bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pressure‐induced depression of synaptic transmission in the cerebellar parallel fibre synapse involves suppression of presynaptic N‐type Ca2+ channels
Authors: Etzion Yoram , Grossman Yoram 
Published: March 2003

AbstractHigh pressure induces CNS hyperexcitability while markedly depressing synaptic transmitter release. We studied the effect of pressure (up to 10.1 MPa) on the parallel fibre (PF) synaptic response in biplanar cerebellar slices of adult guinea pigs. Pressure mildly reduced the PF volley amplitude and to a greater extent depressed the excitatory field postsynaptic potential (fPSP). The depression of the PF volley was noted even at supramaximal stimulus intensities, indicating an effect of pressure on the amplitude of the action potential in each axon. Low concentrations of TTX mimicked the effects of pressure on the PF volley without affecting the fPSP. Application ω‐conotoxin GVIA (ω‐CgTx) reduced the synaptic efficacy by 34.3 ± 2.7%. However, in the presence of ω‐CgTx the synaptic depression at pressure was significantly reduced. Reduced Ca2+ entry by application of Cd2+ or low [Ca2+]o did not have a similar influence on the effects of pressure. Application of ω‐AGA IVA, ω‐AGA TK and Funnel‐web spider toxin did not affect the synaptic response in concentrations that usually block P‐type Ca2+ channels, whilst the N/P/Q‐type blocker ω‐conotoxin MVIIC reduced the response to 52.7 ± 5.0% indicating the involvement of Q‐type channels and R‐type channels in the non‐N‐type fraction of Ca2+ entry. The results demonstrate that N‐type Ca2+ channels play a crucial role in the induction of PF synaptic depression at pressure. This finding suggests a coherent mechanism for the induction of CNS hyperexcitability at pressure.
Changes in direct current (DC) potentials and infra‐slow EEG oscillations at the onset of the luteinizing hormone (LH) pulse
Authors: Marshall Lisa , Mölle Matthias , Fehm Horst L. , Born Jan 
Published: March 2003

AbstractAn essential function of the neuroendocrine system lies in the coordination of hypothalamo‐pituitary secretory activity with neocortical neuronal activity. Cortical direct current (DC) potential shifts and EEG were monitored in conjunction with the circulating concentration of luteinizing hormone (LH) in humans while asleep to assess a hypothalamic–neocortical interaction. The onset of an LH pulse was accompanied (i) at frontocortical locations by a transient positive DC potential shift of ≈ 3 min duration and peak amplitude 50 μV; (ii) at frontal and central locations by an increase in power of infra‐slow EEG oscillations for periodicities between 64 and 320 s. Results uniquely demonstrate a coupling of hypothalamo‐pituitary activity with regulation of neocortical excitability.
BDNF, NT‐3 and NGF induce distinct new Ca2+ channel synthesis in developing hippocampal neurons
Authors: Baldelli Pietro , Forni Paolo E. , Carbone Emilio 
Published: March 2003

AbstractNeurotrophins exert short‐ and long‐term effects on synaptic transmission. The mechanism underlying these forms of synaptic plasticity is unknown although it is likely that intracellular Ca2+ and presynaptic Ca2+ channels play a critical role. Here we show that BDNF, NGF and NT‐3 (10–100 ng/mL) exhibit a selective long‐term up‐regulation of voltage‐gated Ca2+ current densities in developing hippocampal neurons of 6–20 days in culture. NGF and NT‐3 appear more effective in up‐regulating L‐currents, while BDNF predominantly acts on non‐L‐currents (N, P/Q and R). The effects of the three neurotrophins were time‐ and dose‐dependent. The EC50 was comparable for BDNF, NGF and NT‐3 (10–16 ng/mL) while the time of half‐maximal activation was significantly longer for NGF compared to BDNF (58 vs. 25 h). Despite the increased Ca2+ current density, the neurotrophins did not alter the voltage‐dependence of channel activation, the kinetics parameters or the elementary properties of Ca2+ channels (single‐channel conductance, probability of opening and mean open time). Neurotrophin effects were completely abolished by coincubation with the nonspecific Trk‐receptor inhibitor K252a, the protein synthesis blocker anisomycin and the MAP‐kinase inhibitor PD98059, while cotreatment with the PLC‐γ blocker, U73122, was without effect. Immunocytochemistry and Western blotting revealed that neurotrophins induced an increased MAP‐kinase phosphorylation and its translocation to the nucleus. The present findings suggest that on a long time scale different neurotrophins can selectively up‐regulate different Ca2+ channels. The action is mediated by Trk‐receptors/MAP‐kinase pathways and induces an increased density of newly available Ca2+ channels with unaltered gating activity.
Heme oxygenase1 (HSP‐32) is induced in myelin‐phagocytosing Schwann cells of injured sciatic nerves in the rat
Authors: Hirata Kazuho , He Jian‐wen , Kuraoka Akio , Omata Yoshiaki , Hirata Mizuki , Islam A. T. M. Shariful , Noguchi Masato , Kawabuchi Masaru 
Published: March 2003

