bluuebunny/crossref_metadata_2025_split huggingface dataset:
Involvement of a basolateral amygdala complex–nucleus accumbens pathway in glucocorticoid‐induced modulation of memory consolidation
Authors: Setlow Barry , Roozendaal Benno , McGaugh James L. 
Published: March 2003

AbstractSystemic or intracerebral administration of glucocorticoids modulates memory consolidation in several tasks. Previously, we have shown that these memory‐modulatory effects depend on an intact basolateral complex of the amygdala (BLC) and efferents from the BLC that run through the stria terminalis. It is currently unknown, however, what BLC efferent structures mediate these effects. The present experiments were designed to determine whether the nucleus accumbens (NA), which receives BLC efferents through the stria terminalis and is involved in several BLC‐dependent behaviours, is involved in glucocorticoid‐induced modulation of memory consolidation. In experiment 1, rats with bilateral sham or N‐methyl‐ d‐aspartate (NMDA)‐induced lesions of the NA were trained on a one‐trial, footshock‐motivated inhibitory avoidance task, and given immediate post‐training injections of either the synthetic glucocorticoid dexamethasone (0.3 or 1.0 mg/kg, s.c.) or vehicle. Testing 48 h later revealed that dexamethasone significantly enhanced retention in sham‐lesioned rats but that the enhancing effect was blocked in NA‐lesioned rats. An asymmetrical, or crossed‐lesion design was employed in experiment 2. Rats with a unilateral NMDA‐induced lesion of the BLC and a unilateral lesion of either the ipsilateral or contralateral NA were trained as in experiment 1. Testing 48 h later revealed that dexamethasone enhanced retention in ipsilaterally lesioned rats, but that this effect was blocked in contralaterally lesioned rats. These findings indicate that an intact BLC–NA pathway is critical for the enhancing effects of glucocorticoids on memory consolidation, and are consistent with the view that the BLC regulates memory consolidation in other brain regions.
L‐type Ca2+ channels and purinergic P2X2 cation channels participate in calcium‐tyrosine kinase‐mediated PC12 growth cone arrest
Authors: Schindelholz Benno , Reber Bernhard F. X. 
Published: March 2003

AbstractDuring development and regeneration of the nervous system, growth cones of the various nerve cells navigate and direct neurite elongation by detecting and responding to cues in the environment. To investigate changes in growth cone behaviour due to calcium influx we used nerve growth factor (NGF)‐induced growth cones of PC12 (rat pheochromocytoma cells) cells as a model. High external concentrations of potassium and ATP depress growth cone motility, induce club‐shaped growth cones and reduce filopodia length and the number and relative F‐actin contents of single growth cones (r.a.c.), respectively. The cellular responses are mediated by a sustained increase in the intracellular free Ca2+ concentrations ([Ca2+]i) as monitored by calcium‐sensitive fluorescent dyes and confocal microfluorimetry. The responses are not detectable in the presence of the protein tyrosine kinase inhibitor genistein. Immunocytochemistry revealed an increased level of tyrosine‐phosphorylated proteins in cell bodies and growth cones but not in cell nuclei. Paxillin, a cytoskeleton‐associated protein located in neurites and growth cones, was detected among the phosphotyrosine proteins. The sustained (> 30 s) Ca2+ influx through voltage‐gated L‐type but not N‐ or P‐type Ca2+ channels induced the F‐actin loss and tyrosine phosphorylation. Ca2+ entry through P2X2 ligand‐gated channels caused the same effects. Our data suggest the following mechanism: increased [Ca2+]i levels activate tyrosine kinases located close to the ion channels which then leads to changes in morphology due to tyrosine phosphorylation of proteins, e.g. paxillin.
Neuronal and vascular localization of histamine N‐methyltransferase in the bovine central nervous system
Authors: Nishibori Masahiro , Tahara Akihito , Sawada Ken , Sakiyama Junko , Nakaya Naoki , Saeki Kiyomi 
Published: March 2003

