bluuebunny/crossref_metadata_2025_split huggingface dataset:
The small conductance Ca2+‐activated K+ channel SK3 is localized in nerve terminals of excitatory synapses of cultured mouse hippocampal neurons
Authors: Obermair Gerald J. , Kaufmann Walter A. , Knaus Hans‐Günther , Flucher Bernhard E. 
Published: March 2003

AbstractIn the central nervous system small conductance Ca2+‐activated K+ (SK) channels are important for generating the medium/slow afterhyperpolarization seen after single or trains of action potentials. Three SK channel isoforms (SK1,‐2,‐3) are differentially distributed throughout the brain, but little is known about their specific expression in particular neuronal compartments. In the hippocampus SK3 was found in the neuropil, predominantly in the terminal field of the mossy fibres and in fine varicose fibres, but excluded from the pyramidal and granule cell layers. Because this expression pattern suggested a presynaptic localization, we examined the subcellular distribution of SK3 in cultured hippocampal neurons using high‐resolution immunofluorescence analysis. SK3 was localized in a punctate, synaptic pattern. The SK3 clusters were precisely colocalized with the presynaptic marker synapsin and at close range (0.4–0.5 µm) from NMDA‐receptors and PSD‐95. This arrangement is consistent with a localization of SK3 in the presynaptic nerve terminal, but not restricted to the synaptic membrane proper. In agreement with the increasing expression of SK3 during early postnatal development in vivo, the fraction of synapses containing SK3 increased from 14% to 57% over a six‐week culture period. SK3‐containing synapses were equally observed on spiny, glutamatergic and smooth GABAergic neurons. In contrast to its close association with NMDA‐receptors and PSD‐95, SK3 was rarely associated with GABAA‐receptor clusters. Thus, SK3 is a presynaptic channel in excitatory hippocampal synapses, with no preference for glutamatergic or GABAergic postsynaptic neurons, and is probably involved in regulating neurotransmitter release.
Saccadic eye movements evoked by microstimulation of striate cortex
Authors: Tehovnik Edward J. , Slocum Warren M. , Schiller Peter H. 
Published: March 2003

AbstractExperiments were performed to assess the excitability of neural elements activated while inducing saccadic eye movements electrically from different cortical layers of striate cortex (area V1) in rhesus monkeys. Excitability was assessed by measuring current thresholds, saccadic latencies, chronaxies, and the effectiveness of anode‐first vs. cathode‐first pulses. Minimum current thresholds for the evocation of saccades (i.e. less than 5 µA) were observed when the deepest layers of V1 were stimulated. The shortest saccadic latencies were also observed at these depths. The shortest latency at 10 times the threshold current was 49 ms on average. The chronaxies of the elements mediating saccades were less in deep V1 (i.e. 0.17 ms) than in superficial V1 (i.e. 0.23 ms). Anode‐first pulses were more effective at evoking saccades from superficial V1, whereas cathode‐first pulses were more effective at evoking saccades from deep V1. These results indicate that the excitability properties of superficial and deep V1 are distinct for the generation of saccades. Moreover, the excitability of elements mediating saccades in V1 of monkeys is comparable to that of elements mediating phosphenes in human V1.
Presynaptic inhibition of Schaffer collateral synapses by stimulation of hippocampal cholinergic afferent fibres
Authors: Fernández de Sevilla David , Buño Washington 
Published: March 2003

AbstractIt has been known for decades that muscarinic agonists presynaptically inhibit Schaffer collateral synapses contacting hippocampal CA1 pyramidal neurons. However, a demonstration of the inhibition of Schaffer collateral synapses induced by acetylcholine released by cholinergic hippocampal afferents is lacking. We present original results showing that electrical stimulation at the stratum oriens/alveus with brief stimulus trains inhibited excitatory postsynaptic currents evoked by stimulation of Schaffer collaterals in CA1 pyramidal neurons of rat hippocampal slices. The increased paired‐pulse facilitation and the changes in the variance of excitatory postsynaptic current amplitude that paralleled the inhibition suggest that it was mediated presynaptically. The effects of oriens/alveus stimulation were inhibited by atropine, and blocking nicotinic receptors with methyllycaconitine was ineffective, suggesting that the inhibition was mediated via the activation of presynaptic muscarinic receptors. The results provide a novel demonstration of the presynaptic inhibition of glutamatergic neurotransmission by cholinergic fibres in the hippocampus, implying that afferent cholinergic fibres regulate the strength of excitatory synaptic transmission.
Behavioural sensitization and enhanced dopamine response in the nucleus accumbens after intravenous cocaine self‐administration in mice
Authors: Zapata Agustin , Chefer Vladimir I. , Ator Robert , Shippenberg Toni S. , Rocha Beatriz A. 
Published: March 2003