AbstractSchwann cells participate in myelin phagocytosis in the early stage of Wallerian degeneration, prior to the recruitment of macrophages. This is the first report that Schwann cells induce heme oxygenase‐1 (HO‐1), a 32‐kDa heat shock protein, only when they have transformed into myelin‐phagocytosing cells from myelinating cells (days 2–3) immediately after crush injury of rat sciatic nerves. Double immunofluorescent labelling for HO‐1 and transferrin receptors revealed that HO‐1‐immunoreactive Schwann cells also expressed transferrin receptors suggesting activation of iron metabolism. The transient induction of HO‐1 in Schwann cells may contribute to the adaptive function in an altered environment when the cells have lost contact with axons, and may play a crucial role in the ensuing regeneration.
Do neurons have a reserve of sodium channels for the generation of action potentials? A study on acutely isolated CA1 neurons from the guinea‐pig hippocampus
Authors: Madeja Michael 
Published: March 2003

AbstractThe density of voltage‐gated sodium channels is high in several regions of the neuronal membrane. It is unclear if this density of channels represents a reserve for the neuron, or if it fulfils a special role in action potential firing. This problem was addressed by studying sodium currents and action potentials in acutely isolated hippocampal CA1 neurons whose number of active sodium channels was acutely changed by applying the sodium channel blocker tetrodotoxin (TTX) at different concentrations. The results show that more than a third of the sodium channels can fail without affecting the single action potential. Thus, the neurons have a remarkable surplus of sodium channels. The surplus, however, is necessary for repetitive action potential firing, as every decrease in the fraction of sodium channels reduces the maximal frequency of action potentials that can be generated by the neuron.
Spatiotemporal profile of synaptic activation produced by the electrical and visual stimulation of retinal inputs to the optic tectum: a current source density analysis in the pigeon (Columba livia)
Authors: Letelier Juan Carlos , Mpodozis Jorge , Marin Gonzalo , Morales Daniver , Rozas Carlos , Madrid Carlos , Velasco Marcelo 
Published: March 2003

AbstractThe optic tectum of the pigeon is a highly organized, multilayered structure that receives a massive polystratified afference of at least five different populations of retinal ganglion cells and gives rise to various anatomically segregated efferent systems. The synaptic organization of retino‐tectal circuitry is, at present, mostly unknown. To investigate the spatiotemporal profile of synaptic activation produced by differential (electrical and visual) stimulation of the retinal inputs, we performed a high‐spatial‐resolution current source density analysis in the optic tectum of the anaesthetized pigeon. Electrical stimuli consisted of brief pulses of different durations applied to the optic nerve head, while visual stimuli consisted of light flashes of different intensities. Electrical stimulation generated sinks confined to retinorecipient layers. The temporal structure, spatial location and thresholds of these sinks indicated that they are all due to primary tectal synapses of retinal fibers with different conduction velocities. Sinks evoked by the fastest retinal axons were more superficially located than sinks produced by slower retinal fibers. Visual stimulation, on the other hand, resulted in a more complex pattern of current sinks, with various sinks located in the retinorecipient layers and also well below. Visual stimulation induced action potentials at superficial as well as deep tectal levels. We conclude that electrical stimulation activates most of the populations of ganglion cells as well as their primary tectal synapses, but is unable to elicit a significant activation of secondary tectal synapses. Visual stimulation, on the contrary, activates just some of the incoming retinal populations, but in a way that produces noticeable secondary activation of intratectal circuits. Laminar segregation of retinally evoked tectal activity, as reported here, has also been found in other vertebrates. Similarities and differences with previous studies are discussed.
Routes of zinc entry in mouse cortical neurons: role in zinc‐induced neurotoxicity
Authors: Marin Philippe , Israël Maurice , Glowinski Jacques , Prémont Joël 
Published: March 2003

