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Cholinergic synaptic transmission in insect mushroom bodies in vitro

JOURNAL OF NEUROPHYSIOLOGY 1999年第2期82卷 1091-1096页

作者： Oleskevich, S Australian Natl Univ Res Sch Biol Sci Canberra ACT 2601 Australia

The mushroom body of the bee brain is an important site for learning and memory : Here we investigate synaptic transmission in the mushroom body using extracellular recording techniques in a whole bet brain in vitro preparation The postsynaptic response showed attenuation by cadmium-and paired-pulse facilitation, similar to in vivo findings. This confirms the viability of the in vitro preparation and supports the isolated whole bee blain as a useful model of the in vivo preparation. Bath application of the acetylcholine receptor antagonists, D-tubocurarine and alpha-bungarotoxin attenuated the postsynaptic response by 61 and 62% of control, respectively. The glutamate receptor antagonists, (+)-2-amino-5-phosphonopentanoic acid and 6-cyano-7-nitroquinoxaline-2,3-dione, had no effect. The invertebrate monoamine and neuromodulator, octopamine, transiently increased the postsynaptic response by 130% of control. These results suggest that synaptic transmission of the olfactory input pathway in the mushroom body is 1) mediated primarily by acetylcholine and 2) modulated by octopamine.

关键词：乙酰胆碱/生理学蜂/生理学脑图树突/生理学神经递质药/生理学嗅通路/生理学突触传递/生理学动物

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Modulation of glutamate receptor functions by glutathione

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NEUROCHEMISTRY INTERNATIONAL 2000年第2-3期37卷 299-306页

作者： Oja, SS Janáky, R Varga, V Saransaari, P Univ Tampere Sch Med Tampere Brain Res Ctr FIN-33101 Tampere Finland Tampere Univ Hosp Dept Clin Physiol Tampere Finland Univ Debrecen Dept Anim Physiol Debrecen Hungary

In addition to its well-known antioxidant effects, glutathione apparently has an additional double role in the central nervous system as a neurotransmitter and neuromodulator. A number of recent neurochemical, neuropharmacological and electrophysiological studies have yielded evidence on both functions. As an excitatory neurotransmitter, glutathione depolarizes neurons by acting as ionotropic receptors of its own which are different from any other excitatory amino acid receptors. As a neuromodulator, it displaces ionotropic glutamate receptor ligands from their binding sites and regulates calcium influx through N-methyl-D-asyartate receptor-governed ionophores. In brain slices glutathione has been shown to regulate the release of other transmitters, e.g., gamma-aminobutyrate and dopamine, mediated by N-methyl-D-aspartate receptors. In the present article, we review recent findings on the neuromodulatory actions of glutathione and discuss possible physiological and pathophysiological consequences. (C) 2000 Elsevier Science Ltd. All rights reserved.

关键词：钙通道/药物作用钙通道/生理学兴奋性氨基酸激动剂/药理学谷胱甘肽/生理学神经递质药/代谢神经递质药/生理学受体谷氨酸/药物作用受体谷氨酸/生理学动物人类

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Calcium channel gating and modulation by transmitters depend on cellular compartmentalization

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NATURE NEUROSCIENCE 2000年第7期3卷 670-678页

作者： Delmas, P Abogadie, FC Buckley, NJ Brown, DA UCL Dept Pharmacol Wellcome Lab Mol Pharmacol London WC1E 6BT England

Voltage-gated Ca2+ channels participate in dendritic integration, yet functional properties of Ca2+ channels and mechanisms of their modulation by neurotransmitters in dendrites are unknown. Here we report how pharmacologically identified Ca2+ channels behave in different neural compartments. Whole-cell and cell-attached patch-clamp recordings were made on both cell bodies and electrically isolated dendrites of sympathetic neurons. We found not only that Ca2+ channel populations differentially contribute to somatic and dendritic currents but also that families of Ca2+ channels display gating properties and neurotransmitter modulation that depend on channel compartmentalization. By comparison with their somatic counterparts,;dendritic N-type Ca2+ currents were hypersensitive to neurotransmitters and C proteins. Single-channel analysis showed that dendrites express a unique N-type channel that has enhanced interaction with G beta gamma. Thus Ca2+ channels in dendrites seem to be specialized elements with unique regulatory mechanisms.

