bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tuning for the orientation of spatial attention in dorsal premotor cortex
Authors: Lebedev Mikhail A. , Wise Steven P. 
Published: March 2003

AbstractWe tested whether neuronal activity in the dorsal premotor cortex (PMd) reflected the orientation of selective spatial attention, as opposed to the target of a reaching movement, eye position and saccade direction. These four spatial variables were dissociated in two tasks, which both required that a monkey attend to a robot's location in order to know when to make a movement. However, the target of the reaching movement varied; it was the robot's location in one task, but a different location in the other task. Eye position was recorded, but not explicitly controlled. Of 199 PMd neurons sampled, 19% had activity related to eye position, and an overlapping 11% were related to saccade direction (totaling 24% of the PMd sample). Of the 152 PMd neurons that lacked oculomotor relationships, ≈ 20% reflected the orientation of selective spatial attention. Attentional tuning may account, at least in part, for gaze‐independent receptive fields and visuospatial, target or goal relationships in tasks involving stimulus–response incompatibility.
Fibroblast growth factor‐2 is selectively modulated in the rat brain by E‐5842, a preferential sigma‐1 receptor ligand and putative atypical antipsychotic
Authors: Ovalle Sergio , Zamanillo Daniel , Andreu Francesc , Farré Antoni J. , Guitart Xavier 
Published: March 2003

AbstractFibroblast growth factor‐2 (FGF‐2) is a member of a large family of trophic factors whose expression is regulated under several conditions in different areas of the brain. The goal of our experiments was to determine whether the administration of 4‐(4‐fluorophenyl)‐1,2,3,6‐tetrahydro‐1‐[4‐(1,2,4‐triazol‐1‐il)butyl] pyridine citrate (E‐5842), a sigma‐1 receptor ligand and putative atypical antipsychotic, could regulate the expression of FGF‐2. After chronic treatment with E‐5842 (21 days, and the animals killed 24 h after the last administration), an up‐regulation was observed of the expression of FGF‐2 mRNA in the prefrontal cortex and the striatum, and a down‐regulation of the expression of FGF‐2 mRNA in the hypothalamus of the rat brain. Acute treatment with E‐5842 (one single administration and animals killed 6 h later) up‐regulated FGF‐2 expression in the prefrontal cortex, the striatum, the hypothalamus and the hippocampus in a dose‐dependent manner. The acute up‐regulation was transient and disappeared 24 h after E‐5842 administration. The induction of FGF‐2 in the striatum after repeated administration has been described for clozapine, but our data concerning regulation in the prefrontal cortex suggest that this effect is unique to E‐5852 among other antipsychotics. Given the neuroprotective activity of FGF‐2, the data presented here might be relevant to the deficit in cognition and other symptoms that appear in schizophrenia.
Maternal defence as an emotional stressor in female rats: correlation of neuroendocrine and behavioural parameters and involvement of brain oxytocin
Authors: Neumann Inga D. , Toschi Nicola , Ohl Frauke , Torner Luz , Krömer Simone A. 
Published: March 2003

AbstractIn order to study neuroendocrine and behavioural stress responses in female rats post partum we aimed to establish a relevant emotional stressor – the maternal defence test based on maternal aggression of a lactating resident towards a virgin or lactating intruder approaching the cage. Exposure to maternal defence significantly elevated corticotropin (ACTH) and corticosterone responses of the residents and of virgin or lactating intruders, with an attenuated response in lactating residents and lactating intruders. Exposure to maternal defence increased plasma oxytocin in virgin intruders only. The aggressive behaviour displayed by the residents was directly correlated with the amount of defensive behaviour of the intruder and independent of the intruder's reproductive state. However, the amount of maternal and explorative behaviours displayed by the lactating residents was significantly higher when exposed to a lactating, compared to a virgin, intruder. ACTH responses in lactating residents exposed to virgin intruders were significantly correlated to the amount of offensive (direct correlation) and maternal (inverse correlation) behaviours they displayed. Plasma prolactin concentrations, elevated in lactating compared to virgin rats under basal conditions, were found to be reduced in the lactating residents and intruders in response to exposure to the maternal defence test, whereas it was unchanged in virgin intruders. To test for the involvement of brain oxytocin in neuroendocrine and behavioural responses of the lactating residents an oxytocin receptor antagonist (0.1 µg/5 µL) was infused icv 10 min prior to testing. This treatment increased basal, but not stress‐induced, ACTH, corticosterone and oxytocin secretion. Whereas parameters of aggressive behaviour were unchanged, the antagonist reduced signs of maternal behaviour during maternal defence. In summary, the maternal defence test has been characterized as a relevant emotional stressor for female rats which is useful for studying neuroendocrine and emotional responses in females, in particular in the context of reproductive adaptations.
Matrix metalloproteinase (MMP) system in brain: identification and characterization of brain‐specific MMP highly expressed in cerebellum
Authors: Sekine‐Aizawa Yoko , Hama Emi , Watanabe Kaori , Tsubuki Satoshi , Kanai‐Azuma Masami , Kanai Yoshiakira , Arai Hiroyuki , Aizawa Hiroyuki , Iwata Nobuhisa , Saido Takaomi C. 
Published: March 2003

