5-羟色胺对心肺迷走神经节前神经元突触传入的调节作用
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摘要
5-羟色胺(serotonin or 5-hydroxytryptamine,5-HT)是一种小分子吲哚胺化合物,广泛分布于外周组织和中枢神经系统中,作为血管活性物质或神经递质在痛觉调制、睡眠、内分泌功能、心血管功能、呼吸功能以及精神活动等多方面发挥重要作用。脑内5-HT能神经元胞体主要集中在低位脑干中线附近的中缝核群(中缝苍白核,中缝隐核,中缝大核),通过中缝核群发出的纤维下行支配脊髓,上行支配前脑和脑干的广大区域,同时还可通过脑脊液到达其他脑区发挥广泛作用。近年来大量在体动物实验研究表明5-HT参与心血管与呼吸活动的反射性调节,并有多种5-HT受体亚型(5-HT_1,5-HT_2,5-HT_3,5-HT_4,5-HT_7)参与。在中枢阻断5-HT_(1A)受体或5-HT_7受体可以减弱心肺反射引起的心动过缓;在孤束核(nucleus tractus solitarius,NTS),不同5-HT_2受体亚型有不同作用,其中5-HT_(2B)受体起兴奋作用而5-HT_(2C)起抑制作用。但是具体的神经反射通路及作用机制目前还不甚清楚。以往的研究主要采用解剖学和在体电生理研究的方法,采用膜片钳技术在突触水平研究5-HT对心肺迷走神经节前神经元的调节作用有可能在突触水平阐明5-HT对心血管与呼吸功能反射性调节的部分机制。
以往对心肺迷走神经节前神经元的膜片钳研究主要关注的是心迷走节前神经元[cardiac vagal(parasympathetic)preganglionic neurons,CVPNs],其中枢定位及突触支配和调制的研究已经取得了一定的成果,而对肺迷走神经节前神经元突触支配及调制的研究则开展得很少。因此,本论文的研究目的分为三部分:一,研究5-HT对CVPNs突触支配的调节作用。二,研究呼吸道副交感节前神经元[airway-related parasympathetic(vagal)preganglionic neurons,APPNs]在中枢的解剖定位及电生理特性。三,研究5-HT对APPNs突触支配的调节作用。
本实验以2-6天SD大鼠为研究对象,先用荧光染料逆行标记目的神经元,在离体延髓脑片上采用全细胞膜片钳模式对神经元进行研究。结果和结论如下:
一、5-HT_(1A/7)受体激动剂8-OH-DPAT显著抑制CVPNs的自发性GABA能和甘氨酸能抑制性突触后电流(spontaneous inhibitory postsynaptic currents,sIPSCs)的频率和幅度,显著抑制刺激NTS引起的GABA能突触后电流,而对微小的GABA能和甘氨酸能抑制性突触后电流(miniature inhibitory postsynapticcurrents,mIPSCs)、外源性GABA和外源性甘氨酸引起的突触后电流及自发的谷氨酸能兴奋性突触后电流(spontaneous excitatory postsynaptic currents,sEPSCs)均没有明显作用。这些结果提示5-HT_(1A/7)受体激动剂通过突触前机制抑制GABA能和甘氨酸能突触传入间接兴奋CVPNs。这可能是5-HT参与心迷走神经反射调控的机制之一。
二、通过喉返神经标记的APPNs均位于疑核致密部,而通过气管壁标记的APPNs位于疑核致密部或疑核腹侧/腹外侧。位于疑核致密部的APPNs主要接受抑制性GABA能和甘氨酸能突触传入,其中部分神经元这些抑制性突触传入在吸气期间增加,而在另外部分神经元减少;位于疑核腹侧/腹外侧的APPNs除了接受抑制性GABA能和甘氨酸能突触传入外,还接受兴奋性谷氨酸能突触传入,部分神经元在吸气时抑制性突触传入增加从而被抑制,而另外部分神经元在吸气时兴奋性突触传入增加从而被兴奋。吸气时抑制性突触传入增加提示这些神经元在吸气期被抑制,在功能上可能是与呼气或后吸气相关的,而吸气时抑制性突触传入减少或兴奋性突触传入增加提示这些神经元在吸气期兴奋,在功能上可能是与吸气相关的。这些结果表明支配呼吸道不同节段的副交感节前神经元在中枢的定位及功能是分离的。
此外,我们采用消除细胞跨膜电化学梯度的方法,在单个吸气性呼吸道副交感节前神经元(inspiratory airway-related parasympathetic preganglionic neurons,I-APPNs)上成功记录到了电突触电流(gap junction currents,GJCs),并且这些GJCs与呼吸活动是密切相关的。这个结果提示电突触存在于APPNs中,并且可能在呼吸中枢神经元电活动的同步性中起重要作用。这种记录方法可用于快速探测具有自发活动的神经元网络中的GJCs。
关于5-HT对APPNs突触支配的调控作用这一部分实验还处于研究阶段,需要在接下来的时间里继续探索。
5-hydroxytryptamine(serotonin,5-HT),an indolamine that is widely distributed in the peripheral tissue and central nervous system,is involved in a large variety of physiological functions and pathogenesis including pain modulation,sleep,endocrine, cardiopulmonary function and psychiatric disorders such as depression,anxiety and aggressiveness.Anatomical studies have found that 5-HT containing neurons are mainly within the raphe nuclei(pallidus,obscurus,magnus).Serotonergic neurons project to the whole brain and synapse upon many kind of neurons.In recent years, many in vivo electrophysiological studies have shown that 5-HT plays an important role in mediating the reflex control of cardiopulmonary functions,which involves many receptor subtypes including 5-HT_1,5-HT_2,5-HT_3,5-HT_4,5-HT_7.Blocking 5-HT_(1A) or 5-HT_7.receptors attenuated bradycardias evoked by stimulating baroreceptor and cardiopulmonary afferents.In the nucleus tractus solitarius(NTS), 5-HT_2 receptors had variable effects;5-HT_(2B) receptors excite and 5-HT_(2C) receptors inhibit.However,little is known about the neural pathway and the synaptic mechanisms.Using patch-clamp techniques to study the effect of 5-HT on the synaptic inputs of cardiopulmonary vagal preganglionic neurons is important to elucidate the reflex control of cardiopulmonary functions at the synaptic level.
Previous studies have made much progress about the central distribution and the synaptic control of cardiac vagal preganglionic neurons(CVPNs).With respect to pulmonary vagal preganglionic neurons,the study is scarce.So,our aim is to investigate:(1) the effect of 5-HT on the synaptic inputs of CVPNs.(2) the central distribution and electrophysiological characteristics of airway-related parasympathetic preganglionic neurons(APPNs).(3)the effect of 5-HT on the synaptic inputs of APPNs.
The CVPNs were retrogradely labeled by injecting rhodamine into the fat pads of the heart or into the cardiac sac of 2-6-day-old Sprague-Dawley rats and the APPNs were retrogradely labeled by injecting rhodamine into the recurrent laryngeal nerve (RLN) or tracheal wall.The CVPNs and APPNs were identified by the presence of fluorescence in brainstem slices and studied using whole cell patch-clamp recording technique.
Following are the results and conclusions:
1.5-HT_(1A/7) receptor agonist 8-OH-DPAT significantly inhibited the spontaneous inhibitory postsynaptic currents(sIPSCs) of GABAergic and glycinergic inputs and also caused significantly amplitude decrease of the GABAergic currents evoked by stimulation of NTS,whereas it had no effect on the miniature inhibitory postsynaptic currents(mIPSCs) of GABAergic and glycinergic inputs.8-OH-DPAT had no effect on the currents evoked by exogenous GABA and glycine and had no effect on the glutamatergic spontaneous excitatory postsynaptic currents(sEPSCs).These findings suggested that 5-HT_(1A/7) receptor agonist might excite CVPNs through inhibition of their GABAergic and glycinergic inputs.This conclusion at least in part revealed the synaptic mechanisms involved in the 5-HT mediated reflex control of cardiac vagal tone.
