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Role of cAMP in the short-term modulation of a neuromuscular system in Aplysia

JOURNAL OF NEUROPHYSIOLOGY 2000年第3期83卷 1567-1579页

作者： Fox, LE Lloyd, PE Univ Chicago Comm Neurobiol Chicago IL 60637 USA Univ Chicago Dept Neurobiol Pharmacol & Physiol Chicago IL 60637 USA

Role of cAMP in the short-term modulation of a neuromuscular system in Aplysia. J. Neurophysiol. 83: 1567-1579, 2000. Neuromuscular synapses in buccal muscle I3a of Aplysia are modulated by the small cardioactive peptide (SCP), a peptide cotransmitter that is intrinsic to the motor neurons, and by serotonin (5-HT) released from modulatory neurons that are extrinsic to the motor circuit. Although the modulation of excitatory junction potentials (EJPs) and contractions by 5-HT and SCP has been studied extensively in this muscle, little is known about the mechanisms that underlie the modulation. 5-HT and SCP, at 1 mu M, were found to potently increase the level of cAMP in I3a. Therefore we investigated whether the activation of the cAMP pathway was sufficient to modulate EJPs and contractions,The direct activation of adenylyl cyclase with forskolin increased the level of cAMP, facilitated EJPs, and potentiated contractions. Indeed, the short-term effects of forskolin were very similar to all aspects of the short-term effects of 5-HT and SCP. Membrane-permeable cAMP analogues also mimicked the effects of 5-HT and SCP on EJPs and contractions. However, it seems likely that some effects of 5-HT are also mediated through other second-messenger pathways because low concentrations of 5-HT modulate EJPs and contractions but do not significantly increase cAMP levels in I3a. It is possible that lower concentrations of 5-HT function through receptors linked to protein kinase C (PKC) because phorbol, an activator of PKC, modulated EJPs and contractions without increasing the levels of cAMP. In conclusion, we provide evidence that pharmacological agents that activate the cAMP pathway mimicked most of the effects of 5-HT or SCP and that more than one second-messenger system appears to be involved in the modulation of the I3a neuromuscular system.

关键词： 1-甲基-3-异丁基黄嘌呤/药理学海螺/生理学环AMP/生理学环AMP依赖性蛋白激酶类/生理学电刺激酶抑制剂/药理学无脊椎动物激素类/生理学运动神经元/药物作用运动神经元/生理学肌收缩/药物作用肌收缩/生理学肌/药物作用肌/神经支配肌/生理学神经通路/细胞学神经通路/药物作用神经通路/生理学神经肌肉接头/药物作用神经肌肉接头/生理学神经肽类/生理学佛波醇酯类/药理学血清素/生理学动物

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Evidence for transcortical reflex pathways in the lower limb of man

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PROGRESS IN NEUROBIOLOGY 2000年第3期62卷 251-272页

作者： Christensen, LOD Petersen, N Andersen, JB Sinkjær, T Nielsen, JB Univ Copenhagen Dept Med Physiol DK-2200 Copenhagen N Denmark Aalborg Univ Ctr Sensorimotor Interact DK-9220 Aalborg O Denmark

The existence of transcortical reflex pathways in the control of distal arm and hand muscles in man is now widely accepted. Much more controversy exists regarding a possible contribution of such reflexes to the control of leg muscles. It is often assumed that transcortical reflex pathways play no, or only a minor, role in the control of leg muscles. Transcortical reflex pathways according to this view are reserved for the control of the distal upper limb and are seen in close relation to the evolution of the primate hand. Here we review data, which provide evidence that transcortical reflexes do exist for lower limb muscles and may play a significant role in the control of at least some of these muscles. This evidence is based on animal research, recent experiments combining transcranial magnetic stimulation with peripheral electrical and mechanical stimulation in healthy subjects and neurological patients. We propose that afferent activity from muscle and skin may play a role in the regulation of bipedal gait through transcortical pathways. (C) 2000 Published by Elsevier Science Ltd. All rights reserved.

