bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of Cutaneous Sensory Neurons in Transgenic Mice Lacking the Low Affinity Neurotrophin Receptor p75
Authors: Bergmann Ilka , Priestley John V. , McMahon Stephen B. , Bröcker Eva‐B. , Toyka Klaus V. , Koltzenburg Martin 
Published: April 2006

AbstractMice with a targeted mutation of the p75 low affinity neurotrophin receptor display smaller peripheral nerves and dorsal root ganglia. Here we show that transgenic mice have a significant elevation of thresholds to noxious mechanical and heat stimuli compared with p75+/+ control mice. Immunocytochemical analysis using antibodies against PGP 9.5 (a panaxonal marker) and calcitonin gene related peptide (CGRP, which labels peptidergic neurons) showed a reduction to 73% and 54%, respectively, of the epidermal innervation density. However, analysis of the cell size distribution of toluidine blue‐stained dorsal root ganglia showed no selective loss of neurons of particular diameters. Moreover, the neurochemical profile of dorsal root ganglia cells as defined by trkA, CGRP, I84 and RT97 immunostaining revealed no significant differences in comparison with p75+/+ animals. Staining of the dorsal horn of the spinal cord for CGRP and 164 was also normal in p75‐/‐animals. Taking into account a previously reported loss of ‐50% dorsal root ganglion neurons, we conclude that all types of sensory neurons are equally depleted in p75‐/‐ mice and that the absence of p75 impedes the development of more than one neuronal subtype.
Electron Microscopic Distribution of Mu Opioid Receptors on Noradrenergic Neurons of the Locus Coeruleus
Authors: Moyse Emmanuel , Marcel Dominique , Leonard Kathleen , Beaudet Alain 
Published: April 2006

AbstractThe distribution of mu opioid receptors was examined by light and electron microscopic autoradiography in the locus coeruleus of the rat following in vitro labelling with the iodinated agonist [125I]FK‐33824. At the light microscopic level, specific mu opioid binding sites were concentrated over the perikarya and dendrites of neurons that were tyrosine hydroxylase‐immunopositive in adjacent sections. Accordingly, both the number of tyrosine hydroxylase‐immunoreactive neurons and the density of labelled mu receptors decreased markedly throughout the rostrocaudal extent of the nucleus following treatment with the catecholaminergic neurotoxin 6‐hydroxydopamine. By electron microscopy, specifically labelled receptors were detected both inside and on the surface of locus coeruleus neurons. Intracellular sites were found by resolution circle analysis to be highly concentrated within the endoplasmic reticulum and Golgi apparatus, suggesting that the ligand recognizes both glycosylated and preglycosylated forms of receptor. The remainder were found mainly over the cytoplasmic matrix or intracytoplasmic vesicles, and were attributed to newly synthesized or recycled receptors in transit. Cell surface receptors were present over both dendritic and perikaryal membranes of noradrenergic cells. These were most highly concentrated opposite abutting axon terminals, suggesting the existence of receptor ‘hot spots’ at sites of putative endogenous ligand release. However, only a small proportion of these sites was associated with synaptic specializations. Furthermore, an important contingent was detected opposite non‐axonal elements, such as dendrites and glial cells, suggesting that mu opioid ligands act mainly parasynaptically on locus coeruleus neurons. Finally, ˜5% of labelled receptors were associated with axoglial interfaces, indicating that a minor action of mu opioids in the locus may be presynaptic and/or glial.
Oligodendrocyte‐type 2 Astrocyte Progenitors Use a Metalloendoprotease to Spread and Migrate on CNS Myelin
Authors: Amberger Verena R. , Avellana‐Adalid Virginia , Hensel Tamara , Evercooren Anne Baron‐Van , Schwab Martin E. 
Published: April 2006

