bluuebunny/crossref_metadata_2025_split huggingface dataset:
Involvement of the subthalamic nucleus in glutamatergic compensatory mechanisms
Authors: Bezard Erwan , Boraud Thomas , Bioulac Bernard , Gross Christian E. 
Published: March 2003

AbstractThe purpose of the present study was to investigate whether the subthalamic nucleus (STN) was implicated in the glutamatergic compensatory mechanisms which have been shown to mask the parkinsonian motor abnormalities at the end of the presymptomatic period in experimental parkinsonism. Using multiunit electrophysiological recordings, we follow changes of activity occurring in the STN and in both the pars externalis and the pars internalis of the globus pallidus of monkeys chronically intoxicated with 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP), according to a protocol designed to mimic the gradual evolution of dopaminergic neuronal death. STN activity augmented significantly in the course of treatment, even before the first appearance of clinical signs (P < 0.01). This result would indicate that the STN, which increases its level of activity even before the end of the presymptomatic period, is principally responsible for the instigation of glutamatergic compensatory mechanisms which allow the maintenance of the striatal dopaminergic homeostasis.
Positional specificities of retinal growth cones in the mouse superior colliculus
Authors: Llirbat Béatrice , Godement Pierre 
Published: March 2003

AbstractIn the developing retinotectal system, repulsive topographic tectal cues have been demonstrated to contribute to the final mapping. Here, we describe a novel response of nasal axons to growth‐promoting cues expressed by anterior tectal cells. In in vitro experiments, contact of fibres from the nasal (but not temporal) pole of the mouse retina with anterior (but not posterior) tectal membranes leads to their adopting very elongated and filopodial morphologies, and to increase their growth rates. As previously demonstrated, fibres from the temporal pole of the retina are collapsed by posterior tectal membranes in vitro. In addition, a study of retinal growth cone morphologies in vivo, at early stages of target invasion, shows that growth cones of nasal fibres have streamlined morphologies, usually indicative of active elongation growth modes, in the anterior part of the embryonic mouse tectum, and more elaborate morphologies posteriorly. Vice versa, temporal fibres have mainly elaborate growth cones anteriorly, and collapsed growth cones posteriorly.These experiments demonstrate that nasal retinal fibres respond preferentially to permissive or growth‐promoting cues in the embryonic mouse tectal environment, both in vitro and in vivo. This phenomenon might contribute to ingrowth of retinal fibres in their target area, and to promote the homing of nasal fibres towards the posterior aspect of the tectum, which is their normal target region.
Regulation of the murine NMDA‐receptor‐subunit NR2C promoter by Sp1 and fushi tarazu factor1 (FTZ‐F1) homologues
Authors: Pieri Isabelle , Klein Matthias , Bayertz Christian , Gerspach Jeannette , van der Ploeg Anja , Pfizenmaier Klaus , Eisel Ulrich 
Published: March 2003

AbstractWe have cloned the 5′‐region of the murine N‐methyl‐d‐aspartate (NMDA) receptor channel subunit NR2C (GluRε3) gene and characterized the cis‐ and trans‐activating regulatory elements responsible for its tissue specific activity. By using a native ε3‐promoter/lacZ‐construct & various 5′‐deletion constructs, we compared β‐galactosidase expression in non‐neuronal NIH3T3 cells and in neuronal ε3‐gene‐expressing HT‐4 cells and show that large parts of the ε3 promoter are responsible for the repression of the ε3 gene in non‐neuronal cells. Deletion of exon 1 sequences led to an enhancement of ε3 transcription, suggesting a role of the 5′‐untranslated region in ε3 gene regulation. Sequence analysis of the promoter region revealed potential binding sites for the transcription factor Sp1, the murine fushi tarazu factor1 (FTZ‐F1) homologues, embryonic LTR binding proteins (ELP1,2,3) and steroidogenic factor (SF‐1), as well as for the chicken ovalbumin upstream promoter transcription‐factor (COUP‐TF). Electrophoretic mobility shift assays confirmed specific binding of Sp1, SF‐1 and COUP‐TFI. Whereas point mutation studies indicate that, in neuronal HT‐4 cells, Sp1 is apparently not critically involved in basal ε3 gene transcription, SF1 is a positive regulator. This was evident from a selective enhancement of ε3‐promoter‐driven reporter gene expression upon cotransfection of an SF1‐expression vector, which was reverted by deletion and point mutation of the SF1 binding site.
Decision‐related activity in the macaque dorsal visual pathway
Authors: Thiele Alexander , Distler Claudia , Hoffmann Klaus‐Peter 
Published: March 2003

