bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prefrontal and agranular cingulate projections to the dorsal premotor areas F2 and F7 in the macaque monkey
Authors: Luppino Giuseppe , Rozzi Stefano , Calzavara Roberta , Matelli Massimo 
Published: March 2003

AbstractThe superior sector of Brodmann area 6 (dorsal premotor cortex, PMd) of the macaque monkey consists of a rostral and a caudal architectonic area referred to as F7 and F2, respectively. The aim of this study was to define the origin of prefrontal and agranular cingulate afferents to F7 and F2, in the light of functional and hodological evidence showing that these areas do not appear to be functionally homogeneous. Different sectors of F7 and F2 were injected with neural tracers in seven monkeys and the retrograde labelling was qualitatively and quantitatively analysed. The dorsorostral part of F7 (supplementary eye field, F7‐SEF) was found to be a target of strong afferents from the frontal eye field (FEF), from the dorsolateral prefrontal regions located dorsally (DLPFd) and ventrally (DLPFv) to the principal sulcus and from cingulate areas 24a, 24b and 24c. In contrast, the remaining part of F7 (F7‐non SEF) is only a target of the strong afferents from DLPFd. Finally, the ventrorostral part of F2 (F2vr), but not the F2 sector located around the superior precentral dimple (F2d), receives a minor, but significant, input from DLPFd and a relatively strong input from the cingulate gyrus (areas 24a and 24b) and area 24d. Present data provide strong hodological support in favour of the idea that areas F7 and F2 are formed by two functionally distinct sectors.
AMPA/kainate and NMDA‐like glutamate receptors at the chromatophore neuromuscular junction of the squid: role in synaptic transmission and skin patterning
Authors: Lima Pedro A. , Nardi Giovanna , Brown Euan R. 
Published: March 2003

AbstractGlutamate receptor types were examined at the chromatophore synapses of the squids Alloteuthis subulata and Loligo vulgaris, where nerve‐induced muscle contraction causes chromatophore expansion. Immunoblotting with antibody raised against a squid AMPA receptor (sGluR) demonstrated that AMPA/kainate receptors are present in squid skin. Application of l‐glutamate evoked chromatophore muscle contractions in both ventral and dorsal skins, while NMDA was only active on a subpopulation of dorsal chromatophores. In dorsal skin, neurotransmission was partly blocked by either AMPA/kainate receptor antagonists (CNQX and DNQX) or NMDA receptor antagonists (AP‐5 and MK‐801) or completely blocked by simultaneous application of both classes of antagonists. In isolated muscle fibres, ionophoretic application of l‐glutamate evoked fast inward CNQX‐ and DNQX‐sensitive currents with reversal potentials around +14 mV and a high conductance to Na+. In fibres from dorsal skin only, a slower outward glutamate‐sensitive current appeared at positive holding potentials. At negative potentials, currents were potentiated by glycine or by removing external Mg2+ and were blocked by AP‐5 and MK‐801. Glutamate caused a fast, followed by a slow, transient increase in cytoplasmic Ca2+. The slow component was increased in amplitude and duration by glycine or by lowering external Mg2+ and decreased by AP‐5 and MK‐801. In cells from ventral skin, no ‘NMDA‐like responses’ were detected. Thus, while AMPA/kainate receptors mediated fast excitatory synaptic transmission and rapid colour change over the whole skin, activation of both AMPA/kainate and NMDA‐like receptors in a subpopulation of dorsal chromatophores prolonged the postsynaptically evoked Ca2+ elevation causing temporally extended colour displays with behavioural significance.
Modulation of spontaneous and evoked EPSCs and IPSCs in optic lobe neurons of cuttlefish Sepia officinalis by the neuropeptide FMRF‐amide
Authors: Chrachri Abdesslam , Williamson Roddy 
Published: March 2003

