bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interaction Between α and β‐Adrenergic Receptor Agonists Modulating the Slow Ca2+‐activated K+ Current ‐ IAHP in Hippocampd Neurons
Authors: Pedarzani Paola , Storm Johan F. 
Published: April 2006

AbstractNoradrenaline inhibits the Ca2+‐activated K+ current IAHP, which underlies the slow afterhyperpolarization and spike frequency adaptation in hippocampal and neocortical neurons. The resulting increase in excitability probably contributes to the state control of the forebrain during arousal and attention. The modulation of IAHP by noradrenaline has previously been shown to be mediated by β1 receptors, cyclic AMP and protein kinase A, but not by α receptors. We have now tested the possibility that a receptors also contribute to IAHP modulation through interaction with β receptors, by the use of whole‐cell recordings in CA1 pyramidal cells of rat hippocampal slices. The α‐receptor agonist 6‐fluoro‐noradrenaline strongly potentiated the effect of isoproterenol on IAHP. The synergistic effect of 6‐fluoro‐noradrenaline and soproterenol was blocked by the β‐receptor antagonist timolol, but the receptor type mediating the effect of 6‐fluoro‐noradrenaline could not be unequivocally identified by using α‐receptor antagonists. The effect of high concentrations of noradrenaline on IAHP was only partly blocked by the β‐receptor antagonist timolol, and was further reduced by blocking α receptors, again suggesting a contribution from α receptors. In contrast, the effect of low concentrations of noradrenaline seemed to be potentiated by the α‐receptor antagonist phentolamine in 57% of the cells, suggesting concentration dependent antagonistic interaction between α and β receptors. Further tests indicated that the cross‐talk between 6‐fluoro‐noradrenaline and isoproterenol occurs upstream from cyclic AMP production, and that protein kinase A serves as a final common path for the modulation of IAHP by noradrenaline, and by the combination of 6‐fluoro‐noradrenaline and isoproterenol.
Expression of the Transcription Factor Zif268 in the Temporal Cortex of Monkeys during Visual Paired Associate Learning
Authors: Okuno Hiroyuki , Miyashita Yasushi 
Published: April 2006

AbstractIn humans and monkeys, memory consists of various components which were initially revealed through neuropsychological studies of amnesic patients. One memory component, the long‐term memory about facts and events (declarative memory), has been shown to require the integrity of the medial temporal lobe and the neocortex. To investigate a map of gene expression during declarative memory formation in the primate, we monitored expression of immediate early genes in the temporal lobe of macaque monkeys. We trained the monkeys to learn visual associative memory tasks, and immunohistochemically analysed the expression of protein products of immediate early genes. We found that Zif268, a transcription factor regulated by neuronal activity, accumulated in patches in the anterior temporal lobe during visual stimulus‐stimulus association learning, whereas other transcription factors, c‐Fos and JunD, were not. By contrast, the patchy expression of Zif268 was not observed during another type of learning, visual discrimination learning. These results suggest that Zif268 activates a gene cascade related to the formation of long‐term memory in the primate.
Comparative Antagonism of Kainate‐activated Kainate and AMPA Receptors in Hippocampal Neurons
Authors: Paternain Ana V. , Vicente Angeles , Nielsen Elsebet Ø. , Lerma Juan 
Published: April 2006

AbstractNative kainate receptors expressed by cultured hippocampal cells were studied in the whole‐cell configuration of the patch‐clamp technique by using a fast perfusion system. About 80% of the neurons expressed kainate receptors independently of the time in culture (0–4 days), which coincided with the number of cells immunoreactive for a monoclonal antibody against the GluR5/6/7 subunits. Three types of cells were considered: neurons in which the rapid application of kainate induced a rapidly desensitizing current, cells in which kainate induced a more slowly rising, non‐desensitizing, response and those in which a mixture of both responses was apparent. Steady responses induced by 300 μM kainate were inhibited by 6‐cyano‐7‐nitroquinoxaline‐2,3‐dione (CNQX) in a dose‐dependent manner (IC50= 0.92 μM). CNQX was less potent in blocking transient kainite‐induced responses (IC50= 6.1 μM). Responses to kainate, whether steady or transient, were also inhibited by NS102, showing poor selectivity for the transient response (IC50= 4.1 and 2.2 μM respectively). The new α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole (AMPA) receptor antagonist NS394 was very potent in inhibiting steady kainate‐induced currents (IC50= 0.45 μM), but was even more effective in preventing peak responses (IC50= 0.13 μM). In contrast, cyclothiazide did not affect transient kainate‐induced responses but did potentiate current induced by activation of AMPA receptors by AMPA or kainate. These results demonstrate the lack of complete selectivity amongst some available competitive antagonists for AMPA and kainate receptors, and indicate that kainate receptors expressed by hippocampal cells lack the cyclothiazide modulatory site present at AMPA receptors. In addition, the present data support the idea that low‐affinity kainate binding sites in the brain correspond to receptor channels selectively activated by kainate.
Effects of Glutamate Application on the Rhythm of Low Magnesium‐induced Epileptiform Activity in Hippocampal Slices of Guinea‐pigs
Authors: Lücke A. , Köhling R. , Speckmann E.‐J. 
Published: April 2006