AbstractBrain areas at higher levels of cortical organization are thought to be more involved in decision processes than are earlier, i.e. lower, sensory areas. Hence, neuronal activity correlated with decisions should vary with an area's position in the cortical hierarchy. To test this proposal, we investigated whether a change in neuronal activity during error trials depends in a systematic way on cortical hierarchical position. While macaque monkeys discriminated the direction of moving visual stimuli, the activity of direction‐selective neurons was recorded in four extrastriate visual areas: V3A, the middle temporal area, the middle superior temporal area and the posterior part of the superior temporal polysensory area. Neuronal activity was significantly reduced in all areas when the monkeys made errors in judging the direction of stimuli moving in the preferred direction with low and intermediate luminance contrast. The amount of activity reduction was ≈ 50% in all of the visual areas. Thus, the activity on error trials is reduced in early visual processing, independent of the hierarchy in the dorsal visual pathway. The activity reduction depended on stimulus contrast and the direction of the decision relative to the stimulus motion. It was profound and significant in all areas at low stimulus contrast. However, it was nonsignificant at high stimulus contrast. Our data suggest that activity reduction on error trials is due to lack of attention in association with stimulus expectation.
The homeodomain transcription factors Islet 1 and HB9 are expressed in adult alpha and gamma motoneurons identified by selective retrograde tracing
Authors: von Steyern F. Vult , Martinov V. , Rabben I. , Njå A. , de Lapeyrière O. , Lømo T. 
Published: March 2003

AbstractTo study gene expression in differentiated adult motoneuron subtypes, we used fluorescent dextrans for both anterograde and retrograde axonal tracing in adult rat and mouse. Application of these dyes to the cut distal and proximal ends of small extramuscular nerve branches revealed both the peripheral ramifications and the cell bodies of subsets of motoneurons. We show that the soleus muscle is innervated by two nerve branches, one of which contains gamma motor and sensory axons but no alpha motor axons. By retrograde tracing of this branch, we selectively labelled gamma motoneurons. In adult rat, the nerves innervating the soleus and extensor digitorum longus muscles contain almost exclusively axons innervating slow (type I) and fast (type 2) muscle fibres, respectively. We selectively labelled slow and fast type motoneurons by retrograde tracing of these nerves. With immunocytochemistry we show that adult motoneurons express several homeodomain genes that are associated with motoneuron differentiation during early embryonic development. Combining selective retrograde labelling with immunocytochemistry we compared the expression patterns in alpha and gamma motoneurons. The homeodomain transcription factors Islet 1 and HB9 were expressed in slow and fast alpha motoneurons and in soleus gamma motoneurons. Motoneurons in each population varied in their intensity of the immunostaining, but no factor or combination of factors was unique to any one population.
Axoaxonic synapses on terminals of group II muscle spindle afferent axons in the spinal cord of the cat
Authors: Maxwell D. J. , Riddell J. S. 
Published: March 2003

AbstractThe purpose of the present study was to determine if terminals of identified group II muscle spindle afferents participate in axoaxonic synaptic arrangements and, if so, to investigate the transmitter content of presynaptic terminals in these arrangements. Group II muscle afferents supplying the gastrocnemius‐soleus or semitendinosus muscles were identified in adult cats and stained intra‐axonally with horseradish peroxidase. In total, three group II axons were labelled and processed for combined light and electron microscopy. Group II axons gave rise to collaterals which characteristically descended through the superficial dorsal horn and formed relatively sparse terminal arborizations in the dorsal horn (laminae IV and V) and more profuse arbors in the intermediate grey matter (laminae VI–VII). Forty boutons were examined through series of ultrathin sections and all but four were postsynaptic to other axon terminals. Occasionally, more than one axon was presynaptic to a single group II terminal. Immunogold studies showed that all axons in presynaptic apposition to group II boutons contained γ‐aminobutyric acid (GABA) and also that glycine was colocalized in the majority of these axons. This evidence suggests that transmission from group II muscle afferents is under strong presynaptic inhibitory control and that it is mainly the subgroup of GABAergic interneurons with colocalized glycine which mediate this inhibition. Seventeen group II boutons were components of synaptic triads where the presynaptic axoaxonic bouton formed a synapse with the same dendrite as the group II axon. Therefore, a proportion of the interneurons which form axoaxonic synapses with group II axons are also likely to have postsynaptic inhibitory actions on target neurons of group II afferents.
Effects of noradrenaline on frequency tuning of auditory cortex neurons during wakefulness and slow‐wave sleep
Authors: Manunta Yves , Edeline Jean‐Marc 
Published: March 2003

