bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stimulation of 5‐HT1A receptors in the dorsal raphe reverses the impairment of spatial learning caused by intrahippocampal scopolamine in rats
Authors: Carli Mirjana , Bonalumi Pierenrico , Samanin Rosario 
Published: March 2003

AbstractThis study investigated the effect of stimulating 5‐HT1A receptors in the dorsal raphe on the impairment of learning caused by 4 μg/μL scopolamine injected in the CA1 region of the dorsal hippocampus in rats performing a two‐platform spatial discrimination task. At 1 (but not 0.2) μg/0.5 μL administered in the dorsal raphe on each acquisition training day 5 min before bilateral intrahippocampal injection of 4 μg/μL scopolamine, 8‐hydroxy‐2‐ (di‐n‐propylamino) tetralin (8‐OH‐DPAT), a 5‐HT1A receptor agonist, had no effect on choice accuracy and latency or errors of omission but completely antagonized the impairment of choice accuracy by intrahippocampal scopolamine. Administered into the dorsal raphe at 0.2 and 1 μg/0.5 μL, WAY 100635, a 5‐HT1A receptor antagonist, had no effect on rats’ performance or on the impairment caused by intrahippocampal scopolamine but dose‐dependently antagonized the effect of 1 μg/0.5 μL 8‐OH‐DPAT on the scopolamine‐induced deficit. The results show that stimulation of presynaptic 5‐HT1A receptors in the dorsal raphe reverses the deficit caused by intrahippocampal scopolamine, probably by facilitating the transfer of facilitatory information from the entorhinal cortex to the hippocampus. Together with a previous study showing that blockade of postsynaptic hippocampal 5‐HT1A receptors antagonized the effect of intrahippocampal scopolamine in the two‐platform spatial discrimination task (
Carli et al. 1995b
), the results suggest that drugs with presynaptic stimulatory and postsynaptic blocking actions on 5‐HT1A receptors, such as partial agonists at these receptors, may be useful in the symptomatic treatment of human memory disturbances associated with loss of cholinergic innervation to the hippocampus.
Reduced adenosine uptake accelerates ischaemic block of population spikes in hippocampal slices from streptozotocin‐treated diabetic rats
Authors: Cassar Martin , Jones Martyn G. , Szatkowski Marek 
Published: March 2003

AbstractWe have used rats with streptozotocin‐induced diabetes to investigate the effects of hyperglycaemia‐mediated impaired nucleoside uptake on the actions of endogenous adenosine in hippocampal slices. In control tissue under conditions of anoxia and aglycaemia the rise in the extracellular adenosine concentration resulted in complete inhibition of synaptic activity in about 2 min. In slices from previously hyperglycaemic rats the inhibition of synaptically mediated responses occurred significantly faster, although this change could be prevented by insulin treatment. Application of the selective adenosine A1 receptor antagonist [8‐cyclopentyl‐1,3‐dipropylxanthine (DPCPX)] prevented the anoxia/aglycaemia‐mediated inhibition and, furthermore, abolished the differences in the electrophysiological responses between control and diabetic tissue. The effects of impaired nucleoside uptake could be mimicked in control slices by applying the nucleoside uptake blocker hydroxynitrobenzylthioinosine (HNBTI). This had the effect of speeding up the rate of anoxia/aglycaemia‐induced synaptic inhibition in control tissue to that seen in diabetic tissue. However, such treatment had no effect on the responses in diabetic tissue as expected if the HNBTI‐sensitive uptake process was already inhibited by the chronic hyperglycaemia.The impairment of nucleoside uptake by chronic hyperglycaemia results in the potentiation of the modulatory actions of endogenous adenosine in the central nervous system. Such an alteration in adenosine function may be important in explaining behavioural and pathological changes associated with diabetes mellitus.
Functional GABAA receptors on human glioma cells
Authors: Labrakakis Charalampos , Patt Stephan , Hartmann Jana , Kettenmann Helmut 
Published: March 2003