2.Tracer application directly to the RLN only labeled the putative APPNs within the compact portion of the nucleus ambiguous(cNA),while tracer injection into the tracheal wall labeled the putative APPNs both in cNA and in the area ventro/ventrolateral to cNA(vNA).The putative APPNs within cNA receive mainly inhibitory synaptic inputs,which in some neurons showed an inspiratory-related augmentation and in others showed an inspiratory-related attenuation.The putative APPNs in vNA received both excitatory and inhibitory synaptic inputs,and central inspiratory activity excited some of them via augmentation of their excitatory inputs and inhibited others via augmentation of their inhibitory inputs.The APPNs inhibited during inspiration might be expiration-related or postinspiratory-related motoneurons and others excited during inspiration might be inspiratory-related motoneurons. Theses results provide evidence that APPNs controlling different segments of the airway might be dissociated in the ventrolateral medulla both anatomically and in functional control.
In addition,we recorded the gap junction currents(GJCs) in single inspiratory APPN(I-APPN) by elimination of the transmembrane electrochemical gradients in voltage patch-clamp recording.The GJCs were rhythmically activated by central inspiration activity.These findings indicated that gap junctions exist in the APPNs and might play an important role in the synchronization of the central respiratory neurons. This method may be used as a fast way to detect GJCs within spontaneously active neuronal network.
The study about the effect of 5-HT on the synaptic inputs of APPNs is still on the way.
以往对心肺迷走神经节前神经元的膜片钳研究主要关注的是心迷走节前神经元[cardiac vagal(parasympathetic)preganglionic neurons,CVPNs],其中枢定位及突触支配和调制的研究已经取得了一定的成果,而对肺迷走神经节前神经元突触支配及调制的研究则开展得很少。因此,本论文的研究目的分为三部分:一,研究5-HT对CVPNs突触支配的调节作用。二,研究呼吸道副交感节前神经元[airway-related parasympathetic(vagal)preganglionic neurons,APPNs]在中枢的解剖定位及电生理特性。三,研究5-HT对APPNs突触支配的调节作用。
本实验以2-6天SD大鼠为研究对象,先用荧光染料逆行标记目的神经元,在离体延髓脑片上采用全细胞膜片钳模式对神经元进行研究。结果和结论如下:
一、5-HT_(1A/7)受体激动剂8-OH-DPAT显著抑制CVPNs的自发性GABA能和甘氨酸能抑制性突触后电流(spontaneous inhibitory postsynaptic currents,sIPSCs)的频率和幅度,显著抑制刺激NTS引起的GABA能突触后电流,而对微小的GABA能和甘氨酸能抑制性突触后电流(miniature inhibitory postsynapticcurrents,mIPSCs)、外源性GABA和外源性甘氨酸引起的突触后电流及自发的谷氨酸能兴奋性突触后电流(spontaneous excitatory postsynaptic currents,sEPSCs)均没有明显作用。这些结果提示5-HT_(1A/7)受体激动剂通过突触前机制抑制GABA能和甘氨酸能突触传入间接兴奋CVPNs。这可能是5-HT参与心迷走神经反射调控的机制之一。
二、通过喉返神经标记的APPNs均位于疑核致密部,而通过气管壁标记的APPNs位于疑核致密部或疑核腹侧/腹外侧。位于疑核致密部的APPNs主要接受抑制性GABA能和甘氨酸能突触传入,其中部分神经元这些抑制性突触传入在吸气期间增加,而在另外部分神经元减少;位于疑核腹侧/腹外侧的APPNs除了接受抑制性GABA能和甘氨酸能突触传入外,还接受兴奋性谷氨酸能突触传入,部分神经元在吸气时抑制性突触传入增加从而被抑制,而另外部分神经元在吸气时兴奋性突触传入增加从而被兴奋。吸气时抑制性突触传入增加提示这些神经元在吸气期被抑制,在功能上可能是与呼气或后吸气相关的,而吸气时抑制性突触传入减少或兴奋性突触传入增加提示这些神经元在吸气期兴奋,在功能上可能是与吸气相关的。这些结果表明支配呼吸道不同节段的副交感节前神经元在中枢的定位及功能是分离的。
此外,我们采用消除细胞跨膜电化学梯度的方法,在单个吸气性呼吸道副交感节前神经元(inspiratory airway-related parasympathetic preganglionic neurons,I-APPNs)上成功记录到了电突触电流(gap junction currents,GJCs),并且这些GJCs与呼吸活动是密切相关的。这个结果提示电突触存在于APPNs中,并且可能在呼吸中枢神经元电活动的同步性中起重要作用。这种记录方法可用于快速探测具有自发活动的神经元网络中的GJCs。
关于5-HT对APPNs突触支配的调控作用这一部分实验还处于研究阶段,需要在接下来的时间里继续探索。
5-hydroxytryptamine(serotonin,5-HT),an indolamine that is widely distributed in the peripheral tissue and central nervous system,is involved in a large variety of physiological functions and pathogenesis including pain modulation,sleep,endocrine, cardiopulmonary function and psychiatric disorders such as depression,anxiety and aggressiveness.Anatomical studies have found that 5-HT containing neurons are mainly within the raphe nuclei(pallidus,obscurus,magnus).Serotonergic neurons project to the whole brain and synapse upon many kind of neurons.In recent years, many in vivo electrophysiological studies have shown that 5-HT plays an important role in mediating the reflex control of cardiopulmonary functions,which involves many receptor subtypes including 5-HT_1,5-HT_2,5-HT_3,5-HT_4,5-HT_7.Blocking 5-HT_(1A) or 5-HT_7.receptors attenuated bradycardias evoked by stimulating baroreceptor and cardiopulmonary afferents.In the nucleus tractus solitarius(NTS), 5-HT_2 receptors had variable effects;5-HT_(2B) receptors excite and 5-HT_(2C) receptors inhibit.However,little is known about the neural pathway and the synaptic mechanisms.Using patch-clamp techniques to study the effect of 5-HT on the synaptic inputs of cardiopulmonary vagal preganglionic neurons is important to elucidate the reflex control of cardiopulmonary functions at the synaptic level.
Previous studies have made much progress about the central distribution and the synaptic control of cardiac vagal preganglionic neurons(CVPNs).With respect to pulmonary vagal preganglionic neurons,the study is scarce.So,our aim is to investigate:(1) the effect of 5-HT on the synaptic inputs of CVPNs.(2) the central distribution and electrophysiological characteristics of airway-related parasympathetic preganglionic neurons(APPNs).(3)the effect of 5-HT on the synaptic inputs of APPNs.
The CVPNs were retrogradely labeled by injecting rhodamine into the fat pads of the heart or into the cardiac sac of 2-6-day-old Sprague-Dawley rats and the APPNs were retrogradely labeled by injecting rhodamine into the recurrent laryngeal nerve (RLN) or tracheal wall.The CVPNs and APPNs were identified by the presence of fluorescence in brainstem slices and studied using whole cell patch-clamp recording technique.
Following are the results and conclusions:
1.5-HT_(1A/7) receptor agonist 8-OH-DPAT significantly inhibited the spontaneous inhibitory postsynaptic currents(sIPSCs) of GABAergic and glycinergic inputs and also caused significantly amplitude decrease of the GABAergic currents evoked by stimulation of NTS,whereas it had no effect on the miniature inhibitory postsynaptic currents(mIPSCs) of GABAergic and glycinergic inputs.8-OH-DPAT had no effect on the currents evoked by exogenous GABA and glycine and had no effect on the glutamatergic spontaneous excitatory postsynaptic currents(sEPSCs).These findings suggested that 5-HT_(1A/7) receptor agonist might excite CVPNs through inhibition of their GABAergic and glycinergic inputs.This conclusion at least in part revealed the synaptic mechanisms involved in the 5-HT mediated reflex control of cardiac vagal tone.
