bluuebunny/crossref_metadata_2025_split huggingface dataset:
Perineuronal nets ensheath fast spiking, parvalbumin‐immunoreactive neurons in the medial septum/diagonal band complex
Authors: Morris Neil P. , Henderson Zaineb 
Published: March 2003

AbstractPerineuronal nets, composed of extracellular matrix material, have previously been associated with parvalbumin‐immunoreactive neurons in the medial septum/diagonal band (MS/DB) complex of the rat. The aim of this study was to correlate the presence of perineuronal nets with electrophysiological properties and parvalbumin immunoreactivity in MS/DB neurons. Intracellular recordings were made from cells in a brain slice preparation maintained in vitro, and neurons were characterized into four populations: (i) slow‐firing neurons, (ii) burst‐firing neurons, (iii) fast spiking neurons with narrow action potentials and a small degree of spike frequency adaptation, and (iv) regular spiking neurons with broader action potentials and a high degree of spike frequency adaptation. Following electrophysiological characterization, neurons were filled with biocytin, processed for parvalbumin immunoreactivity and stained for perineuronal nets using Wisteria floribunda lectin. The three substances were viewed with triple fluorescence. Fast spiking, nonadapting neurons, shown previously to contain parvalbumin immunoreactivity, were nearly all ensheathed by perineuronal nets. There was a population of small parvalbumin‐immunoreactive neurons which did not possess perineuronal nets, and which were not encountered with the intracellular electrodes. The other three neuron types in the MS/DB did not contain parvalbumin immunoreactivity or perineuronal nets. In keeping with this neurochemical profile for electrophysiologically identified neurons, burst‐firing neurons had action potential parameters more similar to those of regular spiking than of fast spiking neurons. We conclude that fast spiking neurons, presumed to be GABAergic septohippocampal projection neurons, are surrounded by supportive structures to enable the high level of neuronal discharge required for producing disinhibition of hippocampal pyramidal neurons.
Cannabinoid withdrawal is dependent upon PKA activation in the cerebellum
Authors: Tzavara Eleni TH. , Valjent Emmanuel , Firmo Cedric , Mas Magdalena , Beslot Françoise , Defer Nicole , Roques Bernard P. , Hanoune Jacques , Maldonado Rafael 
Published: March 2003

AbstractRegion‐specific up‐regulation of the cyclic AMP pathway is considered an important molecular mechanism in the origin of the somatic manifestations of the withdrawal syndrome to known drugs of abuse. Nevertheless, the existence of a withdrawal syndrome after prolonged cannabinoid administration has long been a controversial issue. Recent studies, in different species, have shown that withdrawal to prolonged cannabinoid exposure precipitated by the cannabinoid antagonist SR141716A is characterized by physical signs underlying impairment of motor coordination. Interestingly, cannabinoid withdrawal is accompanied by an increase of adenylyl cyclase activity in the cerebellum. Here, we investigate the functional role of the cyclic AMP pathway in the cerebellum in the establishment of cannabinoid withdrawal. We show that after SR141716A precipitation of cannabinoid withdrawal, basal and calcium‐calmodulin‐stimulated adenylyl cyclase activities as well as active PKA in the cerebellum increase in a transient manner with a temporal profile which matches that of the somatic expression of abstinence. Selectively blocking the up‐regulation of the cyclic AMP pathway in the cerebellum, by microinfusing the cyclic AMP blocker Rp‐8Br‐cAMPS in this region, markedly reduced both PKA activation and the somatic expression of cannabinoid withdrawal. Our results (i) directly link the behavioural manifestations of cannabinoid withdrawal with the up‐regulation of the cyclic AMP pathway in the cerebellum, pointing towards common molecular adaptive mechanisms for dependence and withdrawal to most drugs of abuse; (ii) suggest a particular role for the cerebellum as a major neurobiological substrate for cannabinoid withdrawal.
Physiological role of group III metabotropic glutamate receptors in visually responsive neurons of the rat superficial superior colliculus
Authors: Cirone J. , Salt T. E. 
Published: March 2003