abstractOligodendrocyte‐type 2 astrocyte (O‐2A) progenitors are highly motile cells which migrate in the developing and adult central nervous system (CNS). Adult CNS myelin, however, contains inhibitory proteins, the neurite growth inhibitors NI 35/250, which block neurite outgrowth and spreading of many different cell types, such as astrocytes and fibroblasts. In the present study we investigated the spreading of dissociated cells and migration out of aggregates (‘spheres’) of primary O‐2A cultures and of a glial precursor cell line (CG‐4) on purified CNS myelin and on CNS tissue. Primary O‐2A progenitors and CG‐4 cells quickly attached to and spread on CNS myelin‐coated culture dishes, showing no inhibition by the neurite growth inhibitors. CG‐4 cells migrated with a velocity of 30 pm/h on a CNS myelin protein extract and at 5.7 μm/h on adult spinal cord tissue. Both cell spreading and migration on a CNS substrate could be specifically blocked by metalloprotease blockers like o‐phenanthroline and the tetrapeptide carbobenzoxy‐phe‐ala‐phe‐tyr‐amide, whereas blockers of the serine, aspartyl and cysteine proteases had no effect. On differentiation to astrocytes, the O‐2A progenitors lost their ability to spread on CNS myelin. These results suggest the crucial involvement of a metalloprotease in the mechanism of migration on a CNS substrate. In vivo, migration of oligodendrocyte progenitors may be an important aspect of myelin repair following local traumatic, inflammatory or toxin‐induced myelin loss.
Morphology, Electrophysiology and Pathophysiology of Supragranular Neurons in Rat Primary Somatosensory Cortex
Authors: Schröder Rita , Luhmann Heiko J. 
Published: April 2006

AbstractIntracellularly biocytin‐labelled neurons in layers 11/111 of adult rat primary somatosensory cortex were analysed for their morphological and electrophysiological properties and studied for their response pattern to transient hypoxia under in vitro conditions. The largest dendritic region is formed by the basal dendrites, which constitute an average area of 0.06 mm2 and which can receive synaptic inputs over horizontal distances of more than 300 μm. The dendritic territories formed by the oblique dendrites situated on the apical trunk and by the apical tuft are much smaller. The spine density is highest on the apical trunk, suggesting that large numbers of excitatory synapses are present in this region of the cell. All neurons revealed intrinsic membrane properties of typical regular spiking cells and received an excitatory and a strong biphasic inhibitory input. Whereas a significant correlation could be detected between the cell's input resistance and soma area, no correlation existed between the cell's total dendritic length and input resistance or membrane time constant/input resistance. Neurons responded to transient hypoxia either with an anoxic hyperpolarization with an apparent reversal potential of ‐82.4 mV, or with a gradual anoxic depolarization which reversed at ‐56 mV. Oxygen deprivation caused a significant reduction in the extent of axonal collaterals, whereas dendritic proportions and spine density were unaffected. The present study indicates that the dendritic tree is well preserved under in vitro conditions, whereas axonal connections are diminished by oxygen deprivation. Our results further suggest that certain structural properties correlate with the cellular physiology, but that the cell's morphology does not determine its responsiveness to hypoxia.
Spontaneous Openings of NMDA Receptor Channels in Cultured Rat Hippocampal Neurons
Authors: Tureček Rostislav , Vlachová Viktorie , Vyklický Ladislav 
Published: April 2006

AbstractSpontaneous and N‐methyl‐D‐aspartate (NMDA)‐evoked single‐channel currents were studied in outside‐out patches isolated from cultured rat hippocampal neurons. Both spontaneous and NMDA‐evoked single‐channel currents reversed at potentials close to 0 mV and exhibited multiple amplitude levels of similar amplitude. Both spontaneous and NMDA‐evoked single‐channel currents were inhibited by Mg2+ in a voltage‐dependent manner and by 7‐chlorokynurenic acid. The activity of spontaneous single‐channel currents was reduced by the competitive NMDA receptor antagonists, but by one to three orders of magnitude less than expected assuming that the spontaneous activity is due to an ambient NMDA receptor agonist present in the extracellular solution. Our results suggest that, similar to other ligand‐gated ion channels, NMDA receptor channels have a dual mode of activation ‐ spontaneous and agonist induced.
Presynaptic Modulation of Glutamate Release Targets Different Calcium Channels in Rat Cerebrocortical Nerve Terminals
Authors: Vázquez Elena , Sánchez‐Prieto José 
Published: April 2006