AbstractGlioma cells in acute slices and in primary culture, and glioma‐derived human cell lines were screened for the presence of functional GABAA receptors. Currents were measured in whole‐cell voltage clamp in response to γ‐aminobutyric acid (GABA). While cells from the most malignant glioma, the glioblastoma multiforme, did not respond to GABA, an inward current (under our experimental conditions with high Cl− concentration in the pipette) was induced in gliomas of lower grades, namely in 71% of oligodendroglioma cells and in 62% of the astrocytoma cells. Glioma cell lines did not express functional GABAA receptors, irrespective of the malignancy of the tumour they originate from. The currents elicited by application of GABA were due to activation of GABAA receptors; the specific agonist muscimol mimicked the response, the antagonists bicuculline and picrotoxin blocked the GABA‐activated current and the benzodiazepine receptor agonist flunitrazepam augmented the GABA‐induced current and the benzodiazepine inverse agonist DMCM decreased the GABA current. Cells were heterogeneous with respect to the direction of the current flow as tested in gramicidin perforated patches: in some cells GABA hyperpolarized the membrane, while in the majority it triggered a depolarization. Moreover, GABA triggered an increase in [Ca2+]i in the majority of the tumour cells due to the activation of Ca2+ channels. Our results suggest a link between the expression of GABA receptors and the growth of glioma cells as the disappearance of functional GABAA receptors parallels unlimited growth typical for malignant tumours and immortal cell lines.
Corneal innervation and sensitivity to noxious stimuli in trkA knockout mice
Authors: De Castro Fernando , Silos‐Santiago Inmaculada , De Armentia Mikel López , Barbacid Mariano , Belmonte Carlos 
Published: March 2003

AbstractMost primary sensory neurones depend on neurotrophins for survival. Mutant mice in which TrkA, the high‐affinity receptor for nerve growth factor (NGF), has been inactivated lack nociceptive neurones in sensory ganglia and do not respond to noxious stimuli. The cornea of the eye is innervated by trigeminal neurones that are activated by noxious mechanical, thermal and chemical stimuli. In the human cornea, these stimuli evoke only sensations of pain. We have analysed the innervation pattern and the response to noxious stimulation of the cornea of trkA (–/–) mutant mice. Corneal nerves were stained with the gold chloride impregnation method. Corneal sensitivity to noxious stimuli was assessed by counting blinking movements evoked by von Frey hairs, topical application of saline at different temperatures and application of acetic acid and capsaicin at different concentrations. In the cornea of trkA (–/–) mutant animals, we observed a drastic reduction in the number of nerve trunks and branches in the corneal stroma. Furthermore, quantitative analysis of the number of thin nerve terminals revealed a marked decrease in the corneal epithelium of trkA (–/–) mice when compared to those present in wild type and trkA (+/–) animals. The blinking response of trkA (–/–) mice to mechanical, thermal and chemical noxious stimuli was also significantly reduced. These results indicate that the population of corneal sensory neurones is markedly depleted in trkA (–/–) mutant mice. However, a small portion of corneal sensory neurones survive in these mice suggesting that they may be NGF independent. On the basis of our results, we propose that these surviving cells are polymodal nociceptive neurones, sensitive to mechanical stimulation, noxious heat and acid.
Block by picrotoxin of a GABAergic chloride channel expressed on crayfish muscle after axotomy
Authors: Adelsberger Helmuth , Brunswieck Sönke , Dudel Josef 
Published: March 2003

AbstractOutside‐out patches containing a γ‐aminobutyric acid (GABA)‐activated chloride channel expressed after axotomy on crayfish deep extensor abdominal muscle were excised. GABA and the blocker picrotoxin (PTX) were applied to the patches using a liquid filament switch to study the effects of picrotoxin on the GABA‐elicited currents. Coapplication of GABA and PTX resulted in a reduction of the current amplitude compared with that elicited by the same GABA concentration alone. This reduction of the amplitude was dependent on both the GABA and PTX concentrations. The rise time of the current decreased after coapplication of GABA and PTX. Evaluation of the single channel currents and off‐currents in the presence of GABA and PTX showed a dramatic shortening of the burst duration of the channel. The open time distributions were not altered, whereas in the closed time distributions a new closed time was apparent in presence of PTX. Preincubation with PTX prior to the GABA pulse resulted in an increase of the rise time. This effect was dependent on the PTX concentration only. Possible mechanisms are discussed to explain the effects of PTX and are implemented into the existing molecular reaction scheme of the channel.
Effect of heparin‐binding growth‐associated molecule (HB‐GAM) on synaptic transmission and early LTP in rat hippocampal slices
Authors: Lauri  , Rauvala  , Kaila  , Taira  
Published: March 2003

