bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regional Forebrain Noradrenalin Release in Response to Focal and Generalized Seizures Induced by Hippocampal Kindling Stimulation
Authors: Bengzon Johan , Kikvadze Irakli , Kokaia Merab , Lindvall Olle 
Published: April 2006

Abstract In vivo microdialysis was used to monitor noradrenalin (NA) release in the rat hippocampus, sensorimotor cortex and amygdala in response to seizures induced by electrical kindling stimulation in the hippocampus. Generalized seizures increased NA output in the hippocampus five‐fold above baseline level (as assessed with 2‐min sampling periods). The peak value was seen 2–4 min after onset of seizure activity and baseline was reached after another 6–8 min. In the sensorimotor cortex, there was a seven‐fold increase showing a similar time‐course. Focal hippocampal seizures gave rise to three‐fold and 80% increases above baseline in the hippocampus and sensorimotor cortex, respectively. A unilateral knife transection of the dorsal noradrenergic bundle reduced hippocampal NA release induced by focal seizures by 53%. In animals subjected to 30 stimulus‐evoked seizures with 5‐min intervals (‘rapid kindling’), maximal NA output was observed after the third seizure in both hippocampus (237% increase) and amygdala (122% increase). NA levels tapered off with repeated stimulation and reached baseline after nine stimulations in the hippocampus; in the amygdala, the NA output was still slightly elevated at the end of the stimulation period. These results indicate that there is a general activation of the locus coeruleus system during focal as well as generalized seizures, as evidenced by marked increases in transmitter release from noradrenergic terminals in all forebrain areas studied. NA output in areas exhibiting seizure activity is dependent on impulse flow in locus coeruleus neurons and probably also on local regulatory mechanisms active at the noradrenergic terminal level. The increase in inhibitory noradrenergic transmission in both epileptic and non‐epileptic brain regions may dampen ongoing seizure activity as well as lessen its spread and generalization.
Physiological Characterization of Pretectal Neurons Projecting to the Lateral Geniculate Nucleus in the Cat
Authors: Schmidt M. , Hoffmann K.‐P. 
Published: April 2006

AbstractSingle neurons in the pretectal nucleus of the optic tract and posterior pretectal nucleus were extracellularly recorded in anaesthetized cats and tested for antidromic activation after electrical stimulation of the ipsilateral dorsal lateral geniculate nucleus. Cells were further characterized by their response latencies to electrical stimulation of the optic nerve head and the optic chiasm, and by responses to various visual stimuli. 46 out of 188 neurons (24%) were antidromically activated from the lateral geniculate nucleus at response latencies of 0.6 ‐ 2.6 ms. They had low spontaneous activities and preferred fast‐moving visual stimuli. 29 of the antidromically activated neurons (63%) could be activated from the optic chiasm with response latencies of 4–10 ms. Together with the mean conduction time of 0.8 ms between the optic nerve head and the optic chiasm, this indicates that they receive an indirect retinal input via fast‐conducting Y‐fibres. Sometimes antidromically activated neurons spontaneously showed irregular burst activity. During unidirectional stimulation with a large moving visual stimulus, burst activity became more regular, and interburst intervals and the duration of single bursts decreased. After the stimulus was stopped, interburst intervals slowly increased until prestimulation activity was restored. The response properties of these neurons could reflect the transfer of saccade‐related visual as well as oculomotor signals through the pretectum to the visual thalamus.
Glutamate Toxicity: An Experimental and Theoretical Analysis
Authors: Garthwaite Giti , Williams Geoffrey D. , Garthwaite John 
Published: April 2006

