bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression and presence of septal neurokinin‐2 receptors controlling hippocampal acetylcholine release during sensory stimulation in rat
Authors: Steinberg R. , Marco N. , Voutsinos B. , Bensaid M. , Rodier D. , Souilhac J. , Alonso R. , Oury‐Donat F. , Fur G. Le , Soubrie P. 
Published: March 2003

AbstractWe examined the expression and presence of NK2 receptors in the septal area of rat brain, and investigated their functional role in the regulation of the septohippocampal cholinergic system. Using reverse transcription‐polymerase chain reaction (RT‐PCR) analysis, we showed the presence of NK2 receptor mRNA expression in the septal area, and detected septal NK2 binding sites by using a fluorescent‐tagged neurokinin A (NKA) derivative. In vivo microdialysis was employed to explore the functional role of NK2 receptors in the release of hippocampal acetylcholine evoked by tactile stimulation in freely moving rats. Two sessions of stroking of the neck and back of the rat for 30 min, at 90 min intervals, produced a marked and reproducible increase in hippocampal acetylcholine release. This effect was dose‐dependently prevented by intraperitoneal administration of the two selective non‐peptide tachykinin NK2 receptor antagonists SR144190 (0.03–0.3 mg/kg, i.p.) and SR48968 (0.3 and 1 mg/kg, i.p.), but not by the inactive enantiomer of SR48968 (SR48965, 1 mg/kg) nor by the two non‐peptide NK1 receptor antagonists SR140333 (3 mg/kg, i.p.) and GR205171 (1 mg/kg, i.p.). Furthermore, the intraseptal application of SR144190 (10–8m) reduced the sensory response. Finally, intraseptal perfusion of neurokinin A (0.01–10 μm) in anaesthetized rats produced a concentration‐dependent increase in hippocampal acetylcholine release. The response to neurokinin A (0.1 μm) was prevented by SR144190 (0.03–0.3 mg/kg, i.p.) and SR48968 (0.3–1 mg/kg, i.p.). In conclusion, this study provides direct evidence for the role of endogenous NKA/substance P, through the activation of NK2 receptors, in regulating the septohippocampal cholinergic function.
PET study of human voluntary saccadic eye movements in darkness: effect of task repetition on the activation pattern
Authors: Dejardin S. , Dubois S. , Bodart J. M. , Schiltz C. , Delinte A. , Michel C. , Roucoux A. , Crommelinck M. 
Published: March 2003

AbstractUsing H215O 3D Positron Emission Tomography (PET), regional cerebral blood flow (rCBF) was measured in six human subjects under two different conditions: at rest and while performing self‐paced horizontal saccadic eye movements in darkness. These two conditions were repeated four times each. First, the comparison between the four saccadic and four resting conditions was investigated in a group and a single subject analysis. Saccades elicited bilateral rCBF increases in the medial part of the superior frontal gyrus (supplementary eye field), precentral gyrus (frontal eye field), superior parietal lobule, anterior medial part of the occipital lobe involving striate and extrastriate cortex (lingual gyrus and cuneus), and in the right inferior parietal lobule. At the subcortical level, activations were found in the left putamen. These results mainly replicate previous PET findings on saccadic control. Second, the interaction between the experimental conditions and their repetition was examined. When activations throughout repetition of the same saccadic task are compared, the supplementary eye fields show a progressive increase of activation. On the contrary, the activation in the cerebellum, left superior parietal lobule and left occipital cortex progressively decreases during the scanning session. Given the existence of such an interaction, the pattern of activations must be interpreted as a function of task repetition. This may be a factor explaining some apparent mismatch between different studies.
A population of cholinergic neurons is present in the macaque monkey thalamus
Authors: Rico Beatriz , Cavada Carmen 
Published: March 2003

AbstractThree new cholinergic markers were employed to study the cholinergic innervation in the thalamus of adult macaque monkeys. They were: two antibodies against choline acetyltransferase (ChAT), one polyclonal and one monoclonal; and a polyclonal antibody against the vesicular transporter of acetylcholine (VAChT), a powerful new marker that colocalizes with ChAT. This approach led to an unexpected finding: the three antibodies positively immunostained a population of neurons in the paracentral nucleus. The immunostained cells are confined to the dorsal region of this nucleus along its rostrocaudal extent. Measurement of the somatic areas of the immunostained neurons indicated that they correspond to a population of large neurons thought to be projection neurons. Because dorsal paracentral neurons are known to project to the dorsal striatum and specific cortical areas involved in visual and visuomotor mechanisms, these structures might be modulated by cholinergic thalamic neurons.
Amelioration of spatial navigation and short‐term memory deficits by grafts of foetal basal forebrain tissue placed into the hippocampus and cortex of rats with selective cholinergic lesions
Authors: Leanza G. , Martìnez‐Serrano A. , Björklund A. 
Published: March 2003