AbstractWe have studied which type/s of Ca2+ ‐channel/s support glutamate exocytosis and its modulation by presynaptic receptors in cerebrocortical nerve terminals. Depolarization of nerve terminals with 30 mM KCI induced a Ca2+ ‐dependent release of 3.64 ± 0.25 nmol/mg of protein. The addition of either 2 μM ω‐conotoxin‐GVIA or 200 nM ω‐agatoxin‐IVA reduced the KCI‐evoked release by 47.7 ± 3.5% and 70.4 ± 8.9% respectively, and by 85.7 ± 4.1% when both toxins were co‐applied. The activation of adenosine A1 receptors with N6‐cyclohexyladenosine or the activation of rnetabotropìc glutamate receptors with L(+)‐2‐amino‐4‐phosphonobutyrate inhibited the KCI‐evoked release by 41.0 ± 5.9 and 54.3 ± 10% respectively. The extent of these inhibitions was not altered by the prior addition of 2 μM ω‐conotoxin‐GVIA but they were significantly enhanced when ω‐agatoxin‐IVA was added together with the adenosine A1 receptor agonist or the metabotropic glutamate receptor agonist, suggesting that ω‐conotoxin‐GVIA‐sensitive and not ω‐agatoxin‐IVA‐sensitive Ca2+‐channels are ínvolved in the action of these inhibitory receptors. By contrast, the facilitation of glutamate release that follows the activation of the protein kinase C, either with phorbol esters or with the stimulation of phospholipase C‐linked metabotropic receptors, was expressed by both ω‐conotoxin‐GVIA‐sensitive and ω‐agatoxin‐sensitive Ca2+‐channels. It is concluded that different Ca2+‐channels support the modulation of glutamate release by presynaptic receptors.
Adhesion Molecules Involved in Macrophage Responses to Wallerian Degeneration in the Murine Peripheral Nervous System
Authors: Brown H. C. , Castaño A. , Fearn S. , Townsend M. , Edwards G. , Streuli C. , Perry V. H. 
Published: April 2006

AbstractWhen a peripheral nerve is damaged the severed axon undergoes Wallerian degeneration. The distal nerve is infiltrated by large numbers of monocyte‐derived macrophages which participate in the phagocytosis of degenerating myelin. In other tissues, adhesion molecules play a crucial role in leukocyte recruitment during inflammation. Blood‐borne cells enter damaged tissue by interacting with adhesion molecules expressed on activated endothelium. Having crossed the endothelium, leukocytes must adhere and migrate within the tissue. We investigated the adhesion molecules involved in both stages of the macrophage response to transection of one sciatic nerve of BALB/c mice. By injecting monoclonal antibodies in vivo, before and after peripheral nerve injury, we showed that intercellular adhesion molecule‐1 (ICAM‐1) and integrins α4β1 (VLA‐4) and αMβ2 (type 3 complement receptor) are unlikely to be involved in the transendothelial migration of monocytes responding to peripheral nerve degeneration. We also studied the adhesion of macrophages within the endoneurium, using an in vitro adhesion assay. Macrophages showed much greater levels of adhesion to cryostat sections of transected nerves than to control nerves. This increased adhesion was partially inhibited by antibodies to the β1 ‐integrin chain, and more strongly inhibited by the extracellular matrix molecules fibronectin and collagen. Adhesion was unaffected by laminin‐I and by antibodies to other adhesion molecules, including α4β1‐ and α5β1‐integrins. Thus we conclude that monocyte entry into a degenerating peripheral nerve is independent of αLβ2/αMβ2‐ICAM‐1 or α4β1/NCAM‐1 interactions, and that adhesion within the endoneurium is mediated in part by a β1 ‐integrin other than α4β1 or α5β1.
Substance P Modulates Sensory Action Potentials in the Lamprey Via a Protein Kinase C‐Mediated Reduction of a 4‐Aminopyridine‐Sensitive Potassium Conductance
Authors: Parker David , Svensson Erik , Grillner Sten 
Published: April 2006

AbstractWe have examined the effects of the tachykinin substance P on the action potential of lamprey mechanosensory dorsal cells. Substance P increased the spike duration and reduced the afterhyperpolarization. These effects were mimicked by stimulation of the dorsal root, which contains tachykinin‐like immunoreactive fibres. The tachykinin antagonist spantide II blocked the effects of both substance P and dorsal root stimulation. The spike broadening was voltage‐dependent, and was due to the reduction of a 4‐aminopyridine‐sensitive potassium conductance. The spike broadening was mimicked by G‐protein activators and blocked by the G‐protein inhibitor GDPβS. Pertussis toxin did not block the effects of substance P. The spike broadening was blocked by the protein kinase C and CAMP‐dependent protein kinase inhibitor H7, and by the specific protein kinase C antagonist chelerythrine, but not by the cAMP and cGMP‐dependent protein kinase inhibitor H8. The phorbol ester phorbol 12,13‐dibutyrate mimicked and blocked the effects of substance P, supporting the role of protein kinase C in the spike modulation. The adenylate cyclase activator forskolin and the cAMP agonist SpcAMPs mimicked but did not block the effects of substance P on the spike duration, suggesting that protein kinase A also modulates the dorsal cell action potential, but that substance P acts independently of this pathway. Substance P also increased the excitability of the dorsal cells. This effect was blocked by 4‐AP, PDBu and chelerythrine, but not by H8, suggesting that the increase in excitability shares the same intracellular and effector pathways as the spike broadening.
Bilateral Lesions of the Subthalamic Nucleus Induce Multiple Deficits in an Attentional Task in Rats
Authors: Baunez Christelle , Robbins Trevor W. 
Published: April 2006

