bluuebunny/crossref_metadata_2025_split huggingface dataset:
Altering the concentration of GABA in the synaptic cleft potentiates miniature IPSCs in rat occipital cortex
Authors: Perrais David , Ropert Nicole 
Published: March 2003

AbstractWe have tested the effect of dextran (40 kDa, 5%) on miniature IPSCs (mIPSCs) recorded in layer V cortical pyramidal cells. This compound increases the amplitude of mIPSCs at room and physiological temperatures by 15%, leaving their duration unaffected at room temperature and slightly increased at physiological temperature. The amplitude increase is attributable to an increase in the number of receptors bound by GABA during synaptic transmission, as shown by the occlusion between the effects of dextran and zolpidem on mIPSC amplitude at room temperature. As dextran presumably enhances the concentration and dwell time of GABA in the synaptic cleft, these results demonstrate that the postsynaptic GABAA receptors are not saturated at room and physiological temperatures.
Inhibition of 11β‐hydroxysteroid dehydrogenase, the foeto‐placental barrier to maternal glucocorticoids, permanently programs amygdala GR mRNA expression and anxiety‐like behaviour in the offspring
Authors: Welberg Leonie A. M. , Seckl Jonathan R. , Holmes Megan C. 
Published: March 2003

AbstractGlucocorticoids may underlie the association between prenatal stress, low birth weight and adult stress‐associated disorders, e.g. hypertension and type 2 diabetes, increased hypothalamic–pituitary–adrenal (HPA) activity and affective dysfunction. Normally, 11β‐hydroxysteroid dehydrogenase type 2 (11β‐HSD2) rapidly inactivates glucocorticoids in placenta and many foetal tissues, thus acting as a ‘barrier’ to maternal steroids. We investigated the effect of inhibiting foeto‐placental 11β‐HSD in rats, using carbenoxolone (CBX), on subsequent HPA activity and regulation and stress‐induced behaviour in adult offspring. Pregnant Wistar rats were injected with CBX (12.5 mg s.c.) or vehicle daily throughout pregnancy. CBX treatment reduced birth weight. Adult offspring of CBX‐treated dams had persistently reduced body weight, increased basal corticosterone (CORT) levels, increased corticotropin‐releasing hormone (CRH) and reduced glucocorticoid receptor (GR) mRNA in the hypothalamic paraventricular nucleus, though hippocampal GR and mineralocorticoid receptor (MR) mRNA expression were unaltered. In addition, these animals showed less grooming and rearing in an open field and reduced immobility in a forced swim test, and had increased GR mRNA expression in the basolateral (BLA), central (CEA) and medial (MEA) nuclei of the amygdala, with unaltered MR mRNA. These data suggest that disturbance of the foeto‐placental enzymatic barrier to maternal glucocorticoids reduces birth and body weight, and produces permanent alterations of the HPA axis and anxiety‐like behaviour in aversive situations. The behavioural and HPA effects may reflect GR gene programming in amygdala and hypothalamus, respectively. Foetal overexposure to endogenous glucocorticoids (prenatal stress or reduced activity of foeto‐placental 11β‐HSD) may represent a common link between the prenatal environment, foetal growth and adult neuroendocrine and affective disorders.
Gq protein α subunits Gαq and Gα11 are localized at postsynaptic extra‐junctional membrane of cerebellar Purkinje cells and hippocampal pyramidal cells
Authors: Tanaka Jun , Nakagawa Shin , Kushiya Etsuko , Yamasaki Miwako , Fukaya Masahiro , Iwanaga Toshihiko , Simon Melvin I. , Sakimura Kenji , Kano Masanobu , Watanabe Masahiko 
Published: March 2003

