bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antagonists‐resistant calcium currents in rat embryo motoneurons
Authors: Magnelli Valeria , Baldelli Pietro , Carbone Emilio 
Published: March 2003

AbstractCa2+channels diversity of cultured rat embryo motoneurons was investigated with whole‐cell current recordings. In 5–20 mmBa2+, the whole‐cell currents were separated in low‐ (LVA) and high‐voltage‐activated (HVA) current. The LVA current was evident since the first day in culture, while the HVA component was small and increased with time. Recordings after 4 days revealed ≈ 20% L‐, ≈ 45% N‐ and ≈ 35% P‐ and R‐type currents. P‐type currents were revealed only in 40% of motoneurons, in which 20–200 nmω‐Aga‐IVA caused 20% irreversible block of total current. The remaining 60% of cells were insensitive even to higher doses of the toxin (500 nmin 5 mmBa2+), suggesting weak expression and heterogeneous distribution of P‐type channels compensated by high densities of HVA Ca2+channels resistant to all the antagonists (R‐type). A significant residual current could also be resolved after prolonged applications of 5 μmω‐CTx‐MVIIC, which allowed separation of N‐ and P‐type currents by the distinct onset of toxin block. The antagonists‐resistant current reveals biophysical characteristics typical of HVA channels, but distinct from the α1Echannel. The current activates around −20 mV in 20 mmBa2+; inactivates slowly and independently of Ca2+; is blocked by low [Cd2+] and high [Ni2+]; and is larger with Ba2+than Ca2+. The uncovered R‐type calcium current can account for part of the presynaptic Ca2+current controlling neurotransmitter release at the mammalian neuromuscular junction whose activity is resistant to DHP‐ and ω‐CTx‐GVIA, and displays anomalous sensitivity to ω‐Aga‐IVA and ω‐CTx‐MVIIC (Hong & Chang (1995)J. Physiol. (Lond.),482,283–290;Lin & Lin‐Shiau (1997)Eur. J. Neurosci.,9,817–823].
Locomotor‐like movements evoked by leg muscle vibration in humans
Authors: Gurfinkel V. S. , Levik Yu. S. , Kazennikov O. V. , Selionov V. A. 
Published: March 2003

AbstractWe attempted to elicit automatic stepping in healthy humans using appropriate afferent stimulation. It was found that continuous leg muscle vibration produced rhythmic locomotor‐like stepping movements of the suspended leg, persisting up to the end of stimulation and sometimes outlasting it by a few cycles. Air‐stepping elicited by vibration did not differ from the intentional stepping under the same conditions, and involved movements in hip and knee joints with reciprocal electromyogram (EMG) bursts in corresponding flexor and extensor muscles. The phase shift between evoked hip and knee movements could be positive or negative, corresponding to ‘backward’ or ‘forward’ locomotion. Such an essential feature of natural human locomotion as alternating movements of two legs, was also present in vibratory‐evoked leg movements under appropriate conditions. It is suggested that vibration evokes locomotor‐like movements because vibratory‐induced afferent input sets into active state the central structures responsible for stepping generation.
Eph receptor–ligand interactions are necessary for guidance of retinal ganglion cell axons in vitro
Authors: Ciossek Thomas , Monschau Bruno , Kremoser Claus , Löschinger Jürgen , Lang Susanne , Müller Bernhard K. , Bonhoeffer Friedrich , Drescher Uwe 
Published: March 2003

AbstractPrevious results of an in vitro guidance test, the stripe assay, have demonstrated the presence of a repulsive axon guidance activity for temporal retinal axons in the posterior part of the vertebrate optic tectum. Ephrin‐A5 and Ephrin‐A2 are ligands for the EphA subfamily of Eph receptor tyrosine kinases, which are expressed in overlapping gradients in the posterior part of the tectum. When recombinantly expressed, both proteins have been shown to guide retinal ganglion cell axons in the stripe assay. While these results suggest that Ephrin‐A5 and Ephrin‐A2 form part of the posterior repulsive guidance activity, they do not elucidate whether they are necessary components. Here we report that soluble forms of the ligands at nanomolar concentrations completely abolish this repulsive activity. Similar results were obtained with the soluble extracellular domain of EphA3, which is a receptor for Ephrin‐A2 and Ephrin‐A5, but not with the corresponding domain of EphB3, a receptor for the transmembrane class of Eph ligands. These experiments show that the repulsive axon guidance activity seen in the stripe assay is mediated by Ephrin‐A ligands.
The constructive nature of vision: direct evidence from functional magnetic resonance imaging studies of apparent motion and motion imagery
Authors: Goebel Rainer , Khorram‐Sefat Darius , Muckli Lars , Hacker Hans , Singer Wolf 
Published: March 2003