AbstractThe extracellular concentration of glutamate has previously been reported to increase to more than 10‐fold the basal level during seizure activity. In the present study, we tested whether localized increases in extracellular glutamate concentration influence the rhythm of epileptiform discharges in the low‐magnesium epilepsy model. In hippocampal slices of guinea‐pigs, epileptiform activity was induced by omission of magnesium from the bath fluid. Glutamate and its subreceptor agonists N‐methyl‐D‐aspartate (NMDA) and α‐amino‐3‐hydroxy‐5‐methyl‐4‐ isoxazolepropionic acid (AMPA) were ejected into different strata of the CA3 and CA1 regions using microiontophoretic and micropressure application. Glutamate, NMDA and AMPA applied to the CA3 region, but not to the CA1 region, induced a short‐lasting increase in epileptiform discharge frequency, often followed by a transient reduction. The effect was most pronounced with application into the stratum lacunosum‐moleculare of the CA3 region and could only be evoked in slices exceeding 400 μm in thickness. The effects on the rhythm of epileptiform discharges induced by NMDA and AMPA were blocked by their specific receptor antagonists. They were not influenced by application of GABAA and GABAB receptor antagonists. Changes in somatic membrane potential of CA3 pyramidal neurons did not correlate with changes in the rhythm of epileptiform discharges elicited in this region. The transient suppression of epileptiform discharges that followed the increase in discharge frequency was abolished by an adenosine A1 receptor antagonist. We propose that localized increases in extracellular glutamate concentration modify the rhythm of epileptiform discharges due to changes in neuronal network activity.
Group II and Group III Metabotropic Glutamate Receptors in the Rat Retina: Distributions and Developmental Expression Patterns
Authors: Koulen Peter , Malitschek Barbara , Kuhn Rainer , Wässle Heinz , Brandstätter Johann Helmut 
Published: April 2006

AbstractWe have studied the distributions of group II metabotropic glutamate receptors, mGluR2 and mGluR3, and a group III metabotropic glutamate receptor, mGluR4, in the adult rat retina and during postnatal development using receptor specific anti‐peptide antisera. Of the three receptors examined, mGluR3 was not expressed in the retina. MGluR2 showed a distinct stratification pattern in the inner plexiform layer (IPL). Double‐labelling immunocytochemistry revealed that mGluR2 was localized in the processes of cholinergic amacrine cells. MGluR4 was found throughout the entire IPL. At the subcellular level, both mGluR2 and mGluR4 were found to be localized exclusively in processes postsynaptic to bipolar cell synapses in the IPL. During postnatal development, labelling for mGluR2 was detected at around postnatal day five. MGluR4 was already present at postnatal day one, prior to the establishment of synaptic connections in the IPL. The differential expression patterns of individual metabotropic glutamate receptors in the adult and developing rat retina suggest distinct roles for these receptors in retinal synaptic circuitry.
Long‐Term Depression in Rat Cerebellum Requires both NO Synthase and NO‐sensitive Guanylyl Cyclase
Authors: Boxall Andrew R. , Garthwaite John 
Published: April 2006

AbstractLong‐term depression (LTD) of synaptic transmission between parallel fibres and Purkinje cells is a well‐known example of synaptic plasticity taking place in the cerebellum. Nitric oxide (NO) has been implicated in synaptic plasticity in other brain areas, but its function in cerebellar LTD is controversial. Even when an involvement is suggested, the NO signal transduction pathway is unclear. One candidate is the cyclic GMP‐synthesizing enzyme, soluble guanylyl cyclase, whose activity in the brain and elsewhere is powerfully stimulated by NO. By recording intracellularly from Purkinje cells in cerebellar slices, we demonstrate that blockade of NO synthase completely inhibits LTD induced by pairing parallel fibre stimulation with postsynaptic Ca2+ spike firing. LTD was also blocked by intracellular application of 1H‐[1, 2, 4]oxadiazolo[4, 3‐a]quinoxalin‐1‐one, a recently identified potent and selective inhibitor of soluble guanylyl cyclase. These findings indicate that soluble guanylyl cyclase is required for cerebellar LTD and suggest that this enzyme, located within Purkinje cells, transduces the NO signal in this form of synaptic plasticity.
Leukaemia Inhibitory Factor Induced in the Sciatic Nerve after Axotomy is Involved in the Induction of Galanin in Sensory Neurons
Authors: Sun Y. , Zigmond R. E. 
Published: April 2006

