bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novelty‐elicited, Noradrenaline‐dependent Enhancement of Excitability in the Dentate Gyrus
Authors: Kitchigina Valentina , Vankov Andrey , Harley Carolyn , Sara Susan J. 
Published: April 2006

AbstractIn order to relate noradrenaline‐dependent potentiation in the dentate gyrus to behavioural events, rats were made to explore an environment in which their encounters with novel stimuli could be strictly controlled and monitored. Previous experiments have shown that an encounter with novel objects in a holeboard elicits a burst response in a large population of noradrenergic neurons of the locus coeruleus. Such a burst response has been demonstrated to produce a large and transient potentiation of the population spike in the dentate gyrus. In the present series of experiments, rats were chronically implanted with stimulating electrodes in the perforant pathway and recording electrodes in the dentate gyrus. Evoked potentials were monitored in the awake rat, first while it was resting quietly in a familiar environment and then while it was exploring the holeboard containing a novel object in a specific hole. There was a tonic increase in population spike amplitude when the rat was placed in the novel holeboard environment, but this effect gradually dissipated. This increase was partly blocked by the β‐noradenergic antagonist propranolol. In addition there was a robust phasic increase in spike amplitude when the rat encountered a novel stimulus. This phasic response lasted ˜T50–75 s and was absent in animals treated with propranolol. These results show that a behavioural encounter with a novel stimulus can transiently enhance information transmission through the hippocampus, and suggest that activation of the noradrenergic system by the novel stimulus mediates this behaviour‐dependent gating.
A Slow Excitatory Postsynaptic Current Mediated by G‐protein‐coupled Metabotropic Glutamate Receptors in Rat Ventral Tegmental Dopamine Neurons
Authors: Shen Ke‐Zhong , Johnson Steven W. 
Published: April 2006

AbstractDopamine neurons in the substantia nigra and ventral tegmental area express metabotropic glutamate receptors, but activation of these receptors by synaptic release of neurotransmitter has not been demonstrated thus far. Patch pipettes were used to record membrane currents under voltage clamp from presumed dopamine‐containing neurons in the whole‐cell configuration in the rat brain slice. A short train of electrical stimuli delivered to bipolar electrodes placed in the slice evoked a slow excitatory postsynaptic current (EPSC; 50–300 pA at ‐70 mV) which peaked 560 ms after onset and lasted several seconds, with a decay time‐constant of 630 ms. This slow EPSC was voltage‐dependent, and was abolished by tetrodotoxin (0.5 μM) or by perfusate containing low calcium (0.5 mM) and high magnesium (10 mM). The metabotropic glutamate receptor antagonist (±)‐α‐methyl‐4‐carboxyphenylglycine (MCPG; 300 μM) blocked the slow EPSC, but L(+)‐2‐amino‐3‐ phosphonopropionic acid (AP3; 300 μM) had no effect. The slow EPSC was largely occluded by inward current produced by the metabotropic receptor agonist trans‐(±)‐1‐amino‐1, 3‐cyclopentanedicarboxylic acid (t‐ACPD; 300 μM), and the EPSC was reduced >90% during acute desensitization produced by prolonged perfusion with f‐ACPD. (±)‐2‐Amino‐4‐phosphonobutyric acid (AP4; 300 μM), another metabotropic receptor agonist, reduced the slow EPSC but had no effect on currents evoked by t‐ACPD applied by pressure‐ejection from micropipettes. The slow EPSC was progressively reduced in amplitude when pipettes contained the G‐protein inhibitor GDP‐β‐S (0.5 mM). When pipettes contained GTP‐γ‐S (0.5 mM), a non‐hydrolysable analogue of GTP, onset of the slow EPSC was more rapid and its decay was significantly prolonged. These results demonstrate that a slow EPSC mediated by G‐protein‐coupled metabotropic glutamate receptors can be evoked in dopamine neurons.
Relationship Between GAP‐43 Expression in the Dentate Gyrus and Synaptic Reorganization of Hippocampal Mossy Fibres in Rats Treated with Kainic Acid
Authors: Bendotti C. , Baldessari S. , Pende M. , Southgate T. , Guglielmetti F. , Samanin R. 
Published: April 2006