AbstractEchoplanar functional magnetic resonance imaging was used to monitor activation changes of brain areas while subjects viewed apparent motion stimuli and while they were engaged in motion imagery. Human cortical areas MT (V5) and MST were the first areas of the ‘dorsal’ processing stream which responded with a clear increase in signal intensity to apparent motion stimuli as compared with flickering control conditions. Apparent motion of figures defined by illusory contours evoked greater activation in V2 and MT/MST than appropriate control conditions. Several areas of the dorsal pathway (V3A, MT/MST, areas in the inferior and superior parietal lobule) as well as prefrontal areas including FEF and BA 9/46 responded strongly when subjects merely imagined moving stimuli which they had seen several seconds before. The activation during motion imagery increased with the synaptic distance of an area from V1 along the dorsal processing stream. Area MT/MST was selectively activated during motion imagery but not during a static imagery control condition. The comparison between the results obtained with objective motion, apparent motion and imagined motion provides further insights into a complex cortical network of motion‐sensitive areas driven by bottom‐up and top‐down neural processes.
Retrograde degeneration of thalamic neurons in the mediodorsal nucleus after neonatal and adult aspiration lesions of the medial prefrontal cortex in the rat. Implications for mechanisms of functional recovery
Authors: Van Eden C. G. , Rinkens A. , Uylings H. B. M. 
Published: March 2003

AbstractThe behavioural consequences of neonatal lesions of the frontal cortex are limited as compared with similar lesions performed in adulthood. The present study has investigated, using unbiased quantitative methods with randomized systematic sampling, the total neuronal cell numbers in the mediodorsal nucleus of the thalamus after aspiration lesions of the medial prefrontal cortex performed in neonatal and in adult rats. It was found that the reduction in total cell numbers after neonatal prefrontal cortex lesions was similar to that found after adult cortex lesions. In neonatally lesioned animals the neuronal cell density was significantly increased by 13%, whereas in adult lesioned animals it was unchanged. On the other hand, the volume of the mediodorsal nucleus was reduced by 27% in neonatally, and 20% in adult lesioned animals. Total neuronal cell number of the mediodorsal nucleus was significantly decreased in neonatally as well as in adult lesioned rats, by 14% and 21%, respectively. These findings are discussed in the light of the previously proposed role of the thalamus as a neural substrate of functional sparing after neonatal cortical lesions.
Changes in the expression of protease‐activated receptor 1 and protease nexin‐1 mRNA during rat nervous system development and after nerve lesion
Authors: Niclou Simone P. , Suidan Hana S. , Pavlik Alfred , Vejsada Richard , Monard Denis 
Published: March 2003

AbstractThrombin causes profound metabolic and morphological changes in cultured neural cells via activation of the thrombin receptor, also called protease‐activated receptor 1 (PAR1). PAR1 mRNA is present in the rat brain, but the role of this receptor in the nervous system remains elusive. The expression of PAR1 and the potent thrombin inhibitor protease nexin‐1 (PN‐1) was investigated in the developing rat brain and spinal cord and after peripheral nerve lesion. As seen by in situ hybridization, the PAR1 mRNA signal in the late embryonic and early postnatal nervous system was widespread, but generally of low intensity whereas in the adult it was more pronounced and confined to particular neuronal cells. These include the mesencephalic dopaminergic neurons, several thalamic and brainstem nuclei, the mitral cells in the olfactory bulb and the Purkinje cells in the cerebellum. In the spinal cord, PAR1 mRNA was abundant in motoneurons and a particularly high expression was detected in the preganglionic neurons of the autonomic nervous system. High PAR1 mRNA expression was also found in the dorsal root ganglia. Interestingly, strong immunoreactivity for the protease inhibitor PN‐1 was present in spinal motoneuron cell bodies, although its transcript was undetectable there. In response to sciatic nerve transection, the signal intensity of PAR1 mRNA as seen by Northern analysis increased in the proximal and the distal part of the lesioned nerve and in the denervated muscle, whereas the PN‐1 mRNA signal strongly increased only in the distal part of the nerve but remained unchanged in the proximal part and in the muscle. After facial nerve transection, PAR1 mRNA expression substantially decreased in facial motoneurons. No PAR1 transcript was detected in reactive astrocytes. Similar to PAR1, PN‐1 mRNA which was expressed in interneurons within the facial nucleus was also decreased following facial nerve transection.
Inhibition of ischaemic hippocampal neuronal death in primates with cathepsin B inhibitor CA‐074: a novel strategy for neuroprotection based on ‘calpain–cathepsin hypothesis’
Authors: Yamashima Tetsumori , Kohda Yukihiko , Tsuchiya Katsuhiro , Ueno Takashi , Yamashita Junkoh , Yoshioka Tohru , Kominami Eiki 
Published: March 2003