AbstractImpairments in learning and memory, induced by surgical or excitotoxic lesions of the septo‐hippocampal or basalo‐cortical pathways, can be ameliorated by grafts of cholinergic‐rich foetal basal forebrain tissue into the hippocampus and/or neocortex. However, the effects of such grafts have been only partial, which may be due to the non‐specific nature of the lesioning procedures used in these studies, known to destroy both cholinergic and non‐cholinergic neuronal projections. In the present study, we have explored the effects of cholinergic‐rich grafts in rats subjected to selective cholinergic lesions, induced by intraventricular injections of the immunotoxin 192 IgG‐saporin. This lesion, which selectively destroyed 85–95% of the cholinergic neurons in both the septal‐diagonal band and nucleus basalis, produced a long‐lasting, substantial impairment in both the acquisition of spatial reference memory in the Morris water maze task and delay‐dependent short‐term memory performance, as seen in a delayed matching‐to‐position test. Foetal cholinergic grafts (but not control grafts of cerebellar tissue) implanted at multiple sites into both the hippocampus and fronto‐parietal neocortex, bilaterally, completely reversed the acquisition deficit in place navigation in the water maze, to an extent that greatly exceeded that previously seen in animals with non‐selective lesions. Most notably, however, the impairment in short‐term memory was only partially and inconsistently affected, and only at the longest delay times. The morphological analysis, performed at about 7 months after transplantation, showed that the grafts had re‐established a close to normal cholinergic innervation in the initially denervated cortical and hippocampal territories. It is proposed that the differential effects of cholinergic‐rich transplants on different aspects of cognitive performance may define intrinsic limitations to the functional capacity of the ectopically placed grafts, which may be due to incomplete integration of the grafted cholinergic neurons into functional regulatory circuitries normally available to the basal forebrain cholinergic system.
Serotonin inhibits synaptic glutamate currents in rat nucleus accumbens neurons via presynaptic 5‐HT1B receptors
Authors: Muramatsu Masatoshi , Lapiz Maria Danet S. , Tanaka Eiichiro , Grenhoff Johan 
Published: March 2003

AbstractNeurons in the nucleus accumbens septi in brain slices from adult male rats were studied with patch clamp recording in the whole‐cell conformation. Cells filled with Lucifer Yellow were identified as medium spiny neurons. Electrical stimulation close to the recorded cell evoked excitatory and inhibitory synaptic currents. In the presence of picrotoxin or bicuculline, stimulation at a holding potential of −90 mV evoked an inward excitatory current that was blocked by 6‐cyano‐7‐nitroquinoxaline‐2,3‐dione (CNQX, 10 μm), identifying it as an excitatory postsynaptic current (EPSC) mediated by glutamate acting at AMPA/kainate receptors. Serotonin (5‐hydroxytryptamine, 5‐HT; 3–100 μm in the bath) decreased the EPSC in about 90% of the cells. The action of 5‐HT was mimicked by N‐(3‐trifluoromethylphenyl)‐piperazine HCl (TFMPP), but not by (±)‐8‐hydroxy‐dipropylaminotetralin (8‐OH‐DPAT) or (±)‐2,5‐dimethoxy‐4‐iodoamphetamine HCl (DOI). The 5‐HT effect was antagonized by pindolol or cyanopindolol, but not by spiperone, ketanserin or tropisetron. Taken together, these results indicate that 5‐HT acts at 5‐HT1B receptors. The effect of 5‐HT was potentiated by cocaine (0.3–3 μm) or the selective serotonin reuptake inhibitor citalopram. Miniature synaptic currents recorded in the presence of tetrodotoxin were inhibited by CNQX, identifying them as spontaneous miniature EPSCs. 5‐HT reduced the frequency of these miniature EPSCs without affecting their amplitude, which indicates a presynaptic site of action. This presynaptic inhibition by 5‐HT might be involved in the behavioural effects of cocaine.
Increase of preprotachykinin mRNA and substance P immunoreactivity in spared dorsal root ganglion neurons following partial sciatic nerve injury
Authors: Ma Weiya , Bisby Mark A. 
Published: March 2003

