bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reduced somatosensory hand representation in thalidomide‐induced dysmelia as revealed by fMRI
Authors: Stoeckel M. Cornelia , Jörgens Silke , Witte Otto W. , Seitz Rüdiger J. 
Published: January 2005

AbstractThe concept of cerebral plasticity suggests that the hand representation in somatosensory cortex is abnormal in congenital malformation disorders. To investigate this issue we studied 11 subjects with different degrees of upper extremity dysmelia due to thalidomide embryopathy in comparison to 10 control subjects. In the affected subjects fingers are typically missing in radio‐ulnar order beginning with the thumb. Haemodynamic responses to electrical stimulation of the radial‐most and ulnar‐most fingers were measured in each subject using functional magnetic resonance tomography. The size of the hand area in the primary somatosensory cortex was estimated by calculating the Euclidian distance between corresponding activation peaks on the lateral postcentral gyrus. The cortical somatosensory hand representation was found to be significantly smaller in dysmelic subjects as compared with the control subjects (P < 0.001). The shrinkage of the hand area was not proportional to the number of missing fingers. Furthermore, the cortical representation of the ulnar fingers in the dysmelic subjects was shifted towards the cortical thumb representation of the control group. We suggest that the unproportional reduction of the hand area together with the observed shift may reflect use‐dependent rather than malformation‐induced reorganization of the somatosensory hand area.
Caffeine, but not nicotine, enhances visual feature binding
Authors: Colzato Lorenza S. , Fagioli Sabrina , Erasmus Vicki , Hommel Bernhard 
Published: January 2005

AbstractThe distributed organization of the human visual cortex calls for a mechanism that integrates and binds the features of a perceived event, and neural synchronization is a prime candidate to serve that purpose. Animal studies suggest that synchronization in the visual cortex is enhanced by the muscarinic cholinergic system. Here we show that in healthy humans the binding of shape and colour, and of shape and location, of visual objects is increased by stimulating the muscarinic cholinergic system (caffeine consumption) but not by stimulating the nicotinic cholinergic system (nicotine consumption). Binding across perception and action is unaffected by either manipulation, suggesting a specific link between the visual system and the muscarinic cholinergic system.
GluR‐ and TrkB‐mediated maturation of GABAA receptor function during the period of eye opening
Authors: Henneberger Christian , Jüttner René , Schmidt Sonja A. , Walter Jan , Meier Jochen C. , Rothe Thomas , Grantyn Rosemarie 
Published: January 2005

AbstractSynapse maturation includes the shortening of postsynaptic currents, due to changes in the subunit composition of respective transmitter receptors. Patch clamp experiments revealed that GABAergic inhibitory postsynaptic currents (ISPCs) of superior colliculus neurons significantly shorten from postnatal day (P)1 to P21. The change started after P6 and was steepest between P12 and P15, i.e. around eye opening. It was accompanied by enhanced sensitivity to zolpidem and increased expression of GABAAR α1 mRNA, whereas the level of α3 mRNA decreased. This result is consistent with the hypothesis that the IPSC kinetics of developing collicular neurons is determined by the level of α1/α3. As α1/α3 peaked when N‐methyl‐D‐aspartate receptor (NMDAR)‐mediated synaptic currents reached their maximum (P12) it was asked whether NMDAR activity can shape the kinetics of GABAergic IPSCs. Cultured collicular neurons were treated with NMDA or NMDAR block, and it was found that the former resulted in faster and the latter in slower IPSC decay. Group I mGluR blockade had no effect. Experiments with bdnf–/– mice revealed that, with some delay, the increase of α1/α3 mRNA also occurred in the chronic absence of brain‐derived neurotrophic factor (BDNF) and, again, this was accompanied by the shortening of IPSCs. In addition, there was an age‐dependent depression of IPSC amplitudes by endogenous BDNF, which might reflect the developmental increase in the expression of GABAAR γ2L, as opposed to γ2S. Together, these experiments suggest that the GABAAR α subunit switch and the associated change in the IPSC kinetics were specifically controlled by NMDAR activity and independent on the signalling through group I mGluRs or TrkB.
Sexual dimorphism in the effect of nonhabituating stress on neurogenic plasma extravasation
Authors: Green Paul G. , Levine Jon D. 
Published: January 2005

