhibit a Gial 5‐Hydroxytryptamine Transporter in Rat Brain
Authors: Bel Nuria , Figueras Gloria , Vilaró M. Teresa , Suñol Cristina , Artigas Francesc 
Published: April 2006

AbstractWe assessed the role of glial cells in the uptake of serotonin (5‐hydroxytryptamine, 5‐HT). Primary cultures of rat and mouse cortical astrocytes took up and deaminated 5‐HT. The antidepressants citalopram, clomipramine, fluoxetine, fluvoxamine, paroxetine and sertraline inhibited this process. The presence of the mRNAs for the 5‐HT transporter and monoamine oxidase‐A (MOA‐A) was established in cultured astrocytes and in adult rat brain areas with (midbrain and brainstem) and without (frontal cortex) serotonergic cell bodies after reverse transcription‐polymerase chain reaction and hybridization with probes complementary to the cloned neuronal 5‐HT transporter and MAO‐A. To examine in vivo the role of astrocytes in the elimination of 5‐HT from the extracellular brain space, 5‐HT was perfused through dialysis probes implanted in the frontal cortex of conscious rats and its concentration was measured at the probe outlet. Tissue 5‐HT recovery was dose‐dependently inhibited by the concurrent perfusion of citalopram, fluoxetine and paroxetine, showing that it essentially measured uptake through the high‐affinity 5‐HT transporter. Rats lesioned with 5,7‐dihydroxytryptamine (5,7‐DHT; 88% reduction of tissue 5‐HT) displayed tissue 5‐HT recovery slightly higher than sham‐operated rats (55 ± 2 vs. 46 ± 3%, P < 0.001), a finding perhaps attributable to the astrogliosis induced by 5,7‐DHT denervation. Rats lesioned with 6‐hydroxydopamine showed tissue 5‐HT uptake similar to controls, suggesting negligible reuptake of 5‐HT by catecholaminergic terminals. These results are consistent with the presence of a glial component of 5‐HT uptake in the rodent brain, sensitive to antidepressants, which takes place through a 5‐HT transporter very similar or identical to that present in neurons.
Neurites of Period‐expressing PDH Cells in the Fly's Optic Lobe Exhibit Circadian Oscillations in Morphology
Authors: Pyza E. , Meinertzhagen I. A. 
Published: April 2006

AbstractCircadian rhythms have been shown both in the expression of the period (per) gene in ‘lateral neurons’ and in cells of the outermost neuropil, or lamina, of the fly's optic lobe. Some lateral neurons also exhibit PDH peptide‐like immunoreactivity, arborizing widely throughout the optic lobe. Using confocal microscopy in the housefly, we analysed the size and spacing of PDH neurite varicosities, sites of possible peptide release exhibiting circadian rhythmicity. During the subjective day in constant darkness, there were fewer, larger varicosities than during subjective night. The endogenous rhythm was masked by the light exposure that occurred under a day‐night cycle and continuous light conditions. Our findings indicate that PDH neurites convey circadian information out from the pacemaker, where they could regulate the circadian rhythms that have been described in the lamina, possibly via cyclical release of their peptide.
Functional Properties of Neuronal Nicotinic Acetylcholine Receptor Channels Expressed in Transfected Human Cells
Authors: Ragozzino D. , Fucile S. , Giovannelli A. , Grassi F. , Mileo A. M. , Ballivet M. , Alemà S. , Eusebi F. 
Published: April 2006

AbstractTo study how subunit composition affects the functional properties of neuronal nicotinic acetylcholine receptors (nAChRs), we examined the behaviour of acetylcholine (ACh)‐induced single‐channel currents in human BOSC 23 cells transiently transfected with various subunit cDNA combinations. For all nAChRs examined (chick and rat α3β4, chick α<3/β2, α4β2, α4β4, α7and α8, expression levels were high enough to allow measurements of acetylcholine‐evoked whole‐cell currents and nicotine‐elicited Ca2+ transients as well as the functional characterization of nAChR channels. Unitary acetylcholine‐evoked events of α8 nAChR had a slope conductance of 23 pS, whereas two conductance classes (19–23 and 32–45 pS) were identified for all other nAChR channels. The mean channel open times were significantly longer for homomeric α7 and α8 nAChRs (6–7 ms) than for heteromeric nAChRs (1–3 ms), with the exception of α3α4nAChRs (8.4 ms for rat, 7 ms for chick). At least two species of heterologously expressed nAChRs (α3α4and α3α2) exhibited single‐channel characteristics similar to those reported for native receptors. The variety of nAChRs channel conductance and kinetic properties encountered in human cells transfected with nAChR subunits contributes to the functional diversity of nAChRs in nerve cells.