AbstractThe effects of the neuropeptide FMRFa on spontaneous excitatory postsynaptic currents (sEPSCs) and inhibitory postsynaptic currents (sIPSCs), as well as on evoked EPSCs and IPSCs, in two types of neurons within the central optic lobe of cuttlefish were examined using the whole‐cell voltage‐clamp technique. FMRFa (1–10 µm) did not affect cell membrane resting potentials, but reversibly reduced both the frequency and amplitude of sEPSCs in neurons within the medulla region of the optic lobe while increasing the frequency and amplitude of their sIPSCs. For centrifugal neurons in the inner granule cell layer of the optic lobe, FMRFa (1–10 µm) decreased both the frequency and amplitude of sEPSCs. In the presence of tetrodotoxin (0.5 µm), neither the interevent interval, nor amplitude distributions of the miniature EPSCs or the miniature IPSCs, were affected by FMRFa, implying a presynaptic action of FMRFa on the optic lobe neurons. Bath application of the neuropeptide also abolished or reduced in amplitude the evoked EPSCs and increased the amplitude of evoked IPSCs in optic lobe neurons, showing that FMRFa induced similar effects on evoked as on spontaneous postsynaptic currents. These results demonstrate the complex range of modulatory effects FMRFa can have within central nervous system circuits.
Sex differences in anxiety, sensorimotor gating and expression of the α4 subunit of the GABAAreceptor in the amygdala after progesterone withdrawal
Authors: Gulinello M. , Orman R. , Smith S. S. 
Published: March 2003

AbstractIn a progesterone withdrawal (PWD) model of premenstrual anxiety, we have previously demonstrated that increased hippocampal expression of the α4 subunit of the GABAAreceptor (GABAA‐R) is closely associated with higher anxiety levels in the elevated plus maze. However, several studies indicate that sex differences in regulation of the GABAA‐R in specific brain regions may be an important factor in the observed gender differences in mood disorders. Thus, we investigated possible sex differences in GABAA‐R subunit expression and anxiety during PWD. To this end, we utilized the acoustic startle response (ASR) to assess anxiety levels in male and female rats undergoing PWD as the ASR is also applicable to the assessment of human anxiety responses. We also investigated GABAA‐R α4 subunit expression in the amygdala, as the amygdala directly regulates the primary startle circuit. Female rats exhibited a greater ASR during PWD than controls, indicating higher levels of anxiety and arousal. In contrast, male rats undergoing PWD did not demonstrate an increased ASR. The sex differences in the ASR were paralleled by sex differences in the expression of the GABAA‐R α4 subunit in the amygdala such that α4 subunit expression was up‐regulated in females during PWD whereas α4 levels in males undergoing PWD were not altered relative to controls. These findings might have implications regarding gender differences in human mood disorders and the aetiology of premenstrual anxiety.
Disabled‐1 mRNA and protein expression in developing human cortex
Authors: Meyer Gundela , De Rouvroit Catherine Lambert , Goffinet Andre M. , Wahle Petra 
Published: March 2003

AbstractDisabled‐1 (Dab1) forms part of the Reelin–Dab1 signalling pathway that controls neuronal positioning during brain development; Dab1 deficiency gives rise to a reeler‐like inversion of cortical layers. To establish a timetable of Dab1 expression in developing human brain, Dab1 mRNA and protein expression were studied in prenatal human cortex. The earliest Dab1 signal was detected at 7 gestational weeks (GW), the stage of transition from preplate to cortical plate, suggesting a role of the Reelin–Dab1 signalling pathway in preplate partition. From 12 to 20 GW, the period of maximum cortical migration, Dab1 expression was prominent in the upper tiers of the cortical plate, to decline after midgestation. Radially orientated apical dendrites of Dab1‐expressing neurons indicated a predominant pyramidal phenotype. Pyramidal cells in hippocampus and entorhinal cortex displayed a more protracted time of Dab1 expression compared to neocortex. In addition, at later stages (18–25 GW), Dab1 was also expressed in large neurons scattered throughout intermediate zone and subplate. From 14 to 22 GW, particularly high levels of Dab1 mRNA and protein were observed in cells of the ventricular/subventricular zone displaying the morphology of radial glia. The partial colocalization of vimentin and Dab1 in cells of the ventricular zone supported a radial glia phenotype. The concentration of Dab1 protein in ventricular endfeet and initial portions of radial processes of ventricular‐zone cells points to a possible involvement of Dab1 in neurogenesis. Furthermore, a subset of Cajal–Retzius cells in the marginal zone colocalized Dab1 and Reelin, and may thus represent a novel target of the Reelin–Dab1 signalling pathway.
Potentiation of glycine responses by dideoxyforskolin and tamoxifen in rat spinal neurons
Authors: Chesnoy‐Marchais Dominique 
Published: March 2003