AbstractHeparin‐binding growth‐associated molecule (HB‐GAM) is an 18‐kDa developmentally regulated protein, which promotes neurite outgrowth, axonal guidance and synaptogenesis through interaction with cell‐surface heparan‐sulphate proteoglycans. We have studied the effect of HB‐GAM on synaptic transmission and long‐term potentiation (LTP) in the area CA1 of rat hippocampal slices, where HB‐GAM mRNA is expressed in an activity‐dependent manner. Injection of recombinant HB‐GAM into the dendritic area inhibited tetanus‐induced LTP without affecting baseline synaptic responses or the N‐methyl‐d‐aspartate (NMDA)‐receptor mediated transmission. HB‐GAM did not depotentiate tetanus‐induced LTP or prevent heterosynaptic LTP induced by application of tetraethylammonium (TEA), indicating that the effect was limited to early, synapse‐specific stages of LTP induction. These results suggest that HB‐GAM is involved in the regulation of synaptic plasticity in hippocampus.
Visuo‐motor transformations for arm reaching
Authors: Lacquaniti  , Caminiti  
Published: March 2003

AbstractVisuomanual co‐ordination requires the merging of ocular and arm information in a common frame of reference. Here we consider behavioural evidence in humans for the use of a viewer‐centred frame in the specification of end point positions of reaching. We then review anatomical and neurophysiological data in the non‐human primate that indicate a prominent role of the parietal cortex in the process of multisensory fusion that leads to egocentric representations of space. Finally, we discuss the functional anatomy of the human parietal cortex in visuomanual co‐ordination as revealed by neuroimaging.
Somatostatin receptor subtypes sst1 and sst2 elicit opposite effects on the response to glutamate of mouse hypothalamic neurones: an electrophysiological and single cell RT‐PCR study
Authors: Lanneau Christophe , Viollet Cécile , Faivre‐Bauman Annie , Loudes Catherine , Kordon Claude , Epelbaum Jacques , Gardette Robert 
Published: March 2003

AbstractWe have previously shown that somatostatin can either enhance or decrease AMPA/kainate receptor‐mediated responses to glutamate in mouse‐dissociated hypothalamic neurones grown in vitro. To investigate whether this effect is due to differential activation of somatostatin (SRIF) receptor subtypes, we compared modulation of the response to glutamate by SRIF with that induced by CH‐275 and octreotide, two selective agonists of sst1 and sst2/sst5 receptors, respectively. Somatostatin either significantly decreased (49%) or increased (30%) peak currents induced by glutamate, and was ineffective in the remaining cells. Only the decreased response was obtained with octreotide, whereas only increased responses were elicited by CH‐275 (47 and 35% of the tested cells, respectively). Mean amplitude variations under somatostatin or octreotide on the one hand, and under somatostatin or CH‐275 on the other hand, were equivalent. Pertussis toxin pretreatment significantly decreased the number of cells inhibited by somatostatin or octreotide, but had no effect on the frequency of neurones showing increased sensitivity to glutamate during somatostatin or CH‐275 application. About half of the neurones tested by single cell reverse transcriptase polymerase chain reaction (RT‐PCR) expressed only one sst receptor (sst1 in 26% and sst2 in 22% of studied cells). Out of the remaining neurones, 34% displayed neither sst1 nor sst2 mRNAs, whereas 18% showed a simultaneous expression of both mRNA subtypes. Expression of sst1 or sst2 mRNA subtypes matched totally with the effects of somatostatin on sensitivity to glutamate in 79% of the neurones processed for PCR after recordings. These data show that pertussis toxin‐insensitive activation of the sst1 receptor subtype mediates somatostatin‐induced increase in sensitivity to glutamate, whereas decrease in the response to glutamate is linked to pertussis toxin‐sensitive activation of the sst2 receptor subtype.
Induction of tumour‐suppressor phosphoprotein p53 in the apoptosis of cultured rat cerebellar neurones triggered by excitatory amino acids
Authors: Uberti Daniela , Belloni Marco , Grilli Mariagrazia , Spano PierFranco , Memo Maurizio 
Published: March 2003