AbstractThis study shows the effects of noradrenaline (NA) on receptive fields of auditory cortex neurons in awake animals; it is the first one to describe the effects of NA on neurons in sensory cortex, in different natural states of vigilance. The frequency receptive field of 250 auditory cortex neurons was determined before, during and after ionophoretic application of NA while recording the state of vigilance of unanaesthetized guinea‐pigs. When NA significantly changed the spontaneous activity (85 out of 250 cells), the dominant effect was a decrease (61 out of 85 cells, 72%). When NA significantly changed the evoked activity (107 out of 250 cells), the dominant effect was also a decrease (84 out of 107 cells, 78%). During and after NA application, the signal‐to‐noise ratio (S/N, i.e. evoked/spontaneous activity) was unchanged, but the selectivity for pure‐tone frequencies was enhanced. When the effects occurring in wakefulness and in slow‐wave sleep (SWS) were compared, it appeared that the predominantly inhibitory effect of NA on spontaneous and evoked activity was present in both states. The S/N ratio was unchanged and the selectivity was increased in both states. However, during SWS, the percentage of cells inhibited by NA was lower, and the effects on the frequency selectivity were smaller than in wakefulness. In contrast, GABA produced similar inhibitory effects on spontaneous and on evoked activity during wakefulness and SWS. Comparisons with previous data obtained using the same protocol in urethane anaesthetized animals (Manunta & Edeline 1997) indicate that the effects of NA were qualitatively the same. Based on these results, we suggest that any hypothesis concerning the role of NA in cortical plasticity should take into account the fact that the predominantly inhibitory effects of NA lead to decrease the size of the receptive field.
Dimethylarginine dimethylaminohydrolase (DDAH) as a nerve‐injury‐associated molecule: mRNA localization in the rat brain and its coincident up‐regulation with neuronal NO synthase (nNOS) in axotomized motoneurons
Authors: Nakagomi S. , Kiryu‐Seo S. , Kimoto M. , Emson P. C. , Kiyama H. 
Published: March 2003

AbstractAs part of a project to identify genes up‐regulated by injury of the motor neuron, a clone encoding dimethylarginine dimethylaminohydrolase (DDAH) was isolated. This enzyme is known to metabolize methylarginines, which are endogenous inhibitors of NOS activity. DDAH may therefore contribute to the control of NO synthesis. The present study demonstrated that both DDAH and nNOS mRNAs are up‐regulated after axotomy in injured hypoglossal motor neurons. The profile of DDAH mRNA up‐regulation in the injured hypoglossal motor neurons paralleled that of NADPH diaphorase staining. While the expression of both DDAH and nNOS was upregulated in motor neurons following nerve injury, the normal distribution of DDAH and nNOS mRNAs in the noninjured central nervous system were distinctly different. We speculate that both genes are involved in the upregulation of NO production following nerve transection, although the role of NO in the process of nerve regeneration is so far unknown.
Spectral sensitivity in hemianopic macaque monkeys
Authors: Cowey Alan , Stoerig Petra 
Published: March 2003

AbstractWe measured the increment threshold sensitivity to 2°, 200‐ms targets presented at a lateral and radial eccentricity of ≈ 20–26° in both visual hemifields of three macaque monkeys whose left striate cortex had been removed 5 years earlier, and in one normal control. As in patients with blindsight, sensitivity of the hemianopic field for blue, green and red stimuli was reduced by as little as 0.5 log units. With increasing light adaptation from scotopic to mesopic to photopic levels, there was a progressive increase in the sensitivity to long wavelengths relative to that for short and medium wavelengths. This shift in relative sensitivity (‘Purkinje shift’) shows that rod and cone mechanisms operate in both the normal and hemianopic fields and that the sensitivity that remains following removal of striate cortex is not mediated exclusively by rods.
Dystrophin and beta‐dystroglycan in photoreceptor terminals from normal and mdx3Cv mouse retinae
Authors: Blank Martina , Koulen Peter , Blake Derek J. , Kröger Stephan 
Published: March 2003