AbstractThe matrix metalloproteinase (MMP) family, comprising more than 20 isoforms, modulates the extracellular milieu by degrading extracellular matrix (ECM) proteins. Because MMP is one of the few groups of proteinases capable of hydrolysing insoluble fibrillar proteins, they are likely to play crucial roles in regulating both normal and pathophysiological processes in the brain. However, little is yet known about their possible neuronal functions due presumably to their unusual redundancy and to the absence of a complete catalogue of isoforms. As an initial step in understanding the MMP system in the brain, we analysed an expression spectrum of MMP in rat brain using RT‐PCR and discovered a novel brain‐specific MMP, MT5‐MMP. MT5‐MMP was the predominant species among the nongelatinase‐type isoforms in brain. MT5‐MMP, present in all brain tissues examined, was most strongly expressed in cerebellum and was localized in the membranous structures of expressing neurons, as assessed biochemically and immunohistochemically. In cerebellum, its expression was regulated developmentally and was closely associated with dendritic tree formation of Purkinje cells, suggesting that MT5‐MMP may contribute to neuronal development. Furthermore, its stable postdevelopmental expression and colocalization with senile plaques in Alzheimer brain indicates possible roles in neuronal remodeling naturally occurring in adulthood and in regulating pathophysiological processes associated with advanced age.
Synthesis of progesterone in Schwann cells: regulation by sensory neurons
Authors: Robert F. , Guennoun R. , Désarnaud F. , Do‐Thi A. , Benmessahel Y. , Baulieu E. E. , Schumacher M. 
Published: March 2003

AbstractIn peripheral nerves, progesterone synthesized by Schwann cells has been implicated in myelination. In spite of such an important function, little is known of the regulation of progesterone biosynthesis in the nervous system. We show here that in rat Schwann cells, expression of the 3β‐hydroxysteroid dehydrogenase and formation of progesterone are dependent on neuronal signal. Levels of 3β‐hydroxysteroid dehydrogenase mRNA and synthesis of [3H]progesterone from [3H]pregnenolone were low in purified Schwann cells prepared from neonatal rat sciatic nerves. However, when Schwann cells were cultured in contact with sensory neurons, both expression and activity of the 3β‐hydroxysteroid dehydrogenase were induced. Regulation of 3β‐hydroxysteroid dehydrogenase expression by neurons was also demonstrated in vivo in the rat sciatic nerve. 3β‐hydroxysteroid dehydrogenase mRNA was present in the intact nerve, but could no longer be detected 3 or 6 days after cryolesion, when axons had degenerated. After 15 days, when Schwann cells made new contact with the regenerating axons, the enzyme was re‐expressed. After nerve transection, which does not allow axonal regeneration, 3β‐hydroxysteroid dehydrogenase mRNA remained undetectable. The regulation of 3β‐hydroxysteroid dehydrogenase mRNA after lesion was similar to the regulation of myelin protein zero (P0) and peripheral myelin protein 22 (PMP22) mRNAs, supporting an important role of locally formed progesterone in myelination.
Signal detection in amplitude‐modulated maskers. I. Behavioural auditory thresholds in a songbird
Authors: Langemann Ulrike , Klump Georg M. 
Published: March 2003

