Adrenergic activation of cardiac preganglionic neurons in the Nucleus Ambiguus

2020 ◽  
Vol 34 (S1) ◽  
pp. 1-1
Author(s):  
Isamu Aiba
2004 ◽  
Vol 96 (6) ◽  
pp. 2279-2287 ◽  
Author(s):  
Alrich L. Gray ◽  
Tannis A. Johnson ◽  
Jean-Marie Lauenstein ◽  
Stephen S. Newton ◽  
Jeffrey L. Ardell ◽  
...  

The vagal postganglionic control of cardiac rate is mediated by two intracardiac ganglia, i.e., the sinoatrial (SA) and posterior atrial (PA) ganglia. Nothing is known about the vagal preganglionic neurons (VPNs) that innervate the PA ganglion or about the neurochemical anatomy of central afferents that innervate these VPNs. These issues were examined using light microscopic retrograde labeling methods and dual-labeling electron microscopic histochemical and immunocytochemical methods. VPNs projecting to the PA ganglion are found in a narrow column exclusively in the ventrolateral nucleus ambiguus (NA-VL). These neurons are relatively large (37.6 ± 2.7 μm by 21.3 ± 3.4 μm) with abundant cytoplasm and intracellular organelles, rare somatic and dendritic spines, round uninvaginated nuclei, and myelinated axons. Previous physiological data indicated that microinjections of neuropeptide Y (NPY) into the NA-VL cause negative chronotropic effects. The present morphological data demonstrate that NPY-immunoreactive nerve terminals formed 18 ± 4% of the axodendritic or axosomatic synapses and close appositions on VPNs projecting to the PA ganglion. Three approximately equal populations of VPNs in the NA-VL were retrogradely labeled from the SA and PA ganglia. One population each projects to the SA ganglion, the PA ganglion, or to both the SA and PA ganglia. Therefore, there are both shared and independent pathways involved in the vagal preganglionic controls of cardiac rate. These data are consistent with the hypothesis that the central and peripheral parasympathetic controls of cardiac rate are coordinated by multiple potentially redundant and/or interacting pathways and mechanisms.


1993 ◽  
Vol 70 (6) ◽  
pp. 2205-2214 ◽  
Author(s):  
K. Inui ◽  
S. Nosaka

1. Both electrical and chemical stimulation of the midbrain periaqueductal gray matter (PAG) inhibit baroreflex vagal bradycardia (BVB). The present study was designed to determine the target site of this inhibition about which little is known. Electrical stimulation of the PAG, in particular of its dorsal portion, markedly suppressed BVB provoked by electrical stimulation of the aortic depressor nerve (ADN; percentage of inhibition = 91.0 +/- 9.7%, mean +/- SD; n = 64). To identify the target site of the inhibition, several types of experiments were conducted in rats under chloralose-urethan anesthesia. 2. The inhibition was exclusively of central origin because inhibition of BVB by stimulation of the PAG was unchanged after transection of the spinal cord at the C1 level. According to Wall's method, we examined whether PAG stimulation affects BVB presynaptically by modulating the excitability of ADN terminals in the nucleus tractus solitarius (NTS). However, excitability changes of ADN terminals by the PAG stimulation were not demonstrated. 3. Vagal bradycardia evoked by microinjection of glutamate into the nucleus ambiguus (NA) region was markedly suppressed by the PAG (percentage of inhibition = 85.9 +/- 9.1%; n = 9), an indication that vagal cardiac preganglionic neurons at this site were subject to the inhibitory action of the PAG. Basal vagal tone due to ongoing preganglionic neuronal activity was also subject to inhibitory control by the PAG because basal heart rate was increased by stimulation of the PAG after either C1 transection or NTS lesion. 4. We found that PAG stimulation suppressed ADN-induced field potentials in the NA region (37.7 +/- 13.8% relative to the control; n = 9) but only slightly in the NTS region (95.8 +/- 15.2%; n = 16). In addition, unitary recordings revealed that ADN-evoked unitary responses of neurons in the NA region were suppressed by PAG stimulation, whereas NTS baroreceptor neurons, either ADN responsive or nonresponsive, were scarcely inhibited by PAG stimulation. 5. These findings suggest that the PAG inhibited BVB mainly at the vagal preganglionic cell level and not at the NTS interneuron level. The conclusion is in harmony with our previous reports that the target site of hypothalamic inhibition of BVB in rats is also the preganglionic neurons and that hypothalamic inhibition of BVB is mediated predominantly by the PAG.