AbstractHistamine N‐methyltransferase (HMT) (EC 2.1.1.8) plays a crucial role in the inactivation of the neurotransmitter histamine in the CNS. However, the localization of HMT remains to be determined. In the present study, we investigated immunohistochemical localization of HMT in the bovine CNS using a polyclonal antibody against bovine HMT. The HMT‐like immunoreactivity was observed mainly in neurons. Strongly immunoreactive neurons were present in the oculomotor nucleus and ruber nucleus in the midbrain, the facial nucleus in the pons, the dorsal vagal nucleus and hypoglossal nucleus in the medulla oblongata and in the anterior horn as well as intermediolateral zone of the spinal cord. Intermediately immunoreactive neurons were present in the piriform cortex and the inferior olivary nucleus. The grey matter of the forebrain regions was diffusely and faintly stained. In the cerebellum and the striatum, the nerve fibres in the white matter were positive. The tuberomammillary nucleus, where histaminergic neurons are present, were weakly positive. The other immunoreactive structures in the CNS were blood vessels. Almost all of the blood vessel walls, irrespective of whether they were arterial or venous, were variably stained. The glial fibrillary acidic protein‐ (GFAP‐) immunoreactive astrocytes were not stained. These findings indicated that histamine released from histaminergic nerve terminals or varicose fibres is methylated mainly in postsynaptic or extrasynaptic neurons rather than in astrocytes. The localization of HMT in the blood vessel wall may mean that blood‐borne histamine and histamine released from mast cells associated with the blood vessels are catabolized in this structure.
Differential sensitivity to Zolpidem of IPSPs activated by morphologically identified CA1 interneurons in slices of rat hippocampus
Authors: Thomson Alex M. , Bannister A. Peter , Hughes David I. , Pawelzik Hannelore 
Published: March 2003

AbstractHippocampal pyramidal cells express several α‐subunits, which determine the affinity of GABAA (γ‐aminobutyric acid) receptors for benzodiazepine site ligands. This study asked whether inhibitory postsynaptic potentials (IPSPs) elicited by specific interneuronal subclasses were differentially sensitive to the α1‐preferring agonist Zolpidem, i.e. whether different receptors mediate different inhibitory connections. Paired intracellular recordings in which the presynaptic cell was an interneuron and the postsynaptic cell a CA1 pyramid were performed in slices of adult rat hippocampus. Resultant IPSPs were challenged with Zolpidem, cells filled with biocytin and identified morphologically. IPSPs elicited by fast spiking (FS) basket cells (n = 9) were enhanced more than IPSPs elicited by regular spiking (RS) basket cells (n = 10). At FS basket cell synapses the efficacy of Zolpidem was equivalent to that of Diazepam, while RS basket cell IPSPs are enhanced 50% less by Zolpidem than by Diazepam. Thus, while α1 subunits may dominate at synapses supplied by FS basket cells, RS basket cell synapses also involve α2/3 subunits. Two bistratified cell IPSPs tested with Zolpidem did not increase in amplitude, despite powerful enhancements of bistratified cell IPSPs by Diazepam, consistent with previous indications that these synapses utilize α5‐containing receptors. Enhancements of basket cell IPSPs by Zolpidem and Diazepam were bi‐ or triphasic with steep amplitude increases separated by plateaux, occurring 10–15, 25–30 and 45–55 min after adding the drug to the bath. The entire enhancement was, however, blocked by the antagonist Flumazenil (n = 7). Flumazenil, either alone (n = 3), or after Zolpidem, reduced IPSP amplitude to ∼ 90% of control, suggesting that α4‐containing receptors were not involved.
Cerebral oligaemia episode triggers free radical formation and late cognitive deficiencies
Authors: Heim Christine , Zhang Jianjun , Lan Jing , Sieklucka Maria , Kurz Tino , Riederer Peter , Gerlach Manfred , Sontag Karl‐Heinz 
Published: March 2003