AbstractDideoxyforskolin, a forskolin analogue unable to stimulate adenylate cyclase, and tamoxifen, an antioestrogen widely used against breast cancer, are both known to block some Cl− channels. Their effects on Cl− responses to glycine or GABA have been tested here by using whole‐cell recording from cultured spinal neurons. Dideoxyforskolin (4 or 16 µm) and tamoxifen (0.2–5 µm) both potentiate responses to low glycine concentrations. They also induce blocking effects, predominant at high glycine concentrations. At 5 µm, tamoxifen increased responses to 15 µm glycine by a factor >4.5, reaching 20 in some neurons. Potentiation by extracellular dideoxyforskolin or tamoxifen persisted after intracellular application of the modulator and was not due to Zn2+ contamination. Potentiation by tamoxifen also persisted in a Ca2+‐free extracellular solution, after intracellular Ca2+ buffering and protein kinase C blockade. Thus, the critical sites of action are not intracellular. The EC50 for glycine was lowered 6.6‐fold by 5 µm tamoxifen. The kinetics and voltage‐dependence of the effects of tamoxifen on glycine responses support the idea that this hydrophobic drug may act from a site located within the membrane. Tamoxifen (5 µm) also increased responses to 2 µm GABA by a factor of 3.5, but barely affected peak responses to 20 µm GABA. The demonstration that tamoxifen affects some of the main inhibitory receptors should be useful for better evaluating its neurological effects. Furthermore, the results identify a new class of molecules that potentiate glycine receptor function.
Acute antinociceptive responses in single and combinatorial opioid receptor knockout mice: distinct mu, delta and kappa tones
Authors: Martin Miquel , Matifas Audrey , Maldonado Rafael , Kieffer Brigitte L. 
Published: March 2003

AbstractWe have examined responses of mice lacking mu, delta and kappa opioid receptor (MOR, DOR and KOR, respectively) genes, as well as combinatorial mutants, in several pain models. This is the first truly comparative study of all three opioid receptor‐deficient mice, with genotypes and gender analysis using mice on the hybrid 50% 129/SV : 50% C57BL/6 genetic background. In the tail‐immersion test, only KOR−/− females showed decreased withdrawal latencies. This modification was also found in MOR/KOR and MOR/DOR/KOR, but not MOR/DOR mutants. The hotplate test revealed increased nociceptive sensitivity for MOR−/−, a phenotype which was also observed in double mutants involving the MOR deletion, and in the triple mutants. The tail‐pressure test showed increased response for both MOR−/− and DOR−/− mutants, a modification which was enhanced in the triple‐mutant mice. In the formalin test, MOR−/− and DOR−/− mice showed increased responses in the early and late phases, respectively, while the triple mutant tended to show enhanced nociception in both phases. Finally, the enhanced response of KOR−/− mice in the writhing test, which we have demonstrated previously, was confirmed in double MOR/KOR‐ and triple‐mutant mice. Together, the data support the existence of an antinociceptive opioid tone. Each receptor presents a distinct pattern of activities, with mu receptors influencing responses to mechanical, chemical and thermal nociception at a supraspinal level, kappa receptors involved in spinally mediated thermal nociception and chemical visceral pain, and delta receptors modulating mechanical nociception and inflammatory pain. Phenotypes of mutant mice were subtle, suggesting a low endogenous opioid tone in the regulation of physiological pain.
Potentiation of intracellular Ca2+ mobilization by hypoxia‐induced NO generation in rat brain striatal slices and human astrocytoma U‐373 MG cells and its involvement in tissue damage
Authors: Meini Antonella , Benocci Alberto , Frosini Maria , Sgaragli Gian Pietro , Garcia Julian Blanco , Pessina Gian Paolo , Aldinucci Carlo , Palmi Mitri 
Published: March 2003