AbstractLesioning the subthalamic nucleus (STN) has been suggested as possible therapy for the treatment of parkinsonism. Previous experiments investigating this hypothesis in rats confirmed that excitotoxic STN lesions alleviate the motor impairment induced by striatal dopamine depletion, which reproduced the degeneration observed in parkinsonism, but elicited presumed non‐motor deficits such as premature rationresponding, suggesting that the STN could be involved in other aspects of response control. The aim of the present study was to extend this analysis to choice paradigms. We thus investigated the behavioural effects of bilateral excitotoxic lesions of the STN in rats performing a five‐choice test of divided and sustained visual attention, modelled on the human continuous performance task. This task required the animals to detect a brief visual stimulus presented in one of five possible locations and respond by a nose‐poke in this illuminated hole within a fixed delay, for food reinforcement. Bilateral lesions of the STN severely impaired several aspects of performance, including discriminative accuracy, but also increased premature, anticipatory ralresponding as well as perseverative panel pushes and nose‐poke responses. While increasing the stimulus duration and reducing the waiting period for the stimulus partially alleviated the accuracy deficit and the premature responding deficit respectively, other deficits, such as perseverative panel pushes and nose‐poke responses were sustained under these conditions. Systemic injection of the mixed dopaminergic D1/D2 receptor antagonist, α‐flupenthixol (0.03–0.18 mg/kg), reduced premature responses and perseverative panel pushing without affecting the perseverative nose‐poke responses, suggesting that some of the deficits were independent of striatal dopaminergic transmission. These results suggest that STN lesions have multiple, dissociable effects on attentional performance, including discriminative deficits, impulsivity and perseverative behaviour They are consistent in part with a hypothesized role of the STN in recent models of basal ganglia function in areaction selection and inhibition. The results also show that other aspects of behaviour should be monitored when examining the capacity of STN lesions to reverse the parkinsonian deficit induced by striatal dopamine depletion.
Anatomical Substrate of Amphibian Basal Ganglia Involvement in Visuomotor Behaviour
Authors: Marin Oscar , González Agustín , Smeets Wilhelmus J.A.J. 
Published: April 2006

AbstractThe optic tectum of amphibians is known to play a major role in the control of visually elicited orienting movements, such as prey‐catching and avoidance behaviours. The recent finding of a direct striato‐tectal connection in the frog Rana perezi prompted us to study in detail the anatomical substrate by which the basal ganglia of amphibians may modulate visuomotor behaviour. Injections of anterograde tracers into the striatum were combined with applications of retrograde tracers in the mid‐brain tectum. Apart from a direct striato‐tectal connection, at least three indirect pathways were observed, viz. a striato‐anterior entopeduncular‐tectal pathway, a striato‐pretectal‐tectal pathway and a striato–tegmento–tectal pathway. The basal ganglia–tectal connections of anurans largely resemble those described for amniotes, but appear to be more extensive. However, a pallio–tectal connection comparable to the cortico–tectal pathways of mammals was not observed in Rana perezi. Therefore, the striatum of anurans, which receives multimodal sensory information, seems to be the sole telencephalic structure that influences the mesencephalic tectum via a direct pathway.
Expression and Subcellular Localization of p42IP4/ Centaurin‐α, a Brain‐specific, High‐affinity Receptor for lnositol 1,3,4,5‐Tetrakisphosphate and Phosphatidylinositol 3,4,5‐Trisphosphate in Rat Brain
Authors: Kreutz M. R. , Böckers T. M. , Sabel B. A. , Hülser E. , Stricker R. , Reiser G. 
Published: April 2006