关键词：步态/生理学腿/生理学运动皮质/细胞学运动皮质/生理学肌骨骼/神经支配肌骨骼/生理学神经通路/细胞学神经通路/生理学反射/生理学躯体感觉皮质/细胞学躯体感觉皮质/生理学动物人类

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Neural organization from the superior colliculus to motoneurons in the horizontal oculomotor system of the cat

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JOURNAL OF NEUROPHYSIOLOGY 1999年第6期81卷 2597-2611页

作者： Izawa, Y Sugiuchi, Y Shinoda, Y Tokyo Med & Dent Univ Sch Med Dept Physiol Bunkyo Ku Tokyo 113 Japan

Neural organization from the superior colliculus to motoneurons in the horizontal oculomotor system of the cat. J. Neurophysiol. 81: 2597-2611, 1999. The neural organization of the superior colliculus (SC) projection to horizontal ocular motoneurons was analyzed in anesthetized cats using intracellular recording and transneuronal labeling. Intracellular responses to SC stimulation were analyzed in lateral rectus (LR) and medial rectus (MR) motoneurons and internuclear neurons in the abducens nucleus (AINs). LR motoneurons and AINs received excitation from the contralateral SC and inhibition from the ipsilateral SC. The shortest excitation (0.9-1.9 ms) and inhibition (1.4-2.4 ms) were mainly disynaptic from the SC and were followed by tri- and polysynaptic responses evoked with increasing stimuli or intensity. All MR motoneurons received excitation from the ipsilateral SC, whereas none of them received any short-latency inhibition from the contralateral SC, but some received excitation. The latency of the ipsilateral excitation in MR motoneurons (1.7-2.8 ms) suggested that this excitation was trisynaptic via contralateral AINs, because conditioning SC stimulation spatially facilitated trisynaptic excitation from the ipsilateral vestibular nerve. To locate interneurons mediating the disynaptic SC inputs to LR motoneurons, last-order premotor neurons were labeled transneuronally after injecting wheat germ agglutinin-conjugated horseradish peroxidase into the abducens nerve, and tectoreticular axon terminals were labeled after injecting dextran-biotin into the ipsilateral or contralateral SC in the same preparations. Transneuronally labeled neurons were mainly distributed ipsilaterally in the paramedian pontine reticular formation (PPRF) rostral to retrogradely labeled LR motoneurons and the vestibular nuclei, and contralaterally in the paramedian pontomedullary reticular formation (PPMRF) caudomedial to the abducens nucleus and the vestibular nuclei. Among the last-ord

关键词：电刺激兴奋性突触后电位/生理学膜电位/生理学微电极分子探针运动神经元/生理学运动神经元/超微结构神经通路/细胞学神经通路/生理学神经通路/超微结构动眼肌/神经支配动眼肌/超微结构上丘/细胞学上丘/生理学上丘/超微结构突触/生理学突触/超微结构麦胚凝集素-辣根过氧化物酶轭合物动物猫

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Effects of testosterone on pelvic autonomic pathways: progress and pitfalls

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JOURNAL OF THE AUTONOMIC NERVOUS SYSTEM 2000年第2-3期79卷 67-73页

作者： Keast, JR Univ Queensland Dept Physiol & Pharmacol St Lucia Qld 4072 Australia

Testosterone has potent effects on reproductive behavior, many of which are due to actions on brain nuclei and spinal motoneurons controlling perineal muscles. The autonomic circuits involved in penile erection, ejaculation and emission, have been less commonly considered as targets for circulating androgens. This review demonstrates that many components of pelvic autonomic reflex pathways, including preganglionic neurons, autonomic ganglion cells and primary afferent neurons, are likely to be influenced by testosterone. The steroid appears to play an important role in maintaining neuronal morphology, transmitter synthesis and receptor expression throughout adulthood. Surprisingly, the effects of testosterone are not limited to neurons involved in reproductive reflexes. The challenge is now to determine the range of neuronal features influenced by androgens, and the mechanisms by which these occur. Studies of androgen receptor location indicate that in many autonomic neurons gene expression may be directly influenced by androgens, but a mismatch between receptor distribution and androgen action shows that in some cells other mechanisms must exist. II is also possible that androgens are metabolised to estrogens by some peripheral neurons. Irrespective of the mechanism, it is time to acknowledge that testosterone is an important "maintenance factor" for autonomic neurons. (C) 2000 Elsevier Science B.V. All rights reserved.