AbstractThe relationship between nitric oxide (NO) and intracellular Ca2+ in hypoxic–ischemic brain damage is not known in detail. Here we used rat striatal slices perfused under low‐oxygen and Ca2+‐free conditions and cultured human astrocytoma cells incubated under similar conditions as models to study the dynamics of intracellular NO and Ca2+ in hypoxia‐induced tissue damage. Exposure of rat striatal slices for 70 min to low oxygen tension elicited a delayed and sustained increase in the release of 45Ca2+. This was potentiated by the NO donors sodium nitroprusside (SNP) and spermine–NO and inhibited by N‐ω‐nitro‐L‐arginine methyl ester (L‐NAME) or by the NO scavenger 2‐phenyl‐4,4,5,5 tetramethylimidazoline‐1‐oxyl‐3‐oxide (PTIO). A membrane‐permeant form of heparin in combination with either ruthenium red (RR) or ryanodine (RY) also inhibited 45Ca2+ release. In human astrocytoma U‐373 MG cells, hypoxia increased intracellular Ca2+ concentration ([Ca2+]i) by 67.2 ± 13.1% compared to normoxic controls and this effect was inhibited by L‐NAME, PTIO or heparin plus RR. In striatal tissue, hypoxia increased NO production and LDH release and both effects were antagonized by L‐NAME. Although heparin plus RR or RY antagonized hypoxia‐induced increase in LDH release they failed to counteract increased NO production. These data therefore indicate that NO contributes to hypoxic damage through increased intracellular Ca2+ mobilization from endoplasmic reticulum and suggest that the NO–Ca2+ signalling might be a potential therapeutic target in hypoxia‐induced neuronal degeneration.
Neurons with distinctive firing patterns, morphology and distribution in laminae V–VII of the neonatal rat lumbar spinal cord
Authors: Szûcs Péter , Odeh Francis , Szokol Karolina , Antal Miklós 
Published: March 2003

AbstractIt is generally accepted that neurons in the ventral spinal grey matter, a substantial proportion of which can be regarded as constituents of the spinal motor apparatus, receive and integrate synaptic inputs arising from various peripheral, spinal and supraspinal sources. Thus, a profound knowledge concerning the integrative properties of interneurons in the spinal ventral grey matter appears to be essential for a fair understanding of operational principles of spinal motor neural assemblies. Using the whole cell patch clamp configuration in a correlative physiological and morphological experimental approach, here we demonstrate that the intrinsic membrane properties of neurons vary widely in laminae V–VII of the ventral grey matter of the neonatal rat lumbar spinal cord. Based on their firing patterns in response to depolarizing current steps, we have classified the recorded neurons into four categories: ‘phasic’, ‘repetitive’, ‘single’ and ‘slow’. Neurons with firing properties characteristic of the ‘phasic’, ‘repetitive’ and ‘single’ cells have previously been reported also in the superficial and deep spinal dorsal horn, but this is the first account in the literature in which ‘slow’ neurons have been recovered and described in the spinal cord. The physiological heterogeneity in conjunction with the morphological correlation and distribution of neurons argues that different components of motor neural assemblies in the spinal ventral grey matter possess different signal processing characteristics.
The eye of the african mole‐ratCryptomys anselli: to see or not to see?
Authors: Cernuda‐Cernuda Rafael , García‐Fernández José M. , Gordijn Marijke C. M. , Bovee‐Geurts Petra H. M. , DeGrip Willem J. 
Published: March 2003

AbstractIn an attempt to clarify its possible physiological role, we studied the eye of the Zambian mole ratCryptomys anselliby light, electron and confocal microscopy using conventional staining as well as immunolabelling with rod and cone cell markers. The small eyes ofCryptomysare located superficially and display all features typical of sighted animals: iris, pupil and well‐developed lens, separating the anterior chamber and the vitreous. The retina shows a well stratified organization and the folds described in blind subterranean or nocturnal mammals were not observed. The major population of the photoreceptor cells in theCryptomysretina consists of rod cells, again with a morphology quite similar to that found in sighted animals. The relatively short outer segments contain numerous well‐stacked disks and show a strong rod‐opsin as well as transducin immunoreaction. Synapses were evident in the spherules, the round basal processes of the rod cell, but they lacked the precise organization reported for sighted mammals. Cone cells were present as well, as indicated by peanut lectin staining, but no immunolabelling with polyclonal M/L‐opsin antisera was detectable. The presence of cone cells was also suggested by some basal processes at the outer plexiform layer which displayed several synaptic active sites and irregular contours. While the other retinal layers also showed an organization typical of sighted mammals, there were signs of less tightly preserved morphology as well. Displaced rods and amacrine and/or ganglion cells were observed, and some sparse rod spherules penetrated into the inner nuclear layer. A major reduction was observed in the number of ganglion cells, estimated from the number of axons in the optic nerve, that was very low (≈1000 per retina on average) relative to sighted mammals. The data we have suggest a slow, ongoing loss of cells with ageing. Apoptotic nuclei, mainly corresponding to photoreceptor cells and ganglion cells, were detected in young individuals, and an overall reduction in the thickness of the retina was observed in older animals. The morphological data presented here allow some first speculations on the physiological role of theCryptomyseye and will hopefully trigger detailed studies on the chronobiology and the anatomy of the retinal projections and of the visual cortex of this remarkable species.
Effects of insulin‐like growth factor I on climbing fibre synapse elimination during cerebellar development
Authors: Kakizawa Sho , Yamada Kazuyuki , Iino Masamitsu , Watanabe Masahiko , Kano Masanobu 
Published: March 2003