2.Tracer application directly to the RLN only labeled the putative APPNs within the compact portion of the nucleus ambiguous(cNA),while tracer injection into the tracheal wall labeled the putative APPNs both in cNA and in the area ventro/ventrolateral to cNA(vNA).The putative APPNs within cNA receive mainly inhibitory synaptic inputs,which in some neurons showed an inspiratory-related augmentation and in others showed an inspiratory-related attenuation.The putative APPNs in vNA received both excitatory and inhibitory synaptic inputs,and central inspiratory activity excited some of them via augmentation of their excitatory inputs and inhibited others via augmentation of their inhibitory inputs.The APPNs inhibited during inspiration might be expiration-related or postinspiratory-related motoneurons and others excited during inspiration might be inspiratory-related motoneurons. Theses results provide evidence that APPNs controlling different segments of the airway might be dissociated in the ventrolateral medulla both anatomically and in functional control.
In addition,we recorded the gap junction currents(GJCs) in single inspiratory APPN(I-APPN) by elimination of the transmembrane electrochemical gradients in voltage patch-clamp recording.The GJCs were rhythmically activated by central inspiration activity.These findings indicated that gap junctions exist in the APPNs and might play an important role in the synchronization of the central respiratory neurons. This method may be used as a fast way to detect GJCs within spontaneously active neuronal network.
The study about the effect of 5-HT on the synaptic inputs of APPNs is still on the way.
引文
1. Loewy AD, Spyer KM. Central regulation of autonomic function. Oxford University Press, New York. eds. 1990.
2. Mendelowitz D. Advances in Parasympathetic Control of Heart Rate and Cardiac Function. News Physiol Sci 1999; 14:155-161.
3. Steinbusch HWM. Distribution of serotonin immunoreactivity in the central nervous system of the rat - cell bodies and terminals. Neuroscience 1981; 6: 557-618.
4. Sykes RM, Spyer KM, Izzo PN. Central distribution of substance P, Calcitonin gene-related peptide, 5-hydroxytryptamine in vagal sensory afferents in the rat dorsal medulla. Neuroscience 1994; 59:195-210.
5. Izzo PN, Jordan D, Ramage AG. Anatomical and pharmacological evidence supporting the involvement of serotonin in the central control of cardiac vagal motoneurones in the anaesthetized cat. J Physiol (London) 1988; 406:19P.
6. Izzo PN, Deuchars J, Spyer KM. Localization of cardiac vagal preganglionic motoneurones in the rat: Immunocytochemical evidence of synaptic inputs containing 5-hydroxytryptamine. J Comp Neurol 1993; 327:572-583.
7. Ramage AG, Fozard JR. Evidence that the putative 5-HT_(1A) receptor agonists, 8-OH-DPAT, ipsapirone, have a central hypotensive action that differs from that of clonidine in anaesthetised cats. Eur J Pharmacol 1987; 138:179-191.
8. McCall RB, Escandon NA, Harris LT, Clement ME. Tolerance development to the vagal-mediated bradycardia produced by 5-HTIA receptor agonists. J. Pharmacol. Exp Ther 1994; 271:777-781.
9. McCall RB, Escandon NA, Harris LT, Clement ME, Shepheard SL, Jordan D et al. Comparison of the effects of IVth ventricular administration of some tryptamine analogues with those of 8-OH-DPAT on autonomic outflow in the anaesthetized cat. Br J Pharmacol 1994; 111:616-624.
10. Shepheard SL , Jordan D, Ramage AG. Comparison of the effects of IVth ventricular administration of some tryptamine analogues with those of 8-OH-DPAT on autonomic outflow in the anaesthetized cat. Br J Pharmacol 1994; 111(2):616-624.
11. Sporton SCE, Shepheard SL, Jordan D, Ramage AG. Microinjections of 5-HT_(1A) agonists into the dorsal motor vagal nucleus produce a bradycardia in the atenolol-pretreated anaesthetized rat. Br J Pharmacol 1991; 104:467-470.
12. Chitravanshi VC, Calaresu FR. Additive effects of dopamine and 8-OH-DPAT microinjected into the nucleus ambiguus in eliciting vagal bradycardia in rats. J Auto Nerv Syst 1992; 41:121-128.
13. Wang Y, Ramage AG. The role of central 5-HT (1A) receptors in the control of B-fibre cardiac and bronchoconstrictor vagal preganglionic neurones in anaesthetized cats. J Physiol (London) 2001; 536(Pt3): 753-767.
14. Bogle RG, Pires JGP, Ramage AG. Evidence that central 5-HT1A receptors play a role in the von Bezold-Jarisch reflex in the rat. Br J Pharmacol 1990 ; 100:757-760.
15. Skinner MR, Ramage AG, Jordan D. Effect of antagonism of central 5-HT_(1A) receptors on baroreceptor and cardiopulmonary receptor reflexes in anaesthetized rabbits. J Physiol (London) 1998; 513P: 85P.
16. Dando SB, Skinner MR, Jordan D, Ramage AG. Modulation of the vagal bradycardia evoked by stimulation of upper airway receptors by central 5-HTi receptors in anaesthetized rabbits. Br J Pharmacol 1998; 125: 409-417.
17. Colino A, Halliwell JV. Differential modulation of three separate K-conductances in hippocampal CA1 neurons by serotonin. Nature 1987; 328:73-77.
18. Melena J, Chidlow G, Osborne NN. Blockade of voltage-sensitive Na(+) channels by the 5-HT(1A) receptor agonist 8-OH-DPAT: possible significance for neuroprotection. Eur J Pharmacol 2000; 406(3):319-324.
19. Wang X, Dergacheva O, Kamendi H, Gorini C, Mendelowitz D. 5-Hydroxytryptamine 1A/7 and 4{alpha} Receptors Differentially Prevent Opioid-Induced Inhibition of Brain Stem Cardiorespirato-ry Function. Hypertension, 2007; doi:10.1161/HYPERTENSION-AHA.107.091009.
20. Haxhiu MA, Jansen ASP, Cherniack NS and Loewy AD. CNS innervation of airway-related parasympathetic preganglionic neurons: a transneuronal labeling study using pseudorabies virus. Brain Res 1993; 618:115-134.
21. Manaker S and Verderame HM. Organization of serotonin 1A and 1B receptors in the nucleus of the solitary tract. J Comp Neurol 1990; 301: 535-553.
22. Thor KB, Blitz-Siebert A and Helke CJ. Autoradiographic localization of 5HT_1 binding sites in autonomic areas of the rat dorsomedial medulla oblongata. Synapse 1992; 10: 217-227.
23. Pompeiano M, Palacios JM and Mengod G. Distribution of the serotonin 5-HT_2 receptor family mRNAs: comparison between 5-HT_(2A) and 5-HT_(2C) receptors. Mol Brain Res, 1994; 23: 163-178.
24. Steward LJ, West KE, Kilpatrick GJ and Barnes NM. Labeling of 5-HT3 receptor recognition sites in the rat brain using the agonist radioligand [3H] meta-chlorophenylbiguanide. Eur J Pharmacol 1993; 243: 13-18.
25. Oliver KR, Kinsey AM, Wainwright A and Sirinathsinghji DJ. Localization of 5-HT_(5A) receptor-like immunoreactivity in the rat brain. Brain Res 2000; 867: 131-142.
26. Gustafson EL, Durkin MM, Bard JA, Zgombick J and Branchek TA. A receptor autoradiographic and in situ hybridization analysis of the distribution of the 5-ht7 receptor in rat brain. Br J Pharmacol 1996; 117: 657-666.