AbstractThe sympathoadrenal axis contributes to the sexual dimorphism of the inflammatory response. As stress both activates the sympathoadrenal axis and profoundly affects inflammation and inflammatory disease, we evaluated whether stress exerts a sexually dimorphic effect on a major component of the inflammatory response, plasma extravasation. We evaluated the effect of a nonhabituating stress, repeated intermittent sound (30 min/day for 4 days), on neurogenic synovial plasma extravasation, induced by bradykinin in the rat knee joint. Sound stress profoundly inhibited bradykinin‐induced plasma extravasation in male rats, but profoundly enhanced it in female rats. These effects took 24 h to fully develop after the last exposure to stress. In gonadectomized males, bradykinin‐induced plasma extravasation was lower than intact males, and sound stress now enhanced it, i.e. gonadectomized males were phenotypically like intact females. In gonadectomized females, bradykinin‐induced plasma extravasation was greater than in intact adult females, and sound stress still enhanced it. Adrenal enucleation significantly attenuated the effect of sound stress on bradykinin‐induced plasma extravasation in both male and female rats. We tested the hypothesis that these effects of sound stress were due to sustained enhanced plasma levels of stress hormones. Corticosterone and epinephrine, only when administered in combination, over five days, produced a qualitatively similar effect as sound stress, i.e. bradykinin‐induced plasma extravasation was significantly decreased in males and increased in females. These findings suggest that a combined effect of the hypothalamic‐pituitary adrenal and sympathoadrenal stress axes are responsible for the marked sexual dimorphism in the effect of stress on the inflammatory response.
New neurons in the dentate gyrus are involved in the expression of enhanced long‐term memory following environmental enrichment
Authors: Bruel‐Jungerman Elodie , Laroche Serge , Rampon Claire 
Published: January 2005

AbstractAlthough thousands of new neurons are continuously produced in the dentate gyrus of rodents each day, the function of these newborn cells remains unclear. An increasing number of reports have provided correlational evidence that adult hippocampal neurogenesis is involved in learning and memory. Exposure of animals to an enriched environment leads to improvement of performance in several learning tasks and enhances neurogenesis specifically in the hippocampus. These data raise the question of whether new neurons participate in memory improvement induced by enrichment. To address this issue, we have examined whether the increase in the number of surviving adult‐generated cells following environmental enrichment contributes to improved memory function. To this end, neurogenesis was substantially reduced throughout the environmental enrichment period using the antimitotic agent methylazoxymethanol acetate (MAM). Recognition memory performance of MAM‐treated enriched rats was evaluated in a novel object recognition task and compared with that of naïve and nontreated enriched rats. Injections of 5‐bromo‐2′‐deoxyuridine were used to label dividing cells, together with double immunofluorescent labelling using glial or neuronal cell‐specific markers. We found that enrichment led to improved long‐term recognition memory and increased hippocampal neurogenesis, and that MAM treatment during environmental enrichment completely prevented both the increase in neurogenesis and enrichment‐induced long‐term memory improvement. These results establish that newborn cells in the dentate gyrus contribute to the expression of the promnesic effects of behavioural enrichment, and they provide further support for the idea that adult‐generated neurons participate in modulating memory function.
Chondroitin 6‐sulphate synthesis is up‐regulated in injured CNS, induced by injury‐related cytokines and enhanced in axon‐growth inhibitory glia
Authors: Properzi Francesca , Carulli Daniela , Asher Richard A. , Muir Elizabeth , Camargo Luiz M. , Van Kuppevelt Toin H. , Ten Dam Gerdy B. , Furukawa Yoko , Mikami Tadishima , Sugahara Kazuyuki , Toida Toshihiko , Geller Herbert M. , Fawcett James W. 
Published: January 2005

