bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential induction of LTP and LTD is not determined solely by instantaneous calcium concentration: an essential involvement of a temporal factor
Authors: Mizuno Tomoyuki , Kanazawa Ichiro , Sakurai Masaki 
Published: March 2003

AbstractTwo opposite types of synaptic plasticity in the CA1 hippocampus, long‐term potentiation (LTP) and long‐term depression (LTD), require postsynaptic Ca2+ elevation. To explain these apparently contradictory phenomena, the current view assumes that a moderate postsynaptic increase in Ca2+ leads to LTD, whereas a large increase leads to LTP. No detailed study has so far been attempted to investigate whether the instantaneous Ca2+ elevation level differentially induces LTP or LTD. We therefore used low‐frequency (1 Hz) stimulation of Schaffer collateral/commissural fibers in rat hippocampal slices, during a Mg2+‐free period, as the conditioning stimulus to investigate this. This allowed low‐frequency afferent stimulation to cause a postsynaptic Ca2+ influx because the voltage‐dependent block of N‐methyl‐d‐aspartate (NMDA) receptor‐channels by Mg2+ was removed. When delivered during the Mg2+‐free period, a single pulse, as well as 2–600 pulses, induced LTP that was occluded with tetanus‐induced LTP. To decrease the Ca2+ influx, α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionic acid (AMPA) receptors were completely blocked by the addition of 10 µm 6‐cyano‐7‐nitroquinoxaline‐2,3‐dione (CNQX) to the conditioning medium, in which 1 Hz afferent stimuli (1–600 pulses) induced less LTP and never induced LTD. To further reduce the Ca2+ influx, NMDA receptors were partially blocked with d‐(–)‐2‐amino‐5‐phosphonopentanoic acid (d‐AP5). A small number of 1 Hz stimuli, however, never induced LTD. Only when the conditioning stimuli exceeded 200 pulses was LTD induced. The present findings provide definitive evidence that protracted conditioning is a prerequisite for the induction of LTD. Thus, not only the amplitude but also the duration of postsynaptic Ca2+ elevation could be essential factors for differentially inducing LTP or LTD.
Exogenous nitric oxide causes potentiation of hippocampal synaptic transmission during low‐frequency stimulation via the endogenous nitric oxide–cGMP pathway
Authors: Bon Christelle L. M. , Garthwaite John 
Published: March 2003

AbstractNitric oxide (NO) is a putative participant in synaptic plasticity and demonstrations that exogenous NO can elicit the same plastic changes have been taken to support such a role. The experiments, carried out on the CA1 region of rat hippocampal slices, were aimed at testing this interpretation. A major component of tetanus‐induced long‐term potentiation (LTP) was lost in response to l‐nitroarginine, which inhibits NO synthase, and 1H‐[1,2,4]oxadiazolo[4,3‐a]quinoxalin‐1‐one (ODQ), which inhibits NO‐sensitive soluble guanylyl cyclase (sGC). At 0.2 Hz afferent fibre stimulation, exogenous NO produced, concentration‐dependently, a synaptic depression that reverted on washout to a persistent potentiation that occluded tetanus‐induced LTP. The NO concentrations necessary (estimated in the 100‐nm range), however, were mostly supramaximal for stimulating hippocampal slice sGC activity. Nevertheless the potentiation, but not the preceding depression, was blocked by ODQ. l‐nitroarginine and an NMDA antagonist were similarly effective, indicating mediation by the endogenous NMDA receptor–NO synthase–sGC pathway. At a concentration normally too low to affect synaptic transmission but sufficient to stimulate sGC (estimated to be 50 nm), exogenous NO reversed the effect of l‐nitroarginine and caused a potentiation which was blocked by ODQ. At a concentration inducing the depression/potentiation sequence, NO partially inhibited hippocampal slice oxygen consumption. It is concluded that, at physiological levels, exogenous NO can directly elicit a potentiation of synaptic transmission through sGC, provided that the synapses are suitably primed. At higher concentrations, NO inhibits mitochondrial respiration, which can result in an enduring synaptic potentiation due to secondary activation of the endogenous NO–cGMP pathway.
Migration of cells into and out of peripheral nerve isografts in the peripheral and central nervous systems of the adult mouse
Authors: Symons Natalie A. , Danielsen Nils , Harvey Alan R. 
Published: March 2003