AbstractKainic acid‐induced seizures in adult rats produce neurodegeneration in the hippocampus followed by sprouting of the mossy fibres in the inner molecular layer of the dentate gyrus and changes in GAP‐43 expression in the granule cells. In the present study we observed that 4 days after kainic acid injection a dense plexus of silver impregnated degenerating terminals detected by Gallyas's method and a decrease of GAP‐43 immunostaining was observed in the inner molecular layer of the dentate gyrus indicating deafferentiation of this region. This was associated with the formation of an intense GAP‐43 immunostained band in the supragranular layer. MK‐801, a non‐competitive inhibitor of the NMDA receptor, which partially inhibited the behavioural seizures induced by KA, also protected from the inner molecular layer deafferentation and markedly reduced the expression of GAP‐43 mRNA in the granule cells and the intense GAP‐43 immunostained band in the supragranular layer, suggesting a relationship among these events. Two months after kainic acid injection the intense supragranular GAP‐43 positive band was no longer evident but the whole inner molecular layer appeared more labelled in association with the formation of the collateral sprouting of the mossy fibres in the inner molecular layer as detected by Timm's staining. These effects were also markedly reduced by the pretreatment with MK‐801. Taken together, these experiments indicate for the first time a direct relationship between the increase of GAP‐43 immunostaining in the inner molecular layer of the dentate gyrus and the collateral sprouting of mossy fibres in this district in response to kainic acid induced seizures. This further supports the hypothesis that the early induction of GAP‐43 in granule cells may be one of the molecular mechanisms required for the synaptic reorganization of the mossy fibres.
Transplant of Schwann Cells Allows Normal Development of the Visual Cortex of Dark‐reared Rats
Authors: Fagiolini Michela , Pizzorusso Tommaso , Porciatti Vittorio , Cenni MariaCristina , Maffei Lamberto 
Published: April 2006

AbstractVisual experience is necessary for the correct development of the visual cortex. Dark‐rearing from birth affects normal maturation of the functional properties of mammalian visual cortex: cortical cells show rapid habituation to repeated stimulation, decreased orientation selectivity, and enlarged receptive fields. Spatial resolution and response latency are also impaired. Recent experiments have demonstrated that visual deprivation reduces the expression of neurotrophins in the visual cortex. We formulated the hypothesis that visual experience drives the maturation of functional properties of the visual cortex by regulating cortical levels of neurotrophins. If this hypothesis is correct, exogenous supply of neurotrophins during dark‐rearing from birth should prevent, or at least ameliorate, the effects of a lack of visual experience. Since Schwann cells are efficient biological minipumps of neurotrophic factors, we transplanted 1.0 or 1.5 × 106 Schwann cells or infused vehicle solution as a control into the lateral ventricles of 13 day old rats reared in total darkness from birth until the end of the critical period (postnatal day 45). Single‐cell responses and visual‐evoked potentials were recorded from the binocular zone of the primary visual cortex of each group. We found that in Schwann cell‐transplanted animals all parameters tested were significantly improved upon those of dark‐reared control rats and were in the range of normal adult values. Thus, Schwann cell transplant contributed to the normal development of visual response properties in the visual cortex, compensating for a complete absence of visual experience.
Vulnerability of Midbrain Dopaminergic Neurons in Calbindin‐D28k‐deficient Mice: Lack of Evidence for a Neuroprotective Role of Endogenous Calbindin in MPTPtreated and Weaver Mice
Authors: Airaksinen Matti S. , Thoenen Hans , Meyer Michael 
Published: April 2006

AbstractCalbindin‐D28k (calbindin) is an intracellular calcium binding protein of unknown in vivo function. It is abundantly expressed in many populations of neurons, and it can, presumably by buffering calcium overload, protect cells against excitotoxic damage. In the midbrain, calbindin is preferentially expressed in those dopamine neurons which are spared from degeneration in Parkinson's disease and its animal models. Whether calbindin itself determines neuronal vulnerability is questioned in other lesion models where calbindin expression is not positively correlated with neuronal resistance. To study the possible neuroprotective role of calbindin in vivo, we generated calbindin‐deficient mice by gene targeting and assessed the viability of midbrain dopamine neurons in both a chemical and a genetic lesion paradigm. Tyrosine hydroxylase‐immunoreactive neurons were counted in calbindin null‐mutant mice treated with the neurotoxin 1 ‐methyl‐4‐phenyl‐1, 2, 3, 6‐tetrahydropyridine (MPTP) and in a calbindin‐deficient weaver strain (homozygous for weaver and the calbindin null mutation). The extent and pattern of neuron loss observed in MPTP‐treated wild‐type and homozygous weaver mice were as previously described. Surprisingly, no significant differences were observed between MPTP‐treated calbindin null mutants and their wild‐type littermates, or between calbindin‐weaver double mutant mice and weaver mice. Thus, in all four groups the same subpopulation of tyrosine hydroxylase‐positive midbrain neurons (i.e. those normally containing calbindin) were preferentially spared. Calretinin, a closely related calcium‐binding protein, which is also expressed in some midbrain dopamine neurons, was not up‐regulated in these surviving neurons. These findings indicate that the resistance of calbindin‐containing neurons in the MPTP and weaver models is not causally related to the expression of calbindin, and that endogenous calbindin is not required for protection of these neurons.
Locatization of Voltaae‐sensitive Ca2+ Fluxes and Neuropeptide Y Immunoreactivity to Varicosities in SH‐SY5Y Human Neuroblastoma Cells Differentiated by Treatment with the Protein Kinase Inhibitor Staurosporine
Authors: Kukkonen Jyrki P. , Shariatmadari Ramin , Courtney Michael J. , Akerman Karl E. O. 
Published: April 2006