AbstractChondroitin sulphate proteoglycans (CSPGs) are up‐regulated in the CNS after injury and inhibit axon regeneration mainly through their glycosaminoglycan (CS‐GAG) chains. We have analysed the mRNA levels of the CS‐GAG synthesizing enzymes and measured the CS‐GAG disaccharide composition by chromatography and immunocytochemistry. Chondroitin 6‐sulfotransferase 1 (C6ST1) is up‐regulated in most glial types around cortical injuries, and its sulphated product CS‐C is also selectively up‐regulated. Treatment with TGFα and TGFβ, which are released after brain injury, promotes the expression of C6ST1 and the synthesis of 6‐sulphated CS‐GAGs in primary astrocytes. Oligodendrocytes, oligodendrocyte precursors and meningeal cells are all inhibitory to axon regeneration, and all express high levels of CS‐GAG, including high levels of 6‐sulphated GAG. In axon growth‐inhibitory Neu7 astrocytes C6ST1 and 6‐sulphated GAGs are expressed at high levels, whereas in permissive A7 astrocytes they are not detectable. These results suggest that the up‐regulation of CSPG after CNS injury is associated with a specific sulphation pattern on CS‐GAGs, mediating the inhibitory properties of proteoglycans on axonal regeneration.
Factors limiting motor recovery after facial nerve transection in the rat: combined structural and functional analyses
Authors: Guntinas‐Lichius Orlando , Irintchev Andrey , Streppel Michael , Lenzen Mithra , Grosheva Maria , Wewetzer Konstantin , Neiss Wolfram F. , Angelov Doychin N. 
Published: January 2005

AbstractIt is believed that a major reason for the poor functional recovery after peripheral nerve lesion is collateral branching and regrowth of axons to incorrect muscles. Using a facial nerve injury protocol in rats, we previously identified a novel and clinically feasible approach to combat axonal misguidance – the application of neutralizing antibodies against neurotrophic factors to the injured nerve. Here, we investigated whether reduced collateral branching at the lesion site leads to better functional recovery. Treatment of rats with antibodies against nerve growth factor, brain‐derived neurotrophic factor, fibroblast growth factor, insulin‐like neurotrophic factor I, ciliary neurotrophic factor or glial cell line‐derived neurotrophic factor increased the precision of reinnervation, as evaluated by multiple retrograde labelling of motoneurons, more than two‐fold as compared with control animals. However, biometric analysis of vibrissae movements did not show positive effects on functional recovery, suggesting that polyneuronal reinnervation – rather than collateral branching – may be the critical limiting factor. In support of this hypothesis, we found that motor end‐plates with morphological signs of multiple innervation were much more frequent in reinnervated muscles of rats that did not recover after injury (51% of all end‐plates) than in animals with good functional performance (10%). Because polyneuronal innervation of muscle fibres is activity‐dependent and can be manipulated, the present findings raise hopes that clinically feasible and effective therapies could be soon designed and tested.
Sound‐guided shaping of the receptive field in the mouse auditory cortex by basal forebrain activation
Authors: Yan Jun , Zhang Yunfeng 
Published: January 2005

AbstractThe mammalian auditory cortex undergoes continuous plasticity following auditory experience. This study demonstrates the instructive roles of sound frequency and amplitude in representational plasticity in the primary auditory cortex of the mouse. Electrical stimulation of the basal forebrain paired with a tone led to a pronounced shift in the receptive field of the cortical neurons in both frequency and amplitude domains, the shift being towards the frequency and amplitude of the tone. Importantly, the plasticity in the frequency tuning of cortical neurons appeared to be largely dependent upon frequency‐specific decreases in the response threshold. The minimum threshold of cortical neurons could be reduced only if the amplitude of the presented tone was lower than the minimum threshold. This finding suggests that training with low‐intensity sound can increase the sensitivity of cortical neurons. Furthermore, all of these effects evoked by basal forebrain activation could be eliminated by cortical application of atropine, the acetylcholine muscarinic receptor antagonist. The data suggest that cortical plasticity is guided by both sound frequency and amplitude. The basal forebrain promotes sound‐guided cortical plasticity by facilitating neural mechanisms intrinsic to the auditory system.
Partial unilateral lesions of the mushroom bodies affect olfactory learning in honeybees Apis mellifera L.
Authors: Komischke Bernhard , Sandoz Jean‐Christophe , Malun Dagmar , Giurfa Martin 
Published: January 2005