AbstractMutations in the dystrophin gene cause muscular dystrophy as well as cognitive impairments, including an abnormal dark‐adapted electroretinogram. To investigate the basis for the ocular phenotype, we analysed dystrophin and the dystrophin‐associated protein β‐dystroglycan in retinae from mdx3Cv mice. This strain has a mutation in the dystrophin gene and abnormalities in the electroretinogram which are similar to those of muscular dystrophy patients. Despite an overall reduction of all dystrophin isoforms and of β‐dystroglycan in retinal tissue from mutant mice, we observed no apparent change in the histotypic layering of the retina, or in the ultrastructure of several specific cell types, including rods and cones. In retinae from wild type and mdx3Cv mice, dystrophin and β‐dystroglycan were concentrated in small extensions of rod and cone photoreceptor terminals protruding into the outer plexiform layer. Beta‐dystroglycan but not dystrophin was also clustered around the inner limiting membrane and the capillary basal laminae. While the labelling pattern around the basal laminae was not altered in the mutant mice, we found that the area as well as the intensity of the dystrophin and β‐dystroglycan immunoreactivity associated with the terminals of rod photoreceptors were severely reduced. The same parameters were much less affected in cone terminals. These results show, that dystrophin and β‐dystroglycan are differentially distributed in the retina, and that a severe reduction of dystrophin has no gross effect on retinal structure, but could influence intraretinal signalling at the level of the photoreceptor terminals. Moreover, the mutation in mdx3Cv mice has a selective effect on rods, providing an explanation for the altered electroretinogram.
C‐fos and c‐jun in the paraventricular nucleus play a role in regulating peptide gene expression, oxytocin and glutamate release, and maternal behaviour
Authors: Da Costa A. P. C. , De La Riva C. , Guevara‐Guzman R. , Kendrick K. M. 
Published: March 2003

AbstractIn sheep, birth leads to the induction of maternal behaviour through brain oxytocin release. Associated with these events is an upregulation of oxytocin, opioid and corticotrophin‐releasing hormone (CRH) gene expression, as well as that of the immediate early gene c‐fos in the paraventricular nucleus (PVN) of the hypothalamus. We investigated the role of c‐fos dimerizing with c‐jun in controlling the induction of maternal behaviour, altered peptide gene expression, and oxytocin and amino acid release in this region at birth. Fluorescence‐labelled antisense oligodeoxyribonucleotides (ODNs) against c‐fos/c‐jun were infused bilaterally in the PVN, via microdialysis probes with 100 kDa cut‐off membranes, and were incorporated into 50–60% of the cells. Compared with the control (scrambled) sequences, they significantly reduced basal concentration of glutamate (to 31.7% of baseline after 10 h) and prevented birth‐induced release of aspartate. In addition, antisense treatment reduced the birth‐induced increase in oxytocin concentration in the PVN, but not in blood. Although all the animals were fully maternal, the antisense treatment did reduce the peak expression of two components of maternal behaviour: low‐pitched bleats; and lamb sniffing. Finally, in situ hybridization histochemistry revealed that the antisense treatment significantly reduced the birth‐induced upregulation of c‐fos, oxytocin, CRH and preproenkephalin mRNA expression in the PVN, whilst not affecting that of arginine vasopressin. These results suggest that c‐fos/c‐jun transcription factors play a role in the birth‐induced upregulation of oxytocin, CRH and preproenkephalin gene expression, as well as on glutamate and oxytocin release in the sheep PVN.
The neuropeptide Y Y1 receptor is a somatic receptor on dorsal root ganglion neurons and a postsynaptic receptor on somatostatin dorsal horn neurons
Authors: Zhang Xu , Tong Yong‐Guang , Bao Lan , Hökfelt Tomas 
Published: March 2003