关键词：自主神经系统/细胞学自主神经系统/药物作用自主神经系统/生理学神经通路/细胞学神经通路/药物作用神经通路/生理学神经元/药物作用神经元/生理学骨盆/神经支配睾酮/药理学动物

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A mouse serine/threonine kinase homologous to C-elegans UNC51 functions in parallel fiber formation of cerebellar granule neurons

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NEURON 1999年第4期24卷 833-846页

作者： Tomoda, T Bhatt, RS Kuroyanagi, H Shirasawa, T Hatten, ME Rockefeller Univ Dev Neurobiol Lab New York NY 10021 USA Tokyo Metropolitan Inst Genet Dept Mol Genet Tokyo 173 Japan

The formation of the cerebellar circuitry depends on the outgrowth of connections between the two principal classes of neurons, granule neurons and Purkinje neurons. To identify genes that function in axon outgrowth, we have isolated a mouse homolog of C. elegans UNC51, which is required for axon formation, and tested its function in cerebellar granule neurons. Murine Unc51.1 encodes a novel serine/threonine kinase and is expressed in granule cells in the cerebellar cortex. Retroviral infection of immature granule cells with a dominant negative Unc51.1 results in inhibition of neurite outgrowth in vitro and in vivo. Moreover, infected neurons fail to express TAG-1 or neuron-specific beta-tubulin, suggesting that development is arrested prior to this initial step of differentiation. Thus, Unc51.1 signals the program of gene expression leading to the formation of granule cell axons.

关键词：氨基酸序列新小杆线虫漂亮/生理学漂亮新小杆线虫蛋白质类细胞分化/生理学小脑/细胞学小脑/生长和发育细胞质颗粒/生理学遗传载体免疫组织化学原位杂交分子序列数据突变神经纤维/生理学神经通路/细胞学神经通路/生长和发育神经通路/生理学神经突/生理学神经元/生理学表型种系发生质粒/遗传学蛋白质丝氨酸苏氨酸激酶/生理学逆转录病毒科/遗传学逆转录聚合酶链反应动物小鼠

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Target-cell-specific facilitation and depression in neocortical circuits

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NATURE NEUROSCIENCE 1998年第4期1卷 279-285页

作者： Reyes, A Lujan, R Rozov, A Burnashev, N Somogyi, P Sakmann, B Max Planck Inst Med Forsch Zellphysiol Abt D-69120 Heidelberg Germany Univ Oxford Dept Pharmacol MRC Anat Neuropharmacol Unit Oxford England

In neocortical circuits, repetitively active neurons evoke unitary postsynaptic potentials (PSPs) whose peak amplitudes either increase (facilitate) or decrease (depress) progressively. To examine the basis for these different synaptic responses, we made simultaneous recordings from three classes of neurons in cortical layer 2/3. We induced repetitive action potentials in pyramidal cells and recorded the evoked unitary excitatory (E)PSPs in two classes of GABAergic neurons. We observed facilitation of EPSPs in bitufted GABAergic interneurons, many of which expressed somatostatin immunoreactivity. EPSPs recorded from multipolar interneurons, however, showed depression. Some of these neurons were immunopositive for parvalbumin. Unitary inhibitory (I)PSPs evoked by repetitive stimulation of a bitufted neuron also showed a less pronounced but significant difference between the two target neurons. Facilitation and depression involve presynaptic mechanisms, and because a single neuron can express both behaviors simultaneously, we infer that local differences in the molecular structure of presynaptic nerve terminals are induced by retrograde signals from different classes of target neurons. Because bitufted and multipolar neurons both formed reciprocal inhibitory connections with pyramidal cells, the results imply that the balance of activation between two recurrent inhibitory pathways in the neocortex depends on the frequency of action potentials in pyramidal cells.