AbstractFollowing cell surface receptor activation, the α subunit of the Gq subclass of GTP‐binding proteins activates the phosphoinositide signalling pathway. Here we examined the expression and localization of Gq protein α subunits in the adult mouse brain by in situ hybridization and immunohistochemistry. Of the four members of the Gq protein α subunits, Gαq and Gα11 were transcribed predominantly in the brain. The highest transcriptional level of Gαq was observed in cerebellar Purkinje cells (PCs) and hippocampal pyramidal cells, while that of Gα11 was noted in hippocampal pyramidal cells. Antibody against the C‐terminal peptide common to Gαq and Gα11 strongly labelled the cerebellar molecular layer and hippocampal neuropil layers. In these regions, immunogold preferentially labelled the cytoplasmic face of postsynaptic cell membrane of PCs and pyramidal cells. Immunoparticles were distributed along the extra‐junctional cell membrane of spines, dendrites and somata, but were almost excluded from the junctional membrane. By double immunofluorescence, Gαq/Gα11 was extensively colocalized with metabotropic glutamate receptor mGluR1α in dendritic spines of PCs and with mGluR5 in those of hippocampal pyramidal cells. Together with concentrated localization of mGluR1α and mGluR5 in a peri‐junctional annulus on PC and pyramidal cell synapses (Baude et al. 1993, Neuron, 11, 771–787; Luján et al. 1996, Eur. J. Neurosci., 8, 1488–1500), the present molecular‐anatomical findings suggest that peri‐junctional stimulation of the group I metabotropic glutamate receptors is mediated by Gαq and/or Gα11, leading to the activation of the intracellular effector, phospholipase Cβ.
Dissociable roles of the central and basolateral amygdala in appetitive emotional learning
Authors: Parkinson John A. , Robbins Trevor W. , Everitt Barry J. 
Published: March 2003

AbstractThe amygdala is considered to be a core component of the brain's fear system. Data from neuroimaging studies of normal volunteers and brain‐damaged patients perceiving emotional facial expressions, and studies of conditioned freezing in rats, all suggest a specific role for the amygdala in aversive motivation. However, the amygdala may also be critical for emotional processing in positive or appetitive settings. Using an appetitive Pavlovian approach procedure we show a theoretically important dissociation in the effects of excitotoxic lesions of the central nucleus and basolateral area of the amygdala, in the rat. Whilst central nucleus lesions impair appetitive Pavlovian conditioning, basolateral lesions do not. Together with other data, these results not only support the hypothesis that the amygdala is critical for appetitive as well as aversive learning, but are also consistent with amygdala subsystems subserving distinct aspects of emotional learning. Lesions of the dorsal or ventral subiculum were without effect on autoshaping, indicating the lack of involvement of hippocampal processing in this form of emotional behaviour and emphasizing further the neural specificity of the effects seen following central amygdala lesions.
Endothelial and neuronal nitric oxide synthases are present in the suprachiasmatic nuclei of Syrian hamsters and rats
Authors: Caillol Monique , Devinoy Eve , Lacroix Marie‐Christine , Schirar Alain 
Published: March 2003

AbstractNitric oxide (NO) is involved in the transmission of light information to suprachiasmatic nuclei (SCN). By immunocytochemistry, we showed that both neuronal and endothelial NO synthase isoforms (nNOS and eNOS) were present in the SCN of rats and hamsters. nNOS‐immunoreactive neurons were located mainly around the SCN with only a few nNOS neurons within the nucleus. By double‐label immunocytochemistry, we also found, within the population of SCN glial fibrillary acidic protein (GFAP)‐immunoreactive astrocytes, a subpopulation of eNOS‐immunoreactive astrocytes. Using Western blot analysis, we detected in SCN protein extracts eNOS and nNOS proteins having the expected 140 and 150 kDa molecular weights, respectively. By in situ hybridization of a 2.4‐kb murine eNOS probe, mRNA for eNOS was located in the SCN of rats and hamsters. The transcript was further identified by detection of a RT‐PCR product of the predicted size, after amplification of total RNA with primers specific for eNOS. In the SCN and cerebellum, the size of the mRNA for nNOS, detected with a rat probe on Northern blot, was ∼ 10.5 kb, corresponding to that previously published. In the same tissues, we found two transcripts, one weakly expressed at ∼ 4.0 kb and another more strongly expressed at ∼ 2.6 kb, both hybridizing with two non‐overlapping murine and rat eNOS probes. These results suggested the existence in the SCN of alternate transcripts for eNOS. We propose that two pathways could link light stimuli and NO release in the SCN: one involving N‐methyl‐ d‐aspartate (NMDA) receptors and nNOS in neurons; the other linking α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) receptors and eNOS in astrocytes.
Neuroanatomical correlates of the near response: voluntary modulation of accommodation/vergence in the human visual system
Authors: Richter Hans O. , Lee Joel T. , Pardo José V. 
Published: March 2003