AbstractThe behavioural effects of cocaine are enhanced in animals with a prior history of repeated cocaine administration. This phenomenon, referred to as sensitization, is also associated with an increase in cocaine‐evoked extracellular dopamine levels in the nucleus accumbens. Behavioural and neurochemical sensitization has been demonstrated in rats with a prior history of cocaine self‐administration and in those that had received experimenter‐administered cocaine. Although it is clear that the repeated non‐contingent administration also results in behavioural sensitization in the mouse, the issue of whether behavioural and neurochemical sensitization also occur in this species following intravenous cocaine self‐administration has not been assessed. The present study used the technique of in vivo microdialysis in conjunction with operant self‐administration to characterize cocaine‐evoked locomotor activity and dopamine levels in the nucleus accumbens in mice with a prior history of intravenous cocaine self‐administration or those that had received yoked infusions of cocaine. Mice that had received contingent or non‐contingent infusions of cocaine exhibited an enhanced behavioural response to cocaine and increased cocaine‐evoked dopamine levels in the nucleus accumbens. There was no difference between groups in the magnitude of this effect. Prior exposure to cocaine did not modify baseline dopamine levels in the nucleus accumbens. These data demonstrate that mice with previous cocaine self‐administration experience show an enhanced behavioural and dopamine response to cocaine in the nucleus accumbens. Furthermore, control over cocaine infusion does not significantly alter the magnitude of the sensitized behavioural and presynaptic dopamine responses observed in response to a challenge dose of cocaine.
Modulatory action of acetylcholine on striatal neurons: microiontophoretic study in awake, unrestrained rats
Authors: Windels François , Kiyatkin Eugene A. 
Published: March 2003

AbstractCholinergic interneurons innervate virtually all medium spiny striatal cells, but the relevance of this input in regulating the activity and afferent responsiveness of these cells remains unclear. Studies in anaesthetized animals and slice preparations have shown that iontophoretic acetylcholine (ACh) either weakly excites or inhibits striatal neurons. These differential responses may reflect cholinergic receptor heterogeneity but may be also related to the different activity states of recorded units and different afferent inputs specific in each preparation. Single‐unit recording was combined with iontophoresis in awake, unrestrained rats to examine the effects of ACh and selective muscarinic (oxotremorine M or Oxo‐M) and nicotinic agonists (nicotine or NIC) on dorsal and ventral striatal neurons. These effects were tested on naturally silent, spontaneously active and glutamate‐stimulated units. We found that iontophoretic ACh primarily inhibited spontaneously active and glutamate‐stimulated units; the direction of the ACh response, however, was dependent on the firing rate. The effects of ACh were generally mimicked by Oxo‐M and, surprisingly, by NIC, which is known to excite units in most central structures, including striatal neurons in anaesthetized preparation. Given that NIC receptors are absent on striatal cells but located primarily on dopamine terminals, we assessed the effects of NIC after complete blockade of dopamine receptors induced by systemic administration of a mixture of D1 and D2 antagonists. During dopamine receptor blockade the number of NIC‐induced inhibitions dramatically decreased and NIC had mainly excitatory effects on striatal neurons. Thus, our data suggest that under physiologically relevant conditions ACh acts as a state‐dependent neuromodulator, and its action involves not only postsynaptic but also presynaptic cholinoreceptors located on dopamine‐ and glutamate‐containing terminals.
Repeated, non‐habituating stress suppresses inflammatory plasma extravasation by a novel, sympathoadrenal dependent mechanism
Authors: Strausbaugh Holly J. , Green Paul G. , Dallman Mary F. , Levine Jon D. 
Published: March 2003