AbstractThe mushroom bodies (MBs) are central structures in the insect brain that have been associated with olfactory learning and memory. Here we used hydroxyurea (HU) to treat honeybee larvae and induce partial MB ablations at the adult stage. We studied olfactory learning in honeybees with unilateral loss of the median calyces of their MBs and compared their ability to solve different forms of olfactory discrimination. When odorants were delivered in a side‐specific manner, ablated bees could not solve either discrimination of the unambiguous problem (Paradigm 1: A+, B– on one antenna, C+, D– on the other; A+B–/C+D–) whereas they could solve at least one of both discriminations of the ambiguous problem (Paradigm 2: A+B–/A–B+), namely that proposed to their intact brain side. Non‐ablated bees could learn side‐specific discriminations on both brain sides. When odorants were delivered simultaneously to both antennae (Paradigm 3: A+B–C+D–), HU‐ablated bees learned slower than HU‐normal bees. Thus, in all three paradigms, the unilateral loss of a median calyx affected olfactory learning. We propose that the MBs are required for solving elemental olfactory tasks whose complexity is increased by the number of stimuli involved and that MB ablations could have an effect on the inhibition of information exchange between brain hemispheres.
Activity‐dependent maturation of excitatory synaptic connections in solitary neuron cultures of mouse neocortex
Authors: Takada Naoki , Yanagawa Yuchio , Komatsu Yukio 
Published: January 2005

AbstractActivity plays important roles in the formation and maturation of synaptic connections. We examined these roles using solitary neocortical excitatory neurons, receiving only self‐generated synaptic inputs, cultured in a microisland with and without spontaneous spike activity. The amplitude of excitatory postsynaptic currents (EPSCs), evoked by applying brief depolarizing voltage pulses to the cell soma, continued to increase from 7 to 14 days in culture. Short‐term depression of EPSCs in response to paired‐pulse or 10‐train‐pulse stimulation decreased with time in culture. These developmental changes were prevented when neurons were cultured in a solution containing tetrodotoxin (TTX). The number of functional synapses estimated by recycled synaptic vesicles with FM4‐64 was significantly smaller in TTX‐treated than control neurons. However, the miniature EPSC amplitude remained unchanged during development, irrespective of activity. Transmitter release probability, assessed by use‐dependent blockade of N‐methyl‐d‐aspartate receptor‐mediated EPSCs with MK‐801, was higher in TTX‐treated than control neurons. Therefore, the activity‐dependent increase in EPSC amplitude was mainly ascribed to the increase in synapse number, while activity‐dependent alleviation of short‐term depression was mostly ascribed to the decrease in release probability. The effect of activity blockade on short‐term depression, but not EPSC amplitude, was reversed after 4 days of TTX removal, indicating that synapse number and release probability are controlled by activity in very different ways. These results demonstrate that activity regulates the conversion of immature synapses transmitting low‐frequency input signals preferentially to mature synapses transmitting both low‐ and high‐frequency signals effectively, which may be necessary for information processing in mature cortex.
Repeated morphine treatment alters polysialylated neural cell adhesion molecule, glutamate decarboxylase‐67 expression and cell proliferation in the adult rat hippocampus
Authors: Kahn Laëtitia , Alonso Gérard , Normand Elisabeth , Manzoni Olivier J. 
Published: January 2005

AbstractAltered synaptic transmission and plasticity in brain areas involved in reward and learning are thought to underlie the long‐lasting effects of addictive drugs. In support of this idea, opiates reduce neurogenesis [A.J. Eisch et al. (2000) Proceedings of the National Academy of Sciences USA, 97, 7579–7584] and enhance long‐term potentiation in adult rodent hippocampus [J.M. Harrison et al. (2002) Journal of Neurophysiology, 87, 2464–2470], a key structure of learning and memory processes. Here we studied how repeated morphine treatment and withdrawal affect cell proliferation and neuronal phenotypes in the dentate gyrus‐CA3 region of the adult rat hippocampus. Our data showed a strong reduction of cellular proliferation in morphine‐dependent animals (54% of control) that was followed by a rebound increase after 1 week withdrawal and a return to normal after 2 weeks withdrawal. Morphine dependence was also associated with a drastic reduction in the expression levels of the polysialylated form of neural cell adhesion molecule (68% of control), an adhesion molecule expressed by newly generated neurons and involved in cell migration and structural plasticity. Polysialylated neural cell adhesion molecule levels quickly returned to normal following withdrawal. In morphine‐dependent rats, we found a significant increase of glutamate decarboxylase‐67 mRNA transcription (170% of control) in dentate gyrus granular cells which was followed by a marked rebound decrease after 1 week withdrawal and a return to normal after 4 weeks withdrawal. Together, the results show, for the first time, that, in addition to reducing cell proliferation and neurogenesis, chronic exposure to morphine dramatically alters neuronal phenotypes in the dentate gyrus‐CA3 region of the adult rat hippocampus.
Internalized GABAA‐receptor subunits are transferred to an intracellular pool associated with the postsynaptic density
Authors: Van Rijnsoever Carolien , Sidler Corinne , Fritschy Jean‐Marc 
Published: January 2005