AbstractThis study identifies brain regions participating in the execution of eye movements for voluntary positive accommodation (VPA) during open‐loop vergence conditions. Neuronal activity was estimated by measurement of changes in regional cerebral blood flow (rCBF) with positron emission tomography and 15O‐water. Thirteen naive volunteers viewed a checkerboard pattern with their dominant right eye, while a lens interrupted the line of gaze during alternate 1.5 s intervals. Three counterbalanced tasks required central fixation and viewing of a stationary checkerboard pattern: (i) through a 0.0 diopter (D) lens; (ii) through a −5.0‐D lens while avoiding volitional accommodation and permitting blur; and (iii) through a −5.0‐D lens while maintaining maximal focus. The latter required large‐amplitude, high‐frequency VPA. As an additional control, seven of the subjects viewed passively a digitally blurred checkerboard through a 0.0‐D lens as above. Optometric measurements confirmed normal visual acuity and ability to perform the focusing task (VPA). Large‐amplitude saccadic eye movements, verified absent by electro‐oculography, were inhibited by central fixation. Image averaging across subjects demonstrated multifocal changes in rCBF during VPA: striate and extrastriate visual cortices; superior temporal cortices; and cerebellar cortex and vermis. Decreases in rCBF occurred in the lateral intraparietal area, prefrontal and frontal and/or supplementary eye fields. Analysis of regions of interest in the visual cortex showed systematic and appropriate task dependence of rCBF. Activations may reflect sensorimotor processing along the reflex arc of the accommodation system, while deactivations may indicate inhibition of systems participating in visual search.
Role of basal ganglia and ectostriatum in the context‐dependent properties of the optocollic reflex (OCR) in the pigeon (Columba livia): a lesion study
Authors: Gioanni H. , Sansonetti A. 
Published: March 2003

AbstractThe possible participation of basal ganglia and associated structures [dorsal striato‐pallidum, nucleus spiriformis lateralis (SpL), ectostriatum] in the elaboration of the optocollic reflex (OCR) was investigated by making bilateral chemical lesions (ibotenic acid). Previous data have shown that both the slow and fast phases of the OCR are dependent on the behavioural context. The slow phase velocity (SPV) and the peak velocity of fast phases obtained in non‐flying pigeons (‘resting condition’) were enhanced in pigeons in which a flying posture was experimentally provoked (‘flying condition’). Therefore, the effect of lesions was analysed in pigeons standing in the ‘resting’ or ‘flying’ condition. In the ‘resting’ as in the ‘flying’ condition, all the lesions provoked a decrease in SPV, which augmented with the stimulation velocity. Velocity step stimuli revealed greater OCR deficits than velocity ramp stimuli. Extensive lesions (including the striato‐pallidum, ectostriatum and a part of the neostriatum), as well as SpL lesions, provoked a greater SPV decrease over a longer time than lesions restricted to the striato‐pallidum or the ectostriatum. The peak velocity of fast phases was only reduced by the ‘extensive lesion’ in the ‘flying condition’. The present data show that the basal ganglia system is involved in the elaboration of optokinetic responses and suggest that, to work in an optimal range, the optokinetic centres need to receive integrated information from basal ganglia in addition to direct visual input.
Cell type‐ and synapse‐specific variability in synaptic GABAA receptor occupancy
Authors: Hájos Norbert , Nusser Zoltan , Rancz Ede A. , Freund Tamás F. , Mody Istvan 
Published: March 2003

AbstractThe degree of postsynaptic type A γ‐aminobutyric acid receptor (GABAA receptor) occupancy was investigated by using the benzodiazepine agonist zolpidem. This drug increases the affinity of GABAA receptors for γ‐aminobutyric acid (GABA) at room temperature (Perrais & Ropert 1999, J. Neurosci., 19, 578) leading to an enhancement of synaptic current amplitudes if receptors are not fully occupied by the released transmitter. We recorded miniature inhibitory postsynaptic currents (mIPSCs) from eight different cell types in three brain regions of rats and mice. Receptors in every cell type were benzodiazepine sensitive, as 10–20 μm zolpidem prolonged the decays of mIPSCs (151–184% of control). The amplitude of the GABAA receptor‐mediated events was significantly enhanced in dentate granule cells, CA1 pyramidal cells, hippocampal GABAergic interneurons, cortical layer V pyramidal cells, cortical layer V interneurons, and in cortical layer II/III interneurons. An incomplete postsynaptic GABAA receptor occupancy is thus predicted in these cells. In contrast, zolpidem induced no significant change in mIPSC amplitudes recorded from layer II/III pyramidal cells, suggesting full GABAA receptor occupancy. Moreover, different degrees of receptor occupancy could be found at distinct GABAergic synapses on a given cell. For example, of the two distinct populations of zolpidem‐sensitive mIPSCs recorded in olfactory bulb granule cells, the amplitude of only one type was significantly enhanced by the drug. Thus, at synapses that generate mIPSCs, postsynaptic receptor occupancy is cell type and synapse specific, reflecting local differences in the number of receptors or in the transmitter concentration in the synaptic cleft.
GABAB receptors mediate frequency‐dependent depression of excitatory potentials in rat perirhinal cortex in vitro
Authors: Ziakopoulos Zoe , Brown Malcolm W. , Bashir Zafar I. 
Published: March 2003