AbstractPeripheral nerve (PN) isografts provide a favourable environment for axon regeneration after peripheral and central nervous system (CNS) injury, but definitive information on the extent of cellular intermixing between donor and host tissues is lacking. We wished to compare migration patterns in fresh and predegenerate PN grafts, and also compare the extent of cell migration after transplantation to peripheral nervous system (PNS) versus CNS. To discern how host and donor cells interact after PN transplantation, sciatic nerve segments were transplanted from inbred adult mice into PN defects (PN–PN grafts) or into lesioned cerebral cortex of opposite gender siblings. Migrating male cells were identified using a Y‐chromosome‐specific probe and in situ hybridization methods, and characterized immunohistochemically. The extent of donor and host cellular intermixing was similar in fresh and predegenerate PN–PN isografts. There was substantial intermixing of donor and host cells by 8 days. Many host cells migrating into epineurial regions of grafts were immunopositive for F4/80 (macrophages). The endoneurium of grafted PN was also colonized by host cells; some were F4/80+ but many were immunostained with S‐100 (Schwann cell marker). Donor S‐100+ Schwann cells rapidly migrated out into proximal and distal host PN and by 12 weeks were found at least 2 mm from the grafts. Endoneurial microvessels in grafts were mostly donor‐derived. By comparison, in male PN grafts to female CNS, even after 6 weeks few donor cells had migrated out into surrounding host cortex, despite the observation that almost all grafts contained regenerating axons and were thus attached to host CNS tissue.
Mobilization of the cell adhesion glycoprotein F3/contactin to axonal surfaces is activity dependent
Authors: Pierre Karin , Dupouy Bernard , Allard Michèle , Poulain Dominique A. , Theodosis Dionysia T. 
Published: March 2003

AbstractF3/contactin is a cell adhesion/recognition molecule of the immunoglobulin superfamily implicated in axonal growth. We examined its subcellular distribution and mobilization to the cell surface in oxytocin‐ (OT‐) secreting neurons, which express it throughout life and the axons of which undergo activity‐dependent remodelling. This was performed in hypothalamic organotypic slice cultures containing OT neurons with properties of adult neurosecretory cells. Immunocytochemistry and immunoblot analysis confirmed that OT neurons express high levels of F3/contactin in vitro. Light and confocal microscopy of cultures that underwent double immunofluorescence after fixation showed F3/contactin immunoreactivity throughout the cytoplasm of OT somata, dendrites and axons, and also in non‐OT axons and in putative synaptic boutons which contacted OT neurons. By contrast, after treatment of live cultures with anti‐F3/contactin antibodies followed by double immunofluorescence for the glycoprotein and OT, F3/contactin immunoreactivity was visible only on the surface of axons, whether or not OT‐immunoreactivity was present. Because of its glycosylphosphatidyl‐inositol (GPI) linkage, F3/contactin can occur in a membrane‐bound or soluble form. As seen from immunocytochemistry of live cells and immunoblot analysis, treatment of cultures with a GPI‐specific phospholipase C (GPI‐PLC) resulted in loss of F3/contactin immunoreactivity from all cell surfaces. F3/contactin immunoreactivity reappeared on axonal surfaces within 5 h after enzyme washout. Such re‐expression was accelerated by neuronal activity facilitation (by K+ depolarization or γ‐aminobutyric acid (GABA)‐A receptor blockade with bicuculline) and inhibited by neuronal activity repression [by blockade of Ca2+ channels with Mn2+, Na+ channels with tetrodotoxin (TTX) or excitatory inputs with glutamate antagonists]. Our observations establish therefore that F3/contactin surface expression in hypothalamic neurons is polarized to the axons where it occurs mainly in a GPI‐linked form. We also provide direct evidence that externalization of F3/contactin depends on Ca2+ entry and neuronal electrical activity. Taken together with our earlier finding that the glycoprotein is localized in neurosecretory granules, we demonstrate that F3/contactin is mobilized to the axonal surface via the activity‐dependent regulated pathway, thus arriving at the correct place and time to intervene in activity‐dependent remodelling of axons.
Doublecortin expression in the adult rat telencephalon
Authors: Nacher Juan , Crespo Carlos , McEwen Bruce S. 
Published: March 2003