AbstractComplete sciatic nerve injury reduces substance P (SP) expression in primary sensory neurons of the L4 and L5 dorsal root ganglia (DRG), due to loss of target‐derived nerve growth factor (NGF). Partial nerve injury spares a proportion of DRG neurons, whose axons lie in the partially degenerating nerve, and are exposed to elevated NGF levels from Schwann and other endoneurial cells involved in Wallerian degeneration. To test the hypothesis that SP is elevated in spared DRG neurons following partial nerve injury, we compared the effects of complete sciatic nerve transection (CSNT) with those of two types of partial injury, partial sciatic nerve transection (PSNT) and chronic constriction injury (CCI). As expected, a CSNT profoundly decreased SP expression at 4 and 14 days postinjury, but after PSNT and CCI the levels of preprotachykinin (PPT) mRNA, assessed by in situ hybridization, and the SP immunoreactivity (SP‐IR) of the L4 and L5 DRGs did not decrease, nor did dorsal horn SP‐IR decrease. Using retrograde labelling with fluorogold to identify spared DRG neurons, we found that the proportion of these neurons expressing SP‐IR 14 days after injury was much higher than in neurons of normal DRGs. Further, the highest levels of SP‐IR in individual neurons were detected in ipsilateral L4 and L5 DRG neurons after PSNT and CCI. We conclude that partial sciatic nerve injury elevates SP levels in spared DRG neurons. This phenomenon might be involved in the development of neuropathic pain, which commonly follows partial nerve injury.
Action sequencing is impaired in D1A‐deficient mutant mice
Authors: Cromwell Howard C. , Berridge Kent C. , Drago John , Levine Michael S. 
Published: March 2003

AbstractThe role of dopamine in the production of behaviour is multifarious in that it can influence different aspects of movement (e.g. movement initiation, sensorimotor integration, and movement sequencing). A characteristic of the dopamine system which seems to be critical for the expression of this diverse influence is its varied receptor population. Previous studies have shown that specific receptor subtype activation leads to specific behavioural responses or alterations of selective aspects of movement. It is known that one of the important influences of dopamine includes sequential co‐ordination of ‘syntactic’ patterns of grooming movements because moderate loss of the dopaminergic nigrostriatal projections specifically disrupts these patterns without affecting grooming actions in a general fashion (Berridge, K.C. Psychobiology, 15, 336 1989). The specific receptors of the dopamine family which play a key part in this co‐ordination of movement sequences is not known. In the present study, we examined the serial order of particular syntactic sequences or chains of grooming actions in mice lacking D1A receptors to explore the relationship between this receptor subtype and movement sequencing. Mutant mice had shorter grooming bouts and a disruption of the organization of sequential patterns compared with wild‐type littermate controls. Sequential disruption was reflected in the failure of D1A mutants to follow the syntactic pattern of grooming to completion. This sequential disruption deficit appeared to be specific, as mutant mice initiated more syntactic chains than wild‐type controls even though they were less likely to complete them. These results support the hypothesis that D1A receptor activation plays a part in the sequencing of natural action. This conclusion has important implications for the understanding of the functional heterogeneity of dopamine receptor subtypes and of the aetiology of symptoms observed in patients with basal ganglia disease.
Cytokine‐induced changes in the ability of astrocytes to support migration of oligodendrocyte precursors and axon growth
Authors: Fok‐Seang Juin , DiProspero Nicholas A. , Meiners Sally , Muir Elizabeth , Fawcett James W. 
Published: March 2003

AbstractRepair of demyelination in the CNS requires that oligodendrocyte precursors (OPs) migrate, divide and then myelinate. Repair of axon damage requires axonal regeneration. Limited remyelination and axon regeneration occurs soon after injury, but usually ceases in a few days. In vivo and in vitro experiments have shown that astrocytic environments are not very permissive for migration of OPs or for axonal re‐growth. Yet remyelination and axon sprouting early after injury occurs in association with astrocytes, while later astrocytes can exclude remyelination and prevent axon regeneration. A large and changing cast of cytokines are released following CNS injury, so we investigated whether some of these alone or in combination can affect the ability of astrocytes to support migration of OPs and neuritic outgrowth. Interleukin (IL) 1α, tumour necrosis factor α, transforming growth factor (TGF) β, basic fibroblast growth factor (bFGF), platelet‐derived growth factor and epidermal growth factor alone exerted little or no effect on migration of OPs on astrocytes, whereas interferon (IFN) γ was inhibitory. The combination of IL‐1α + bFGF was found to be pro‐migratory, and this effect could be neutralized by TGFβ. We also examined neuritic outgrowth from dorsal root ganglion explants in three‐dimensional astrocyte cultures treated with cytokines and found that IL‐1α + bFGF greatly increased axon outgrowth and that this effect could be blocked by TGFβ and IFNγ. All these effects were absent or much smaller when OP migration or axon growth was tested on laminin, so the main effect of the cytokines was via astrocytes. The cytokine effects did not correlate with expression on astrocytes of laminin, fibronectin, tenascin, chondroitin sulphate proteoglycan, N‐cadherin, polysialyated NCAM (PSA‐NCAM), tissue plasminogen activator (tPA) or urokinase (uPA).
Mechanisms of spontaneous cytosolic Ca2+ transients in differentiated human neuronal cells
Authors: Gao Zhi‐yong , Chen Meng , Collins Heather W. , Matschinsky Franz M. , Lee Virginia M. ‐Y. , Wolf Bryan A. 
Published: March 2003