AbstractThe distribution of voltage‐sensitive elevations of the level of Ca2+ in untreated SH‐SY5Y cells and cells that had been induced to differentiate with staurosporine was investigated by monitoring fura‐2 fluorescence in cell suspensions, and by using microfluorometry and quantitative fluorescence imaging on cell bodies and on cellular processes. Cell bodies of both types of cells displayed small Ca2+ elevations, which were composed of transient and sustained components. Elevations were partially sensitive to the L‐ and N‐channel blockers nifedipine (1 μM) and ω‐conotoxin GVIA (100 nM) respectively. Up to ten times higher Ca2+ elevations were observed in varicosities of treated cells than in cell bodies of treated and untreated cells. These elevations were insensitive to compounds known to release Ca2+ from intracellular stores. Elevations of Ca2+ were sustained, and they were insensitive to 5 pM nifedipine, 100 nM ω‐agatoxin IVA and 100 nM ω‐conotoxin GVIA, and partially sensitive to 2 pM ω‐conotoxin GVIA, indicating predominance of non‐L‐type, non‐N‐type, non‐P‐type channel activity. The intracellular localization of neuropeptide Y, a marker of differentiation in these cells, was also investigated by fluorescence immunocytochemistry. Varicosities of treated cells displayed marked fluorescence when viewed in a confocal microscope. These findings show that the varicosities of staurosporine‐treated cells exhibit some of the functional properties of nerve terminals. The varicosities resemble boutons en passant nerve endings and they seem to express Ca2+ channels different from those in the cell body.
AL‐1‐induced Growth Cone Collapse of Rat Cortical Neurons is Correlated with REK7 Expression and Rearrangement of the Actin Cytoskeleton
Authors: Meima Leonie , Kljavin Ivar J. , Moran Paul , Shih Ai , Winslow John W. , Caras Ingrid W. 
Published: April 2006

AbstractPrevious experiments identified AL‐1 as a glycosylphosphatidylinositol (GPI)‐linked ligand for the Eph‐related receptor, REK7, and showed that a REK7‐IgG fusion protein blocks axon bundling in co‐cultures of cortical neurons on astrocytes, suggesting a role for REK7 and AL‐1 in axon fasciculation. Subsequent identification of RAGS, the chick homologue of AL‐1, as a repellent axon guidance molecule in the developing chick visual system led to speculation that AL‐1, expressed on astrocytes, provides a repellent stimulus for cortical axons, inducing them to bundle as an avoidance mechanism. Using a growth cone collapse assay to test this hypothesis, we show that a soluble AL‐1‐IgG fusion protein is a potent collapsing factor for embryonic rat cortical neurons. The response is strongly correlated with REK7 expression, implicating REK7 as a receptor mediating AL‐1‐induced collapse. Morphological collapse is preceded by an AL‐1‐IgG‐induced reorganization of the actin cytoskeleton that resembles the effects of cytochalasin D. This suggests a pathway whereby REK7 activation by AL‐1 leads to perturbation of the actin cytoskeleton, possibly by an effect on actin polymerization, followed by growth cone collapse. We further show that AL‐1‐IgG causes collapse of rat hippocampal neurons and rat retinal ganglion cells. These data suggest a role for REK7 and AL‐1 in the patterning of axonal connections in the developing cortex, hippocampus and visual system.
Cytochemical Evidence for Nitric Oxide/Cyclic GMP Signal Transmission in the Visual System of the Locust
Authors: Bicker Gerd , Schmachtenberg Oliver 
Published: April 2006