AbstractThe mechanism by which chronic stress affects the course of inflammatory diseases is still not well understood. We have evaluated the effect of two types of nonhabituating stress on a major component of the inflammatory response, synovial plasma extravasation, induced by perfusion of the potent inflammatory mediator, bradykinin and evaluated the underlying neuroendocrine mechanism in the rat. Chronic intermittent noise or ether stress induced profound inhibition of bradykinin‐induced plasma extravasation, which is associated with increased adjuvant‐arthritis severity. This inhibition, however, took 24 h to fully develop after the last exposure to stress and persisted for at least 48 h. The inhibition could be reversed by an additional exposure to the stressor, just prior to measuring the inflammatory response, suggesting that the delay is due to stress‐induced release of a factor that acutely masks the inhibition of the inflammatory response. This novel, unexpected feature of the effect of nonhabituating stress on inflammation may help explain variability in effects of stress in patients with inflammatory disease. The effect of nonhabituating stress on inflammation was dependent on the sympathoadrenal axis with no detectable contribution by the hypothalamic–pituitary–adrenal axis.
Synaptic localization of the glutamate receptor subunit GluR2 in the rat nucleus tractus solitarii
Authors: Lachamp Philippe , Balland Bénédicte , Tell Fabien , Crest Marcel , Kessler Jean‐Pierre 
Published: March 2003

AbstractThe GluR2 subunit controls several key features of the alpha amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionate (AMPA)‐type glutamate receptor including calcium permeability, rectification and gating. In the present study, electrophysiological recordings and immunocytochemistry were used to document the synaptic localization of GluR2 in the rat nucleus tractus solitarii (NTS). Synaptic responses recorded in NTS neurons exhibited linear current–voltage relationships suggestive of GluR2‐containing AMPA receptor responses. Furthermore, after antigen retrieval GluR2 immunolabelling in the NTS mainly consisted of small puncta. Double‐labelling experiments showed that these GluR2 puncta were apposed to glutamatergic synaptic terminals identified by type II vesicular glutamate transporter immunoreactivity. These results indicate that NTS glutamatergic synapses are endowed with AMPA receptors which contain the GluR2 subunit and are therefore likely to be both calcium‐impermeable and slowly desensitizing.
Group I metabotropic glutamate receptor‐mediated calcium signalling and immediate early gene expression in cultured rat striatal neurons
Authors: Mao Limin , Wang John Q. 
Published: March 2003

AbstractGroup I metabotropic glutamate receptors (mGluRs) are positively coupled to phospholipase C (PLC) via Gαq‐proteins and are expressed in the medium‐sized projection neurons of striatum. To characterize the group I mGluR/PLC‐sensitive modulation of intracellular Ca2+ ([Ca2+]i) signalling, primary neuronal cultures were prepared from the striatum of E19 rat embryos or neonatal day‐1 rat pups. Cytoplasmic Ca2+ signals were examined with fura‐2/AM at a signal cell level. After 17–18 days in culture, a profound Ca2+ response consisting of two phases was induced in cultured striatal neurons following bath application of the selective group I agonist, 3,5‐dihydroxyphenylglycine (DHPG). The [Ca2+]i elevation was concentration‐ and time‐dependent, and was blocked by coexposure to the group I antagonist, N‐phenyl‐7‐(hydroxyimino)cyclopropa[b]chromen‐1a‐carboxamide (PHCCC), or the PLC inhibitor, U‐73122, but not to the group II/III antagonist (RS)‐α‐methylserine‐O‐phosphate monophenyl ester (MSOPPE). A series of further pharmacological studies demonstrated that the initial spike‐like transient was dependent on intracellular Ca2+ mobilization through 1,4,5‐triphosphate‐sensitive stores, and the second long‐lasting rise was dependent on extracellular Ca2+ influx through N‐methyl‐d‐aspartate (NMDA) receptors and especially L‐type voltage‐operated Ca2+ channels. Lastly, using an immediate early gene c‐fos as a report of inducible gene expression, the resultant [Ca2+]i elevation contributes to DHPG‐stimulated c‐fos mRNA and Fos protein expression in striatal neurons as revealed by quantitative in situ hybridization and immunocytochemistry, respectively. These results demonstrate that group I mGluRs are able to affect Ca2+ homeostasis at multiple levels and trigger Ca2+‐sensitive gene transcription in striatal neurons.
Attenuation of sucrose reinforcement in dopamine D1 receptor deficient mice
Authors: El‐Ghundi Mufida , O'Dowd Brian F. , Erclik Mary , George Susan R. 
Published: March 2003