AbstractFunctional neural circuit formation includes the process by which redundant synaptic connections formed earlier during development are subsequently eliminated. We report that insulin‐like growth factor I (IGF‐I) is a candidate factor that influences the developmental transition from multiple to mono innervation of cerebellar Purkinje cells (PCs) by climbing fibres (CFs). Continuous local application of exogenous IGF‐I to the mouse cerebellum by means of ethylene‐vinyl acetate copolymer (Elvax) significantly increased the degree of multiple CF innervation, when the IGF‐I containing Elvax was implanted at postnatal day 8 (P8). In contrast, the IGF‐I application starting at P12 had no effect on CF innervation. Conversely, continuous local application of antisera against IGF‐I and its receptor significantly decreased the degree of multiple CF innervation when the application started at P8. We found that chronic treatment of exogenous IGF‐I from P8 significantly enhanced the CF‐mediated excitatory postsynaptic currents (CF‐EPSCs). This effect was manifest for the smaller CF‐EPSCs but not for the largest CF‐EPSC of the multiple‐innervated PCs. Conversely, chronic application of antisera from P8 caused attenuation of the largest CF‐EPSCs. Other parameters for basic synaptic functions and cerebellar morphology were largely normal after the IGF‐I or antisera treatment. These results suggest that IGF‐I enhances the strength of developing CF synapses and may promote their survival, whereas the shortage of IGF‐I impairs the development of CF synapses and, as a result, may facilitate their elimination. Thus, IGF‐I is a potentially important factor among various signalling molecules that can influence CF synapse elimination during cerebellar development.
A hVIPR transgene as a novel tool for the analysis of circadian function in the mouse suprachiasmatic nucleus
Authors: King V. M. , Chahad‐Ehlers S. , Shen S. , Harmar A. J. , Maywood E. S. , Hastings M. H. 
Published: March 2003

AbstractA mouse bearing a novel transgene encoding the human VPAC2 receptor (hVIPR; Shen et al. (2000) PNAS, 97, 11575–11580) was used to investigate circadian function in the hypothalamic suprachiasmatic nuclei (SCN). Neurons expressing hVPAC2R, detected by a beta‐galactosidase (β‐GAL) tag, have a distinct distribution within the SCN, closely matching that of neurophysin (NP) neurons and extending into the region of peptide histidine isoleucine (PHI) cells. In common with NP and PHI cells, neurons expressing hVPAC2R are circadian in nature, as revealed by synchronous rhythmic expression of mPERIOD (mPER) proteins. A population of SCN cells not expressing PHI, NP or hVPAC2R exhibited circadian PER expression antiphasic with the rest of the SCN. Nocturnal light exposure induced mPER1 in the ventral SCN and mPER2 widely across the nucleus. Induction of nuclear mPER2 in hVPAC2R cells confirmed their photic responsiveness. Having established their circadian properties, we tested the utility of SCN neurons expressing the hVIPR transgene as functionally and anatomically explicit markers for SCN tissue grafts. Prenatal SCN tissue from hVIPR transgenic pups survived transplantation into adult CD1 mice, and expressed β‐GAL, PER and PHI. Over a series of studies, hVIPR transgenic SCN grafts restored circadian activity rhythms to 17 of 72 arrhythmic SCN lesioned recipients (23.6%). By using heterozygous hVIPR transgenic grafts on a heterozygous Clock mutant background we confirmed that restored activity rhythms were conferred by the donor tissue. We conclude that the hVIPR transgene is a powerful and flexible tool for examination of circadian function in the mouse SCN.