关键词：钙通道 N型/生理学细胞培养的树突/生理学 GTP结合蛋白质类/生理学离子通道闸门/生理学动力学膜电位神经突/生理学神经元/生理学神经递质药/生理学膜片钳术颈上神经节/生理学动物大鼠

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Neural mechanisms of delirium: Current hypotheses and evolving concepts

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JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES 1999年第6期54卷 B239-B246页

作者： Flacker, JM Lipsitz, LA Beth Israel Hosp Hebrew Rehabil Ctr Aged Res & Training Inst Dept Med Boston MA USA Harvard Univ Sch Med Div Aging Boston MA 02115 USA

The purpose of this article is to review current knowledge regarding potential neural mechanisms of delirium. A MEDLINE search for relevant English language articles was undertaken using various combinations of delirium (including cognitive disorders, encephalopathy, and confusion) with pathogenesis and pathophysiology. These articles were scanned for content related to hypotheses concerning the neurobiology of delirium Additional references were obtained from a manual search of the bibliography of these articles. A secondary MEDLINE search of delirium with the mechanism in question (i.e., serotonin, acetylcholine, etc.) was then undertaken. Literature review was last updated as of April 1998. Despite being a common problem among elderly patients, the mechanisms of delirium are poorly understood Delirium is a syndrome that may occur as the result of multiple complex interacting neurotransmitter systems and pathologic processes. The neurotransmitters acetylcholine and serotonin may play particularly important roles in common medical and surgical delirium. Other neurotransmitters such as dopamine and gamma-aminobutyric acid each may be involved in the development of delirium under special conditions. Other neurobiologic factors such as cytokines, cortisol abnormalities, and oxygen free radicals win require further study to define their role in delirium. Distinct meuropathologic processes leading to delirium are beginning to be defined Such mechanisms may differ in various clinical settings. There is probably no final common pathway to delirium but rather delirium is the final common symptom of multiple neurotransmitter abnormalities. Further situation-specific studies of delirium pathophysiology should lead to more effective prevention and treatment strategies.

关键词：乙酰胆碱/生理学氨基酸类/生理学谵妄/病理生理学内啡肽类/生理学氢化可的松/生理学神经递质药/生理学血清素/生理学老年人动物人类

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Is histamine the final neurotransmitter in the entrainment of circadian rhythms in mammals?

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TRENDS IN PHARMACOLOGICAL SCIENCES 2000年第8期21卷 293-298页

作者： Jacobs, EH Yamatodani, A Timmerman, H Free Univ Amsterdam Leiden Amsterdam Ctr Drug Res Div Med Chem NL-1081 HV Amsterdam Netherlands Osaka Univ Sch Allied Hlth Sci Dept Phys Med Fac Med Suita Osaka 565 Japan

Adaptation of circadian rhythms to the environmental light-dark cycle is necessary for the survival of organisms. This synchronization or entrainment is only caused by light (photic input) during the dark period, according to the internal biological clock of an organism. During the light period, internal factors (non-photic input), rather than light, are able to entrain circadian rhythms. In this article, the data that implicate the neurotransmitter system for histamine in circadian entrainment are reviewed, Furthermore, we speculate that histamine receptors are the final gate at which both photic and non-photic entrainment mechanisms converge before sending a resetting signal to the intra cellular biological clock.