AbstractDoublecortin (DCX) is a protein required for normal neuronal migration in the developing cerebral cortex, where it is widely expressed in both radially and tangentially migrating neuroblasts. Moreover, it has been observed in the adult rostral migratory stream, which contains the neuronal precursors traveling to the olfactory bulb. We have performed DCX immunocytochemistry in the adult rat brain to identify precisely the neuronal populations expressing this protein. Our observations confirm the presence of DCX immunoreactive cells with the characteristic morphology of migrating neuroblasts in the subventricular zone, rostral migratory stream and the main and accessory olfactory bulbs. We have also found putative migratory cells expressing DCX in regions were no adult neuronal migration has been described, as the corpus callosum, the piriform cortex layer III/endopiriform nucleus and the striatum. Surprisingly, many cells with the phenotype of differentiated neurons were DCX immunoreactive; e.g. certain granule neurons in the hilar border of the granular layer of the dentate gyrus, some neuronal types in the piriform cortex layer II, granule and periglomerular neurons in the main and accessory olfactory bulbs, and isolated cells in the striatum. Almost all DCX immunoreactive cells also express the polysialylated form of neural cell adhesion molecule and have a similar distribution to rat collapsin receptor‐mediated protein‐4, two molecules involved in neuronal structural plasticity. Given these results, we hypothesize that DCX expression in differentiated neurons could be related to its capacity for microtubule reorganization and that this fact could be linked to axonal outgrowth or synaptogenesis.
Regional pacemakers composed of multiple oscillator neurons in the rat suprachiasmatic nucleus
Authors: Nakamura Wataru , Honma Sato , Shirakawa Tetsuo , Honma Ken‐ichi 
Published: March 2003

AbstractRegional specificities of the dorsal and ventral regions of the suprachiasmatic nucleus (SCN) were examined to elucidate the structure of multioscillator circadian organization. The circadian rhythms of arginine vasopressin (AVP) and vasoactive intestinal polypeptide (VIP) release, and of electrical activity of individual neurons were measured in an organotypic, static slice culture of the SCN obtained from neonatal rats. Five days after the start of culture, robust circadian rhythms were detected in AVP release with a peak located consistently at the middle of the original light phase, while the 24 h profiles of VIP release were either arrhythmic or rhythmic. In the latter case, a phase delay of 5–7 h was observed in the circadian peak from the AVP rhythm. Multi‐channel, extracellular recording revealed that 51 (76.1%) out of 67 firing neurons, examined in the SCN, showed circadian rhythms in their firing rate. The percentage of rhythmic neurons was significantly larger in the dorsal (86.8%) than in the ventral (62.1%) region of the SCN, where the AVP and VIP containing neurons predominate, respectively. Twenty‐seven percent of the firing rhythms were almost antiphasic from the majority of rhythms. There was no regional specificity in the distribution of the antiphasic rhythm. These findings, that the dorsal and ventral regions of the SCN both contain circadian pacemakers with different properties that regulate the AVP and VIP release separately, is probably due to differences in the number and, hence, the coupling strength of oscillating neurons.
Identification of corticosteroid‐responsive genes in rat hippocampus using serial analysis of gene expression
Authors: Datson Nicole A. , Van Der Perk Jeannette , De Kloet E. Ronald , Vreugdenhil Erno 
Published: March 2003

AbstractAdrenal corticosteroids (CORT) have a profound effect on the function of the hippocampus. This is mediated in a coordinated manner by mineralocorticoid (MR) and glucocorticoid receptors (GR) via activation or repression of target genes. The aim of this study was to identify, using serial analysis of gene expression (SAGE), CORT‐responsive hippocampal genes regulated via MR and/or GR. SAGE profiles were compared under different conditions of CORT exposure, resulting in the identification of 203 CORT‐responsive genes that are involved in many different cellular processes like, energy expenditure and cellular metabolism; protein synthesis and turnover; signal transduction and neuronal connectivity and neurotransmission. Besides some previously identified CORT‐responsive genes, the majority of the genes identified in this study were novel. In situ hybridization revealed that six randomly chosen CORT‐responsive genes had distinct expression patterns in neurons of the hippocampus. In addition, using in situ hybridization, we confirmed that these six genes were indeed regulated by CORT, underscoring the validity of the SAGE data. Comparison of MR‐ and GR‐dependent expression profiles revealed that the majority of the CORT‐responsive genes were regulated either by activated MR or by activated GR, while only a few genes were responsive to both activated MR and GR. This indicates that the molecular basis for the differential effects of activated MR and GR is activation or repression of distinct, yet partially overlapping sets of genes. The putative CORT‐responsive genes identified here will provide insight into the molecular mechanisms underlying the differential and sometimes opposing effects of MR and GR on neuronal excitability, memory formation and behaviour as well as their role in neuronal protection and damage.
Rat microglial cells secrete predominantly the precursor of interleukin‐1β in response to lipopolysaccharide
Authors: Chauvet Nathalie , Palin Karine , Verrier Danielle , Poole Steve , Dantzer Robert , Lestage Jacques 
Published: March 2003