AbstractAlthough Cornu Ammonis (CA) 1 neurons of the hippocampus are known to be vulnerable to transient ischaemia, the mechanism of ischaemic neuronal death is still unknown, and there are very few strategies to prevent neuronal death at present. In a previous report we demonstrated μ‐calpain activation at the disrupted lysosomal membrane of postischaemic CA1 neurons in the monkey undergoing a complete 20 min whole brain ischaemia. Using the same experimental paradigm, we observed that the enzyme activity of the lysosomal protease cathepsin B increased throughout the hippocampus on days 3–5 after the transient ischaemia. Furthermore, by immunocytochemistry cathepsin B showed presence of extralysosomal immunoreactivity with specific localization to the cytoplasm of CA1 neurons and the neuropil of the vulnerable CA1 sector. When a specific inhibitor of cathepsin B, the epoxysuccinyl peptide CA‐074 (C18H29N3O6) was intravenously administered immediately after the ischaemic insult, ≈ 67% of CA1 neurons were saved from delayed neuronal death on day 5 in eight monkeys undergoing 20 min brain ischaemia: the extent of inhibition was excellent in three of eight and good in five of eight monkeys. The surviving neurons rescued by blockade of lysosomal activity, showed mild central chromatolysis and were associated with the decreased immunoreactivity for cathepsin B. These observations indicate that calpain‐induced cathepsin B release is crucial for the development of the ischaemic neuronal death, and that a specific inhibitor of cathepsin B is of potential therapeutic utility in ischaemic injuries to the human CNS.
The expression of Huntingtin‐associated protein (HAP1) mRNA in developing, adult and ageing rat CNS: implications for Huntington's disease neuropathology
Authors: Page Keith J. , Potter Laurence , Aronni Silvia , Everitt Barry J. , Dunnett Stephen B. 
Published: March 2003

AbstractUsing radioactivein situhybridization, we have mapped the expression of Huntingtin‐associated protein (HAP1) mRNA in rat brain at developmental stages (E12–E19, P0–P21), in adult rats (3 months) and in ‘aged’ (19–21 months) rats. Using two pairs of 45mer oligonucleotide probes specific for HAP1A and a probe which recognizes regions of both the HAP1A and HAP1B mRNA sequences (panHAP1), we find that the expression of HAP1 mRNA is specific to the CNS and restricted predominantly to anatomically connected limbic structures, particularly the amygdala (medial and corticomedial nuclei), the hypothalamus (arcuate, preoptic, paraventricular and lateral hypothalamic area), bed nucleus of the stria terminalis (BNST) and the lateral septal nuclei. HAP1 mRNA was detected in embryos at E12 and displayed a prevalent distribution in the developing limbic structures by E15. In aged, 19–21‐months‐old, rats there is a downregulation of HAP1 mRNA expression across all CNSlociwhere HAP1 was previously abundant. The lowest levels of HAP1 mRNA expression corresponded with the areas of greatest pathological cell loss in Huntington's disease (HD); the caudate putamen, globus pallidus and neocortex. These observations support the suggestion that HAP1 plays an important role in the neuropathology of HD.
Local nitric oxide synthase activity in a model of neuropathic pain
Authors: Levy Dan , Zochodne Douglas. W. 
Published: March 2003