AbstractIn slices of 8‐day‐old rat cerebellum, the lowest concentration of glutamate that induced toxicity (30 min exposure; 90 min recovery) was 100 μM, but the damage only occurred in the outermost regions. As the concentration was raised, the band of necrosis became progressively deeper until, at 3 mM, it was uniform across the slice thickness. At a test concentration of 300 μM, the width of the necrotic band did not change when either the exposure time or the recovery period was varied between 30 min and 3 h. These results are predicted by a theoretical model in which the diffusion of glutamate into brain tissue is countered by cellular uptake of the amino acid, and they argue against the idea that glutamate toxicity is inherently self‐propagating. When slices were examined immediately after exposure (300 μM), a prominent swelling of glial cells was present at the slice surface. Swelling per se did not appear to compromise their uptake function, and the model predicts that cellular swelling, by reducing the rate of diffusion of glutamate, protects against glutamate toxicity. The damage produced by 3 mM glutamate, which was primarily exerted against granule cells, was prevented by W‐methyl‐D‐aspartate (NMDA) receptor blockade, whereas antagonists acting at α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionate (AMPA) receptors were ineffective. Under conditions of energy deprivation, the neurotoxic potency of glutamate was markedly enhanced and a normally non‐toxic concentration (30 μM) became maximally toxic towards granule cells. Dark vacuolar degeneration of Purkinje cells was also present, and this could be inhibited by blocking AMPA receptors. The results and theoretical analysis suggest that intact brain tissue is remarkably resistant to glutamate toxicity, chiefly because of the formidable properties of the uptake system. However, under special circumstances, glutamate can become a potent neurotoxin and its toxicity can then involve both NMDA and AMPA receptors.
P21ras Oncogene Protein Selectively Increases Low‐voltage‐activated Ca2+ Current Density in Embryonic Chick Dorsal Root Ganglion Neurons
Authors: Hahnel C. , Gottmann K. , Wittinghofer A. , Lux H.‐D. 
Published: April 2006

Abstractp21ras protein resembles the α subunit of trimeric G‐proteins, which regulate ion channel function. We now report a modulation of Ca2+ channels in vertebrate sensory neurons by p21ras in addition to its role in cell growth and differentiation. Quantitative microinjection of oncogenic p21‐H‐ras into embryonic chick dorsal root ganglion neurons was performed. After 4 h the current density of the low‐voltage‐activated (LVA; T‐type) Ca2+ channels was increased. However, in contrast to trimeric G‐proteins, which inhibit high‐voltage‐activated (HVA) Ca2+ channels in chick dorsal root ganglion neurons, p21ras did not significantly affect HVA Ca2+ currents. To study the time course of p21ras action, guanosine triphosphate‐preloaded p21ras was added to the patch pipette. Full‐length ras was effective only after a delay of 20 ‐30 min. C‐terminal modification by cellular enzymes is required to activate full‐length ras, and can account for the observed delay. Unexpectedly, C‐terminal‐truncated p2lras, which was found to be inactive in biological assays, enhanced LVA Ca2+ currents within minutes. This suggests a G‐protein‐like modulation of the LVA Ca2+ channel by p21ras. In an early phase of neuronal differentiation, dorsal root ganglion neurons express only LVA Ca2+ currents. The regulatory role of p21ras on LVA channels may therefore be particularly important during differentiation.
Differential Regulation of Nerve Growth Factor (NGF) Synthesis in Neurons and Astrocytes by Glucocorticoid Hormones
Authors: Lindholm Dan , Castrén Eero , Hengerer Bastian , Zafra Francisco , Berninger Benedikt , Thoenen Hans 
Published: April 2006

AbstractGlucocorticoid hormones are important regulators of brain development and ageing. Here we show that dexamethasone, a synthetic glucocorticoid, differentially affects the expression of nerve growth factor (NGF) in cultured neurons and astrocytes. Dexamethasone increased the levels of NGF mRNA in cultured hippocampal neurons in a time‐ and concentration‐dependent manner, whereas it down‐regulated the NGF mRNA levels in astrocytes. However, dexamethasone had no effect on the mRNA levels of brain‐derived neurotrophic factor in the hippocampal neurons. Aldosterone, a mineralocorticoid, in higher concentrations also up‐regulated NGF mRNA levels in the hippocampal neurons. Dexamethasone increased the levels of NGF mRNA in the rat hippocampus in vivo, but not to the same extent as observed with kainic acid, a glutamate receptor agonist. There is no apparent diurnal rhythm in the hippocampal NGF protein levels corresponding to circadian variations in the levels of glucocorticoid hormones in serum. The increase in NGF mRNA in the hippocampus in vivo following dexamethasone treatments may reflect the physiological response of hippocampal neurons to high glucocorticoid levels reached under conditions of stress.
A Nitric Oxide Synthase Activity Selectively Stimulated by NMDA Receptors Depends on Protein Kinase C Activation in Mouse Striatal Neurons
Authors: Marin P. , Lafon‐Cazal M. , Bockaert J. 
Published: April 2006