AbstractLittle is known on the forms of interleukin‐1β (IL‐1β) that are produced by microglial cells in the nervous system. Mixed glial cell cultures of rats produced IL‐1β in response to lipopolysaccharide (LPS). Using Western blot, pro‐IL‐1β was found to be localized both intracellularly and in the supernatant, whereas mature IL‐1β was found only in the supernatant but in lower quantities than pro‐IL‐1β. Immunocytochemistry confirmed that microglial cells are the exclusive source of IL‐1β. Blockade of the IL‐1β‐converting enzyme (ICE) by Tyr‐Val‐Ala‐Asp‐aldehyde (YVAD‐CHO) decreased the levels of mature IL‐1β but had no effect on pro‐IL‐1β. Release of pro‐IL‐1β was not associated with cell death nor with the extracellular release of ICE. Using gelatin zymography, glial cells were found to express constitutive matrix metalloproteinases (MMP) in the form of MMP‐2. Exposure to LPS induced MMP‐9 expression in a time‐dependent manner similar to the pro‐IL‐1β expression profile. MMP activation and inhibition experiments indicated a possible role of MMPs in the cleavage of pro‐IL‐1β but not in the generation of mature IL‐1β. Microglial cells share with macrophages the ability to release large amounts of pro‐IL‐1β of which the extracellular role remains to be determined.
Differential activation of hippocampus and amygdala following spatial learning under stress
Authors: Akirav Irit , Sandi Carmen , Richter‐Levin Gal 
Published: March 2003

AbstractWe examined the activation of memory‐related processes in the hippocampus and the amygdala following spatial learning under stress, in the rat. Animals were trained in a water maze in a massed spatial task under two stress conditions (cold and warm water). In the dorsal CA1, training was accompanied by increased phosphorylation of ERK2 only in animals that have acquired the task (irrespective of whether they were trained in cold or warm water). In the amygdala, significant activation of ERK2 was found only in animals that learned the task well under high levels of stress. Hence, the results suggest that the amygdala and the hippocampus are differentially activated following spatial learning, depending on the level of stress involved.
Cloning, characterization and central nervous system distribution of receptor activity modifying proteins in the rat
Authors: Oliver K. R. , Kane S. A. , Salvatore C. A. , Mallee J. J. , Kinsey A. M. , Koblan K. S. , Keyvan‐Fouladi N. , Heavens R. P. , Wainwright A. , Jacobson M. , Dickerson I. M. , Hill R. G. 
Published: March 2003