AbstractThere is evidence from immunohistochemical and in situ hybridization studies for the presence of Group I, II and III metabotropic glutamate receptors (mGluRs) in the rat superficial superior colliculus (SSC). The purpose of this study was to investigate if manipulation of Group III mGluRs affects visual responses in the SSC. Drugs were applied by iontophoresis and single neuron activity was recorded extracellularly. L‐AP4 (Group III agonist) resulted in a reduction of visual responses in most neurons, but also a potentiation in others. The effect of L‐AP4 is drug‐ and stereospecific in that application of D‐AP4 did not significantly affect visual responses. L‐AP4 application also resulted in a potentiation of the response to iontophoretically applied NMDA. The effects of MPPG and CPPG (Group III antagonists) were compared with the effect of L‐AP4 in the same neuron and were found to produce the opposite effect to L‐AP4. Furthermore, the effect of L‐AP4 could be blocked by coapplication of MPPG or CPPG. Presynaptic depression of glutamate release is a possible mechanism by which L‐AP4 could reduce visual responses in the SSC whereas the potentiation of visual responses by L‐AP4 could be due to a reduction of GABAergic inhibition. The finding that MPPG and CPPG, as well as antagonizing the L‐AP4 effect, have a direct effect on visual responses suggests that Group III mGluRs are activated by endogenous transmitter released during visual stimulation.
Metabolic coupling between glia and neurons is necessary for maintaining respiratory activity in transverse medullary slices of neonatal mouse
Authors: Hülsmann Swen , Oku Yoshitaka , Zhang Weiqi , Richter Diethelm W. 
Published: March 2003

AbstractThe respiratory rhythm is generated and regulated by a neuronal network within the lower brainstem. While the neuronal mechanisms of rhythm generation have been extensively investigated, the contribution of glial cells remains to be determined. Here we report the effect of specific blockade of the glial Krebs cycle and glutamine synthetase on the neuronal activity of the respiratory network. Application of 5 mm fluoroacetate, which selectively blocks the glial Krebs cycle, suppressed rhythmic respiratory burst activity. Substitution of either the Krebs cycle substrate isocitrate (3 mm) or glutamine (3 mm) restored rhythmic network activity. Blockade of glutamine synthetase by methionine sulfoximine (0.5 mm) suppressed rhythmic burst activity as well. Resubstitution of glutamine (3 mm) was able to restore rhythmic activity in the presence of methionine sulfoximine. This data demonstrates that the glutamate–glutamine cycle in astrocytes and their supply of glutamine to neuronal glutamatergic terminals is essential for the rhythm generation in the respiratory centre.
Location of calcium transporters at presynaptic terminals
Authors: Juhaszova Magdalena , Church Paul , Blaustein Mordecai P. , Stanley Elis F. 
Published: March 2003

AbstractThe plasma membrane ATP‐driven Ca2+ pump (PMCA) and the Na+/Ca2+ exchanger (NCX) are the major means of Ca2+ extrusion at presynaptic nerve terminals, but little is know about the location of these transporters relative to the major sites of Ca2+ influx, the transmitter release sites. We used immunocytochemistry to identify these transport proteins in a calyx‐type presynaptic nerve terminal from the ciliary ganglion of the chick. The PMCA clusters were localized to the transmitter release sites, as identified by staining for the secretory vesicle‐specific protein synaptotagmin I. This colocalization was not due to the presence of the pump on the secretory vesicle itself because membrane fractionation of chick brain synaptosomes demonstrated comigration of the pump with surface membrane and not vesicle markers. In contrast, the NCX did not colocalize with synaptotagmin but tended to be located at nonsynaptic regions of the terminal. The PMCA location, near the transmitter release sites, suggests that it plays a role in priming the release site by maintaining a low free Ca2+ level, facilitating the dissociation of the ion from its binding sites. The PMCA may also replenish external Ca2+ in the synaptic cleft following periods of synaptic activity. In contrast, the NCX location suggests a role in the rapid emptying of cytoplasmic Ca2+ uptake organelles which serve as the main line of defence against high free Ca2+.
Differential effects of NT‐3 on reinnervation of the fast extensor digitorum longus (EDL) and the slow soleus muscle of rat
Authors: Simon M. , Terenghi G. , Green C. J. , Coulton G. R. 
Published: March 2003