AbstractIn mouse striatal neurons in primary culture, the maximal increase in intracellular cyclic guanosine monophosphate level evoked by N‐methyl‐d ‐aspartic acid (NMDA) receptor activation was twice that induced by kainate, KCI and ionomycin. Quisqualate was almost inactive. All responses were mediated by nitric oxide (NO) production since they were blocked by haemoglobin (a NO scavenger) and by L‐NG‐monomethylarginine and L‐NG nitroarginine, the effects of both arginine analogues being reversed by an excess of L‐arginine. Several results indicate that NMDA receptors stimulate a specific NO synthase activity. This specifically NMDA‐activated NO synthase was blocked by nanomolar concentrations of L‐NG nitroarginine, whereas the responses evoked by other agents, including kainate, KCI and ionomycin, were only blocked by micromolar concentrations of this NO synthase inhibitor. The NMDA response could not be totally reproduced by an increase in cytosolic calcium (Ca2+) alone. In contrast, in the presence of staurosporine, an inhibitor of protein kinases C (PKC), as well as after desensitization of PKC induced by long‐term treatment with the phorbol ester, phorbol‐12, 13‐dibutyrate, NMDA‐stimulated NO production was selectively reduced, reaching the level evoked by kainate or Ca2+ increase. In conclusion, our results suggest that in striatal neurons, NMDA selectively stimulates a NO synthase activity which is inhibited by low concentrations of L‐NG nitroarginine, through a mechanism involving PKC.
Monoclonal Antibodies to Late‐differentiating Epitopes Identify Mossy Fibre Terminals Innervating Normal and Transplanted Hippocampal CA3 Pyramidal Cells
Authors: Fonseca Montserrat , Woodhams Peter L. , Webb Michael , Field Pauline M. , Raisman Geoffrey 
Published: April 2006

AbstractWe have derived two monoclonal antibodies, MF‐1 and MF‐2, which both recognize the same 58‐kD antigen. Light and electron microscopic immunocytochemistry showed that this antigen is highly expressed in the large mossy fibre terminals innervating the proximal portion of the apical dendrites of pyramidal neurons in hippocampal field CA3. Staining was seen in the adult hippocampus in rats and mice, and in a post mortem human sample. Comparison with the Timm stain showed that the antibodies recognize mossy fibres from all parts of the adult dentate gyrus except for the tip of the infrapyramidal blade (the latest part of the dentate gyrus to develop). The MF antigen is expressed by mature terminals, and is not detected immunohistochemically in developing hippocampal mossy terminals until the end of the first postnatal week (i.e. later than the Timm‐positive material). It was also found in host mossy fibre terminals innervating embryonic CA3 pyramids transplanted into adult hosts, but not in areas of the graft containing transplanted CA1 pyramids. These results indicate that this previously undescribed, late‐developing antigen provides a useful specific marker for the mossy fibre projection in both the normal hippocampus and in situations of experimentally manipulated connectivity.
Correlates of Habituation of a Polysynaptic Reflex in Crayfish In Vivo and In Vitro
Authors: Marchand A. R. , Barnes W. J. P. 
Published: April 2006

AbstractReflex leg levation habituates during repeated electrical stimulation of mechanosensory afferents in the dactyl of the fifth walking leg of the crayfish, Procambarus clarkii. This was investigated in decerebrate crayfish, and reproduced in an isolated thoracic ganglion preparation. In vivo, trains of stimuli delivered every 2.5 s produced a gradual decrease in the amplitude of the mechanical response, and a concomitant decrease in the number of impulses per burst in the levator muscle myogram. Near complete recovery occurred after 10 min rest, and transient dishabituation was observed after electrical stimulation of the telson. Less frequent or stronger stimuli led to less rapid habituation. In vitro, the same parametric characteristics of habituation were observed in the levator nerve responses, while the intrinsic variability of the reflex was reduced. The response decrement was shown to be unrelated to changes in the afferent excitation. Evoked polysynaptic excitatory postsynaptic potentials (EPSPs) in levator motorneurons decreased in parallel with the levator neurogram. This decrease was unrelated to any change in the resting membrane potential of the levator motorneurons. Intemeurons with habituating EPSPs, antagonistic depressor motorneurons with habituating inhibitory postsynaptic potentials and non‐habituating responses in other motorneuronal groups were also found. These findings point to a central locus of habituation upstream from the motorneurons, and offer prospects for a detailed investigation of the mechanisms of habituation in a polysynaptic system.
Responses of Visual‐Tracking Neurons from Cortical Area MST‐I to Visual, Eye and Head Motion
Authors: Thier P. , Erickson R. G. 
Published: April 2006