AbstractExcitatory synaptic transmission in the perirhinal cortex exhibits marked homosynaptic paired pulse depression (PPD) at inter‐pulse intervals between 100 and 1000 ms, being maximal at 200 ms. Additionally, there is greater PPD with stimulation of the pathway from the temporal cortex side than with stimulation of the pathway from the entorhinal cortex side. We establish that this frequency‐dependent depression relies on the activation of GABAB (γ‐aminobutyric acid) receptors. PPD in both temporal and entorhinal pathways is abolished by either of the selective GABAB receptor antagonists, 3‐N[1‐(s)‐(3,4‐dichlorophenyl)ethyl]amino‐2‐(s)‐hydroxypropyl‐p‐benzyl‐phosphinic acid (CGP55845A) or 3‐amino‐propyl(diethoxymethyl)phosphinic acid (CGP35348). Barium which blocks G‐protein‐coupled, inwardly rectifying potassium channels, does not block PPD. Heterosynaptic depression mediated by GABAB receptors was also observed. The depression of the entorhinal pathway by stimulation of the temporal pathway is greater than depression of the temporal pathway by stimulation of the entorhinal pathway. Moreover, PPD increases with stimulus strength and the depression is enhanced by short trains of stimuli, consistent with stronger stimulation resulting in more GABA reaching GABAB receptors on excitatory glutamatergic synapses. Synaptic activation of GABAB receptors may be important in regulating excitability in a frequency‐dependent manner with maximal depression occurring at ∼ 5 Hz, which approximates to the theta rhythm. That homosynaptic and heterosynaptic depression by stimulation of the temporal pathway is greater than by stimulation of the entorhinal pathway suggests that activation of temporal feedforward connections to the perirhinal cortex can dominate the GABAergic control of synaptic activity within the perirhinal cortex.
Differences in Bcl‐2‐ and Bax‐independent function in regulating apoptosis in sensory neuron populations
Authors: Middleton Gayle , Cox Sean Wyatt andrew , Korsmeyer Stanley , Davies Alun M. 
Published: March 2003

AbstractBcl‐2 and Bax are cytoplasmic proteins that have antagonistic actions on apoptosis. To investigate the extent to which these proteins function independently in regulating neuronal apoptosis, we studied the in vivo and in vitro development of two populations of sensory neurons of mouse embryos that lack one or both proteins. Absence of Bcl‐2 increased neuronal apoptosis and reduced the number of neurons in both the trigeminal and nodose ganglia during the period of naturally occurring neuronal death. Absence of Bax reduced neuronal apoptosis and increased the number of surviving neurons in these ganglia and promoted sustained neuronal survival in neurotrophin‐free cultures. In contrast, the elimination of both Bcl‐2 and Bax had different consequences for these populations of neurons. In nodose ganglia, apoptosis was suppressed just as effectively in embryos lacking both proteins as in embryos lacking Bax alone, and neurons that lacked both proteins survived just as effectively in neurotrophin‐free medium as Bax‐deficient neurons. This suggests that for nodose neurons, the suppression of apoptosis by Bcl‐2 is entirely dependent on the presence of Bax. In trigeminal ganglia, although neuronal apoptosis was reduced in embryos lacking both proteins compared with wild‐type embryos, there were significantly more apoptotic neurons and significantly fewer surviving neurons in embryos lacking both proteins compared with Bax‐deficient embryos, and significantly fewer trigeminal neurons from embryos lacking both proteins survived in neurotrophin‐free medium compared with trigeminal neurons that lacked Bax alone. This suggests that for trigeminal neurons, Bcl‐2 functions partly independently of Bax in regulating survival. Our results therefore suggest that the relative independence of Bcl‐2 and Bax in regulating neuronal survival differs from one population of neurons to another.
Galanin knockout mice reveal nociceptive deficits following peripheral nerve injury
Authors: Kerr Bradley J. , Cafferty William B. J. , Gupta YurI. K. , Bacon Andrea , Wynick David , McMahon Stephen B. , Thompson Stephen W. N. 
Published: March 2003