AbstractA local inflammatory reaction may play an important role in the development of neuropathic pain following peripheral nerve injury. One important participant in the inflammatory response of injured peripheral nerve may be nitric oxide (NO). In this work, we examined physiological and morphological evidence for nitric oxide synthase (NOS) activation in the chronic constriction injury model of neuropathic pain in rats. Physiological evidence of local NO action was provided by studying NO‐mediated changes in local blood flow associated with the injury site. Immunohistochemistry was used to localize isoforms of NOS that might generate NO. Sciatic nerve injury associated with behavioural evidence of neuropathic pain had substantial rises in local blood flow. The NOS inhibitor NG‐nitro‐l‐arginine methyl ester (L‐NAME), but not NG‐nitro‐d‐arginine methyl ester (D‐NAME), reversed the hyperaemia in a dose‐dependent fashion proximal to the constriction at 48 h and distally at 14 days post‐operation when applied systemically or topically. Aminoguanidine, a NOS inhibitor with relatively greater selectivity for the inducible NOS (iNOS) isoform, reversed nerve hyperaemia distal to the constriction only at 14 days. NOS‐like immunoreactivity of the neuronal and endothelial isoforms was identified just proximal to the constriction at 48 h. iNOS‐like immunoreactivity was observed at 7 and 14 days at the constriction and distal sites, respectively. This work provides evidence for local NOS expression and NO action in the chronic constriction injury model of neuropathic pain. NO has local physiological actions that include vasodilatation of microvessels and that may be important in the development of pain sensitivity.
Initially expressed early rat embryonic GABAA receptor Cl– ion channels exhibit heterogeneous channel properties
Authors: Serafini Ruggero , Ma Wu , Maric Dragan , Maric Irina , Lahjouji Fatiha , Sieghart Werner , Barker Jeffery L. 
Published: March 2003

AbstractWe have studied the earliest expression of GABA‐induced Cl– channels in the rat embryonic dorsal spinal cord (DSC) using in situ hybridization, immunocytochemistry, flow cytometry and electrophysiology. At embryonic day 13 (E13) cells in the dorsal region are still proliferating. In situ hybridization consistently showed transcripts encoding only three GABAa receptor subunits (α4, β1 and γ1); immunocytochemistry both in tissue sections and in acutely isolated cells in suspension demonstrated the expression of the corresponding proteins and also revealed staining for other subunits (α2, α3, β3, γ2). In patch‐recordings performed in cells acutely isolated from the dorsal cord, responses to GABA were detected in 356 out of 889 cells. GABA‐evoked responses, which often displayed the opening of a few channels, were mediated by Cl– ions, were inhibited by bicuculline and picrotoxin, and potentiated by benzodiazepines. Taken together, these observations indicate that Cl– channels likely involve GABAa type receptors. Fluctuation analysis revealed channel kinetics consisting of three exponential components (τs: ≈ 1, 9 and 90 ms) and a wide variety of inferred unitary conductance values, ranging between 4 and 40 pS. A comparison of these results with observations in other, later embryonic cell types and recombinant receptors suggests that most of the earliest E13 DSC GABAa receptors may include α3 subunit. These GABAa receptor Cl– channels may be activated physiologically as both GABA synthesizing enzymes and GABA are present in the E13 dorsal cord.
Direct evidence of cubic difference tone propagation by intracochlear acoustic pressure measurements in the guinea‐pig
Authors: Avan Paul , Magnan Pascal , Smurzynski Jacek , Probst Rudolf , Dancer Armand 
Published: March 2003