AbstractThirty‐one neurons which exhibited ocular pursuit‐related activity [visual‐tracking (VT) neurons] were found clustered within area MST‐I (the lateral part of area MST) of two rhesus monkeys. Their responses were studied to determine whether this activity was correlated only with pursuit eye movement or with head movement as well. The latter hypothesis appeared to be preferable since visual, eye movement and head movement inputs were found to be mapped in register onto most of these cells. First, in each cell tested (n=19) the pursuit response persisted even in the absence of retinal image motion, offering clear evidence for non‐visual input. Second, 22 of the 31 cells were directionally responsive to moving visual stimuli and in 20 of these the preferred directions for the visual motion and pursuit responses agreed closely. Responses were also obtained from many of the same cells during suppression of both the horizontal and the vertical vestibulo‐ocular reflex (VOR). In each case, where directional visual, pursuit and VOR suppression responses were each obtained, vector addition of responses during suppression of the horizontal and vertical VOR resulted in an estimated preferred direction for head rotation which was closely aligned with the preferred direction previously obtained for eye motion or visual motion. In addition, the preferred direction of head movement was conserved even when the VOR was elicited by passive head rotation in complete darkness, although the responses in this instance were, on average, only 62% of those obtained during VOR suppression. Our interpretation is that, at present, MST‐I VT neurons are best described as encoding the direction of target motion in space‐centred coordinates by integrating inputs reflecting retinal image motion plus eye and head movement.
Autoradiographic Localization of Cholecystokinin A and B Receptors in Rat Brain Using [125I]D‐Tyr25 (NIe28,31)‐CCK 25‐33S
Authors: Carlberg M. , Gundlach A. L. , Mercer L. D. , Beart P. M. 
Published: April 2006

AbstractThe distribution of receptors for the sulphated octapeptide cholecystokinin 26–33 (CCK‐8S) in rat brain was investigated by radioligand binding in conjunction with autoradiography using the novel iodinable, non‐oxidizable, amino‐ and thiolendopeptidase‐resistant CCK analogue, d‐Tyr25(Nle28,31)‐CCK 25–33S. Labelling of the peptide was achieved by synthesis utilizing Na125l and Chloramine‐T. [125l]D‐Tyr25(Nle26,31)‐CCK 25–33S (100 pM) bound rapidly and reversibly to a single population of sites on slide‐mounted coronal sections of rat forebrain with a dissociation constant of 34 pM. Specific binding was fully inhibited by CCK‐8S, CCK‐8, CCK‐4, L‐365,260 and L‐364,718, with inhibition constants 2.7, 9.8, 35, 7.0 and 130 nM, respectively. These inhibition data may indicate that the [125l] ligand binds preferentially to a CCKB subtype of receptor, but may also reflect the relative paucity of CCKA receptors in the rat forebrain. Optimum conditions for autoradiography combined the preincubation of brain sections in unlabelled 10 pM d‐Tyr25(Nle28,31)‐CCK 25–33S with a 60‐min wash after incubation with the [125l] ligand. Analyses of the autoradiograms obtained from the use of coronal and horizontal brain sections were aided by the high levels of specific binding (80–90%), and revealed that CCK receptors were topographically distributed through the neuroaxis. High densities of receptor‐associated silver grains were found in the olfactory bulb (internal plexiform layer), neocortex (layer III), nucleus accumbens, parasubiculum, subbrachial nucleus, parabigeminal nucleus, dorsal vagal complex, area postrema and the A2 region. Moderate labelling was observed in many telencephalic and diencephalic nuclei. The majority of these receptors were of the CCKB subtype, as shown by the use of subtype‐selective antagonists, although CCKA receptors were present in moderate to high densities in the A2 area, area postrema and nucleus tractus solitarii, and at low density in the interpeduncular nucleus and central amygdala. These findings provide further evidence for the widespread, topographic distribution of CCK receptors and indicate that [125l]d‐Tyr25(Nle28,31)‐CCK 25–33S is very suitable for autoradiographic investigations because of its low non‐specific binding.
Embryonic Purkinje Cells Grafted on the Surface of the Cerebellar Cortex Integrate in the Adult Unlesioned Cerebellum
Authors: Rossi Ferdinando , Borsello Tiziana , Strata Piergiorgio 
Published: April 2006