AbstractCalcitonin gene‐related peptide (CGRP), adrenomedullin (ADM), amylin and calcitonin (CT) are structurally and functionally related neuropeptides. It has recently been shown that the molecular pharmacology of CGRP and ADM is determined by coexpression of one of three receptor activity‐modifying proteins (RAMPs) with calcitonin receptor‐like receptor (CRLR). Furthermore, RAMP proteins have also been shown to govern the pharmacology of the calcitonin receptor, which in association with RAMP1 or RAMP3, binds amylin with high affinity. In this study, we have cloned the rat RAMP family and characterized the pharmacology of rat CGRP and ADM receptors. Rat RAMP1, RAMP2 and RAMP3 shared 72%, 69% and 85% homology with their respective human homologues. As expected CRLR‐RAMP1 coexpression conferred sensitivity to CGRP, whilst association of RAMP2 or RAMP3 with CRLR conferred high affinity ADM binding. Using specific oligonucleotides we have determined the expression of RAMP1, RAMP2 and RAMP3 mRNAs in the rat central nervous system by in situ hybridization. The localization of RAMP mRNAs was heterogeneous. RAMP1 mRNA was predominantly expressed in cortex, caudate putamen and olfactory tubercles; RAMP2 mRNA was most abundant in hypothalamus; and RAMP3 was restrictively expressed in thalamic nuclei. Interestingly, in specific brain areas only a single RAMP mRNA was often detected, suggesting mutual exclusivity in expression. These data allow predictions to be made of where each RAMP protein may heterodimerize with its partner G‐protein‐coupled receptor(s) at the cellular level and consequently advance current understanding of cellular sites of action of CGRP, ADM, amylin and CT. Furthermore, these localization data suggest that the RAMP family may associate and modify the behaviour of other, as yet unidentified neurotransmitter receptors.
Pattern and component motion selectivity in cortical area PMLS of the cat
Authors: Li Bing , Chen Yao , Li Bao‐Wang , Wang Lian‐Hong , Diao Yun‐Cheng 
Published: March 2003

AbstractVisual motion perception is one of the most prominent functions performed by the mammalian cerebral cortex. The moving images are commonly considered to be processed in two stages. The first‐stage neurons are sensitive to the motion of one‐dimensional orientated components, and their outputs are combined at the second stage to perceive the global motion of the whole pattern. Alternatively, the pattern motion may be signalled by monitoring a distinctive feature of the image, such as a line‐end or a corner. In the present study, a series of ‘random‐line’ patterns were used to measure the direction‐tuning responses of 138 neurons in the posteromedial lateral suprasylvian area of the cat. The novel stimuli comprised identical thin line segments, with a length : width ratio no less than 10 : 1, which were moved perpendicularly or obliquely to their common orientation during the recordings. When the component lines were much shorter than the size of receptive field, the majority of cells were selective to the direction of pattern motion while only a small subset was sensitive to the direction of component motion. However, the response profiles of most cells became more component‐motion selective with the increment of orientation element in stimulus by elongating the component lines in the patterns. These findings imply that the two‐stage theory might be incomplete for modelling the visual motion analysis. Even at relatively low levels of the visual system, some kind of nonorientation‐based processing may coexist with the orientation‐sensitive processing in a dynamic competition, where one rises as the other falls depending upon the strength of the orientation element in the stimulus, so that under some circumstances it becomes possible to signal the veridical direction of pattern motion.
Development of brain‐derived neurotrophic factor and neurotrophin‐3 immunoreactivity in the lower auditory brainstem of the postnatal gerbil
Authors: Tierney Travis S. , P. Doubell Timothy , Xia Gao , Moore David R. 
Published: March 2003

AbstractThe localization of brain‐derived neurotrophic factor (BDNF) and neurotrophin‐3 (NT‐3) in the gerbil auditory brainstem was studied during normal postnatal development. The principal objective of this paper was to compare the developmental distribution of BDNF and NT‐3 proteins to the known developmental distribution of their cognate, high‐affinity tyrosine kinase receptors. BDNF and NT‐3 proteins were localized using standard immunohistochemistry. No specific immunoreactivity for BDNF or NT‐3 was detected on the day of birth (P0) in any auditory structure, although fibers comprising the spinal tract of the Vth cranial nerve were well labelled with antibodies against BDNF. Diffuse immunoreactivity for both BDNF and NT‐3 was first detected at P3 in the cochlear nucleus and in several second order auditory nuclei in the superior olivary complex. This diffuse immunoreactivity became clustered and restricted to neuronal cell bodies by P10. Immunoreactivity for both BDNF and NT‐3 transiently disappeared in the lateral and medial superior olivary nuclei at P10. However, neurons in the medial nucleus of the trapezoid body remained immunopositive for both BDNF and NT‐3. Fibers in the trapezoid body were labelled with BDNF immunoreactivity by P12. Between P12 and P15, the distribution of BDNF and NT‐3 immunoreactivity in the cochlear nucleus and superior olivary complex became comparable to adult (P140) immunolabel. These results show that the normal developmental distribution of the neurotrophins BDNF and NT‐3 in the lower auditory brainstem occurs during the first two postnatal weeks in parallel with the developmental expression of their cognate receptors, trkB and trkC.