AbstractPrevious studies of gastrocnemius muscle reinnervation showed specific normalization of the proportion and diameter of fast type 2b muscle fibres following NT‐3 delivery to the proximal stump of the cut sciatic nerve. Here, we investigate if normalization was related to greater improvement of muscle reinnervation of fast (extensor digitorum longus; EDL) than slow (soleus) motor units. NT‐3‐impregnated (NT‐3 group) or plain fibronectin (FN group) mats were inserted into a sciatic nerve gap. Neuromuscular junctions (NMJs) labelled with TRITC‐α‐bungarotoxin were colabelled with calcitonin gene‐related peptide (CGRP) or 4E2 antisera and imaged using confocal microscopy. CGRP and 4E2 were used as markers for newly reinnervated and structurally mature NMJs, respectively. At 40 days postsurgery, denervated NMJs in EDL and soleus muscles of both groups presented a 50% decrease of surface area due to decreased width. At day 80 in EDL, more NMJs were reinnervated by CGRP‐immunoreactive terminals in the NT‐3 (7.1%) than in the FN group (4.2%); there was no difference between groups for soleus. At 120 days, 4E2‐immunoreactive NMJs were more numerous in EDL of the NT‐3 (40.0%) than in the FN group (7.3%), unlike in soleus (NT‐3, 1.6%; FN, 1.8%), and presented a partial size recovery. These results indicate that NT‐3 preferentially improves reinnervation of fast muscles over slow muscle, although the mechanism of this improvement is still unclear.
Enlarged cholinergic forebrain neurons and improved spatial learning in p75 knockout mice
Authors: Greferath Ursula , Bennie Antoinette , Kourakis Angela , Bartlett Perry F. , Murphy Mark , Barrett Graham L. 
Published: March 2003

AbstractThe p75 low affinity neurotrophin receptor (p75) can induce apoptosis in various neuronal and glial cell types. Because p75 is expressed in the cholinergic neurons of the basal forebrain, p75 knockout mice may be expected to show an increased number of neurons in this region. Previous studies, however, have produced conflicting results, suggesting that genetic background and choice of control mice are critical. To try to clarify the conflicting results from previous reports, we undertook a further study of the basal forebrain in p75 knockout mice, paying particular attention to the use of genetically valid controls. The genetic backgrounds of p75 knockout and control mice used in this study were identical at 95% of loci. There was a small decrease in the number of cholinergic basal forebrain neurons in p75 knockout mice at four months of age compared with controls. This difference was no longer apparent at 15 months due to a reduction in numbers in control mice between the ages of 4 and 15 months. Cholinergic cell size in the basal forebrain was markedly increased in p75 knockout mice compared with controls. Spatial learning performance was consistently better in p75 knockout mice than in controls, and did not show any deterioration with age. The results indicate that p75 exerts a negative influence on the size of cholinergic forebrain neurons, but little effect on neuronal numbers. The markedly better spatial learning suggests that the function, as well as the size, of cholinergic neurons is negatively modulated by p75.
Formation of hippocampal synapses on patterned substrates of a laminin‐derived synthetic peptide
Authors: Matsuzawa Mieko , Tabata Toshihide , Knoll Wolfgang , Kano Masanobu 
Published: March 2003

AbstractWe created a new culture system which provides simple, stereotyped neuronal circuitries suitable for investigating synaptic events between mammalian central neurons. We used surface chemistry and laser‐lithography to produce geometrical patterns of neuron‐compatible substrate spaced by less neuron‐compatible surfaces. The patterned substrates were composed of a laminin‐derived synthetic peptide, PA22‐2, and the spacing surfaces of either decyldimethylsilane (DDMS) or trimethylsilane (TMS). Dissociated rat hippocampal neurons survived on the patterned substrates for several days without the aid of glia and extended their neurites along the substrates. The TMS spacing surfaces appeared more favourable for the excitability development and axonal differentiation of the hippocampal neurons, but less favourable for the development of the resting conductance than the DDMS spacing surfaces. Furthermore, neurons grown on the patterned substrates frequently made synaptophysin‐positive contacts with one another. Spontaneous post‐synaptic currents recorded from such neurons suggest that these contacts were indeed functional synapses. When hippocampal neurons were plated at a very low density, they often formed circuitries consisting of only two neurons on the patterned substrate. Such a simple circuitry allowed us to analyse synaptic transmission in a single neuronal pair without the influence of the third neurons. With the clarity of analysis and the readiness of manipulation, our culture system would offer a powerful tool for studying development and functions of mammalian central synapses.
Survival effects of BDNF and NT‐3 on axotomized rubrospinal neurons depend on the temporal pattern of neurotrophin administration
Authors: Novikova Liudmila N. , Novikov Lev N. , Kellerth Jan‐Olof 
Published: March 2003