AbstractDramatic changes occur in neuropeptide expression in sensory and sympathetic neurons following axonal injury. Based on the finding that the cytokine leukemia inhibitory factor (LIF) plays an important role in mediating these changes in sympathetic neurons, its participation in triggering changes in sensory neurons was examined. By the use of transgenic mice in which the LIF gene had been knocked out, LIF was found to contribute to the induction of galanin expression in dorsal root ganglia (DRG) after sciatic nerve lesion. On the other hand, two other neuropeptide changes that occur in DRG under these conditions, the reduction of substance P and induction of neuropeptide Y, were independent of LIF expression. In the sympathetic superior cervical ganglion, transection of the postganglionic nerves close to the ganglion resulted in a rapid induction of LIF mRNA in the ganglion and in the lesioned nerve trunk. In contrast, transection of the sciatic nerve close to or distant from the DRG caused a rapid induction of LIF mRNA in the lesioned nerve, but not in the DRG. DRG were capable of making substantial amounts of LIF mRNA when placed in explant cultures, but,in vivo, only a slight induction was found even when both central and peripheral nerve processes of these sensory neurons were transected. These latter observations suggest that, in contrast to the superior cervical ganglia, the DRG environment inhibits the lesion‐induced expression of LIFin vivo, and/or explanted DRG produce stimulatory signals not foundin vivo., Together with the data on the induction of galanin, these observations provide evidence that LIF, generated at a site at some distance from the ganglion, is involved in triggering part of the cell body reaction in sensory neurons.
Functional Demarcation of a Border Between Areas V6 and V6A in the Superior Parietal Gyrus of the Macaque Monkey
Authors: Galletti C. , Fattori P. , Battaglini P. P. , Shipp S. , Zeki S. 
Published: April 2006

AbstractWe have compared physiological data recorded from three alert macaque monkeys with separate observations of local connectivity, to locate and characterize the functional border between two related but distinct visual areas on the caudal face of the superior parietal gyrus. We refer to these areas as V6 and V6A. They occupy almost the entire extent of the anterior bank of the parieto‐occipital sulcus, V6A being the more dorsal. These two areas are strongly interconnected. Anatomically, we have defined the border as the point at which labelled axon terminals first adopt a recognizably ‘descending’ pattern in their laminar characteristics, after injections of wheatgerm agglutinin‐horseradish peroxidase into the dorsal half of the gyrus (in presumptive V6A). A similar principle was used to recognize the same border by the pattern of input from area V5, except that in this case the relevant transition in laminar characteristics is that between an ‘intermediate’ pattern (in V6) and an ‘ascending’ pattern (in V6A). V6A was found to be distinct from V6 in a number of its physiological properties. Unlike V6, it contains visually unresponsive cells as well as units with craniotopic receptive fields (‘real‐position’ cells), units tuned to very slow stimulus speeds, units with complex visual selectivities and units with activity related to attention. V6A was also found to have a larger mean receptive field size and scatter than V6. By contrast, response properties related to the basic orientation and direction of moving bar stimuli were indistinguishable between V6 and V6A, as was the influence of gaze direction on cell activity in the two areas. Two‐dimensional maps of the recording sites allowed reconstruction of the V6/V6A border. For comparison, the anatomical results were rendered on two‐dimensional maps of identical format to those used to summarize the physiological data. After normalizing for relative size, the physiological and connectional estimates of the border between V6 and V6A were found to coincide, at least within the range of individual variation between hemispheres. An architectonic map in the same format was also made from a hemisphere stained for myelin and Nissl substance. Area PO, defined by its general density of myelination was not distinct in this material, but several architectural features were traceable and one of these was also found to approximate the V6/V6A border. The particular criteria that distinguish V6 from V6A differ from a recent description of areas PO and POd in the Cebus monkey; we believe it most likely that PO and POd together may correspond to V6.
Differential Distribution of MAP1a and Aldolase c in Adult Mouse Cerebellum
Authors: Touri F. , Hawkes R. , Riederer B. M. 
Published: April 2006