关键词：动作电位/生理学电刺激电生理学兴奋性突触后电位/生理学中间神经元/代谢中间神经元/生理学新皮质/细胞学新皮质/生理学神经抑制/生理学神经通路/细胞学神经通路/生理学神经元/生理学锥体细胞/生理学生长抑素/代谢突触/生理学 γ氨基丁酸/生理学动物大鼠

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Squeezing axons out of the gray matter: A role for slit and semaphorin proteins from midline and ventral spinal cord

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CELL 2000年第3期102卷 363-375页

作者： Zoo, YM Stoeckli, E Chen, H Tessier-Lavigne, M Univ Calif San Francisco Howard Hughes Med Inst Dept Anat San Francisco CA 94143 USA Univ Calif San Francisco Howard Hughes Med Inst Dept Biochem & Biophys San Francisco CA 94143 USA Univ Basel Dept Integrat Biol CH-4051 Basel Switzerland

Commissural axons cross the nervous system midline and then turn to grow alongside it, neither recrossing nor projecting back into ventral regions. In Drosophila, the midline repellent Slit prevents recrossing: axons cross once because they are initially unresponsive to Slit, becoming responsive only upon crossing. We show that commissural axons in mammals similarly acquire responsiveness to a midline repellent activity upon crossing. Remarkably, they also become responsive to a repellent activity from ventral spinal cord, helping explain why they never reenter that region. Several Slit and Semaphorin proteins, expressed in midline and/or ventral tissues, mimic these repellent activities, and midline guidance defects are observed in mice lacking neuropilin-2, a Semaphorin receptor. Thus, Slit and Semaphorin repellents from midline and nonmidline tissues may help prevent crossing axons from reentering gray matter, squeezing them into surrounding fiber tracts.

关键词：轴突细胞间通讯果蝇蛋白质类胞间信号肽类和蛋白质类分子序列数据形态发生神经组织蛋白质类/代谢神经通路/细胞学神经通路/胚胎学神经纤毛蛋白质1 脊髓/细胞学脊髓/胚胎学动物大鼠

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Leptin differentially regulates NPY and POMC neurons projecting to the lateral hypothalamic area

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NEURON 1999年第4期23卷 775-786页

作者： Elias, CF Aschkenasi, C Lee, C Kelly, J Ahima, RS Bjorbæk, C Flier, JS Saper, CB Elmquist, JK Harvard Univ Sch Med Dept Neurol Beth Israel Deaconess Med Ctr Boston MA 02215 USA Harvard Univ Sch Med Program Neurosci Boston MA 02215 USA Beth Israel Deaconess Med Ctr Dept Med Boston MA 02215 USA Beth Israel Deaconess Med Ctr Div Endocrinol Boston MA 02215 USA Harvard Univ Sch Med Boston MA 02215 USA

Recent studies have reinforced the view that the lateral hypothalamic area (LHA) regulates food intake and body weight. We identified leptin-sensitive neurons in the arcuate nucleus of the hypothalamus (Arc) that innervate the LHA using retrograde tracing with leptin administration. We found that retrogradely labeled cells in the Are contained neuropeptide Y (NPY) mRNA or proopiomelanocortin (POMC) mRNA. Following leptin administration, NPY cells in the Are did not express Fos but expressed suppressor of cytokine signaling-3 (SOCS-3) mRNA. In contrast, leptin induced both Fos and SOCS-3 expression in POMC neurons, many of which also innervated the LHA. These findings suggest that leptin directly and differentially engages NPY and POMC neurons that project to the LHA, linking circulating leptin and neurons that regulate feeding behavior and body weight homeostasis.