AbstractThis study shows that both BDNF and NT‐3 can prevent cell death in axotomized adult rat rubrospinal neurons (RSNs), but that the efficacy of neuroprotection depends on the temporal pattern of treatment. At 8 weeks after cervical spinal cord injury, 51% of the RSNs had died. Subarachnoidal BDNF infusion into the cisterna magna for 4 weeks resulted in neuronal hypertrophy and 71% survival. Continuous infusion for 8 weeks into the lumbar subarachnoidal space with either BDNF or NT‐3 gave similar survival rates, while a combination of BDNF and NT‐3 resulted in 96% survival, although the cells were atrophic. When administration of either BDNF or NT‐3 was delayed and performed during postoperative weeks 5–8, the number of surviving neurons was increased compared to early treatment. Delayed treatment with a combination of BDNF and NT‐3 resulted in complete survival and a reduction in neuronal atrophy. A decreased expression of TrkB receptors and microtubule‐associated protein‐2 in the RSNs after axotomy was counteracted by BDNF and NT‐3. Microglial activity remained increased even when complete cell survival was achieved. Thus, the combination of neurotrophins as well as the temporal pattern of treatment need to be adequately defined to optimize survival of injured spinal tract neurons.
Cyclooxygenase‐1 is a marker for a subpopulation of putative nociceptive neurons in rat dorsal root ganglia
Authors: Chopra B. , Giblett S. , Little J. G. , Donaldson L. F. , Tate S. , Evans R. J. , Grubb B. D. 
Published: March 2003

AbstractImmunocytochemical and morphometric techniques were used to quantify the distribution of cyclooxygenase (cox)‐containing neurons in rat L5 dorsal root ganglia (DRG). Cox‐1 immunolabelling was almost exclusively restricted to small diameter DRG neurons (< 1000 μm2), and was extensively colocalized with calcitonin gene‐related peptide (CGRP) and isolectin B4 (IB4). Cox‐1 was present in 65% and 70% of CGRP‐ and IB4‐labelled neurons, respectively. Cox‐1 labelling was also found in neurons expressing the sensory neuron‐specific (SNS) Na+ channel. Cox‐2 labelling was absent in DRG from normal rats. In the Freund's adjuvant model of monoarthritis, the proportion of cox‐1‐positive DRG neurons was unchanged and no neurons were found to be labelled for cox‐2. In primary tissue culture, cox‐1 immunolabelling persisted in vitro for up to 9 days and was present in morphologically identical neurons. The selective expression of cox‐1 in peripheral ganglia was confirmed by the small number of nodose ganglion neurons and superior cervical ganglion (SCG) neurons labelled for cox‐1. These data suggest that cox‐1 is a marker for a subpopulation of putative nociceptive neurons in vitro and in vivo, and suggests that the prostaglandins synthesized by these neurons may be important for nociceptor function. These data may have important implications for the mode and mechanism of action of non‐steroidal anti‐inflammatory drugs (NSAIDs).
Developmental and adult expression of rat calcium‐sensing receptor transcripts in neurons and oligodendrocytes
Authors: Ferry Sandrine , Traiffort Elisabeth , Stinnakre Jacques , Ruat Martial 
Published: March 2003

AbstractThe calcium‐sensing receptor (CaSR) is a member of a growing family of heptahelical receptors with an unusually large extracellular domain. To further delineate its functions in neurons and glia, we have investigated the expression pattern of CaSR transcripts in the postnatal and adult rat brain, spinal cord and dorsal root ganglia by in situ hybridization. CaSR‐expressing cells were spatially and temporally regulated in myelinated structures with a caudo‐rostral pattern that paralleled that of myelin basic protein, a marker of myelination, with a downregulation observed in the adult. Double‐labelling studies demonstrated that CaSR mRNA colocalizes with myelin basic protein‐expressing cells within fibre tracts, suggesting that CaSR is expressed by mature oligodendrocytes. In cultured rat oligodendrocytes, Ca2+ induced stimulation of phosphatidylinositol hydrolysis with an EC50 of 1.4 mm and increased intracellular calcium. NPS R‐568 (1 μm), a calcimimetic, significantly stimulates the inositol phosphate response, whereas a less potent stereoisomer, NPS S‐568 (1 μm), was without effect. These data suggest that a functional CaSR is expressed in mature oligodendrocytes with a potential role in myelination. CaSR expression was also developmentally regulated in neurons of the orbital cortex and in the CA2 region of the hippocampus, and present in olfactory nuclei, hypothalamic areas and in the area postrema through postnatal days to adulthood. This expression is consistent with a role of CaSR in olfactory or gustatory signal integration, and with the regulation of fluid and mineral homeostasis. CaSR expression in a subpopulation of small cells in dorsal root ganglia suggests additional roles for extracellular Ca2+ in sensory nerves.
Acidic motif responsible for plasma membrane association of the voltage‐dependent calcium channel β1b subunit
Authors: Bogdanov Y. , Brice N. L. , Canti C. , Page K. M. , Li M. , Volsen S. G. , Dolphin A. C. 
Published: March 2003