27. Brooks PA and Albert AP. 5-HT3 receptors in the dorsal vagal complex. In serotonin and the scientific basis of anti-emetic therapy, ed Reynolds DJM, Andrews PLR and Davis CJ, 1995; PP. 106-110. Oxford Clinical Communication. Oxford.
28. Wang Y, Ramage AG and Jordan D. Mediation by 5-HT3 receptors of an excitatory effect of 5-HT on dorsal vagal preganglionic neurons in anaesthetized rats: an ionophoretic study. Br J Pharmacol, 1996; 118: 1697-1704.
29. Sevoz-Couche C, Spyer KM, Jordan D. In vivo modulation of vagal-identified dorsal medullary neurones by activation of different 5-Hydroxytryptamine (2) receptors in rats. Br J Pharmacol. 2000 Dec; 131(7): 1445-53.
30. Sevoz-Couche C, Wang Y, Ramage AG, Spyer KM, Jordan D. In vivo modulation of nucleus tractus solitarius (NTS) neurones by activation of 5-hydroxytryptamine (2) receptors in rats. Neuropharmacology. 2000 Aug 23; 39(11):2006-16.
31. Kellett DO, Ramage AG, Jordan D. Central 5-HT7 receptors are critical for reflex activation of cardiac vagal drive in anaesthetized rats. J Physiol. 2005 Feb 15; 563 (Pt 1):319-31. Epub 2004 Dec 20.
1. Akasu T & Nishimura T (1995). Synaptic transmission and function of parasympathetic ganglia. Prog Neurobiol 45, 459-522.
2. Coburn RF (1984). Neural coordination of excitation of ferret tra-chealis muscle. Am J Physiol Cell Physiol 246, C459-C466.
3. Myers AC, Undem BJ &Weinreich D (1990). Electrophysiological properties of neurons in guinea pig bronchial parasympathetic ganglia. Am J Physiol Lung Cell Mol Physiol 259, L403-L409.
4. Waldbaum S, Hadziefendic S, Erokwu B, Zaidi SIA & Haxhiu MA (2001). CNS innervation of posterior cricoarytenoid muscles: a transneuronal labeling study. Resp Physiol 126, 113-125.
5. Haxhiu MA, Jansenb ASP, Cherniack NS & Loewy AD (1993). CNS innervation of airway-related parasympathetic preganglionic neurons: a transneuronal labeling study using pseudorabies virus. Brain Res 618, 115-134.
6. Hadziefendic S & Haxhiu MA (1999). CNS innervation of vagal preganglionic neurons controlling peripheral airways: a transneuronal labeling study using pseudorabies virus. J Auton Nerv Syst 76, 135-145.
7. Irnaten M, Neff RA,Wang J, Loewy AD, Mettenleiter TC & Mendelowitz D (2001a). Activity of cardiorespiratory networks revealed by transsynaptic virus expressing GFP. J Neurophysiol 85, 435-438.
8. Irnaten M,Wang J & Mendelowitz D (2001b). Firing properties of identified superior laryngeal neurons in the nucleus ambiguus in the rat. Neurosci Lett 303, 1-4.
9. Barazzoni AM, Clavenzani P, Chiocchetti R, Bompadre GA, Grandis A, Petrosino G, Costerbosa GL & Bortolami R (2005). Localisation of recurrent laryngeal nerve motoneurons in the sheep by means of retrograde fluorescent labeling. Res Vet Sci 78, 249-253.
10. Okano H, Toyoda KI, Bamba H, Hisa Y, Oomura Y, Imamura T, Furukawa S, Kimura H & Tooyama I (2006). Localization of fibroblast growth factor-1 in cholinergic neurons innervating the rat larynx. J Histochem Cytochem 54, 1061-1071.
11. Fox EA & Powley TL (1989). False-positive artifacts of tracer strategies distort autonomic connectivity maps. Brain Res Rev 14, 53-77.
12. Meier C, Dermietzel R. Electrical synapses — gap junctions in the brain. Results Probl Cell Differ 2006; 43: 99-128.
13. Solomon IC, Halat TJ, El-Maghrabi R, O'Neal MH. Differential expression of connexin26 and connexin32 in the pre-Botzinger complex of neonatal and adult rat. J Comp Neurol 2001; 440(1): 12-19.
14. Rekling JC, Shao XM, Feldman JL. Electrical coupling and excitatory synaptic transmission between rhythmogenic respiratory neurons in the preBotzinger complex. J Neurosci 2000; 20(23): RC113.
15. Wang J, Irnaten M, Venkatesan P, Evans C, Baxi S, Mendelowitz D. Synaptic activation of hypoglossal respiratory motoneurons during inspiration in rats. Neurosci Lett 2002; 332(3): 195-199.
16. Rekling JC, Feldman JL. Bidirectional electrical coupling between inspiratory motoneurons in the newborn mouse nucleus ambiguus. J Neurophysiol 1997; 78(6): 3508-3510.
17. Smith JC, Ellenberger HH, Ballanyi K, Richter DW, Feldman JL. Pre-Botzinger complex: a brainstem region that may generate respiratory rhythm in mammals. Science 1991; 254 (5032): 726-729.
18. Irnaten M, Neff RA,Wang J, Loewy AD, Mettenleiter TC & Mendelowitz D (2001a). Activity of cardiorespiratory networks revealed by transsynaptic virus expressing GFP. J Neurophysiol 85, 435-438.
19. Irnaten M, Wang J & Mendelowitz D (2001b). Firing properties of identified superior laryngeal neurons in the nucleus ambiguus in the rat. Neurosci Lett 303, 1-4.
20. Barazzoni AM, Clavenzani P, Chiocchetti R, Bompadre GA, Grandis A, Petrosino G, Costerbosa GL & Bortolami R (2005). Localization of recurrent laryngeal nerve motoneurons in the sheep by means of retrograde fluorescent labeling. Res Vet Sci 78, 249-253.
21. Okano H, Toyoda KI, Bamba H, Hisa Y, Oomura Y, Imamura T, Furukawa S, Kimura H & Tooyama I (2006). Localization of fibroblast growth factor-1 in cholinergic neurons innervating the rat larynx. J Histochem Cytochem 54, 1061-1071.
22. Barillot JC, Grelot L, Reddad S & Bianchi AL (1990). Discharge patterns of laryngeal motoneurones in the cat: an intracellular study. Brain Res 509, 99-106.
23. Ono K, Shiba K, Nakazawa K & Shimoyama I (2006). Synaptic origin of the respiratory-modulated activity of laryngeal motoneurons. Neuroscience 140, 1079-1088.
24. Hayakawa T, Takanaga A, Maeda S, Ito H & Seki M (2000). Monosynaptic inputs from the nucleus tractus solitarii to the laryngeal motoneurons in the nucleus ambiguous of the rat. Anat Embryol (Berl) 202, 411—420.
25. Liebermann-Meffert DM,Walbrun B, Hiebert CA & Siewert JR (1999). Recurrent and superior laryngeal nerves: a new look with implications for the esophageal surgeon. Ann Thorac Surg 67, 217-223.
26. Kruszewska B, Lipski J & Kanjhan R (1994). An electrophysiological and morphological study of esophageal motoneurons in rats. Am J Physiol Regul Integr Comp Physiol 266, R622-R632.
27. Bartlett DJ (1986). Upper airway motor systems. In Handbook of Physiology, section 3, The Respiratory System,vol. II, ed. Cherniack NS &Widdicombe JG, pp. 223-245. American Physiological Society, Bethesda, MD, USA.
28. Baker DG (1986). Parasympathetic motor pathways to the trachea: recent morphologic and electrophysiologic studies. Clin Chest Med 7, 223-229.
29. Paton JF, Ramirez JM & Richter DW(1994). Mechanisms of respiratory rhythm generation change profoundly during early life in mice and rats. Neurosci Lett 170, 167-170.