AbstractWe have studied Ca2+ homeostasis in a unique model of human neurons, the NT2N cell, which differentiates from a human teratocarcinoma cell line, NTera2/C1.D1 by retinoic acid treatment. When perifused with Krebs–HEPES buffer containing 2.5 mm CaCl2, fura‐2 loaded NT2N cells produced spontaneous cytosolic Ca2+ oscillations, or Ca2+ transients. These cytosolic Ca2+ transients were not blocked by antagonists of glutamate (6‐cyano‐7‐nitroquinoxaline‐2,3‐dione and d(–)‐2‐amino‐5‐phosphonopentanoic acid) or muscarinic (atropine) receptors. Omission of extracellular Ca2+ completely abolished Ca2+ oscillations and decreased the average Ca2+ level from 106 ± 14 nm to 59 ± 8 nm. Addition of the L‐type Ca2+ channel blocker nifedipine (1 or 10 μm) or of the N‐type inhibitor ω‐conotoxin GVIA (5 μm) significantly, although incompletely, suppressed Ca2+ oscillations, while ω‐conotoxin MVIIC (5 μm), a selective antagonist of P‐ and Q‐channels, had no effect. Ni2+, at 100 μm, a concentration selective for T‐type channels, did not inhibit Ca2+ transients. Non‐specific blockage of Ca2+ channels by higher concentrations of Ni2+ (2–5 mm) or Co2+ (1 mm) abolished Ca2+ oscillations completely. The endoplasmic reticulum Ca2+‐ATPase inhibitor, thapsigargin (1 μm), slightly decreased Ca2+ oscillation frequency, and induced a small transitory increase in the average cytosolic Ca2+ concentration. The mRNAs of L‐ (α1D subunit) and N‐type (α1B subunit) Ca2+ channel were present in NT2N cells, while that of a T‐type Ca2+ channel (α1‐subunit) was not present in the NT2N cells as shown by reverse transcription–polymerase chain reaction. In conclusion, NT2N neuronal cells generate cytosolic Ca2+ oscillations mainly by influx of extracellular Ca2+ through multiple channels, which include L‐ and N‐type channels, and do not require activation of glutamate or muscarinic receptors.
Immunorecognition, ultrastructure and phosphorylation status of astrocytic gap junctions and connexin43 in rat brain after cerebral focal ischaemia
Authors: Li W. E. I. , Ochalski P. A. Y. , Hertzberg E. L. , Nagy J. I. 
Published: March 2003

AbstractGap junctions between astrocytes support a functional syncytium that is thought to play an important role in neural homeostasis. In order to investigate regulation of this syncytium and of connexin43 (Cx43), a principal astrocytic gap junction protein, we determined the sequelae of gap junction and Cx43 disposition in a rat cerebral focal ischaemia model with various ischaemia/reperfusion times using sequence‐specific anti‐Cx43 antibodies (designated 13‐8300, 18A, 16A and 71‐0700) that exhibit differential recognition of Cx43, perhaps reflecting functional aspects of gap junctions. Antibody 13‐8300 specifically detects only an unphosphorylated form of Cx43 in both Western blots and tissue sections. In hypothalamus after brief (15 min) ischaemic injury, Cx43 at intact gap junctions undergoes dephosphorylation, accompanied by reduced epitope recognition by antibodies 16A and 71‐0700. Tissue examined 24 h after reperfusion showed that these effects were reversible. Astrocytic gap junction internalization occurring 1 h after ischaemia was accompanied by decreased immunodetection with 13‐8300. At this time, gap junctions were absent in the ischaemic core, coinciding with a loss of Cx43 recognition with 18A and 13‐8300, but elevated labelling of internalized Cx43 with 16A and 71‐0700. Unphosphorylated Cx43 persisted at intact gap junctions confined to a thin corridor at the ischaemic penumbra which contained presumptive apoptotic cell profiles. Similar results were obtained in ischaemic striatum and cerebral cortex, though with a delayed time course that depended on the severity of the ischaemic insult. These results demonstrate that astrocytic Cx43 epitope masking, dephosphorylation and cellular redistribution occur after ischaemic brain injury, proceed as a temporally and spatially ordered sequence of events and culminate in differential patterns of Cx43 modification and sequestration at the lesion centre and periphery. These observations suggest an attempt by astrocytes in the vicinity of injury to remodel the junctional syncytium according to altered tissue homeostatic requirements.
Learning‐specific, time‐dependent increases in hippocampal Ca2+/calmodulin‐dependent protein kinase II activity and AMPA GluR1 subunit immunoreactivity
Authors: Cammarota Martín , Bernabeu Ramón , Levi de Stein Miguelina , Izquierdo Iván , Medina Jorge H. 
Published: March 2003