AbstractExposure of central neurons to Zn2+ triggers neuronal death. The routes of Zn2+ entry were investigated in living cortical neurons from the mouse using the specific Zn2+ fluorescent dye N‐(6‐methoxy‐8‐quinolyl)‐p‐toluene sulphonamide (TSQ), which preferentially detects membrane‐bound Zn2+. Exposure of cortical neurons to increasing concentrations of Zn2+ (1–100 μm) induced a progressive increase in the fluorescence of TSQ. This fluorescence signal was not attenuated by the permeation of plasma membrane with digitonin. Accordingly, the major part of TSQ fluorescence (two‐thirds) was associated to the particulate fraction of cortical neurons exposed to Zn2+. These results suggest that Zn2+ detected with TSQ in neurons is mainly bound to membranes. TSQ fluorescence measured in neurons exposed to 3 μm Zn2+ was enhanced by Na+‐pyrithione, a Zn2+ ionophore, α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionic acid (AMPA), N‐methyl‐d‐aspartate (NMDA) or KCl‐induced depolarization. However, in the absence of any treatment, TSQ labelling of neurons exposed to 3 μm Zn2+ was only decreased by NMDA receptor antagonists, whereas it remained unaltered in the presence of antagonists of AMPA receptors or L‐type voltage‐gated Ca2+ channels. Zn2+ entry through NMDA receptors did not contribute to Zn2+‐induced neuronal death, as it was prevented by antagonists of NMDA receptors only when they were added after the Zn2+ exposure. Finally, Zn2+ induced a delayed accumulation of extracellular glutamate which might be responsible for the delayed NMDA receptor activation that leads to neuronal death.
Differential regulation of the dopamine D1, D2 and D3 receptor gene expression and changes in the phenotype of the striatal neurons in mice lacking the dopamine transporter
Authors: Fauchey Valérie , Jaber Mohamed , Caron Marc G. , Bloch Bertrand , Le Moine Catherine 
Published: March 2003

AbstractMice with a genetic disruption of the dopamine transporter (DAT–/–) exhibit locomotor hyperactivity and profound alterations in the homeostasis of the nigrostriatal system, e.g. a dramatic increase in the extracellular dopamine level. Here, we investigated the adaptive changes in dopamine D1, D2 and D3 receptor gene expression in the caudate putamen and nucleus accumbens of DAT–/– mice. We used quantitative in situ hybridization and found that the constitutive hyperdopaminergia results in opposite regulations in the gene expression for the dopamine receptors. In DAT–/– mice, we observed increased mRNA levels encoding the D3 receptor (caudate putamen, +60–85%; nucleus accumbens, +40–107%), and decreased mRNA levels for both D1 (caudate putamen, −34%; nucleus accumbens, −45%) and D2 receptors (caudate putamen, −36%; nucleus accumbens, −33%). Furthermore, we assessed the phenotypical organization of the striatal efferent neurons by using double in situ hybridization. Our results show that in DAT+/+ mice, D1 and D2 receptor mRNAs are segregated in two different main populations corresponding to substance P and preproenkephalin A mRNA‐containing neurons, respectively. The phenotype of D1 or D2 mRNA‐containing neurons was unchanged in both the caudate putamen and nucleus accumbens of DAT–/– mice. Interestingly, we found an increased density of preproenkephalin A‐negative neurons that express the D3 receptor mRNA in the nucleus accumbens (core, +35%; shell, +46%) of DAT–/– mice. Our data further support the critical role for the D3 receptor in the regulation of D1–D2 interactions, an action being restricted to neurons coexpressing D1 and D3 receptors in the nucleus accumbens.
Transient neuromotor phenotype in transgenic spastic mice expressing low levels of glycine receptor β‐subunit: an animal model of startle disease
Authors: Becker Lore , Hartenstein Bettina , Schenkel Johannes , Kuhse Jochen , Betz Heinrich , Weiher Hans 
Published: March 2003