30. Denavit-Saubie M, Kalia M, Pierrefiche O, Schweitzer P, Foutz AS & Champagnat J (1994). Maturation of brain stem neurons involved in respiratory rhythmogenesis: biochemical, bioelectrical and morphological properties. Biol Neonate 65, 171-175.
31. Onimaru H & Homma I (2002). Development of the rat respiratory neuron network during the late fetal period. Neurosci Res 42, 209-218.
32. Grkovic I, Fernandez K, McAllen RM & Anderson CR (2005). Misidentification of cardiac vagal pre-ganglionic neurons after injections of retrograde tracer into the pericardial space in the rat. Cell Tissue Res 321, 335-340.
1. Mendelowitz D. Advances in parasympathetic control of heart rate and cardiac function. News Physiol Sci, 1999 , 14 :155-161.
2. Loewy AD , Spyer KM. Central regulation of autonomic function. Oxford University Press , New York , 1990.
3. McAllen RM, Spyer KM. 1976. The location of cardiac vagal preganglionic motoneurones in the medulla of the cat. J Physiol 258(1):187-204.
4. McAllen RM, Spyer KM. 1978. Two types of vagal preganglionic motoneurones projecting to the heart and lungs. J Physiol 282:353-364.
5. Ciriello J, Calaresu FR. 1980. Distribution of vagal cardioinhibitory neurons in the medulla of the cat. Am J Physiol 238(1):R57-64.
6. Nosaka S, Yasunaga K, Tamai S. 1982. Vagal cardiac preganglionic neurons: distribution, cell types, and reflex discharges. Am J Physiol 243(1):R92-98.
7. Izzo Pn, Deuchars J, Spyer KM. Localization of cardiac vagal preganglionic motoneurones in the rat: immunocytochemical evidence of synaptic inputs containing 52hydroxytryptamine. J Comp Neurol, 1993 , 327 : 572—-583.
8. Mendelowitz D. Firing properties of identified parasympathetic cardiac neurons innucleus ambiguous. Am J Physiol. 271(6Pt2):H2609-14,1996.
9. Mendelowitz D, Kunze DL. Identification and dissociation of cardiovascular neurons from the medulla for patch clamp analysis. Neurosci. Lett. 132(1991):217-221.
10. Mihalevich M, Neff R, Mendelowitz D. Voltage gated currents in identified cardiac vagal neurons in the nucleus ambiguous. Brain Res. 739(1-2)(1996): 258-262.
11. Gilbey MP, Jordan D, Richter DW, Spyer KM. Synaptic mechanisms involved in the inspiratory modulation of vagal cardio-inhibitory neurones in the cat. J Physiol. 1984 Nov;356:65-78.
12. Robert A.Neff, Michael K.Hansen, David Mendelowitz. Acetylcholine activates a nicotinic receptor and an inward current in dorsal motor nucleus of the vagus neurons in vitro. Neuroscience Letters 195(3)163-6,1995.
13. Krammer EB, Streinzer W, Millesi W, Ellbock E, Zrunek M. Central localization of motor components in the internal branch of the superior laryngeal nerve: a horseradish peroxidase study in the rat. Laryngol Rhinol Otol (Stuttg). 1986 Nov;65(11):617-20.Links
14. Mendelowitz D. Superior laryngeal neurons directly excite cardiac vagal neurons within the nucleus ambiguous. Brain Res Bull,2000, 51 :135—138.
15. Lanier B, Richardson MA, Cummings C. Effect of hypoxia on laryngeal reflex apnea—implications for sudden infant death. Otolaryngol Head Neck Surg. 1983 Dec;91(6):597-604.
16. Van Der Velde L, Curran AK, Filiano JJ, Darnall RA, Bartlett D Jr, Leiter JC. Prolongation of the laryngeal chemoreflex after inhibition of the rostral ventral medulla in piglets: a role in SIDS? J Appl Physiol. 2003 May;94(5): 1883-95
17. Neff RA, Mihalevich M, Mendelowitz D. Stimulation of NTS activates NMDA and non-NMDA receptors in rat cardiac vagal neurons in the nucleus ambiguous. Brain Res , 1998 , 792 :277-282.
18. Neff RA, Humphrey J , Mihalevich M, et al. Nicotine enhances presynaptic and postsynaptic glutamatergic neurotransmission to activate cardiac parasympathetic neurons. Circ Res , 1998 , 83 : 1241 - 1247.
19. Mendelowitz D.Nicotine excites cardiac vagal neurons via three sites of action. Clin Exp Pharmacol Physiol, 1998 , 25 :453-456.
20. Wang J, Irnaten M, Mendelowitz D. Characteristics of spontaneous and evoked GABAergic synaptic currents in cardiac vagal neurons in rats. Brain Res , 2001 , 889 :78-83.
21. Wang J, Wang X, Irnaten M, Venkatesan P, Evans C, Baxi S, Mendelowitz D. Endogenous acetylcholine and nicotine activation enhances GABAergic and glycinergic inputs to cardiac vagal neurons. J Neurophysiol. 2003 May;89(5):2473-81. Epub 2003 Jan 22.
22. Venkatesan P, Baxi S , Evans C , et al. Glycinergic inputs to cardiac vagal neurons in the nucleus ambiguous are inhibited by nociceptin and (micro )-selective opioids. J Neurophysiol, 2003 , 90 :1581 — 1588.
23. Venkatesan P, Wang J , Evans C , et al. Nociceptin inhibits gamma-aminobutyric acidergic inputs to cardiac parasympathetic neurons in the nucleus ambiguous. J Pharmacol Exp Ther, 2002 , 300 :78-82.
24. Wang J, Irnaten M, Venkatesan P, Evans C and Mendelowitz D. Arginine vasopressin enhances GABAergic inhibition of cardiac parasympathetic neurons in the nucleus ambiguous.
25. Irnaten M,. Walwyn WM, Wang J, Venkatesan P, Evans C, Kyoung SK Chang, Andresen MC, Hales TG, Mendelowitz D. Pentobarbital enhances GABAergic neurotransmission to cardiac parasympathetic neurons, which is prevented by expression of GABA_A ∈ subunit. Anesthesiology 2002; 97:717-24.
26. Irnaten M, Wang J, Kyoung SK Chang, Andresen MC, Mendelowitz D. Ketamine inhibits sodium currents in identified cardiac parasympathetic neurons in nucleus ambiguus. Anesthesiology 2002; 96:659-66.
27. Hayano J, Yasuma F, Okada A, Mukai S, Fujinami T. Respiratory sinus arrhythmia: a phenomenon improving pulmonary gas exchange and circulatory efficiency. Circulation. 1996;94:842-847.
28. Loewy AD, Spyer KM, eds. Central Regulation of Autonomic Functions. New York, NY: Oxford University Press; 1990.
29. Taylor EW, Jordan D, Coote JH. Central control of the cardiovascular and respiratory systems and their interactions in vertebrates. Physiol Rev. 1999;79:855-916.
30. Hathorn MK. Respiratory sinus arrhythmia in new-born infants. J Physiol. 1987;385:1-12.
31. Neff RA, Wang J, Baxi S, Evans C, Mendelowitz D. Respiratory sinus arrhythmia: endogenous activation of nicotinic receptors mediates respiratory modulation of brainstem cardioinhibitory parasympathetic neurons. Circ Res. 2003 Sep 19;93(6):565-72. Epub 2003 Aug 7.
32. Buisson B, Bertrand D. Chronic exposure to nicotine upregulates the human (alpha)4((beta)2 nicotinic acetylcholine receptor function. J Neurosci. 2001 Mar 15;21(6):1819-29.
33. Evans C, Wang J, Neff R, Mendelowitz D. Hypoxia recruits a respiratory-related excitatory pathway to brainstem premotor cardiac vagal neurons in animals exposed to prenatal nicotine. Neuroscience. 2005;133(4):1073-9.