AbstractEndocytosis represents an important mechanism regulating cell‐surface expression of neurotransmitter receptors, including GABAAreceptors, in neurons. Little is known, however, about trafficking of internalized receptors. Here, we used antibody tagging in living rat hippocampal neurons in culture to monitor GABAAreceptor internalization. We show that cell‐surface receptors have a homogeneous distribution reflecting their mobility in the membrane. Unexpectedly, internalized GABAAreceptors were detected mainly in a subsynaptic pool associated with gephyrin at postsynaptic sites, whereas AMPA‐type glutamate receptors were accumulated in the soma. This process was time‐dependent and could be prevented by blocking clathrin‐coated vesicle endocytosis. In control experiments, the existence of an intracellular pool of GABAAreceptors associated with gephyrin was confirmed independently of internalization of surface receptors, and constitutive endocytosis, unrelated to antibody‐tagging, could be demonstrated for both AMPA and GABAAreceptors using a biotinylation assay. These results suggest that cycling of GABAAreceptors between the cell surface and the subsynaptic pool provides a mechanism for the short‐term regulation of GABAergic neurotransmission. Furthermore, the close association of gephyrin with internalized GABAAreceptors suggests a role in intracellular receptor trafficking.
Morphine withdrawal increases intrinsic excitability of oxytocin neurons in morphine‐dependent rats
Authors: Brown Colin H. , Stern Javier E. , Jackson Keshia L. M. , Bull Philip M. , Leng Gareth , Russell John A. 
Published: January 2005

AbstractTo determine whether intrinsic mechanisms drive supraoptic nucleus oxytocin neuron excitation during morphine withdrawal, we calculated the probability of action potential (spike) firing with time after each spike for oxytocin neurons in morphine‐naïve and morphine‐dependent rats in vivo and measured changes in intrinsic membrane properties in vitro. The opioid receptor antagonist, naloxone, increased oxytocin neuron post‐spike excitability in morphine‐dependent rats; this increase was greater for short interspike intervals (< 0.1 s). Naloxone had similar, but smaller (P = 0.04), effects in oxytocin neurons in morphine‐naïve rats. The increased post‐spike excitability for short interspike intervals was specific to naloxone, because osmotic stimulation increased excitability without potentiating excitability at short interspike intervals. By contrast to oxytocin neurons, neither morphine dependence nor morphine withdrawal increased post‐spike excitability in neighbouring vasopressin neurons. To determine whether increased post‐spike excitability in oxytocin neurons during morphine withdrawal reflected altered intrinsic membrane properties, we measured the in vitro effects of naloxone on transient outward rectification (TOR) and after‐hyperpolarization (AHP), properties mediated by K+ channels and that affect supraoptic nucleus neuron post‐spike excitability. Naloxone reduced the TOR and AHP (by 20% and 60%, respectively) in supraoptic nucleus neurons from morphine‐dependent, but not morphine‐naïve, rats. In vivo, spike frequency adaptation (caused by activity‐dependent AHP activation) was reduced by naloxone (from 27% to 3%) in vasopressin neurons in morphine‐dependent, but not morphine‐naïve, rats. Thus, multiple K+ channel inhibition increases post‐spike excitability for short interspike intervals, contributing to the increased firing of oxytocin neurons during morphine withdrawal.