关键词：昼夜节律 cAMP反应元件结合蛋白质/生理学组胺/生理学神经递质药/生理学受体 N-甲基-D-天冬氨酸/生理学血清素/生理学上交叉核/生理学动物人类小鼠

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Neuromodulation during motor development and behavior

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CURRENT OPINION IN NEUROBIOLOGY 1999年第6期9卷 683-689页

作者： Pflüger, HJ Free Univ Berlin Inst Biol Neurobiol D-14195 Berlin Germany

Important recent advances have been made in understanding the role of aminergic modulation during the maturation of Xenopus larvae swimming rhythms, including effects on particular ion channel types of component neurons, and the role of peptidergic modulation during development of adult central patterns generators in the stomatogastric ganglion of crustaceans. By recording from octopaminergic neuromodulatoty neurons during ongoing motor behavior in the locust, new insights into the role of this peripheral neuromodulatory mechanism have been gained. In particular, it is now clear that the octopaminergic neuromodulatory system is automatically activated in parallel to the motor systems, and that both excitation and inhibition play important functional roles.

关键词：衰老/生理学行为动物/生理学运动(Movement)/生理学神经递质药/生理学动物

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Is agmatine a novel neurotransmitter in brain?

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TRENDS IN PHARMACOLOGICAL SCIENCES 2000年第5期21卷 187-193页

作者： Reis, DJ Regunathan, S Columbia Univ Weill Med Coll Div Neurobiol New York NY 10021 USA Columbia Univ Weill Med Coll Dept Neurol & Neurosci New York NY 10021 USA

Recent evidence suggests that agmatine, which is an intermediate in polyamine biosynthesis, might be an important neurotransmitter in mammals. Agmatine is synthesized in the brain, stored in synaptic vesicles in regionally selective neurons, accumulated by uptake, released by depolarization, and inactivated by agmatinase. Agmatine binds to alpha(2)-adrenoceptors and imidazoline binding sites, and blocks NMDA receptor channels and other ligand-gated cationic channels. Furthermore, agmatine inhibits nitric oxide synthase, and induces the release of some peptide hormones. As a result of its ability to inhibit both hyperalgesia and tolerance to, and withdrawal from, morphine, and its neuroprotective activity, agmatine has potential as a treatment of chronic pain, addictive states and brain injury.

关键词：胍丁胺脑/生理学脑化学/生理学神经递质药/生理学动物人类

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Contribution of single-channel properties to the time course and amplitude variance of quantal glycine currents recorded in rat motoneurons

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JOURNAL OF NEUROPHYSIOLOGY 1999年第4期81卷 1608-1616页

作者： Singer, JH Berger, AJ Univ Washington Sch Med Dept Physiol & Biophys Seattle WA 98195 USA

The amplitude of spontaneous. glycinergic miniature inhibitory postsynaptic currents (mIPSCs) recorded in hypoglossal motoneurons (HMs) in an in vitro brain stem slice preparation increased over the first 3 postnatal weeks, from 42 +/- 6 pA in neonate (P0-3) to 77 +/- ii pA in juvenile (P11-18) HMs. Additionally, mIPSC amplitude distributions were highly variable: CV 0.68 +/- 0.05 (means +/- SE) for neonates and 0.83 +/- 0.06 for juveniles, We wished to ascertain the contribution of glycine receptor (GlyR)channel properties to this change in quantal amplitude and to the amplitude variability and time course of mIPSCs. To determine whether a postnatal increase in GlyR-channel conductance accounted for the postnatal change in quantal amplitude, the conductance of synaptic GlyR channels was determined by nonstationary, variance analysis of mIPSCs. It was 48 +/- 8 pS in neonate and 46 +/- 10 pS in juvenile HMs, suggesting that developmental changes in mIPSC amplitude do not result from a postnatal alteration of GlyR-channel conductance. Next we determined the open probability (P-open) of GlyR channels in outside-out patches excised from HMs to estimate the contribution of stochastic channel behavior to quantal amplitude variability. Brief (1 ms) pulses Of glycine (I mM) elicited patch currents that closely resembled mIPSCs. The GlyR channels' P-open, calculated by nonstationary variance analysis of these currents, was similar to 0.70 (0.66 +/- 0.09 in neonates and 0.72 +/- 0.05 in juveniles). The decay rate of patch currents elicited bq brief application of saturating concentrations of glycine (10 mM) increased postnatally, mimicking previously documented changes in mIPSC time course, Paired pulses of glycine (10 mM) were used to determine if rapid GlyR-channel desensitization contributed to either patch current time course or quantal amplitude variability. Because we did not observe any fast desensitization of patch currents, we believe that fast desensitization of Gly