AbstractMAP1a is a microtubule‐associated protein with an apparent molecular weight of 360 kDa that is found in the axonal and dendritic processes of neurons. Two monoclonal anti‐MAP1a antibodies, anti‐A and anti‐BW6, revealed different epitope distributions in the adult mouse cerebellum. Anti‐A stained Purkinje and granule cells uniformly throughout the cerebellum. In contrast, anti‐BW6 selectively stained the dendrites of a subset of Purkinje cells, revealing parasagittal bands of immunoreactivity in the molecular layer. The compartmentation of the BW6 epitope was compared to the Purkinje cells as revealed by immunostaining with anti‐zebrin II, a well known antigen expressed selectively by bands of Purkinje cells. The anti‐BW6 staining pattern was complementary to the zebrin II bands, the zebrin II‐ Purkinje cells having BW6+ dendrites. These results demonstrate that MAP1a is present in two forms in the mouse cerebellum, one of which is segregated into parasagittal bands. This may indicate a unique MAP1a isoform or may reflect differences in the metabolic states of Purkinje cell classes, and regional differences in their functions.
Characterization of Excitatory Amino Acid Neurotoxicity in N‐methyl‐D‐aspartate Receptor‐deficient Mouse Cortical Neuronal Cells
Authors: Tokita Yoshihito , Bessho Yasumasa , Masu Masayuki , Nakamura Kenji , Nakao Kazuki , Katsuki Motoya , Nakanishi Shigetada 
Published: April 2006

AbstractRoles and mechanisms of N‐methyl‐D‐aspartate (NMDA) receptors in glutamate neurotoxicity were investigated in cultures of NMDA receptor‐deficient cortical neuronal cells. Mutant mice lacking a functional NMDA receptor were generated by gene targeting of the NR1 NMDA receptor subunit. Cortical neuronal cells prepared from wild‐type NR1+/+, heterozygous NR1+/‐ and homozygous mutant NR1‐/‐ mice at 15–17 days of gestation grew indistinguishably from each other. Brief exposures (5 min) of both NR1+/+ and NR1+/‐ neuronal cells to glutamate or NMDA, but not kainate or α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionate (AMPA), resulted in widespread neuronal degeneration by the following day. In contrast, neither glutamate nor NMDA treatment caused neuronal degeneration in NR1‐/‐ cells, indicating that NMDA receptors are responsible for rapidly triggered glutamate neurotoxicity. The above four compounds were all effectivein inducing the death of NR1+/+ and NR1+/‐ neuronal cells after prolonged exposure (20–24 h). However, NMDA had no neurotoxic effects on NR1‐/‐ cells, although the other three compounds were neurotoxic with potencies comparable to those for NR1+/+ and NR1+/‐ cells. The AMPA and kainate receptors are thus sufficient for inducing slowly triggered glutamate neurotoxicity. Brief exposure of a mixed population of NR1+/+ and NR1‐/‐ neuronal cells to NMDA selectively killed the NMDA receptor‐expressing cells without any appreciable effects on neighbouring NMDA receptor‐deficient cells. This finding further supports a direct and indispensable role for NMDA receptors in NMDA‐evoked neuronal cell death.
Immunocytochemical Evidence that Glutamate is a Neurotransmitter in the Cochlear Nerve: A Quantitative Study in the Guinea‐pig Anteroventral Cochlear Nucleus
Authors: Hackney Carole M. , Osen Kirsten K. , Ottersen Ole Petter , Storm‐Mathisen Jon , Manjaly George 
Published: April 2006