AbstractStartle disease or hereditary hyperekplexia has been shown to result from mutations in the α1‐subunit gene of the inhibitory glycine receptor (GlyR). In hyperekplexia patients, neuromotor symptoms generally become apparent at birth, improve with age, and often disappear in adulthood. Loss‐of‐function mutations of GlyR α or β‐subunits in mice show rather severe neuromotor phenotypes. Here, we generated mutant mice with a transient neuromotor deficiency by introducing a GlyR β transgene into the spastic mouse (spa/spa), a recessive mutant carrying a transposon insertion within the GlyR β‐subunit gene. In spa/spa TG456 mice, one of three strains generated with this construct, which expressed very low levels of GlyR β transgene‐dependent mRNA and protein, the spastic phenotype was found to depend upon the transgene copy number. Notably, mice carrying two copies of the transgene showed an age‐dependent sensitivity to tremor induction, which peaked at ∼ 3–4 weeks postnatally. This closely resembles the development of symptoms in human hyperekplexia patients, where motor coordination significantly improves after adolescence. The spa/spa TG456 line thus may serve as an animal model of human startle disease.
Glucocorticoid receptor impairment alters CNS responses to a psychological stressor: an in vivo microdialysis study in transgenic mice
Authors: Linthorst Astrid C. E. , Flachskamm Cornelia , Barden Nicholas , Holsboer Florian , Reul Johannes M. H. M. 
Published: March 2003

AbstractTo study the consequences of impaired functioning of the glucocorticoid receptor (GR) for behavioural, neuroendocrine and neurochemical responses to a psychological stressor, a transgenic mouse expressing antisense RNA against GR was used. Previous studies on these transgenic mice have shown that impairment of GR evolves in disturbed neuroendocrine regulation and certain behavioural responses to stress. Here we investigated putative disturbances on the level of brain neurotransmission in GR‐impaired (GR‐i) mice using an in vivo microdialysis method. Through a microdialysis probe in the hippocampus, serotonin (5‐HT), 5‐hydroxyindoleacetic acid (5‐HIAA) and free corticosterone [as an index of hypothalamic–pituitary–adrenocortical (HPA) axis activity] were monitored. Moreover, specific behaviours (e.g. grooming, eating/drinking, sniffing, nest building and locomotion) displayed by the mice during collection of the dialysates were scored. Measurement of dialysate concentrations of corticosterone on days 1 and 3 after insertion of the microdialysis probe showed that the free levels of this glucocorticoid were significantly lower in GR‐i mice toward the evening. On day 2 after insertion of the microdialysis probe, baseline values of dialysate corticosterone, 5‐HT and 5‐HIAA were assessed, after which mice were exposed to a rat placed into their home cage. The rat and mouse were separated by a Plexiglas wall. A positive correlation between baseline hippocampal extracellular levels of 5‐HT and 5‐HIAA and the time spent performing active behaviours was observed in both genotypes. The main active behaviour performed at the baseline was grooming behaviour. During the rat exposure period, control mice remained mostly sitting and/or lying with their eyes fixed on the rat. Moreover, they showed a profound rise in free corticosterone levels. In contrast, GR‐i mice displayed significantly more activities along the separation wall and a trend toward more grooming behaviour, but no increase of free corticosterone. In both mouse lines, exposure to a rat increased hippocampal extracellular levels of 5‐HT and 5‐HIAA. The rise in 5‐HT was, however, more pronounced in the GR‐i mice. From these data it may be concluded that life‐long GR impairment has profound consequences for behavioural and neuroendocrine responses to a psychological stressor. Moreover, long‐term impaired functioning of GR evolves in hyper‐responsiveness of the raphe‐hippocampal serotonergic system.
Convergence of segregated pheromonal pathways from the accessory olfactory bulb to the cortex in the mouse
Authors: Von Campenhausen Harald , Mori Kensaku 
Published: March 2003

AbstractThe accessory olfactory system mediates intraspecies pheromonal communication. Two subsets of spatially segregated vomeronasal sensory neurons, presumably handling functionally and structurally different sets of ligand molecules, can be distinguished. The two subsets of sensory neurons project their axons to segregated zones of the accessory olfactory bulb (AOB) and connect with zonally separated mitral/tufted (M/T) cells, suggesting that the accessory olfactory system is divided into two distinct pathways up to the level of the AOB. To examine whether the segregation is maintained at the accessory olfactory cortical (AOC) regions, we selectively tracer‐labelled mitral/tufted cells located in the rostral, caudal or in both zones of the adult mouse AOB. The results demonstrate that the axonal projection patterns of rostral zone and caudal zone M/T cells were indistinguishable in the AOC regions. Mitral/tufted cell axons from either zone of the AOB covered the entire area of all four AOC regions: the bed nucleus of the accessory olfactory tract, the medial amygdaloid nucleus, the posteromedial cortical amygdaloid nucleus and the bed nucleus of the stria terminalis. Therefore, over the entire area of each AOC region, ensembles of cortical neurons receive input from both zonal subsets of M/T cells of the AOB. However, the present results do not rule out the possibility that individual cortical neurons sample information from M/T cells of a single zone. These results are consistent with the idea that the segregation of zonal pathways collapses in the AOC regions. Clusters of cortical neurons in each AOC region may combine information from both families of pheromone receptors and thus handle signals from structurally and functionally different categories of pheromone molecules.
Impaired cerebral autoregulation 24 h after induction of transient unilateral focal ischaemia in the rat
Authors: MacGregor D. G. , Carswell H. V. O. , Graham D. I. , McCulloch J. , Macrae I. M. 
Published: March 2003