34. Anderson RN. Deaths: leading causes for 2000. National Vital Statistics Reports. 2002,50:11.
35. Bulterys MG, Greenland S, Kraus JF. Chronic fetal hypoxia and sudden infant death syndrome: interaction between maternal smoking and low hematocrit during pregnancy. Pediatrics ,1990; 86:535-540.
36. Haglund B, Cnattinglus S. Cigarette smoking as a risk factor for sudden infant death syndrome: a population-based study. Am J Public Health, 1990;80:29-32.
37. Meny RG, Carroll JL, Carbone MT, Kelly DH. Cardiorespiratory recording from infants dying suddenly and unexpectedly at home. Pediatrics, 1994; 93:44-49.
38. Hunt CE. Sudden infant death syndrome and other cause of infant mortality: diagnosis, mechanisms, and risk of recurrence in siblings. Am J Respir Cirt Care Med,2001; 164:346-357.
2. Mendelowitz D. Advances in Parasympathetic Control of Heart Rate and Cardiac Function. News Physiol Sci 1999; 14:155-161.
3. Steinbusch HWM. Distribution of serotonin immunoreactivity in the central nervous system of the rat - cell bodies and terminals. Neuroscience 1981; 6: 557-618.
4. Sykes RM, Spyer KM, Izzo PN. Central distribution of substance P, Calcitonin gene-related peptide, 5-hydroxytryptamine in vagal sensory afferents in the rat dorsal medulla. Neuroscience 1994; 59:195-210.
5. Izzo PN, Jordan D, Ramage AG. Anatomical and pharmacological evidence supporting the involvement of serotonin in the central control of cardiac vagal motoneurones in the anaesthetized cat. J Physiol (London) 1988; 406:19P.
6. Izzo PN, Deuchars J, Spyer KM. Localization of cardiac vagal preganglionic motoneurones in the rat: Immunocytochemical evidence of synaptic inputs containing 5-hydroxytryptamine. J Comp Neurol 1993; 327:572-583.
7. Ramage AG, Fozard JR. Evidence that the putative 5-HT_(1A) receptor agonists, 8-OH-DPAT, ipsapirone, have a central hypotensive action that differs from that of clonidine in anaesthetised cats. Eur J Pharmacol 1987; 138:179-191.
8. McCall RB, Escandon NA, Harris LT, Clement ME. Tolerance development to the vagal-mediated bradycardia produced by 5-HTIA receptor agonists. J. Pharmacol. Exp Ther 1994; 271:777-781.
9. McCall RB, Escandon NA, Harris LT, Clement ME, Shepheard SL, Jordan D et al. Comparison of the effects of IVth ventricular administration of some tryptamine analogues with those of 8-OH-DPAT on autonomic outflow in the anaesthetized cat. Br J Pharmacol 1994; 111:616-624.
10. Shepheard SL , Jordan D, Ramage AG. Comparison of the effects of IVth ventricular administration of some tryptamine analogues with those of 8-OH-DPAT on autonomic outflow in the anaesthetized cat. Br J Pharmacol 1994; 111(2):616-624.
11. Sporton SCE, Shepheard SL, Jordan D, Ramage AG. Microinjections of 5-HT_(1A) agonists into the dorsal motor vagal nucleus produce a bradycardia in the atenolol-pretreated anaesthetized rat. Br J Pharmacol 1991; 104:467-470.
12. Chitravanshi VC, Calaresu FR. Additive effects of dopamine and 8-OH-DPAT microinjected into the nucleus ambiguus in eliciting vagal bradycardia in rats. J Auto Nerv Syst 1992; 41:121-128.
13. Wang Y, Ramage AG. The role of central 5-HT (1A) receptors in the control of B-fibre cardiac and bronchoconstrictor vagal preganglionic neurones in anaesthetized cats. J Physiol (London) 2001; 536(Pt3): 753-767.
14. Bogle RG, Pires JGP, Ramage AG. Evidence that central 5-HT1A receptors play a role in the von Bezold-Jarisch reflex in the rat. Br J Pharmacol 1990 ; 100:757-760.
15. Skinner MR, Ramage AG, Jordan D. Effect of antagonism of central 5-HT_(1A) receptors on baroreceptor and cardiopulmonary receptor reflexes in anaesthetized rabbits. J Physiol (London) 1998; 513P: 85P.
16. Dando SB, Skinner MR, Jordan D, Ramage AG. Modulation of the vagal bradycardia evoked by stimulation of upper airway receptors by central 5-HTi receptors in anaesthetized rabbits. Br J Pharmacol 1998; 125: 409-417.
17. Colino A, Halliwell JV. Differential modulation of three separate K-conductances in hippocampal CA1 neurons by serotonin. Nature 1987; 328:73-77.
18. Melena J, Chidlow G, Osborne NN. Blockade of voltage-sensitive Na(+) channels by the 5-HT(1A) receptor agonist 8-OH-DPAT: possible significance for neuroprotection. Eur J Pharmacol 2000; 406(3):319-324.
19. Wang X, Dergacheva O, Kamendi H, Gorini C, Mendelowitz D. 5-Hydroxytryptamine 1A/7 and 4{alpha} Receptors Differentially Prevent Opioid-Induced Inhibition of Brain Stem Cardiorespirato-ry Function. Hypertension, 2007; doi:10.1161/HYPERTENSION-AHA.107.091009.
20. Haxhiu MA, Jansen ASP, Cherniack NS and Loewy AD. CNS innervation of airway-related parasympathetic preganglionic neurons: a transneuronal labeling study using pseudorabies virus. Brain Res 1993; 618:115-134.
21. Manaker S and Verderame HM. Organization of serotonin 1A and 1B receptors in the nucleus of the solitary tract. J Comp Neurol 1990; 301: 535-553.
22. Thor KB, Blitz-Siebert A and Helke CJ. Autoradiographic localization of 5HT_1 binding sites in autonomic areas of the rat dorsomedial medulla oblongata. Synapse 1992; 10: 217-227.
23. Pompeiano M, Palacios JM and Mengod G. Distribution of the serotonin 5-HT_2 receptor family mRNAs: comparison between 5-HT_(2A) and 5-HT_(2C) receptors. Mol Brain Res, 1994; 23: 163-178.
24. Steward LJ, West KE, Kilpatrick GJ and Barnes NM. Labeling of 5-HT3 receptor recognition sites in the rat brain using the agonist radioligand [3H] meta-chlorophenylbiguanide. Eur J Pharmacol 1993; 243: 13-18.
25. Oliver KR, Kinsey AM, Wainwright A and Sirinathsinghji DJ. Localization of 5-HT_(5A) receptor-like immunoreactivity in the rat brain. Brain Res 2000; 867: 131-142.
26. Gustafson EL, Durkin MM, Bard JA, Zgombick J and Branchek TA. A receptor autoradiographic and in situ hybridization analysis of the distribution of the 5-ht7 receptor in rat brain. Br J Pharmacol 1996; 117: 657-666.
27. Brooks PA and Albert AP. 5-HT3 receptors in the dorsal vagal complex. In serotonin and the scientific basis of anti-emetic therapy, ed Reynolds DJM, Andrews PLR and Davis CJ, 1995; PP. 106-110. Oxford Clinical Communication. Oxford.
28. Wang Y, Ramage AG and Jordan D. Mediation by 5-HT3 receptors of an excitatory effect of 5-HT on dorsal vagal preganglionic neurons in anaesthetized rats: an ionophoretic study. Br J Pharmacol, 1996; 118: 1697-1704.
29. Sevoz-Couche C, Spyer KM, Jordan D. In vivo modulation of vagal-identified dorsal medullary neurones by activation of different 5-Hydroxytryptamine (2) receptors in rats. Br J Pharmacol. 2000 Dec; 131(7): 1445-53.