AbstractVertebrates have evolved mechanisms to exploit amplitude modulations in background noise for improving signal detection. However, the mechanisms underlying this masking release are not yet well understood. Here we present evidence for masking release observed in European starlings (Sturnus vulgaris, Aves) that were trained in a Go/NoGo paradigm to report the detection of a short tone (20 ms) in 100% sinusoidally amplitude‐modulated noise maskers (400 ms duration). Maskers centred at the tone frequency were composed of one, three, or five spectrally adjacent noise bands each of auditory filter bandwidth. Envelopes of the masking noise bands were either in‐phase (i.e. coherent) or successively phase shifted by 90° (i.e. incoherent). A release from masking of up to 28 dB was observed for detection of signals presented in dips of the envelope of coherent maskers compared with those presented in peaks of coherent maskers and in incoherent maskers. For maskers limited to one auditory filter (i.e. limited to the analysis channel tuned to the test signal) this masking release was about 10 dB less than that observed for maskers allowing a comparison across three or five auditory filters. This indicates that both within‐channel cues and across‐channel cues are important for signal detection. These behavioural data provide the reference for the study of responses of auditory forebrain neurons in the same species reported in a companion paper [Nieder & Klump (2001) Eur. J. Neurosci., 13, 1033–1044].
Signal detection in amplitude‐modulated maskers. II. Processing in the songbird's auditory forebrain
Authors: Nieder Andreas , Klump Georg M. 
Published: March 2003

AbstractIn the natural environment, acoustic signals have to be detected in ubiquitous background noise. Temporal fluctuations of background noise can be exploited by the auditory system to enhance signal detection, especially if spectral masking components are coherently amplitude modulated across several auditory channels (a phenomenon called ‘comodulation masking release’). In this study of neuronal mechanisms of masking release in the primary auditory forebrain (field L) of awake European starlings (Sturnus vulgaris), we determined and compared neural detection thresholds for 20‐ms probe tones presented in a background of sinusoidally amplitude modulated (10‐Hz) noise maskers. Responses of a total of 34 multiunit clusters were recorded via radiotelemetry with chronically implanted microelectrodes from unrestrained birds. For maskers consisting of a single noise band centred around the recording site's characteristic frequency, a substantial reduction in detection threshold (21 dB on average) was found when probe tones were presented during envelope dips rather than during envelope peaks. Such effects could also explain results obtained for masking protocols where the on‐frequency noise band was presented together with excitatory or inhibitory flanking bands that were either coherently modulated (in‐phase) or incoherently modulated (phase‐shifted). Generally, masking release for probe tones in maskers with flanking bands extending beyond the frequency range of a cell cluster's excitatory tuning curve was not substantially improved. Only some of the neurophysiological results are in agreement with behavioural data from the same species if only the average population response is considered. A subsample of individual neurons, however, could account for behavioural thresholds.
Overexpression of the myristoylated alanine‐rich C kinase substrate decreases uptake and K+‐evoked release of noradrenaline in the human neuroblastoma SH‐SY5Y
Authors: Hartness Matthew E. , Wade Jennifer A. , Walker John H. , Vaughan Peter F. T. 
Published: March 2003

AbstractThe aim of this study was to investigate a possible role of the myristoylated alanine‐rich C kinase substrate (MARCKS) in the mechanism of noradrenaline uptake and release in the human neuroblastoma cell line SH‐SY5Y. A stable cell line showing a twofold overexpression of MARCKS was prepared by transfecting SH‐SY5Y with pCEP4 containing MARCKS cDNA in the sense orientation. This cell line showed no changes in the expression of neurofilaments or markers of noradrenergic large dense‐cored vesicles compared with both untransfected SH‐SY5Y and SH‐SY5Y transfected with pCEP4 only (mock transfected). Similarly, no differences in the rate of cell growth could be detected between these three cell lines. In contrast, specific uptake and depolarization‐evoked (100 mm K+) release of noradrenaline from the cell line overexpressing MARCKS was inhibited by approximately 50% compared with mock‐transfected SH‐SY5Y. K+‐evoked noradrenaline release enhanced by pretreatment with 12‐O‐tetradecanoylphorbol 13‐acetate (100 nm) was also inhibited by 50%. In contrast, carbachol‐evoked noradrenaline release was unaffected. Thus, in SH‐SY5Y cells, overexpression of MARCKS leads to a decrease in the K+‐evoked noradrenaline release possibly by increased actin cross‐linking preventing the movement of noradrenaline containing large dense‐cored vesicles to the plasma membrane in response to depolarization.
Subfield‐specific immediate early gene expression associated with hippocampal long‐term potentiation in vivo
Authors: French P. J. , O'Connor V. , Jones M. W. , Davis S. , Errington M. L. , Voss K. , Truchet B. , Wotjak C. , Stean T. , Doyère V. , Maroun M. , Laroche S. , Bliss T. V. P. 
Published: March 2003