关键词：年龄因素动物新生脑干/细胞学脑干/生理学剂量效应关系药物甘氨酸/药理学甘氨酸类药/药理学舌下神经/化学舌下神经/细胞学舌下神经/生理学膜电位/药物作用膜电位/生理学运动神经元/化学运动神经元/药物作用运动神经元/生理学神经抑制/生理学神经递质药/生理学膜片钳术大鼠 Sprague-Dawley 反应时间/药物作用反应时间/生理学受体甘氨酸/生理学呼吸士的宁/药理学突触/药物作用突触/生理学氚动物大鼠

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Schizophrenia: a purinergic hypothesis

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MEDICAL HYPOTHESES 2000年第2期54卷 157-166页

作者： Lara, DR Souza, DO Univ Fed Rio Grande do Sul Dept Bioquim ICBS BR-90035003 Porto Alegre RS Brazil

Knowledge of the physiological roles of the purinergic system and its influence on other neurotransmitter systems has greatly advanced. In this article, a purinergic model is proposed as an attempt to integrate several findings in schizophrenia. According to this hypothesis, a purinergic system dysfunction would mainly result in reduced adenosinergic activity. This model also addresses the systemic aspects of schizophrenia, based on peripheral roles of purines, such as modulation of the immune system. (C) 2000 Harcourt Publishers Ltd.

关键词：腺嘌呤核苷酸类/生理学多巴胺/生理学模型神经学神经递质药/生理学嘌呤类/代谢精神分裂症/病理生理学人类

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Neurosteroids: Biosynthesis and function of these novel neuromodulators

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FRONTIERS IN NEUROENDOCRINOLOGY 2000年第1期21卷 1-56页

作者： Compagnone, NA Mellon, SH Univ Calif San Francisco Dept Obstet Gynecol & Reprod Sci Ctr Reprod Sci San Francisco CA 94143 USA Univ Calif San Francisco Metab Res Unit San Francisco CA 94143 USA

Over the past decade, it has become clear that the brain is a steroidogenic organ. The steroids synthesized by the brain and nervous system, given the name neurosteroids, have a wide variety of diverse functions. In general, they mediate their actions, not through classic steroid hormone nuclear receptors, but through ion-gated neurotransmitter receptors. This paper summarizes what is known about the biosynthesis of neurosteroids, the enzymes mediating these reactions, their localization during development and in the adult, and their function and mechanisms of action in the developing and adult central and peripheral nervous systems. The expression of the steroidogenic enzymes is developmentally regulated, with some enzymes being expressed only during development, while others are expressed during development and in the adult. These enzymes are expressed in both neurons and glia, suggesting that these two cell types must work in concert to produce the appropriate active neurosteroid. The functions attributed to specific neurosteroids include modulation of GABA(A), and NMDA function, modulation of sigma receptor function, regulation of myelinization, neuroprotection, and growth of axons and dendrites. Neurosteroids have also been shown to modulate expression of particular subunits of GABA(A) and NMDA receptors, providing additional sites at which these compounds can regulate neural function. The pharmacological properties of specific neurosteroids are described, and potential uses of neurosteroids in specific neuropathologies and during normal aging in humans are also discussed. (C) 2000 Academic Press.

关键词：脑/生理学神经递质药/生物合成神经递质药/生理学受体 GABA-A/生理学甾类/生物合成甾类/生理学动物人类

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