30. Sevoz-Couche C, Wang Y, Ramage AG, Spyer KM, Jordan D. In vivo modulation of nucleus tractus solitarius (NTS) neurones by activation of 5-hydroxytryptamine (2) receptors in rats. Neuropharmacology. 2000 Aug 23; 39(11):2006-16.
31. Kellett DO, Ramage AG, Jordan D. Central 5-HT7 receptors are critical for reflex activation of cardiac vagal drive in anaesthetized rats. J Physiol. 2005 Feb 15; 563 (Pt 1):319-31. Epub 2004 Dec 20.
1. Akasu T & Nishimura T (1995). Synaptic transmission and function of parasympathetic ganglia. Prog Neurobiol 45, 459-522.
2. Coburn RF (1984). Neural coordination of excitation of ferret tra-chealis muscle. Am J Physiol Cell Physiol 246, C459-C466.
3. Myers AC, Undem BJ &Weinreich D (1990). Electrophysiological properties of neurons in guinea pig bronchial parasympathetic ganglia. Am J Physiol Lung Cell Mol Physiol 259, L403-L409.
4. Waldbaum S, Hadziefendic S, Erokwu B, Zaidi SIA & Haxhiu MA (2001). CNS innervation of posterior cricoarytenoid muscles: a transneuronal labeling study. Resp Physiol 126, 113-125.
5. Haxhiu MA, Jansenb ASP, Cherniack NS & Loewy AD (1993). CNS innervation of airway-related parasympathetic preganglionic neurons: a transneuronal labeling study using pseudorabies virus. Brain Res 618, 115-134.
6. Hadziefendic S & Haxhiu MA (1999). CNS innervation of vagal preganglionic neurons controlling peripheral airways: a transneuronal labeling study using pseudorabies virus. J Auton Nerv Syst 76, 135-145.
7. Irnaten M, Neff RA,Wang J, Loewy AD, Mettenleiter TC & Mendelowitz D (2001a). Activity of cardiorespiratory networks revealed by transsynaptic virus expressing GFP. J Neurophysiol 85, 435-438.
8. Irnaten M,Wang J & Mendelowitz D (2001b). Firing properties of identified superior laryngeal neurons in the nucleus ambiguus in the rat. Neurosci Lett 303, 1-4.
9. Barazzoni AM, Clavenzani P, Chiocchetti R, Bompadre GA, Grandis A, Petrosino G, Costerbosa GL & Bortolami R (2005). Localisation of recurrent laryngeal nerve motoneurons in the sheep by means of retrograde fluorescent labeling. Res Vet Sci 78, 249-253.
10. Okano H, Toyoda KI, Bamba H, Hisa Y, Oomura Y, Imamura T, Furukawa S, Kimura H & Tooyama I (2006). Localization of fibroblast growth factor-1 in cholinergic neurons innervating the rat larynx. J Histochem Cytochem 54, 1061-1071.
11. Fox EA & Powley TL (1989). False-positive artifacts of tracer strategies distort autonomic connectivity maps. Brain Res Rev 14, 53-77.
12. Meier C, Dermietzel R. Electrical synapses — gap junctions in the brain. Results Probl Cell Differ 2006; 43: 99-128.
13. Solomon IC, Halat TJ, El-Maghrabi R, O'Neal MH. Differential expression of connexin26 and connexin32 in the pre-Botzinger complex of neonatal and adult rat. J Comp Neurol 2001; 440(1): 12-19.
14. Rekling JC, Shao XM, Feldman JL. Electrical coupling and excitatory synaptic transmission between rhythmogenic respiratory neurons in the preBotzinger complex. J Neurosci 2000; 20(23): RC113.
15. Wang J, Irnaten M, Venkatesan P, Evans C, Baxi S, Mendelowitz D. Synaptic activation of hypoglossal respiratory motoneurons during inspiration in rats. Neurosci Lett 2002; 332(3): 195-199.
16. Rekling JC, Feldman JL. Bidirectional electrical coupling between inspiratory motoneurons in the newborn mouse nucleus ambiguus. J Neurophysiol 1997; 78(6): 3508-3510.
17. Smith JC, Ellenberger HH, Ballanyi K, Richter DW, Feldman JL. Pre-Botzinger complex: a brainstem region that may generate respiratory rhythm in mammals. Science 1991; 254 (5032): 726-729.
18. Irnaten M, Neff RA,Wang J, Loewy AD, Mettenleiter TC & Mendelowitz D (2001a). Activity of cardiorespiratory networks revealed by transsynaptic virus expressing GFP. J Neurophysiol 85, 435-438.
19. Irnaten M, Wang J & Mendelowitz D (2001b). Firing properties of identified superior laryngeal neurons in the nucleus ambiguus in the rat. Neurosci Lett 303, 1-4.
20. Barazzoni AM, Clavenzani P, Chiocchetti R, Bompadre GA, Grandis A, Petrosino G, Costerbosa GL & Bortolami R (2005). Localization of recurrent laryngeal nerve motoneurons in the sheep by means of retrograde fluorescent labeling. Res Vet Sci 78, 249-253.
21. Okano H, Toyoda KI, Bamba H, Hisa Y, Oomura Y, Imamura T, Furukawa S, Kimura H & Tooyama I (2006). Localization of fibroblast growth factor-1 in cholinergic neurons innervating the rat larynx. J Histochem Cytochem 54, 1061-1071.
22. Barillot JC, Grelot L, Reddad S & Bianchi AL (1990). Discharge patterns of laryngeal motoneurones in the cat: an intracellular study. Brain Res 509, 99-106.
23. Ono K, Shiba K, Nakazawa K & Shimoyama I (2006). Synaptic origin of the respiratory-modulated activity of laryngeal motoneurons. Neuroscience 140, 1079-1088.
24. Hayakawa T, Takanaga A, Maeda S, Ito H & Seki M (2000). Monosynaptic inputs from the nucleus tractus solitarii to the laryngeal motoneurons in the nucleus ambiguous of the rat. Anat Embryol (Berl) 202, 411—420.
25. Liebermann-Meffert DM,Walbrun B, Hiebert CA & Siewert JR (1999). Recurrent and superior laryngeal nerves: a new look with implications for the esophageal surgeon. Ann Thorac Surg 67, 217-223.
26. Kruszewska B, Lipski J & Kanjhan R (1994). An electrophysiological and morphological study of esophageal motoneurons in rats. Am J Physiol Regul Integr Comp Physiol 266, R622-R632.
27. Bartlett DJ (1986). Upper airway motor systems. In Handbook of Physiology, section 3, The Respiratory System,vol. II, ed. Cherniack NS &Widdicombe JG, pp. 223-245. American Physiological Society, Bethesda, MD, USA.
28. Baker DG (1986). Parasympathetic motor pathways to the trachea: recent morphologic and electrophysiologic studies. Clin Chest Med 7, 223-229.
29. Paton JF, Ramirez JM & Richter DW(1994). Mechanisms of respiratory rhythm generation change profoundly during early life in mice and rats. Neurosci Lett 170, 167-170.
30. Denavit-Saubie M, Kalia M, Pierrefiche O, Schweitzer P, Foutz AS & Champagnat J (1994). Maturation of brain stem neurons involved in respiratory rhythmogenesis: biochemical, bioelectrical and morphological properties. Biol Neonate 65, 171-175.
31. Onimaru H & Homma I (2002). Development of the rat respiratory neuron network during the late fetal period. Neurosci Res 42, 209-218.
32. Grkovic I, Fernandez K, McAllen RM & Anderson CR (2005). Misidentification of cardiac vagal pre-ganglionic neurons after injections of retrograde tracer into the pericardial space in the rat. Cell Tissue Res 321, 335-340.
1. Mendelowitz D. Advances in parasympathetic control of heart rate and cardiac function. News Physiol Sci, 1999 , 14 :155-161.