AbstractIt is not known whether NMDA receptor‐dependent long‐term potentiation (LTP) is mediated by similar molecular mechanisms in different hippocampal areas. To address this question we have investigated changes in immediate early gene and protein expression in two hippocampal subfields following the induction of LTP in vivo and in vitro. In granule cells of the dentate gyrus, LTP induced in vivo by tetanic stimulation of the perforant path was followed by strong induction of the immediate early genes (IEGs) Zif268, Arc and Homer. The increase in Zif268 mRNA was accompanied by an increase in protein expression. In contrast, we were unable to detect modulation of the IEGs Zif268, Arc, Homer and HB‐GAM following induction of LTP by high‐frequency stimulation of the commissural projection to CA1 pyramidal cells in vivo. In this pathway, we also failed to detect modulation of Zif268 protein levels. Zif268, Arc and Homer can be modulated in CA1 pyramidal cells approximately twofold after electroshock‐induced maximal seizure, which demonstrates potential responsiveness to electrical stimuli. When LTP was induced in vitro neither CA1 pyramidal cells nor granule cells showed an increase in Zif268, Arc or Homer mRNA. However, in the slice preparation, granule cells have a different transcriptional state as basal IEG levels are elevated. These results establish the existence of subfield‐specific transcriptional responses to LTP‐inducing stimulation in the hippocampus of the intact animal, and demonstrate that in area CA1‐enhanced transcription of Zif268, Arc and Homer is not required for the induction of late LTP.
Nonactivated microglia promote oligodendrocyte precursor survival and maturation through the transcription factor NF‐κB
Authors: Nicholas Richard ST. J. , Wing Mark G. , Compston Alastair 
Published: March 2003

AbstractWe demonstrate a role for nonactivated rat microglia in the survival and maturation of oligodendrocyte precursor cells (OPCs). Media conditioned by nonactivated microglia increase the number of surviving galactocerebroside+ (GalC+) oligodendrocytes in vitro at 48 h by inhibiting the apoptosis of OPCs and stimulating their maturation to GalC+ oligodendrocytes. These effects are not observed with medium conditioned by microglia activated with interferon‐γ (IFN‐γ). Conditioned medium from nonactivated microglia is associated with upregulation in OPCs of nuclear factor of kappa binding (NF‐κB) p65 subunit. The use of antisense to the inhibitor of kappa binding (IκB) induces p65 subunit activation in OPCs and, in common with medium conditioned by nonactivated microglia, also inhibits OPC apoptosis and promotes cell maturation. Anti‐platelet‐derived growth factor (PDGF) antibody abolishes this effect even though PDGF‐A chain is expressed at similar levels within both nonactivated and IFN‐γ‐activated microglia and both conditioned media have similar levels of PDGF‐A chain bioactivity. However, only conditioned medium from nonactivated microglia recruit phosphatidyl‐3‐inositol (PI‐3) kinase to the PDGF‐α receptor and synergise with endogenous PDGF‐A chain to increase NF‐κB activation. These results suggest that, dependent on their state of activation, microglia produce soluble factors that promote oligodendrocyte development through an effect on the PDGF‐α receptor‐signalling pathway.
Dopamine and noradrenaline efflux in the rat prefrontal cortex after classical aversive conditioning to an auditory cue
Authors: Feenstra M. G. P. , Vogel M. , Botterblom M. H. A. , Joosten R. N. J. M. A. , De Bruin J. P. C. 
Published: March 2003

AbstractWe used bilateral microdialysis in the medial prefrontal cortex (PFC) of awake, freely moving rats to study aversive conditioning to an auditory cue in the controlled environment of the Skinner box. The presentation of the explicit conditioned stimuli (CS), previously associated with foot shocks, caused increased dopamine (DA) and noradrenaline (NA) efflux. This conditioned response was dependent on the immediate pairing of the two stimuli; in the pseudoconditioned group that received an equal number of both stimuli, but in an unpaired fashion, no conditioned increases in efflux were observed.
Activation of frontoparietal cortices during memorized triple‐step sequences of saccadic eye movements: an fMRI study
Authors: Heide W. , Binkofski F. , Seitz R. J. , Posse S. , Nitschke M. F. , Freund H.‐J. , Kömpf D. 
Published: March 2003