AbstractDopaminergic systems are thought to mediate the rewarding and reinforcing effects of palatable food. However, the relative contribution of different dopamine receptor subtypes is not clear. We used dopamine D1 receptor deficient mice (D^{\,‐/‐}_{1}) and their wild‐type and heterozygous littermates to study the role of the D1 receptor in palatable food reinforced behaviour using operant responding and free access paradigms. Non‐deprived mice were trained to press a lever for sucrose pellets under three schedules of reinforcement including fixed ratios (FR‐1 and FR‐4) and a progressive ratio (PR). Responding on one lever was reinforced by the delivery of a sucrose pellet or solution while responding on a second lever had no programmed consequences. Initially, D1 mutant mice took longer to learn to discriminate between the two levers and had significantly lower operant responding for sucrose pellets and solution than wild‐type and heterozygous mice under all schedules of reinforcement. Food deprivation enhanced responding on the active lever in all mice although it remained significantly lower in D^{\,‐/‐}_{1} mice than in control mice. Following extinction of sucrose reinforcement and reversal of the levers, D^{\,‐/‐}_{1} mice showed deficits in extinguishing and reversing previously learned responses. Home cage intake and preference of sucrose pellets and solutions when given under free‐choice access paradigms were similar among the groups.These results suggest that the dopamine D1 receptor plays a role in the motivation to work for reward (palatable food) but not in reward perception and is critical in learning new but relevant information and discontinuing previously learned responses.
Connecting the dots: trafficking of neurotrophins, lectins and diverse pathogens by binding to the neurotrophin receptor p75NTR
Authors: Butowt Rafal , Von Bartheld Christopher S. 
Published: March 2003

AbstractThe common receptor for neurotrophins, p75, has important roles in internalization and trafficking of neurotrophins along axons. Recent studies show that an astonishing array of proteins, including lectins, pathogens and neurotoxins, bind the p75 receptor, suggesting that they can hijack and utilize this receptor for trafficking between neuronal populations within the nervous system. Such pathogens include the neurologically important rabies viruses, prion proteins, β‐amyloid and possibly tetanus toxin. These proteins may hijack existing transport machineries designed to traffick neurotrophins, thus allowing the infiltration and distribution of pathogens and toxins among vulnerable neuronal populations with devastating effects, as seen in rabies, prion encephalopathies, Alzheimer's disease and tetanic muscle spasm. The discovery of an entry and transport machinery that is potentially shared between pathogens and neurotrophins sheds light ono trafficking systems in the nervous system and may assist the design of novel therapeutic avenues that prevent or slow the progression of diverse chronic and acute neurological disorders.
Functional NMDA receptor channels generated by NMDAR2B gene transfer in rat cerebellar Purkinje cells
Authors: Kakegawa Wataru , Tsuzuki Keisuke , Iino Masae , Ozawa Seiji 
Published: March 2003

AbstractThe adult cerebellar Purkinje cell is an exceptional neuron in the central nervous system in that it expresses high levels of NMDAR1 (NR1) mRNA without expressing any NMDAR2 (NR2) mRNAs. It has no functional NMDA receptor (NMDAR) channels, although it receives enormous numbers of excitatory inputs. Despite the high level of NR1 mRNA expression, the presence and localization of NR1 protein in mature Purkinje cells are controversial. To examine the presence of NR1 protein and its ability to form functional NMDARs, we expressed the NR2B subunit in rat mature Purkinje neurons by Sindbis viral‐mediated gene transfer. The recombinant virus encoding both the NR2B and enhanced green fluorescent protein (GFP) genes (designated as SIN–EG–NR2B) infected Purkinje cells without infecting glial cells. GFP fluorescence was detected in the soma and throughout dendrites of Purkinje cells 18–24 h postinfection. In most of GFP‐positive cells, the expression of NR2B protein was detected by immunostaining with NR2B‐specific antibodies. In Purkinje cells infected with SIN–EG–NR2B, the iontophoretic application of NMDA induced prominent NMDAR‐mediated current responses, indicating that the exogenous NR2B was assembled with endogenous NR1 to form functional NMDARs. Furthermore, NMDAR‐mediated synaptic currents were detected at both the climbing fibre and parallel fibre synapses in infected Purkinje cells. Thus, the mature Purkinje cell produces NR1 protein that is ready to combine with NR2 to form functional NMDARs in excitatory synapses.
Protective effect of HSV‐mediated gene transfer of nerve growth factor in pyridoxine neuropathy demonstrates functional activity of trkA receptors in large sensory neurons of adult animals
Authors: Chattopadhyay Munmun , Goss James , Lacomis David , Goins William C. , Glorioso Joseph C. , Mata Marina , Fink David J. 
Published: March 2003