AbstractNitric oxide is a membrane‐permeant messenger molecule which activates soluble guanylyl cyclase. Using NADPH diaphorase staining as a marker for the enzyme nitric oxide synthase and an antiserum against cyclic GMP (cGMP), we investigated the possible sites of nitric oxide and cGMP synthesis in the retina and lamina of Schisfocerca gregaria. The photoreceptor cells did not express NADPH diaphorase staining but monopolar cells of the lamina were strongly stained. After inhibition of phosphodiesterase activity and incubation of tissue in a nitric oxide donor, the photoreceptor cells showed cGMP immunoreactivity. In contrast to the photoreceptors, the monopolar cells of the lamina were not stained. Since the presynaptic photoreceptors were cGMP‐immunoreactive and the postsynaptic targets of the monopolar cells did not express immunoreactivity, it is conceivable that nitric oxide released by monopolar cells may play a role as a retrograde messenger in visual information processing.
Nociceptin/Orphanin FQ Microinjected into Hippocampus Impairs Spatial Learning in Rats
Authors: Sandin Johan , Georgieva Jeanette , Schött Pär A. , Ögren Sven O. , Terenius Lars 
Published: April 2006

AbstractThe newly discovered peptide nociceptin/orphanin FQ has been found to increase reactivity to pain and to influence locomotor activity after intracerebroventricular administration. This study investigated the possible role of hippocampal nociceptin/orphanin FQ in spatial learning and in spontaneous locomotion. Male rats were trained in the Morris water task after microinjection of 10 nmol nociceptin/orphanin FQ or artificial cerebrospinal fluid (as control) into the CA3 region of the dorsal hippocampus. Nociceptin/orphanin FQ was found to severely impair spatial learning without interfering with swimming performance. Itrahippocampal injection of nociceptin/orphanin FQ markedly decreased exploratory locomotor activity including vertical movements (rearing). The data suggest that nociceptin/orphanin FQ is a potent modulator of synaptic plasticity within the hippocampus.
Regulation of NMDA Receptor Subunit mRNA Expression in the Guinea Pig Vestibular Nuclei Following Unilateral Labyrinthectomy
Authors: Sans Nathalie , Sans Alain , Raymond Jacqueline 
Published: April 2006

AbstractThe localization of neurons expressing mRNAs for the NRI and NR2A‐D subunits of the glutamatergic NMDA receptor was examined by non‐radioactive in situ hybridization throughout the guinea pig vestibular nuclei. After deafferentation of the vestibular nuclei by unilateral labyrinthectomy, modifications of the mRNA distributions were followed for 30 days. A quantitative analysis was performed in the medial vestibular nucleus by comparison of the labelled neurons in the ipsi‐ and contra‐lateral nuclei. In vestibular nuclei, the NR1 subunit mRNA was found in various populations of neurons. The NR2A and NR2C subunit mRNAs were less widely distributed, whereas little NR2D mRNA was detected and only rare cells contained NR2B mRNA. NRI and NR2A‐D mRNAs were colocalized in some but not other neuronal types. Twenty hours after the lesion, there was a transient ipsilateral increase of NR1 mRNA level in the medial vestibular nucleus, followed by a decrease 48 h after the lesion and, at 3 days, by recovery to the control level. An ipsilateral increase in the mRNA level of NR2C subunit was detected 20 h after lesion and maintained at 48 h. No significant changes were apparent in NR2A, NR2B and NR2D mRNA levels. The distributions and the differential signal intensities of NR2A‐D mRNAs suggest various subunit organizations of the NMDA receptors in different neurons of the vestibular nuclei. Neuronal plasticity reorganizations in the vestibular nuclei following unilateral labyrinthectomy appear to include only changes in NR1 and NR2C mRNA levels modifying the functional diversity of the NMDA receptor in the ipsilateral medial vestibular nucleus neurons. The transient changes in NRI and the NR2C subunit mRNA expressions in response to sensory deprivation are consistent with an active role for NMDA receptors in the appearance and development of the vestibular compensatory process.
Quantitative Autoradiographic Analysis of lonotropic Glutamate Receptor Subtypes in Human Temporal Lobe Epilepsy: Up‐regulation in Reorganized Epileptogenic Hippocampus
Authors: Brines Michael L. , Sundaresan Sanjoy , Spencer Dennis D. , de Lanerolle Nihal C. 
Published: April 2006