AbstractSixty minutes of cerebral oligaemic hypoxia, induced by bilateral clamping of the carotid arteries (BCCA) in pentobarbital‐anaesthetized normotensive rats, induces a late progressive cognitive decline when compared with sham‐operated controls. Analysis at BCCA of hippocampal metabolism using microdialysis showed increased release of glutamate, aspartate and γ‐aminobutyric acid, followed by a progressive rise in the formation of hydroxyl free radicals measured as 2,3‐dihydroxybenzoic acid (2,3‐DHBA), their reaction product with salicylate, though only in the re‐perfusion phase. In the striatum increased dopamine release occurred during BCCA, whereas glutamate and aspartate showed an increase only during the late re‐perfusion phase. γ‐Aminobutyric acid (GABA) concentration increased during BCCA and early re‐perfusion. An increase in 2,3‐DHBA was seen during BCCA, and persisted over 2 h of re‐perfusion. Six and 13 months after surgery, though not as early as 3 months, BCCA‐treated rats perform worse than sham‐operated controls in a water‐maze, where decreased swimming speed reveals striatal dysfunction, while hippocampal dysfunction manifested as diminished spatial bias. These results show that cerebral oligaemia, similarly to cerebral ischaemia, leads to increased extracellular dopamine, aspartate and glutamate, and the production of hydroxyl radicals in structures associated with learning and memory processes. Unlike cerebral ischaemia, in cerebral oligaemia the appearance of spatial memory deficits is delayed.
Selective suppression of horizontal propagation in rat visual cortex by norepinephrine
Authors: Kobayashi Masayuki , Imamura Kazuyuki , Sugai Tokio , Onoda Norihiko , Yamamoto Masao , Komai Shoji , Watanabe Yasuyoshi 
Published: March 2003

AbstractThe release of norepinephrine in the cerebral cortex from axon terminals of locus coeruleus neurons was suggested to be involved in the control of attention. Accumulating data indicate that the responses of cortical neurons are varied when norepinephrine is applied iontophoretically in the vicinity of the cells being recorded. However, it is not known how the pattern of excitatory propagation is modified when norepinephrine is applied over a wide area in the visual cortex. By applying optical imaging to rat visuocortical slices, we found a new mode of norepinephrine action; a prominent suppression of the horizontal propagation in layers II/III. This action of norepinephrine was confirmed by the simultaneous recording of field potentials from multiple sites by use of a multi‐electrode dish. Furthermore, our electrophysiological recordings showed that this norepinephrine action is exerted through suppression of excitatory neural transmission and enhancement of inhibitory transmission to the pyramidal neurons in these layers. Because the release of norepinephrine in the visual cortex is regulated by the level of attention, the neural basis of visual attention may relate partially to the suppression of the integration of visual information by norepinephrine resulting in a state‐dependent restructuring of the receptive field.
Light‐adaptive effects of retinoic acid on receptive field properties of retinal horizontal cells
Authors: Pottek Mark , Weiler Reto 
Published: March 2003

AbstractBesides its role in ocular development, retinoic acid (RA), which is a light‐correlated byproduct of the phototransduction cycle, was recently shown to affect light‐driven synaptic plasticity in the outer plexiform layer of the adult fish retina. Tuning by ambient light conditions of the retinal network properties is very prominent in outer plexiform layer circuits, and we therefore examined whether RA could affect cone horizontal cell physiology similar to ambient light. Performing intracellular recordings and dye injections in the dark‐adapted inverted eyecup preparation of the carp, we found that RA reduced the receptive fields of horizontal cell somata and impaired gap junctional communication. This action was not observed among coupled axon terminals of horizontal cells and appeared to be stereospecific because it could only be attributed to all‐trans and 13‐cis RA but not to the 9‐cis isomer and photoisomerized all‐trans RA. Modulation of receptive field size occurred independently of the dopaminergic system. Furthermore, RA affected the light responsiveness of cone horizontal cells. Compared to the dark‐adapted condition, responsiveness to intense light stimulation was enhanced but decreased when low intensities were used. Moreover, following RA treatment H2‐type horizontal cells of dark‐adapted retinae which do not give rise to colour‐opponent light properties became colour‐opponent and performed depolarizing responses to long‐wavelength stimulation. In all these cases RA perfectly matched the effects of light adaptation, supporting the notion that RA acts as an endogenous neuromodulator.
The novel brain neuropeptide, orexin‐A, modulates the sleep–wake cycle of rats
Authors: Piper David C. , Upton Neil , Smith Martin I. , Hunter A. Jackie 
Published: March 2003