2. Loewy AD , Spyer KM. Central regulation of autonomic function. Oxford University Press , New York , 1990.
3. McAllen RM, Spyer KM. 1976. The location of cardiac vagal preganglionic motoneurones in the medulla of the cat. J Physiol 258(1):187-204.
4. McAllen RM, Spyer KM. 1978. Two types of vagal preganglionic motoneurones projecting to the heart and lungs. J Physiol 282:353-364.
5. Ciriello J, Calaresu FR. 1980. Distribution of vagal cardioinhibitory neurons in the medulla of the cat. Am J Physiol 238(1):R57-64.
6. Nosaka S, Yasunaga K, Tamai S. 1982. Vagal cardiac preganglionic neurons: distribution, cell types, and reflex discharges. Am J Physiol 243(1):R92-98.
7. Izzo Pn, Deuchars J, Spyer KM. Localization of cardiac vagal preganglionic motoneurones in the rat: immunocytochemical evidence of synaptic inputs containing 52hydroxytryptamine. J Comp Neurol, 1993 , 327 : 572—-583.
8. Mendelowitz D. Firing properties of identified parasympathetic cardiac neurons innucleus ambiguous. Am J Physiol. 271(6Pt2):H2609-14,1996.
9. Mendelowitz D, Kunze DL. Identification and dissociation of cardiovascular neurons from the medulla for patch clamp analysis. Neurosci. Lett. 132(1991):217-221.
10. Mihalevich M, Neff R, Mendelowitz D. Voltage gated currents in identified cardiac vagal neurons in the nucleus ambiguous. Brain Res. 739(1-2)(1996): 258-262.
11. Gilbey MP, Jordan D, Richter DW, Spyer KM. Synaptic mechanisms involved in the inspiratory modulation of vagal cardio-inhibitory neurones in the cat. J Physiol. 1984 Nov;356:65-78.
12. Robert A.Neff, Michael K.Hansen, David Mendelowitz. Acetylcholine activates a nicotinic receptor and an inward current in dorsal motor nucleus of the vagus neurons in vitro. Neuroscience Letters 195(3)163-6,1995.
13. Krammer EB, Streinzer W, Millesi W, Ellbock E, Zrunek M. Central localization of motor components in the internal branch of the superior laryngeal nerve: a horseradish peroxidase study in the rat. Laryngol Rhinol Otol (Stuttg). 1986 Nov;65(11):617-20.Links
14. Mendelowitz D. Superior laryngeal neurons directly excite cardiac vagal neurons within the nucleus ambiguous. Brain Res Bull,2000, 51 :135—138.
15. Lanier B, Richardson MA, Cummings C. Effect of hypoxia on laryngeal reflex apnea—implications for sudden infant death. Otolaryngol Head Neck Surg. 1983 Dec;91(6):597-604.
16. Van Der Velde L, Curran AK, Filiano JJ, Darnall RA, Bartlett D Jr, Leiter JC. Prolongation of the laryngeal chemoreflex after inhibition of the rostral ventral medulla in piglets: a role in SIDS? J Appl Physiol. 2003 May;94(5): 1883-95
17. Neff RA, Mihalevich M, Mendelowitz D. Stimulation of NTS activates NMDA and non-NMDA receptors in rat cardiac vagal neurons in the nucleus ambiguous. Brain Res , 1998 , 792 :277-282.
18. Neff RA, Humphrey J , Mihalevich M, et al. Nicotine enhances presynaptic and postsynaptic glutamatergic neurotransmission to activate cardiac parasympathetic neurons. Circ Res , 1998 , 83 : 1241 - 1247.
19. Mendelowitz D.Nicotine excites cardiac vagal neurons via three sites of action. Clin Exp Pharmacol Physiol, 1998 , 25 :453-456.
20. Wang J, Irnaten M, Mendelowitz D. Characteristics of spontaneous and evoked GABAergic synaptic currents in cardiac vagal neurons in rats. Brain Res , 2001 , 889 :78-83.
21. Wang J, Wang X, Irnaten M, Venkatesan P, Evans C, Baxi S, Mendelowitz D. Endogenous acetylcholine and nicotine activation enhances GABAergic and glycinergic inputs to cardiac vagal neurons. J Neurophysiol. 2003 May;89(5):2473-81. Epub 2003 Jan 22.
22. Venkatesan P, Baxi S , Evans C , et al. Glycinergic inputs to cardiac vagal neurons in the nucleus ambiguous are inhibited by nociceptin and (micro )-selective opioids. J Neurophysiol, 2003 , 90 :1581 — 1588.
23. Venkatesan P, Wang J , Evans C , et al. Nociceptin inhibits gamma-aminobutyric acidergic inputs to cardiac parasympathetic neurons in the nucleus ambiguous. J Pharmacol Exp Ther, 2002 , 300 :78-82.
24. Wang J, Irnaten M, Venkatesan P, Evans C and Mendelowitz D. Arginine vasopressin enhances GABAergic inhibition of cardiac parasympathetic neurons in the nucleus ambiguous.
25. Irnaten M,. Walwyn WM, Wang J, Venkatesan P, Evans C, Kyoung SK Chang, Andresen MC, Hales TG, Mendelowitz D. Pentobarbital enhances GABAergic neurotransmission to cardiac parasympathetic neurons, which is prevented by expression of GABA_A ∈ subunit. Anesthesiology 2002; 97:717-24.
26. Irnaten M, Wang J, Kyoung SK Chang, Andresen MC, Mendelowitz D. Ketamine inhibits sodium currents in identified cardiac parasympathetic neurons in nucleus ambiguus. Anesthesiology 2002; 96:659-66.
27. Hayano J, Yasuma F, Okada A, Mukai S, Fujinami T. Respiratory sinus arrhythmia: a phenomenon improving pulmonary gas exchange and circulatory efficiency. Circulation. 1996;94:842-847.
28. Loewy AD, Spyer KM, eds. Central Regulation of Autonomic Functions. New York, NY: Oxford University Press; 1990.
29. Taylor EW, Jordan D, Coote JH. Central control of the cardiovascular and respiratory systems and their interactions in vertebrates. Physiol Rev. 1999;79:855-916.
30. Hathorn MK. Respiratory sinus arrhythmia in new-born infants. J Physiol. 1987;385:1-12.
31. Neff RA, Wang J, Baxi S, Evans C, Mendelowitz D. Respiratory sinus arrhythmia: endogenous activation of nicotinic receptors mediates respiratory modulation of brainstem cardioinhibitory parasympathetic neurons. Circ Res. 2003 Sep 19;93(6):565-72. Epub 2003 Aug 7.
32. Buisson B, Bertrand D. Chronic exposure to nicotine upregulates the human (alpha)4((beta)2 nicotinic acetylcholine receptor function. J Neurosci. 2001 Mar 15;21(6):1819-29.
33. Evans C, Wang J, Neff R, Mendelowitz D. Hypoxia recruits a respiratory-related excitatory pathway to brainstem premotor cardiac vagal neurons in animals exposed to prenatal nicotine. Neuroscience. 2005;133(4):1073-9.
34. Anderson RN. Deaths: leading causes for 2000. National Vital Statistics Reports. 2002,50:11.
35. Bulterys MG, Greenland S, Kraus JF. Chronic fetal hypoxia and sudden infant death syndrome: interaction between maternal smoking and low hematocrit during pregnancy. Pediatrics ,1990; 86:535-540.
36. Haglund B, Cnattinglus S. Cigarette smoking as a risk factor for sudden infant death syndrome: a population-based study. Am J Public Health, 1990;80:29-32.
37. Meny RG, Carroll JL, Carbone MT, Kelly DH. Cardiorespiratory recording from infants dying suddenly and unexpectedly at home. Pediatrics, 1994; 93:44-49.
38. Hunt CE. Sudden infant death syndrome and other cause of infant mortality: diagnosis, mechanisms, and risk of recurrence in siblings. Am J Respir Cirt Care Med,2001; 164:346-357.
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