AbstractMedically intractable temporal lobe epilepsy is a common disease typically associated with hippocampal damage (sclerosis) and synaptic remodelling. These changes could include increased glutamate receptor expression, enhancing excitability and the potential for neuronal injury. We directly assessed this hypothesis using quantitativein vitroreceptor autoradiography to determine the densities of glutamate‐, NMDA‐, quisqualateh‐amino‐3‐hydroxy‐5‐methyl‐isoxazoleproprionic acid (AMPA)‐ and kainic acid‐preferring binding sites in surgically removed hippocampi from patients with mesial temporal lobe epilepsy (sclerosis; MTLE) and patients with mass‐associated temporal lobe epilepsy (no sclerosis: MaTLE), compared with autopsy material. Neuronal cell counts andin situtotal protein densities were also obtained. In general, MaTLE and autopsy binding densities were indistinguishable. In contrast, some regions of MTLE hippocampi exhibited decreased receptor densities, with a corresponding loss of protein. In the hilus and CA1, however, ligand binding densities did not differ from the comparison groups in spite of markedly reduced protein content, consistent with increased glutamate receptor density. Kainate‐preferring sites were distributed differently from the other glutamate subtypes and were uniformly decreased throughout the MTLE hippocampus, except for a unique expression within the outer dentate molecular layer. Along with increased NMDA and AMPA receptor densities in the hilus and CA1, this distinctive population of kainate receptors establishes that increased glutamate receptor expression is a feature of the remodelled MTLE hippocampus. These observations suggest that enhanced sensitivity to glutamate may be an important element in the pathophysiology of temporal lobe epilepsy.
Severe Sensory Deficits but Normal CNS Development in Newborn Mice Lacking TrkB and TrkC Tyrosine Protein Kinase Receptors
Authors: Silos‐Santiago Inmaculada , Fagan Anne M. , Garber Melinda , Fritzsch Bernd , Barbacid Mariano 
Published: April 2006

AbstractAnalysis of mice carrying targeted mutations in genes encoding neurotrophins and their signalling Trk receptors has provided critical information regarding the role that these molecules play in the mammalian nervous system. In this study we generated mice defective in both TrkB and TrkC tyrosine kinase receptors to determine the biological effects of these receptors in the absence of compensatory mechanisms. trkB(–/–);trkC(–/–) double‐mutant mice were born at the expected frequency, indicating that TrkB and TrkC signalling are not required for embryonic survival. However, these double‐mutant mice had a significantly shorter lifespan and displayed more severe sensory defects than their single‐mutant trkB(–/–) and trkC(–/–) littermates. The most dramatic sensory deficit observed in trkB(–/–); trKC(–/–) mutant mice was the absence of vestibular and cochlear ganglia. Interestingly, these mice developed inner ear sensory epithelia in spite of the complete absence of sensory innervation. Analysis of the CNS in trkB(–/–); trkC(–/–) mutant mice revealed a well formed hippocampus, cortex and thalamus. Moreover, the pattern of expression of several neuronal markers appeared normal in these animals. These observations suggest that neurotrophin signalling through TrkB and TrkC receptors is essential for the development of sensory ganglia: however, it does not play a major role in the differentiation and survival of CNS neurons during embryonic development.
Contribution of Blockade of the Noradrenaline Carrier to the Increase of Extracellular Dopamine in the Rat Prefrontal Cortex by Amphetamine and Cocaine
Authors: Tanda Gianluigi , Pontieri Francesco E. , Frau Roberto , Di Chiara Gaetano 
Published: April 2006

AbstractThis study was performed to investigate the relative role of noradrenaline (NA) and dopamine (DA) carrier blockade in the effects of psychostimulants on DA transmission in the rat prefrontal cortex (PFCX). To this end, changes of extracellular DA and NA in the PFCX and of extracellular DA in the nucleus accumbens (NAc) were measured following the administration of amphetamine and cocaine, which are known to bind to both DA and NA carriers, or GBR 12909, a selective DA carrier blocker. After non‐intravenous injection, amphetamine (0.25 and 0.5 mg/kg, s.c.) and cocaine (5 and 10 mg/kg, i.p.) increased extracellular DA in the PFCX to a larger extent than in the NAc, while the reverse applied to GBR 12909 (2.5 and 5 mg/kg, i.p.). These differences were obtained in spite of the fact that the three drugs elicited at each dose level a similar peak increase of extracellular DA in the NAc. Amphetamine and cocaine also increased extracellular NA in the PFCX and this effect was quantitatively similar to that on extracellular DA in the same area. Intravenous doses of cocaine and GBR 12909, corresponding to those which maintain self‐administration in the rat, while equieffective in raising extracellular DA in the NAG, had different effects on extracellular DA in the PFCX. In fact, in contrast to cocaine, GBR 12909 increased extracellular DA in the PFCX to a lesser extent than in the NAc or did not modify it at all. The peak increase of extracellular DA in the PFCX was highly correlated to that of NA in the same area but was poorly correlated to the increase of extracellular DA in the NAc. These results suggest that amphetamine and cocaine increase extracellular DA in the PFCX largely through the blockade of the NA carrier. Direct evidence for this hypothesis was provided by the observation that, when the NA carrier was blocked by reverse dialysis of the PFCX with desipramine (1 μM), cocaine and GBR 12909 lost their differences in the ability to increase extracellular DA in the PFCX.