AbstractThe fine tuning mechanisms involved in the normal processing of sound in the cochlea are non‐linear, hence combination tones are generated inside the cochlea when a pair of low‐level pure tones with neighbouring frequencies f1 and f2 is used as a stimulus. Their detection as sounds in the ear canal proves that they undergo backward propagation in the cochlea and through the middle ear, and the non‐invasive measurement of the combination tone at 2f1–f2, called the cubic difference tone (CDT), has become a routine method of monitoring cochlear function. In order to gain information on the hypothetical places where CDTs are generated, on their intracochlear levels and propagation velocities, direct measurements of CDT pressure waves were carried out in scala vestibuli and tympani of the first and second turn of the guinea‐pig cochlea. Cubic difference tones at2f1–f2 varied from 0.75 to 9 kHz and were measured with a miniature piezoresistive transducer. Its high sensitivity allowed the detection of CDTs whenever their levels exceeded 5 dB SPL in the ear canal, i.e. 40 dB SPL (re: 20 μPa) inside the cochlea. The levels of CDTs were similar in scala vestibuli of the first and second turn. Phase comparisons between measurements at 2f1–f2 in the first and second turn allowed determination of the place where the CDT phase was minimum. It provided an estimation of the generation site of the CDT, which appeared to be close to the place tuned to f2 for stimulus levels lower than 70 dB SPL. Forward and backward travel times from one turn to the other were assessed at several frequencies, and both values were shorter than 0.2 ms. In contrast, the overall ‘round‐trip’ delay of CDTs, measured in the ear canal, was about five times larger, suggesting that local filtering processes rather than propagation delays account for the overall CDT delay.
Spectral characteristics of sleep EEG in chronic insomnia
Authors: Merica H. , Blois R. , Gaillard J. ‐M. 
Published: March 2003

AbstractTo determine whether the spectral characteristics of the sleep electroencephalogram (EEG) of insomniacs differ from that of healthy subjects, we compared in each of the first four non‐rapid eye movement (NREM) and rapid eye movement (REM) episodes: (a) the time courses of absolute power, averaged over the subjects in each group, for the delta, theta, alpha, sigma and beta frequency bands; (b) the relationship between these time courses; and (c) the overnight trend of integrated power in each frequency band. The results show that NREM power, for all frequencies below the beta range, has slower rise rates and reaches lower levels in the insomniac group, whereas beta power is significantly increased. In REM, insomniacs show lower levels in the delta and theta bands, whereas power in the faster frequency bands is significantly increased. Thus, the pathophysiology of insomnia is characterized not only by the generally acknowledged slow wave deficiency, but also by an excessive hyperarousal of the central nervous system throughout the night, affecting both REM and NREM sleep. This hyperarousal is interpreted in terms of the neuronal group theory of sleep which provides a possible explanation for the discrepancies observed between subjective impressions and objective measures of sleep. Also, it is suggested that the progressive hyperpolarization of the thalamocortical neurons as sleep deepens is slower in the patient population and that this may explain the observed slow wave deficiency. The homeostatic control of slow wave activity, on the other hand, would appear to be intact in the patient population.
Enkephalin‐containing interneurons are specialized to innervate other interneurons in the hippocampal CA1 region of the rat and guinea‐pig
Authors: Blasco‐Ibáñez J. M. , Martínez‐Guijarro F. J. , Freund T. F. 
Published: March 2003

AbstractEnkephalins are known to have a profound effect on hippocampal inhibition, but the possible endogenous source of these neuropeptides, and their relationship to inhibitory interneurons is still to be identified. In the present study we analysed the morphological characteristics of met‐enkephalin‐immunoreactive cells in the CA1 region of the rat and guinea‐pig hippocampus, their coexistence with other neuronal markers and their target selectivity at the light and electron microscopic levels. Several interneurons in all subfields of the hippocampus were found to be immunoreactive for met‐enkephalin. In the guinea‐pig, fibres arising from immunoreactive interneurons were seen to form a plexus in the stratum oriens/alveus border zone, and basket‐like arrays of boutons on both enkephalin‐immunoreactive and immunonegative cell bodies in all strata. Immunoreactive boutons always established symmetric synaptic contacts on somata and dendritic shafts. Enkephalin‐immunoreactive cells co‐localized GABA, vasoactive intestinal polypeptide and calretinin. Postembedding immunogold staining for GABA showed that all the analysed enkephalin‐immunoreactive boutons contacted GABAergic postsynaptic structures. In double‐immunostained sections, enkephalin‐positive axons were seen to innervate calbindin D28k‐, somatostatin‐, calretinin‐ and vasoactive intestinal polypeptide‐immunoreactive cells with multiple contacts. Based on these characteristics, enkephalin‐containing cells in the hippocampus are classified as interneurons specialized to innervate other interneurons, and represent a subset of vasoactive intestinal polypeptide‐ and calretinin‐containing cells. The striking match of ligand and receptor distribution in the case of enkephalin‐mediated interneuronal communication suggests that this neuropeptide may play an important role in the synchronization and timing of inhibition involved in rhythmic network activities of the hippocampus.