AbstractVoltage‐dependent calcium channels consist of a pore‐forming transmembrane α1‐subunit, which is known to associate with a number of accessory subunits, including α2‐δ‐ and β‐subunits. The β‐subunits, of which four have been identified (β1–4), are intracellular proteins that have marked effects on calcium channel trafficking and function. In a previous study, we observed that the β1b‐subunit showed selective plasma membrane association when expressed alone in COS7 cells, whereas β3 and β4 did not. In this study, we have examined the basis for this, and have identified, by making chimeric β‐subunits, that the C‐terminal region, which shows most diversity between β‐subunits, of β1b is responsible for its plasma membrane association. Furthermore we have identified, by deletion mutations, an 11‐amino acid motif present in the C terminus of β1b but not in β3 (amino acids 547–556 of β1b, WEEEEDYEEE), which when deleted, reduces membrane association of β1b. Future research aims to identify what is binding to this sequence in β1b to promote membrane association of this calcium channel subunit. It is possible that such membrane association is important for the selective localization or clustering of particular calcium channels with which β1b is associated.
Mirtazapine enhances frontocortical dopaminergic and corticolimbic adrenergic, but not serotonergic, transmission by blockade of α2‐adrenergic and serotonin2C receptors: a comparison with citalopram
Authors: Millan M. J. , Gobert A. , Rivet J. ‐M. , Adhumeau‐Auclair A. , Cussac D. , Newman‐Tancredi A. , Dekeyne A. , Nicolas J. ‐P. , Lejeune F. 
Published: March 2003

AbstractMirtazapine displayed marked affinity for cloned, human α2A‐adrenergic (AR) receptors at which it blocked noradrenaline (NA)‐induced stimulation of guanosine‐5′‐O‐(3‐[35S]thio)‐triphosphate ([35S]‐GTPγS) binding. Similarly, mirtazapine showed high affinity for cloned, human serotonin (5‐HT)2C receptors at which it abolished 5‐HT‐induced phosphoinositide generation. Alpha2‐AR antagonist properties were revealed in vivo by blockade of UK‐14,304‐induced antinociception, while antagonist actions at 5‐HT2C receptors were demonstrated by blockade of Ro 60 0175‐induced penile erections and discriminative stimulus properties. Mirtazapine showed negligible affinity for 5‐HT reuptake sites, in contrast to the selective 5‐HT reuptake inhibitor, citalopram. In freely moving rats, in the dorsal hippocampus, frontal cortex (FCX), nucleus accumbens and striatum, citalopram increased dialysate levels of 5‐HT, but not dopamine (DA) and NA. On the contrary, mirtazapine markedly elevated dialysate levels of NA and, in FCX, DA, whereas 5‐HT was not affected. Citalopram inhibited the firing rate of serotonergic neurons in dorsal raphe nucleus, but not of dopaminergic neurons in the ventral tegmental area, nor adrenergic neurons in the locus coeruleus. Mirtazapine, in contrast, enhanced the firing rate of dopaminergic and adrenergic, but not serotonergic, neurons. Following 2 weeks administration, the facilitatory influence of mirtazapine upon dialysate levels of DA and NA versus 5‐HT in FCX was maintained, and the influence of citalopram upon FCX levels of 5‐HT versus DA and NA was also unchanged. Moreover, citalopram still inhibited, and mirtazapine still failed to influence, dorsal raphe serotonergic neurons. In conclusion, in contrast to citalopram, mirtazapine reinforces frontocortical dopaminergic and corticolimbic adrenergic, but not serotonergic, transmission. These actions reflect antagonist properties at α2A‐AR and 5‐HT2C receptors.