AbstractThe neuropeptide galanin has been identified as a potential neurotransmitter/neuromodulator within the central nervous system. In the present study, the role of endogenous galanin in nociceptive processing in the nervous system has been analysed by using mice carrying a targeted mutation in the galanin gene. Supporting this, the effect of chronic administration of exogenous galanin on nociceptive sensory inputs has been assayed in adult rats. In the absence of peripheral nerve injury, the sensitivity to threshold noxious stimuli is significantly higher in galanin mutant mice than wild‐type controls. Following peripheral nerve injury, in conditions under which endogenous galanin levels are elevated, spontaneous and evoked neuropathic pain behaviours are compromised in mutant mice. Conversely, chronic intrathecal delivery of exogenous galanin to nerve‐intact adult rats is associated with persistent behavioural hypersensitivity, a significant increase in c‐fos expression and an increase in PKCγ immunoreactivity within the spinal cord dorsal horn. The present results demonstrate that a relationship exists between the degree of nerve injury‐induced galanin expression and the degree of behavioural hypersensitivity, and show that galanin may play a role in nociceptive processing in the spinal cord, with interrelated inhibitory and excitatory effects.
Basal expression of c‐Fos and Zif268 in the rat basal ganglia: immunohistochemical characterization of striatal Zif268‐positive neurons
Authors: Ishida Yasushi , Hashiguchi Hiroyuki , Ishizuka Yuta , Todaka Kazunari , Kuwahara Itsumi , Mitsuyama Yoshio , Nishimori Toshikazu 
Published: March 2003

AbstractBasal expression of the protein products of the inducible immediate early genes (IEGs), c‐Fos and Zif268, was investigated in five regions of the rat basal ganglia using immunohistochemistry. In particular, high basal levels of Zif268 but very low levels of c‐Fos were seen in the caudate‐putamen (CPu). Double immunostaining revealed that many of the constitutively expressed Zif268‐positive neurons were GABAergic but very few were cholinergic or neuronal nitric oxide synthase (nNOS)‐positive, and some of the Zif268‐positive neurons were also immunopositive for a glutamate NMDA receptor subunit NR1 or NR2A. No regional difference between the medial and lateral parts of the CPu was observed in the cellular phenotypes of Zif268‐positive neurons. Almost no basal levels of Zif268 were seen in the other four regions: the globus pallidus, entopeduncular nucleus, subthalamic nucleus and substantia nigra pars reticulata. As in the CPu, negligible levels of c‐Fos were seen in these four regions. Differential expression of these two IEGs may suggest gene‐specific and region‐specific functions of c‐Fos and Zif268 in the basal ganglia. Constitutive expression of Zif268 existing mainly in the GABAergic neurons in the CPu may at least in part be maintained by glutamatergic afferents.
Chronic psychosocial stress reduces the density of dopamine transporters
Authors: Isovich Eleonora , Mijnster M. Janneke , Flügge Gabriele , Fuchs Eberhard 
Published: March 2003

AbstractThe effect of different types of physical stress on brain dopaminergic function has been well established in rodents; however, the role of the dopaminergic system in more naturalistic stress situations is poorly understood. Therefore, the aim of the current study was to investigate the effect of chronic psychosocial stress on the dopamine transporter, which is an important component in the regulation of dopaminergic neurotransmission. For this purpose, we used the well‐characterized paradigm of subordination stress in male tree shrews (Tupaia belangeri). In the present study, the animals were subjected to psychosocial stress for 28 days. Animals were daily videotaped and locomotor activity was quantified. In subordinate animals, urinary cortisol and noradrenaline, as well as adrenal weight, were increased, whereas body weight, locomotor activity and testicular function were decreased. Brain dopamine transporter binding sites were quantified by in vitro autoradiography using [3H] WIN 35,428 as ligand. Chronic stress reduced the number of binding sites (Bmax) in the caudate nucleus and the putamen without affecting the affinity (Kd). Stress did not influence the binding parameters in the nucleus accumbens, the substantia nigra or the ventral tegmental area. Furthermore, we found a positive correlation between locomotor activity and the Bmax values for [3H] WIN 35,428 binding in the caudate nucleus, the putamen and the nucleus accumbens. The present study shows that a naturalistic stressor, such as chronic psychosocial conflict, decreases dopamine transporter binding sites in motor‐related brain areas, suggesting that the reduction in locomotor activity in subordinate tree shrews is related to the downregulation of dopamine transporter binding sites.