AbstractOrexin‐A is a novel neuropeptide initially isolated from hypothalamic extracts but now known to be present in fibres distributed throughout the rat CNS including many regions associated with sleep–wake regulation. The recognition of a particularly dense innervation of orexinergic nerves in the locus coeruleus, together with the observed increase in firing rate of locus coeruleus neurons following application of orexin‐A in vitro, further highlighted a potential involvement of the peptide in modulating the arousal state. The present study was undertaken to determine the effects of intracerebroventricularly (ICV) administered orexin‐A on the sleep–wake cycle of conscious rats using electroencephalographic and electromyographic recordings. When administered at the onset of the normal sleep period, orexin‐A (1, 10 or 30 μg/rat ICV) produced a dose‐dependent increase in the time rats spent awake during the second and third hours after dosing. The enhancement of arousal was accompanied by a marked reduction in paradoxical sleep and deep slow wave sleep at the highest dose. The latency to the first occurrence of paradoxical sleep was also prolonged. This overall profile of increased arousal and decreased paradoxical sleep is consistent with a high rate of firing of locus coeruleus neurons as would be expected to occur following ICV administration of orexin‐A. It is concluded that orexin‐A may play an important physiological role in regulating the sleep–wake state, a hypothesis considerably strengthened by the recently reported narcoleptic phenotype of prepro‐orexin (the precursor for orexin‐A) knockout mice.
Localization of the fragile X mental retardation 2 (FMR2) protein in mammalian brain
Authors: Miller William J. , Skinner Judith A. , Foss Grethe S. , Davies Kay E. 
Published: March 2003

AbstractThe transcriptional silencing of the FMR2 gene has been implicated in FRAXE mental retardation. FRAXE individuals have been shown to exhibit learning deficits, including speech delay, reading and writing problems. FMR2 encodes a large protein of 1311 amino acids and is a member of a gene family encoding proline–serine‐rich proteins that have properties of nuclear transcription factors. To characterize the expression of the fragile X mental retardation 2 (FMR2) protein, polyclonal antibodies were raised against two regions of the human FMR2 protein and used in immunofluorescence experiments on mouse brain cryosections. Our results demonstrate for the first time that the FMR2 protein is localized in neurons of the neocortex, Purkinje cells of the cerebellum and the granule cell layer of the hippocampus. FMR2 staining is shown to colocalize with the nuclear stain 4,6‐diamidino‐2‐phenylindole (DAPI) confirming that FMR2 is a nuclear protein. The localization of FMR2 protein to the mammalian hippocampus and other brain structures involved with cognitive function is consistent with the learning deficits seen in FRAXE individuals.
Leukaemia inhibitory factor is required for normal inflammatory responses to injury in the peripheral and central nervous systems in vivo and is chemotactic for macrophages in vitro
Authors: Sugiura Shigeki , Lahav Ronit , Han Jing , Kou Shi‐Ying , Banner Lisa R. , De Pablo Flora , Patterson Paul H. 
Published: March 2003

AbstractThe cytokine leukaemia inhibitory factor (LIF) is up‐regulated in glial cells after injury to the peripheral and central nervous systems. In addition, LIF is required for the changes in neuropeptide expression that normally occur when the axons of sympathetic and sensory neurons are transected. We investigated whether LIF is also necessary for the initial inflammatory response that follows mechanical injury to the sciatic nerve and cerebral cortex of adult mice. We find that inflammatory cell infiltration into crushed sciatic nerve is significantly slower in LIF knock‐out (KO) mice compared with wild‐type (WT) mice. Similarly, the microglial and astroglial responses to surgical injury of the cortex are significantly slower in LIF KO mice compared with WT mice. Consistent with these in vivo results, LIF is chemotactic for peritoneal macrophages in a microchamber culture assay. Thus, LIF is a key regulator of neural injury in vivo, where it is produced by glia and can act directly on neurons, glia and inflammatory cells. We also find that the initial inflammatory response to cortical injury is diminished in interleukin (IL)‐6 KO mice. Surprisingly, however, the inflammatory response in LIF‐IL‐6 double KO mice is very similar to that of the single KO mice, suggesting that these cytokines may act in series rather than in parallel in this response.
Acetylcholine receptors are required for postsynaptic aggregation driven by the agrin signalling pathway
Authors: Grow Wade A. , Gordon Herman 
Published: March 2003