AbstractUsing indirect immunofluorescence, neuropeptide Y Y1 receptor (Y1 receptor)‐like immunoreactivity (LI) was localized close to the plasmalemma of small neurons in lumbar dorsal root ganglia (DRGs) and neurons in the inner lamina II of the lumbar spinal cord of the rat. Using confocal microscopy, colocalization of Y1 receptor‐LI and transferrin receptor‐LI, a marker for endosomes and coated vesicles, was observed in dot‐like structures along the plasmalemma. Under the electron microscope, Y1 receptor‐LI was localized in coated vesicles and endosomes, in the membrane of tubular cisternae, sometimes connected to multivesicular bodies, and in the plasmalemma. These complex distribution patterns may reflect receptor turnover and internalization processes. In the lamina II of the spinal dorsal horn, Y1 receptor‐LI was localized in the plasmalemma of neurons without any apparent association with paramembrane structures, as described above for the DRG neurons. Many dendrites were Y1 receptor‐positive, and some of them made synaptic contacts with unstained axonal terminals. In general, Y1 receptor‐LI was localized in the membrane outside the postsynaptic density. Double‐immunofluorescence staining showed that most Y1 receptor‐immunoreactive neurons in lamina II contained somatostatin‐LI. Both in DRG and dorsal horn neurons, the Y1 receptor thus seems to represent a postjunctional/postsynaptic receptor.
Expression of glutamate transporters in rat optic nerve oligodendrocytes
Authors: Domercq María , Sánchez‐Gómez María Victoria , Areso Pilar , Matute Carlos 
Published: March 2003

AbstractTo investigate the role of glutamate transport in non‐synaptic glia, we characterized the expression of three major glutamate transporters (EAAC1, GLAST and GLT‐1) in rat optic nerve in situ using reverse transcription‐polymerase chain reaction in combination with Western blot and immunochemistry with specific antibodies. GLAST was localized to interfascicular oligodendrocytes, whereas a subpopulation of cells, probably immature oligodendrocyte cells, expressed EAAC1. In contrast, astrocytes, expressed only GLT‐1, consistent with the idea that this is the major glutamate transporter in this cell type. In addition, we observed that glutamine synthetase, a key enzyme in glutamate metabolism, was localized in oligodendrocytes in situ. To examine the properties of these glutamate transporters, we conducted uptake experiments in glial cultures. The kinetics of sodium‐dependent glutamate uptake in cultured oligodendrocytes from the perinatal rat optic nerve were markedly different from those observed in type‐1 astrocytes from the newborn rat cerebral cortex, with higher affinity and lower Vmax. In both cell types, glutamate transport was inhibited by
l‐trans‐pyrrolidine‐2,4‐dicarboxylate (t‐PDC). In contrast, dihydrokainate exhibited significantly more uptake inhibition in oligodendrocytes than in type‐1 astrocytes. These results provide evidence for the expression of functional sodium‐dependent glutamate transporters in optic nerve oligodendrocytes, and suggest that this cell type may play a role in the glutamate–glutamine cycle.
Overexpression of GAP‐43 induces prolonged sprouting and causes death of adult motoneurons
Authors: Harding D. I. , Greensmith L. , Mason M. , Anderson P. N. , Vrbová G. 
Published: March 2003

AbstractIn neurodegenerative diseases, neurons undergo prolonged periods of sprouting. Whether this sprouting compromises these neurons is unknown. Here, we examined the effect of axotomy on adult motoneurons undergoing prolonged sprouting in transgenic mice that overexpress GAP‐43 (growth‐associated protein). Sciatic nerve injury in these adult mice results in motoneuron death, but has no effect in non‐transgenic mice. Thus, continued growth of motor axons renders adult motoneurons susceptible to nerve injury and compromises their long‐term survival. The progressive nature of neurodegenerative diseases may therefore be caused by prolonged sprouting.
Endogenous interleukin‐6 contributes to hypersensitivity to cutaneous stimuli and changes in neuropeptides associated with chronic nerve constriction in mice
Authors: Murphy P. G. , Ramer M. S. , Borthwick L. , Gauldie J. , Richardson P. M. , Bisby M. A. 
Published: March 2003

AbstractPartial nerve injury is a potential cause of distressing chronic pain for which conventional analgesic treatment with opiates or anti‐inflammatory agents is not very effective. Constriction nerve injury, widely used to study neuropathic pain, was shown here to induce interleukin‐6 (IL‐6) mRNA in a subset of rat primary sensory neurons. When we inflicted chronic nerve constriction on mice with null mutation of the IL‐6 gene, the hypersensitivity to cutaneous heat and pressure that is induced in wild‐type mice was not evident, the loss of substance P in sensory neurons was excessive and the induction of galanin in central sensory projections was reduced. In additional experiments, intrathecal infusion of IL‐6 in rats was shown to stimulate synthesis of galanin in approximately one‐third of lumbar dorsal root ganglion neurons. The results of these experiments indicate that endogenous IL‐6 mediates some of the hypersensitive responses that characterize peripheral neuropathic pain, and influences two neuropeptides that have been implicated in pain transmission.