AbstractRecently emerging evidence suggests important roles for inositol polyphosphates and inositol phospholipids in neuronal Ca2+ signalling, membrane vesicle trafficking and cytoskeletal rearrangement. A prerequisite for a detailed physiological characterization of the signalling of both potential second messengers inositol‐(1,3,4,5)‐tetrakisphosphate (InsP4) and phosphatidylinositol‐3,4,5‐trisphosphate (PtdlnsP3) in the nervous system is the precise cellular localization of their receptors. Based on the cDNA sequence of a recently cloned brain‐specific receptor with high affinity for both InsP4 and PtdlnsP3 (InsP4–PtdlnsP3R), p42IP4/centaurin‐α, we localized the mRNA and the protein in rat brain. In situ hybridization revealed a widespread expression of the InsP4–PtdlnsP3R with prominent labelling in cerebellum, hippocampus, cortex and thalamus, which moreover is developmentally regulated. Using peptide‐specific antibodies, the immunoreactivity was localized in the adult brain in the vast majority of neuronal cell types and probably also in some glial cells. Prominent immunoreactivity was found in axonal processes and in cell types characterized by extensive neurites. In the hypothalamus a subpopulation of parvocellular neurons in the peri‐ and paraventricular nuclei was most heavily labelled. This was confined by strong immunoreactivity in the lamina externa of the median eminence in close proximity to portal plexus blood vessels. Electron microscopy revealed that the InsP4‐PtdlnsP3R was frequently associated with presynaptic vesicular structures. Further studies should identify the role of the InsP4‐PtdlnsP3R in cellular neural processes.
Involvement of a c‐fos‐Dependent Mechanism in Caffeine‐Induced Expression of the Preprotachykinin A and Neurotensin/Neuromedin N Genes in Rat Striatum
Authors: Svenningsson Per , Georgieva Jeanette , Kontnyi Ewa , Heilig Markus , Fredholm Bertil B. 
Published: April 2006

AbstractStriatal c‐fos induction was blocked by local administration of phosphorothioated c‐fos antisense oligonucleotides (AS‐ODN) to examine the possible role of caffeine‐induced c‐fos expression in transcriptional regulation of striatal preproenkephalin, prodynorphin, preprotachykinin A and neurotensin/neuromedin N. Caffeine (100 mg/kg i.p.) induced both c‐fos mRNA and Fos‐protein, and this induction was significantly attenuated by intrastriatal injection of 4 (but not 1) nmol c‐fos AS‐ODN. This suggests that, in addition to translational arrest, other mechanisms may be involved in the mediation of antisense action. The action of the AS‐ODN was sequence specific. The antisense blockade of c‐fos reduced the effect of caffeine on the expression of mRNAs for preprotachykinin A and neurotensin/neuromedin N in the ventrolateral caudate–putamen. Levels of preproenkephalin and prodynorphin transcripts were unaffected. Thus caffeine induction of striatal preprotachykinin A mRNA and neurotensin/neuromedin N mRNA, but not of preproenkephalin mRNA or prodynorphin mRNA, may at least in part be mediated by a pathway involving Fos protein. The findings illustrate the utility of blockade of gene expression with antisense oligonucleotides for in vivo studies of drug actions.
The Primate Striatum: Neuronal Activity in Relation to Spatial Attention Versus Motor Preparation
Authors: Boussaoud Driss , Kermadi Imane 
Published: April 2006

AbstractThe primate basal ganglia are known to be involved in the initiation and control of visually guided movements. However, the precise role of these structures is not clear, partly because most neurophysiological studies have not dissociated neuronal activity related to visuomotor processing from that reflecting other aspects of behaviour, such as shifts of spatial attention. Moreover, the way the basal ganglia function together with the frontal cortex during movement initiation and execution is still a matter of debate. In an effort to clarify these issues, we recorded single neurons from the striatum (caudate nucleus and putamen) in two rhesus monkeys trained to perform a conditional visuomotor task, and compared their properties with those of the frontal cortex. The experimental paradigm was designed to distinguish neuronal activity associated with shifts of attention from that reflecting motor preparation. In a given trial, an identical visual stimulus could serve as a cue for the reorientation of spatial attention or as a cue for establishing a motor set depending on when it occurred during that trial. Additional aspects of the paradigm were designed to identify neurons whose activity differed when various stimulus configurations instructed the same action (stimulus effect), as well as neurons whose activity differed when two different actions were instructed by the same stimulus (movement effect). The majority of cells (60%) were preferentially active after instructional cues, 38% discharged preferentially after attentional cues, and the remaining 2% of cells discharged equally after both types of cue. Neurons active after instructional cues were further analysed for stimulus and movement effects. During movement preparation, the activity of the vast majority of striatal cells (putamen, 81%; caudate, 76%) varied significantly when different stimuli instructed the same action. Likewise, when different movements were instructed by the same stimulus, preparatory activity of a majority of cells (putamen, 92%; caudate, 82%) changed. Consequently, a substantial proportion of cells showed combined stimulus and movement effects. Comparison of these neuronal properties with those of the dorsal premotor cortex showed significantly higher proportions of cells in the striatum whose activity reflected sensory or sensorimotor processing. These results suggest that the basal ganglia are involved in shifting attentional set and in high‐order processes of movement initiation, including the linking of sensory information with behavioural responses.