AbstractTo investigate the role of acetylcholine receptors (AChRs) in the aggregation of postsynaptic molecules on muscle cells, we utilized the 1R– genetic variant of C2 muscle cells which has very little expression of AChRs in its cell membrane. On C2 myotubes, AChRs cluster spontaneously, with the frequency of clustering greatly enhanced by motor neuron‐derived agrin. Signal transduction events driven by agrin, including the tyrosine phosphorylation of muscle‐specific kinase (MuSK) and the AChR β subunit, have been implicated as requirements of postsynaptic scaffold assembly. We show here that some molecules of the postsynaptic scaffold spontaneously aggregate and colocalize on 1R– myotubes at very low frequency, including an as yet unidentified agrin binding molecule, β‐dystroglycan and MuSK. Agrin is unable to increase the frequency of these aggregations, but does cause tyrosine phosphorylation of MuSK. We conclude that free molecules can associate into aggregates independently of AChRs, but AChRs are required for high‐frequency molecular aggregation driven by the agrin signalling pathway. MuSK tyrosine phosphorylation appears to precede a requisite event involving AChRs that aggregates postsynaptic molecules.
A dynamic regulation of GDNF‐family receptors correlates with a specific trophic dependency of cranial motor neuron subpopulations during development
Authors: Mikaels Åsa , Livet Jean , Westphal Heiner , De Lapeyrière Odile , Ernfors Patrik 
Published: March 2003

AbstractGlial cell line‐derived neurotrophic factor (GDNF) family ligands promote the survival of developing motor neurons in vivo and in vitro. However, not all neurons survive with any single ligand in culture and GDNF null mutant mice display only a partial motor neuron loss. An interesting possibility is that subpopulations of motor neurons based on their function and/or their myotopic organization require distinct members of GDNF family ligands. Because responsiveness to the different ligands depends on the expression of their cognate ligand‐binding receptor we have herein addressed this issue by examining the expression of GDNF‐family receptors (gfr) during development and in the adult in cranial motor nuclei subpopulations. We have furthermore examined the in vivo role of GDNF for cranial motor neuron subpopulations. The shared ret receptor was expressed in all somatic, branchial and visceral cranial embryonic motor nuclei examined, showing that they are all competent to respond to GDNF family ligands during development. At early stages of development both the GDNF receptor, gfrα1, and the neurturin (NTN) receptor, gfrα2, were expressed in the oculomotor, facial and spinal accessory, and only gfrα1 in the trochlear, superior salivatory, trigeminal, hypoglossal and weakly in the dorsal motor nucleus of the vagus and the ambiguus nucleus. The abducens nucleus was negative for both gfrα1 and gfrα2. The artemin (ART) receptor, gfrα3, was expressed only in the superior salivatory nucleus. A motor neuron subnuclei‐specific expression of gfrα1 and gfrα2 was seen in the facial and trigeminal nuclei which corresponded to their dependence on GDNF in null mutant mice. We found that the expression was dynamic in these nuclei, which may reflect developmental changes in their trophic factor dependency. Analysis of GDNF null mutant mice revealed that the dynamic receptor expression is regulated by the ligand in vivo, indicating that the acquirement of changes in dependency could be ligand induced. Our results indicate that specific GDNF family ligands support selective muscle–motor neuron circuits during development.
NOS inhibition during postnatal development leads to increased ipsilateral retinocollicular and retinogeniculate projections in rats
Authors: Vercelli A. , Garbossa D. , Biasiol S. , Repici M. , Jhaveri S. 
Published: March 2003

AbstractSynthesis of nitric oxide (NO) occurs downstream from activation of N‐methyl‐ d‐aspartate (NMDA) receptors; NO reportedly acts as a retrograde messenger, influencing the refinement and stabilization of coactive afferent terminals. Cells and neuropil in the rat superior colliculus (SC) and lateral geniculate body (LGB) show intense, developmentally regulated activity for NO synthase (NOS). To study the role of NO in the development of retinogeniculate and retinotectal axon arbors, we examined primary visual projections of rats that had received intraperitoneal injections of Nω‐nitro‐l‐arginine (L‐NoArg, an NOS inhibitor) on postnatal day 0, and daily thereafter for 4–6 weeks. Treated rats showed significant alterations in ipsilateral retinotectal projections, in the mediolateral and anteroposterior axes; there was an increase in the density of fibres entering the SC, in branch length, and in the numbers of boutons on retinotectal arbors in the treated group. Ipsilaterally projecting retinal axons also showed an increase in density and distribution in the dorsal nucleus of the LGB. If animals were allowed to survive for several months after stopping treatment, similar changes were also noted, but these were much less striking. Our results support the hypothesis that, in the mammalian visual system, NO released from target neurons in the SC and LGB serves as a retrograde signal which feeds back on retinal afferents, influencing their growth. The effects of NOS inhibition are partially reversed after treatment is stopped, indicating that lack of NO synthesis delays the maturation of retinofugal connections, and also that NO plays a constitutive role in their development.