AbstractWe found that primary cultures of rat cerebellar granule cells, although definitely postmitotic and terminally differentiated, express the tumour‐suppressor phosphoprotein p53. In particular, granule cells both expressed significant levels of p53 mRNA and positively reacted to an anti‐p53 antibody, from the first day of culturing. During neurone differentiation, p53 mRNA content did not significantly change, at least up to 12 days in vitro, while p53 immunoreactivity increased gradually. p53 expression appeared to be further modulable being upregulated after stimulation of glutamate ionotropic receptors by glutamate or kainate. Although qualitatively similar, p53 induction by glutamate and kainate differed in terms of intensity and time‐course. The glutamate increase of p53 immunoreactivity appeared within 30 min after the treatment and lasted for at least 2 h. Kainate‐induced increase of p53 immunoreactivity was delayed, becoming apparent within 2 h and lasting for at least 8 h. Both kainate‐ and glutamate‐induced increases of p53 immunoreactivity were prevented by the non‐competitive NMDA receptor antagonist MK 801. As shown by the electrophoretic mobility shift analysis, both glutamate and kainate induced increases of p53 DNA binding activity. Blockade of p53 induction by a specific p53 antisense oligonucleotide resulted in a partial reduction of excitotoxicity with a complete inhibition of the excitatory amino acids induced apoptosis.Our data suggest that stimulation of ionotropic glutamate receptors in neurones results in a p53‐dependent apoptosis.
Compartments within human primary auditory cortex: evidence from cytochrome oxidase and acetylcholinesterase staining
Authors: Clarke Stephanie , Rivier François 
Published: March 2003

AbstractThe human primary auditory area (AI) corresponds to granular cortex located on Heschl’s gyrus. We studied its pattern of cytochrome oxidase and acetylcholinesterase activity in 10 normal human hemispheres. In cytochrome‐oxidase‐stained coronal sections layer IV was prominent by its dark staining. The overall staining intensity varied along the medio‐lateral extent of AI; a 2.0–2.5‐mm‐wide antero‐posterior dark band was present at mid‐AI. In acetylcholinesterase‐stained coronal sections a dark antero‐posterior band appeared at the same location, corresponding to the highly granular part of AI. In cytochrome‐oxidase‐stained tangential sections of flattened AI, ≈ 500‐μm thick alternating dark and light cytochrome oxidase stripes were present in layers III and IV. These stripes were perpendicular to the dark band. Comparison with tonotopic maps of human AI obtained by activation studies suggests that the cytochrome oxidase and acetylcholinesterase dark band is most likely parallel to isofrequency lines and may correspond to the representation of frequencies critical for speech comprehension. The narrow stripes may be related to particular binaural or ampliotopic domains, whose presence is suggested by evidence from electrophysiological recordings in cat AI and from magnetoencephalographic studies in humans.
MAP2d mRNA is expressed in identified neuronal populations in the developing and adult rat brain and its subcellular distribution differs from that of MAP2b in hippocampal neurones
Authors: Ferhat Lotfi , Represa Alfonso , Ferhat Walid , Ben‐Ari Yezekiel , Khrestchatisky Michel 
Published: March 2003

AbstractThe brain microtubule‐associated protein MAP2 family is composed of high‐molecular‐weight (MAP2a and MAP2b) and low‐molecular‐weight (MAP2c and MAP2d) isoforms. The common C‐terminal region of HMW MAP2 and MAP2c contains three repeated microtubule‐binding domains while MAP2d comprises four repeats. MAP2c mRNA is known to be expressed at high levels in the immature brain. We show that in the brains of rat pups, MAP2c mRNAs are indeed expressed at high levels compared with MAP2d. However, in adult rat brains, MAP2d mRNA levels are higher than MAP2c. In order to identify the neural cells expressing MAP2d, we used in situ hybridization. In vivo, we show that MAP2d mRNA is expressed in well‐identified neuronal populations of the brain. In primary cultures of hippocampal neurones, double‐labelling experiments confirm that MAP2d is clearly expressed in neurones. We also evaluated in this study the subcellular distribution of the MAP2d mRNAs in cultured hippocampal neurones and we report that in contrast with MAP2b mRNAs, mostly localized in dendrites, MAP2d mRNAs are essentially located in neuronal cell bodies.
Nongenomic effects of oestrogen: embryonic mouse midbrain neurones respond with a rapid release of calcium from intracellular stores
Authors: Beyer Cordian , Raab Heike 
Published: March 2003