AbstractTo determine the cortical areas controlling memory‐guided sequences of saccadic eye movements, we performed functional magnetic resonance imaging (fMRI) in six healthy adults. Subjects had to perform a memorized sequence of three saccades in darkness, after a triple‐step stimulus of successively flashed laser targets. To assess the differential contribution of saccadic subfunctions, we applied several control conditions, such as central fixation with or without triple‐step visual stimulation, self‐paced saccades in darkness, visually guided saccades and single memory‐guided saccades. Triple‐step saccades strongly activated the regions of the frontal eye fields, the adjacent ventral premotor cortex, the supplementary eye fields, the anterior cingulate cortex and several posterior parietal foci in the superior parietal lobule, the precuneus, and the middle and posterior portion of the intraparietal sulcus, the probable location of the human parietal eye field. Comparison with the control conditions showed that the right intraparietal sulcus and parts of the frontal and supplementary eye fields are more involved in the execution of triple‐step saccades than in the other saccade tasks. In accordance with evidence from clinical lesion studies, we propose that the supplementary eye field essentially controls the triggering of memorized saccadic sequences, whereas activation near the middle portion of the right intraparietal sulcus appears to reflect the necessary spatial computations, including the use of extraretinal information (efference copy) about a saccadic eye displacement for updating the spatial representation of the second or third target of the triple‐step sequence.
Immunophilin ligands can prevent progressive dopaminergic degeneration in animal models of Parkinson's disease
Authors: Costantini Lauren C. , Cole Douglas ,   Pravin Chaturvedi, Isacson Ole 
Published: March 2003

AbstractSlowing or halting the progressive dopaminergic (DA) degeneration in Parkinson's disease (PD) would delay the onset and development of motor symptoms, prolong the efficacy of pharmacotherapies and decrease drug‐induced side‐effects. We tested the potential of two orally administered novel immunophilin ligands to protect against DA degeneration in two animal models of PD. First, in an MPTP (N‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine) mouse model, we compared an immunophilin ligand (V‐10,367) documented to bind the immunophilin FKBP12 with V‐13,661, which does not bind FKBP12. Both molecules could prevent the loss of striatal DA innervation in a dose‐dependent fashion during 10 days of oral administration. Second, to determine whether an immunophilin ligand can protect against progressive and slow DA degeneration typical of PD, an intrastriatal 6‐hydroxydopamine‐infusion rat model was utilized. Oral treatment with the FKBP12‐binding immunophilin ligand began on the day of lesion and continued for 21 days. At this time point, post mortem analyses revealed that the treatment had prevented the progressive loss of DA innervation within the striatum and loss of DA neurons within the substantia nigra, related to functional outcome as measured by rotational behaviour. Notably, DA fibres extending into the area of striatal DA denervation were observed only in rats treated with the immunophilin ligand, indicating neuroprotection or sprouting of spared DA fibres. This is the first demonstration that immunophilin ligands can prevent a slow and progressive DA axonal degeneration and neuronal death in vivo. The effects of orally administered structurally related immunophilin ligands in acute and progressive models of DA degeneration are consistent with the idea that these compounds may have therapeutic value in PD.
Bacterial endotoxin sensitizes the immature brain to hypoxic–ischaemic injury
Authors: Eklind Saskia , Mallard Carina , Leverin Anna‐Lena , Gilland Erik , Blomgren Klas , Mattsby‐Baltzer Inger , Hagberg Henrik 
Published: March 2003

AbstractEpidemiological studies show a markedly increased risk of cerebral palsy following the combined exposure of infection and birth asphyxia. However, the underlying mechanisms of this increased vulnerability remain unclear. We have examined the effects of a low dose of bacterial endotoxin on hypoxic–ischaemic injury in the immature brain of rats. Bacterial endotoxin (lipopolysaccharide 0.3 mg/kg) was administered to 7‐day‐old rats 4 h prior to unilateral hypoxia–ischaemia and the neurological outcome was determined 3 days later. Rectal temperature and cerebral blood flow was measured during the study and the expression of CD14 and toll‐like receptor‐4 mRNA in the brain was examined. We found that a low dose of endotoxin dramatically sensitizes the immature brain to injury and induces cerebral infarction in response to short periods of hypoxia–ischaemia that by themselves caused no or little injury. This effect could not be explained by a reduction in cerebral blood flow or hyperthermia. In association with the sensitization of injury we found an altered expression of CD14 mRNA and toll‐like receptor‐4 mRNA in the brain. These results suggest that the innate immune system may be involved in the vulnerability of the immature brain following the combination of infection and hypoxia–ischaemia.