AbstractThe distinct distribution of trkA receptors on small neurons and trkC receptors on large neurons in the dorsal root ganglion correlates with the dependence of these two classes of neurons on nerve growth factor and neurotrophin‐3, respectively, for survival during development. In adult animals, the distribution of high affinity neurotrophin (trk) is complex and overlapping; neurotrophins are not required for cell survival, but may influence cell phenotype and the response to injury. In order to test the functional activity of trkA receptors in the sensory ganglia of adult animals in vivo, we examined the ability of a nerve growth factor‐expressing recombinant replication‐defective herpes simplex virus‐based vector to prevent the selective degeneration of large sensory fibres caused by intoxication with pyridoxine. Transduction of dorsal root ganglion neurons in vivo by subcutaneous inoculation of the nerve growth factor‐expressing vector prevented the development of pyridoxine‐induced neuropathy measured by electrophysiological, morphological and behavioural measures. These results demonstrate a functional activity of trkA receptors expressed on large neurons in the dorsal root ganglion in mature animals; this observation has important implications for the choice of neurotrophic factors for treatment of peripheral nerve disease.
Long‐term potentiation of glutamatergic synaptic transmission induced by activation of presynaptic P2Y receptors in the rat medial habenula nucleus
Authors: Price Gareth D. , Robertson Susan J. , Edwards Frances A. 
Published: March 2003

AbstractA novel form of long‐term potentiation of glutamatergic synaptic transmission is described in the rat medial habenula nucleus. It occurs when uridine 5′‐triphosphate is bath applied at low micromolar concentrations and is prevented by Reactive Blue 2, suggesting that it is mediated by P2Y4 receptors. Uridine 5′‐diphosphate can also cause such a Reactive Blue 2‐sensitive potentiation, but at higher concentrations (200 µm), suggesting that this might also be an effect on the relatively uridine 5′‐diphosphate‐insensitive P2Y4 receptor. The potentiation is due to an increase in presynaptic release probability. It requires neither depolarization nor calcium influx postsynaptically and is thus probably non‐Hebbian. When potentiation due to low concentrations of uridine 5′‐triphosphate is inhibited in the presence of Reactive Blue 2, uridine 5′‐triphosphate causes instead a significant inhibition of glutamate release. We suggest that this inhibition may be mediated by a Reactive Blue 2‐insensitive P2Y2‐like receptor. At higher concentrations of uridine 5′‐triphosphate (200 µm), the inhibitory effect dominates such that even in the absence of Reactive Blue 2 no potentiation is seen.
Vagal modulation of nociception is mediated by adrenomedullary epinephrine in the rat
Authors: G. Khasar Sachia , G. Green Paul , Miao Frederick J.‐P. , Levine Jon D. 
Published: March 2003

AbstractVagal afferent activity modulates mechanical nociceptive threshold and inflammatory mediator‐induced hyperalgesia, effects that are mediated by the adrenal medulla. To evaluate the role of epinephrine, the major hormone released from the adrenal medulla, the β2‐adrenergic receptor antagonist ICI 118,551 was chronically administered to vagotomized rats and epinephrine to normal rats. In vagotomized rats, chronic administration of ICI 118,551 markedly attenuated vagotomy‐induced enhancement of bradykinin hyperalgesia but had no effect on nociceptive threshold. In normal rats, chronic epinephrine had the opposite effect, enhancing bradykinin hyperalgesia. Like vagotomy‐, epinephrine‐induced enhancement of hyperalgesia developed slowly, taking 14 days to reach its peak. Vagotomy induced a chronic elevation in plasma concentrations of epinephrine. We suggest that ongoing activity in vagal afferents inhibits the release of epinephrine from the adrenal medulla. Chronically elevated levels of epinephrine, occurring after vagotomy, desensitize peripheral β2‐adrenergic receptors and lead to enhancement of bradykinin hyperalgesia. The ability of prolonged elevated plasma levels of epinephrine to sensitize bradykinin receptors could contribute to chronic generalized pain syndromes.