AbstractCa2+/calmodulin‐dependent protein kinase II (CAMK II) and one of its target, α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionic acid (AMPA), glutamate receptors have been shown to participate in both long‐term potentiation (LTP) in the hippocampus, and in spatial, as well as in a variety, of learning paradigms. Recently, we were able to demonstrate that the intrahippocampal infusion of a specific inhibitor of CAMK II (KN62) provoked full retrograde amnesia of an inhibitory avoidance learning in rats when given immediately, but not 120 or 240 min, after training. Furthermore, this task is accompanied by a rapid, selective and reversible increase in hippocampal [3H] AMPA receptor binding. Here we report the effect of this aversively motivated learning task on CAMK II activity, and AMPA GluR1 subunit phosphorylation and immunoreactivity in the hippocampus. One trial inhibitory avoidance training is associated with a learning‐specific, time‐dependent increase (25–78%) in both total and Ca2+‐independent activities of CAMK II in the hippocampus of rats killed immediately (0 min), but not 120 min, after training. In addition, immunoblotting experiments showed an increment in the amount of the α‐subunit of CAMK II at 0, 30 and 120 min after training. An increase in the in vitro phosphorylation of α‐ and β‐subunits of CAMK II was also observed in hippocampal synaptosomal membranes (SPM) of trained rats killed immediately and 30 min post‐training. In addition, inhibitory avoidance is accompanied by a 20% increase in GluR1 phosphorylation and a 33% increase in GluR1 immunoreactivity 120 min after training. No significant changes were observed in shocked animals. Phosphorylation of hippocampal SPM from naive control animals in conditions suitable for CAMK II activation resulted in a large increase in the density of [3H] AMPA binding (+ 100%). Taken together, these findings confirm and extend previous data suggesting that CAMK II and AMPA glutamate receptors in the hippocampus participate in the early phase of memory formation of an inhibitory avoidance learning.
Action potential broadening induced by lithium may cause a presynaptic enhancement of excitatory synaptic transmission in neonatal rat hippocampus
Authors: Colino Asunción , García‐Seoane Jorge J. , Valentín Antonio 
Published: March 2003

AbstractLithium enhances excitatory synaptic transmission in CA1 pyramidal cells, but the mechanisms remain unclear. The present study demonstrates that lithium enhances the N‐methyl‐d‐aspartate (NMDA) and α‐amino‐3‐hydroxy‐5‐methyl‐isoxazole propionic acid (AMPA) receptor‐mediated components of the excitatory postsynaptic current (EPSC). Lithium decreased the magnitude of paired‐pulse facilitation and presented an inverse correlation between the lithium‐induced enhancement of synaptic transmission and initial paired‐pulse facilitation, which is consistent with a presynaptic mode of action. The enhancement of synaptic strength is likely to act, at least in part, by increasing the amplitude of the presynaptic Ca2+ transient. One mechanism which could account for this change of the presynaptic Ca2+ transient is an increase in the duration of the action potential. We investigated action potential in hippocampal pyramidal neurons and found that lithium (0.5–6 mm) increased the half‐amplitude duration and reduced the rate of repolarization, whereas the rate of depolarization remained similar. To find out whether the lithium synaptic effects might be explained by spike broadening, we investigated the field recording of the excitatory postsynaptic potential (EPSP) in hippocampal slices and found three lines of evidence. First, the prolongation of the presynaptic action potential with 4‐aminopyridine and tetraethylammonium blocked or reduced the synaptic effects of lithium. Second, the lithium‐induced synaptic enhancement was modulated when presynaptic Ca2+ influx was varied by changing the external Ca2+ concentration. Finally, both effects, the synaptic transmission increment and the action potential broadening, were independent of inositol depletion. These results suggest that lithium enhances synaptic transmission in the hippocampus via a presynaptic site of action: the mechanism underlying the potentiating effect may be attributable to an increased Ca2+ influx consequent to the broadening effect of lithium on the action potential.