AbstractEvidence is emerging that oestrogen, besides acting via classical nuclear receptors, can rapidly influence the physiology of nerve cells through other mechanisms. Oestrogens have been shown to modulate the differentiation and function of embryonic midbrain dopaminergic neurones by stimulating neurite outgrowth, expression of tyrosine hydroxylase mRNA, dopamine uptake and release in spite of the fact that dopaminergic cells in the prenatal midbrain do not express the classical oestrogen receptor. This study therefore intended to unravel possible signal transduction pathways activated by oestrogen which might be associated with the above oestrogen effects. As a physiological second‐messenger mechanism, we studied the influence of oestrogen on fluctuations of intracellular Ca2+ levels [Ca2+]i by microspectrofluorimetry of the Ca2+‐sensitive indicator Fura‐2, in primary cultures from embryonic mouse midbrains. 17β‐estradiol (10 n
m–1 p
m) but not 17α‐estradiol increased [Ca2+]i within 1–3 s in a dose‐dependent way. Removal of extracellular Ca2+ abrogated K+‐stimulated Ca2+ rise but did not affect 17β‐estradiol stimulation. Pretreatment of cells with thapsigargin (1 μm, 10 min), an inhibitor of Ca2+‐pumping ATPases in the endoplasmic reticulum, abolished the 17β‐estradiol effect but not the K+‐stimulated [Ca2+]i rise. Oestrogen effects on [Ca2+]i were completely mimicked by using a membrane‐impermeant oestrogen‐BSA construct. In order to identify oestrogen‐sensitive cells, some cultures were subsequently immunostained for microtubule‐associated protein II, tyrosine hydroxylase, or GABA. All oestrogen‐sensitive cells were immunocytochemically characterized as neurones, and about half of these responsive neurones was found to be dopaminergic or GABAergic. These results demonstrate that 17β‐estradiol is capable of rapidly modulating physiological parameters of developing midbrain neurones by directly interacting with specific membrane binding sites coupled to a signal transduction mechanism that causes a calcium release from intracellular Ca2+ stores. It is suggested that oestrogen effects on differentiation and function of midbrain dopaminergic neurones are mediated by intracellular Ca2+ signalling.
In utero gene transfer reveals survival effects of nerve growth factor on rat brain cholinergic neurones during development
Authors: Martínez‐Serrano Alberto , Olsson Martin , Gates Monte A. , Björklund Anders 
Published: March 2003

AbstractNerve growth factor (NGF) is a maintenance factor for cholinergic neurones in the brain, but its properties as a developmental survival factor are largely unknown. The low accessibility of the developing mammalian brain to experimental manipulation makes it difficult to increase NGF levels during the early phases of brain development. In the present study we have used an in utero, ex‐vivo gene transfer approach to explore NGF actions during development of the cholinergic system in the rat brain. Significantly increased numbers of cholinergic neurones were found only in the mesopontine complex in animals receiving NGF‐secreting transplants, whereas the cholinergic neurones in the basal forebrain and striatum were not clearly affected. The present results suggest that overexpression of NGF during development may promote the survival of distinct populations of central cholinergic neurones into adulthood.
Nitric oxide sensitive depolarization‐induced hyperpolarization: a possible role for gap junctions during development
Authors: Strata Fabrizio , Atzori Marco , Molnar Margherita , Ugolini Gabriele , Berretta Nicola , Cherubini Enrico 
Published: March 2003

AbstractElectrical coupling is a widespread feature of developing neuronal circuits and it contributes to the generation of patterned activity. In the developing rat hippocampus, release of GABA by coactive hilar interneurones generates widespread synchronized activity. Here it is shown that hilar interneurones strongly rectify in the outward direction when depolarized. This depolarization‐induced hyperpolarization, abolished by gap junction uncouplers, is modulated by nitric oxide. This phenomenon might represent a current‐shunting mechanism of the excess current by providing functional inhibition at a developmental stage when GABA is excitatory. Spatial buffering of the current might represent an osmotic mechanism for growth and differentiation.