AbstractThe presence of an injury or the selective degeneration of specific neuronal populations is commonly assumed to be a necessary prerequisite for the survival and the integration of grafted neurons in the recipient brain. In the present study we have placed solid grafts of cerebellar anlage in the fourth ventricle of adult rats, in close contact with the host cerebellar cortex, to assess the capacity of embryonic Purkinje cells to interact with adult neurons and integrate in the unlesioned cerebellar cortex. Numerous grafted Purkinje cells are indeed able to leave the implant and migrate into the host molecular layer, where they develop adult structural features. In addition, such cells are able to elicit the growth of host climbing fibre sprouts which end in newly formed arborizations impinging upon their dendritic trees. Climbing fibre collateral branches also penetrate the implant to innervate Purkinje cells which have not migrated in the host cerebellum. These results show that embryonic Purkinje cells are able to survive and integrate in an adult unlesioned cerebellar cortex. In addition, adult olivary axons respond to the increased size of the target population by expanding their terminal domain to innervate grafted Purkinje cells.
Training Chicks on a Passive Avoidance Task Modulates Glutamate‐stimulated Inositol Phosphate Accumulation
Authors: Bullock Sarah , Rose Steven P. R. , Pearce Brian , Potter Jenny 
Published: April 2006

AbstractThe effects of glutamate, N‐methyl‐d‐aspartate (NMDA), (+)‐5‐methyl‐10,11‐dihydro‐5H‐dibenzo‐(a,d)‐cyclohepten 5,10‐imine maleate (MK801), α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionate (AMPA) and quisqualate on the accumulation of inositol phosphates (IP) from the breakdown of phosphoinositides in vitro have been studied in tissue prisms derived from a region of the chick forebrain, the intermediate medial hyperstriatum ventrale (IMHV). In prisms from the left IMHV, glutamate stimulated IP accumulation by 10–20%, AMPA by 55% and quisqualate by 650%. These effects were more marked in the right IMHV, where AMPA stimulated IP accumulation by 157% and quisqualate by 920%. MK801 and NMDA had no significant effect on IP accumulation in either hemisphere. The left IMHV is known to be the site of a biochemical cascade resulting in synaptic remodelling following training day‐old chicks on a one‐trial passive avoidance task. The effect of such training was to reduce glutamate‐stimulated accumulation of IP by 27% (P < 0.05) in prisms taken 30 min after training. There was no effect on prisms taken at 5 or 180 min after training, and no effect at any time in the right IMHV. MK801, injected intraperitoneally before training at a concentration known to produce amnesia for the passive avoidance task, abolished the training‐induced decrease without itself affecting IP accumulation. Taken in conjunction with pharmacological and autoradiographic evidence, these results indicate that memory formation for the passive avoidance task involves the activation of NMDA receptor channels, but not quisqualate or AMPA receptors, in the left IMHV of the chick 30 min after training.
Alteration of Sodium Currents by New Peptide Toxins From the Venom of a Molluscivorous Conus Snail
Authors: Hasson Arik , Fainzilber Michael , Gordon Dalia , Zlotkin Eliahu , Spira Micha E. 
Published: April 2006

AbstractTxIA and TxIB, peptides with 27‐amino acid residues recently isolated from the molluscivorous marine snail Conus textile neovicarius, exhibit strong paralytic activity in molluscs, with no paralytic effects on arthropods and vertebrates. At concentrations of 0.25 – 0.5 μM the toxins cause spontaneous repetitive firing and dramatic broadening of the action potential of cultured Aplysia neurons. The action potential duration partially recovers within 30 min in the presence of the toxins. Under these conditions a second toxin application does not change the spike duration. TxI‐induced spike broadening occurs when potassium and calcium conductances are blocked. Voltage‐clamp experiments revealed that the toxins alter the kinetics of the sodium current either by slowing down the rate of sodium current inactivation or by recruiting silent sodium channels with slower activation and inactivation kinetics. The toxins shift the voltage‐dependent steady‐state Na+ current inactivation curve to more positive values by 6 mV. These changes are not associated with alteration in the rate of sodium current activation, in the peak sodium current, or the sodium current reversal potential. TxI apparently represents a new class of conotoxins with an unusual phylogenic specificity and may therefore be useful as a probe for the study of molluscan neuronal sodium channels.