AbstractThe large so‐called type I afferents of the cochlear nerve carry the majority of the auditory input from the cochlea to the cochlear nuclei in the brainstem. These fibres are excitatory and previous studies have suggested they may use glutamate as their neurotransmitter. In the present investigation therefore, antibodies to glutamate and to the glutamate precursor, glutamine, were applied to resin sections of perfusion‐fixed brains and of in vitro brain slices subjected to depolarizing levels of potassium before fixation to study glutamate handling and synaptic release. Ultrathin sections were labelled by the immunogold technique, and the immunoreactivity was quantified by recording the density of gold particles over the various tissue profiles. Non‐primary, presumably inhibitory, terminals and glial processes were used as reference structures. The cochlear primary terminals proved to be strongly immunoreactive for glutamate. The density of glutamate labelling was higher in primary terminals than in non‐primary ones, and lowest in glial processes. The ratio between the mean glutamate and glutamine labelling densities was also higher in primary terminals than in non‐primary ones, and lowest in glial processes in each case. In the primary terminals, the glutamate immunoreactivity was higher over vesicle‐containing regions than over vesicle‐free regions, whilst glutamine was evenly distributed throughout. The in vitro brain slices showed a potassium‐induced, partly calcium‐dependent depletion of glutamate from the primary terminals but not from the non‐primary ones. These observations strongly support the conclusion that glutamate is a neurotransmitter of type I cochlear afferents.
The Effects of Lesions to the Mammillary Region and the Hippocampus on Conditional Associative Learning by Rats
Authors: Sziklas V. , Petrides M. , Leri F. 
Published: April 2006

AbstractRats with extensive lesions to the mammillary body region, the hippocampus, or rats which had received a control operation were trained postoperatively on two visuo‐spatial conditional associative learning tasks in which they had to learn to associate spatial cues with particular visual/auditory stimuli. The animals were subsequently trained on a spatial working memory task, the eight‐arm radial maze. Rats with lesions to the mammillary body region were able to acquire the conditional associative learning tasks at a rate comparable to that of operated control animals, whereas those with hippocampal lesions were not. By contrast, rats with a lesion of the mammillary body region or the hippocampus were significantly impaired in comparison with the operated control animals in the radial maze. The findings suggest that lesions to the mammillary body region impair spatial working memory without affecting the capacity to associate particular exteroceptive cues with spatial locations.
Glutamate Depresses Release by Activating Non‐conventional Glutamate Receptors at Crayfish Nerve Terminals
Authors: Parnas I. , Dudel J. , Parnas H. , Ravin R. 
Published: April 2006

AbstractThe present study shows that release of glutamate from crayfish nerve terminals is inhibited at low depolarizing current pulses by glutamate, N‐methyl‐D‐aspartate (NMDA) and quisqualate. These agonists elicit inhibitory effects at concentrations as low as 10‐8 M (quisqualate) and 10‐7 M (glutamate and NMDA). The NMDA‐mediated inhibition is blocked by (±)‐2‐amino‐5‐phosphonovaleric acid (APV). The quisqualate‐mediated inhibition is blocked by 6‐cyano‐7‐nitroquinoxaline‐2, 3‐dione (CNQX). Both CNQX and APV are needed to block glutamate‐mediated inhibition. The inhibition of release is not accompanied by a detectable change in presynaptic membrane conductance at the secondary branch. Using fura‐2, Ca2+ accumulation during repetitive stimulation (100 Hz) was monitored in single release boutons. Inhibition of release, elicited by 10‐4 M glutamate, was not associated with a reduction in the accumulation of Ca2+. We show that the glutamate released from a single or a few release boutons during normal activity acts similarly to glutamate added externally, i.e. it inhibits its own release.
Distribution and Sites of Synthesis of NTT4, an Orphan Member of the Na+/Cl‐‐dependent Neurotransmitter Transporter Family, in the Rat CNS
Authors: Luque J. M. , Jursky F. , Nelson N. , Richards J. G. 
Published: April 2006

AbstractThe distribution and sites of synthesis in rat CNS of NTT4, a novel orphan member of the Na+/Cl‐‐dependent neurotransmitter transporter family, were determined by immunohistochemistry and hybridization histochemistry. Antibodies raised against recombinant fusion proteins, corresponding to residues of NTT4, and 35S‐labelled oligodeoxyribonucleotide probes, were used to delineate the cellular distribution of the transporter at the protein and mRNA levels. High levels of immunoreactivity (mainly in the neuropil) were found in the olfactory bulb, cerebral cortex, striatum, hippocampus, thalamus, substantia nigra, pontine nuclei, cerebellum and spinal cord. The lowest levels were associated with the lateral hypothalamic area and deep mesencephalic nuclei. In situ hybridization signals correlated well with the immunoreactivity, and demonstrated a widespread distribution of NTT4 transcripts exclusively in neurons. NTT4 transcripts appeared widely codistributed with the N‐methyl‐D‐aspartate receptor subunit 1 (1–4b), i.e. spliced variants characterized by a common 5’63 bp insertion. These results indicate that the transporter was associated with neuronal processes in specific glutamate innervated CNS regions. Although the substrate transported by NTT4 remains unknown, our findings suggest a possible role for this carrier protein in glutamate/glycine neurotransmission.