关键词：体重/生理学细胞计数进食/生理学内环境稳定/生理学下丘脑区侧/细胞学下丘脑区侧/生理学免疫组织化学原位杂交瘦素神经通路/细胞学神经通路/生理学神经元/生理学神经肽Y/生理学前阿片黑素细胞皮质激素/生理学蛋白质生物合成蛋白质类/生理学原癌基因蛋白质c-fos/生物合成原癌基因蛋白质c-fos/遗传学 RNA 信使/生物合成 RNA 信使/遗传学大鼠 Sprague-Dawley 阻遏蛋白质类信号传导/生理学细胞因子信号转导蛋白抑制因子转录因子动物男(雄)性大鼠

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Processing of gustatory information by spiking local interneurons in the locust

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JOURNAL OF NEUROPHYSIOLOGY 1999年第6期82卷 3149-3159页

作者： Newland, PL Univ Southampton Sch Biol Sci Dept Cell Sci Southampton SO16 7PX Hants England

Despite the importance of gustation, little is known of the central pathways responsible for the processing and coding of different chemical stimuli. Here I have analyzed the responses of a population of spiking local interneurons, with somata at the ventral midline of the metathoracic ganglion, during stimulation of chemo- and mechanoreceptors on the legs of locusts. Volatile acidic stimuli were used to selectively activate the chemosensory neurons. Different members of the population of local interneurons received depolarizing or hyperpolarizing inputs during chemosensory stimulation. Many of the same interneurons that received chemosensory input also received mechanosensory inputs from tactile hairs on the leg, but others received exclusively mechanosensory inputs. Chemosensory inputs occurred with a short and constant latency, typical of monosynaptic connections. The chemosensory receptive fields of the spiking local interneurons mapped the surface of a hind leg so that spatial information relating to the location of a taste receptor was preserved. The amplitude of potentials in interneurons during chemosensory stimulation varied in a graded manner along the long axis of the leg, thus creating gradients in the chemosensory receptive fields of inteneurons. Some interneurons were depolarized to a greater extent by chemical stimuli applied to basiconic sensilla on distal parts of the leg, whereas others were depolarized more by chemical stimulation of more proximal sensilla.

关键词：化学感受器细胞/生理学电生理学蚱蜢/生理学中间神经元/生理学神经通路/细胞学神经通路/生理学味觉/生理学触觉/生理学动物女(雌)性男(雄)性

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Spiking-bursting activity in the thalamic reticular nucleus initiates sequences of spindle oscillations in thalamic networks

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JOURNAL OF NEUROPHYSIOLOGY 2000年第2期84卷 1076-1087页

作者： Bazhenov, M Timofeev, I Steriade, M Sejnowski, T Salk Inst Biol Studies Howard Hughes Med Inst Computat Neurobiol Lab La Jolla CA 92037 USA Univ Laval Sch Med Neurophysiol Lab Quebec City PQ G1K 7P4 Canada Univ Calif San Diego Dept Biol La Jolla CA 92093 USA

Recent intracellular and local field potential recordings from thalamic reticular (RE) neurons in vivo as well as computational modeling of the isolated RE nucleus suggest that, at relatively hyperpolarized levels of membrane potentials, the inhibitory postsynaptic potentials (IPSPs) between RE cells can be reversed and gamma-aminobutyric acid-A (GABA(A))-mediated depolarization can generate persistent spatio-temporal patterns in the RE nucleus. Here we investigate how this activity affects the spatio-temporal properties of spindle oscillations with computer models of interacting RE and thalamocortical (TC) cells. In a one-dimensional network of RE and TC cells, sequences of spindle oscillations alternated with localized patterns of spike-burst activity propagating inside the RE network. New sequences of spindle oscillations were initiated after removal of I-h-mediated depolarization of the TC cells. The length of the interspindle lulls depended on the intrinsic and synaptic properties of RE and TC cells and was in the range of 3-20 s. In a two-dimensional model, GABA(A)-mediated 2-3 Hz oscillations persisted in the RE nucleus during interspindle lulls and initiated spindle sequences at many foci within the RE-TC network simultaneously. This model predicts that the intrinsic properties of the reticular thalamus may contribute to the synchrony of spindle oscillations observed in vivo.

关键词：动作电位/生理学钙通道/生理学去脑皮质术兴奋性突触后电位/生理学神经抑制/生理学神经通路/细胞学神经通路/生理学周期性受体 AMPA/生理学受体 GABA-A/生理学突触/化学突触/生理学丘脑核/生理学动物猫

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