AbstractCerebral blood flow (CBF) and cerebral autoregulation have been investigated 24 h after transient focal ischaemia in the rat. Cerebral blood flow was measured autoradiographically before and during a moderate hypotensive challenge, to test autoregulatory responses, using two CBF tracers, 99mTc‐d,l‐hexamethylproyleneamine oxide and 14C‐iodoantipyrine. Prior to induced hypotension, CBF was significantly reduced within areas of infarction; cortex (28 ± 20 compared with 109 ± 23 mL/100 g/min contralateral to ischaemic focus, P = 0.001) and caudate (57 ± 31 compared with 141 ± 32 mL/100 g/min contralaterally, P = 0.005). The hypotensive challenge (mean arterial pressure reduced to 60 mmHg by increasing halothane concentration) did not compromise grey matter autoregulation in the contralateral hemisphere; CBF data were not significantly different at normotension and during hypotension. However, in the ipsilateral hemisphere, a significant volume of cortex adjacent to the infarct, which exhibited normal flow at normotension, became oligaemic during the hypotensive challenge (e.g. frontal parietal cortex 109 ± 15% to 65 ± 15% of cerebellar flow, P < 0.01). This resulted in a 2.5‐fold increase in the volume of cortex which fell below 50% cerebellar flow (39 ± 34 to 97 ± 46 mm3, P = 0.003). Moderate hypotension induced a significant reduction in CBF in both ipsilateral and contralateral subcortical white matter (P < 0.01). In peri‐infarct caudate tissue, CBF was not significantly affected by hypotension. In conclusion, a significant volume of histologically normal cortex within the middle cerebral artery territory was found to have essentially normal levels of CBF but impaired autoregulatory function at 24 h post‐ischaemia.
Combined lesions of cholinergic and serotonergic neurons in the rat brain using 192 IgG‐saporin and 5,7‐dihydroxytryptamine: neurochemical and behavioural characterization
Authors: Lehmann Olivia , Jeltsch Hélène , Lehnardt Olivia , Pain Laure , Lazarus Christine , Cassel Jean‐Christophe 
Published: March 2003

AbstractThis study assessed behavioural and neurochemical effects of i.c.v. injections of both the cholinergic toxin 192 IgG‐saporin (2 μg) and the serotonergic toxin 5,7‐dihydroxytryptamine (5,7‐DHT; 150 μg) in Long–Evans female rats. Dependent behavioural variables were locomotor activity, forced T‐maze alternation, beam walking, Morris water‐maze (working and reference memory) and radial‐maze performances. After killing by microwave irradiation, the concentrations of acetylcholine, monoamines and 5‐hydroxyindoleacetic acid (5‐HIAA) were measured in the hippocampus, frontoparietal cortex and striatum. 192 IgG‐saporin reduced the concentration of acetylcholine by ∼ 40% in the frontoparietal cortex and hippocampus, but had no effect in the striatum. 5,7‐DHT lesions reduced the concentration of serotonin by 60% in the frontoparietal cortex and 80% in the hippocampus and striatum. Noradrenaline was unchanged in all structures except the ventral hippocampus where it was slightly increased in rats given 192 IgG‐saporin. Cholinergic lesions induced severe motor deficits but had no other effect. Serotonergic lesions produced diurnal and nocturnal hyperactivity but had no other effect. Rats with combined lesions were more active than those with only serotonergic lesions, showed motor dysfunctions similar to those found in rats with cholinergic lesions alone, and exhibited impaired performances in the T‐maze alternation test, the water‐maze working memory test and the radial‐maze. Taken together and although cholinergic lesions were not maximal, these data show that 192 IgG‐saporin and 5,7‐DHT lesions can be combined to selectively damage cholinergic and serotonergic neurons, and confirm that cholinergic–serotonergic interactions play an important role in some aspects of memory, particularly in spatial working memory.