2019 ◽  
Vol 121 (4) ◽  
pp. 1266-1278 ◽  
Author(s):  
Isamu Aiba ◽  
Jeffrey L. Noebels

Cholinergic vagal nerves projecting from neurons in the brain stem nucleus ambiguus (NAm) play a predominant role in cardiac parasympathetic pacemaking control. Central adrenergic signaling modulates the tone of this vagal output; however, the exact excitability mechanisms are not fully understood. We investigated responses of NAm neurons to adrenergic agonists using in vitro mouse brain stem slices. Preganglionic NAm neurons were identified by ChAT-tdTomato fluorescence in young adult transgenic mice, and their cardiac projection was confirmed by retrograde dye tracing. Juxtacellular recordings detected sparse or absent spontaneous action potentials (AP) in NAm neurons. However, bath application of epinephrine or norepinephrine strongly and reversibly activated most NAm neurons regardless of their basal firing rate. Epinephrine was more potent than norepinephrine, and this activation largely depends on α1-adrenoceptors. Interestingly, adrenergic activation of NAm neurons does not require an ionotropic synaptic mechanism, because postsynaptic excitatory or inhibitory receptor blockade did not occlude the excitatory effect, and bath-applied adrenergic agonists did not alter excitatory or inhibitory synaptic transmission. Instead, adrenergic agonists significantly elevated intrinsic membrane excitability to facilitate generation of recurrent action potentials. T-type calcium current and hyperpolarization-activated current are involved in this excitation pattern, although not required for spontaneous AP induction by epinephrine. In contrast, pharmacological blockade of persistent sodium current significantly inhibited the adrenergic effects. Our results demonstrate that central adrenergic signaling enhances the intrinsic excitability of NAm neurons and that persistent sodium current is required for this effect. This central balancing mechanism may counteract excessive peripheral cardiac excitation during increased sympathetic tone. NEW & NOTEWORTHY Cardiac preganglionic cholinergic neurons in the nucleus ambiguus (NAm) are responsible for slowing cardiac pacemaking. This study identified that adrenergic agonists can induce rhythmic action potentials in otherwise quiescent cholinergic NAm preganglionic neurons in brain stem slice preparation. The modulatory influence of adrenaline on central parasympathetic outflow may contribute to both physiological and deleterious cardiovascular regulation.


2003 ◽  
Vol 284 (3) ◽  
pp. G357-G366 ◽  
Author(s):  
Howard Y. Chang ◽  
Hiroshi Mashimo ◽  
Raj K. Goyal

Vagal efferents, consisting of distinct lower motor and preganglionic parasympathetic fibers, constitute the motor limb of vagally mediated reflexes. Arising from the nucleus ambiguus, vagal lower motor neurons (LMN) mediate reflexes involving striated muscles of the orad gut. LMNs provide cholinergic innervation to motor end plates that are inhibited by myenteric nitrergic neurons. Preganglionic neurons from the dorsal motor nucleus implement parasympathetic motor and secretory functions. Cholinergic preganglionic neurons form parallel inhibitory and excitatory vagal pathways to smooth muscle viscera and stimulate postganglionic neurons via nicotinic and muscarinic receptors. In turn, the postganglionic inhibitory neurons release ATP, VIP, and NO, whereas the excitatory neurons release ACh and substance P. Vagal motor effects are dependent on the viscera's intrinsic motor activity and the interaction between the inhibitory and excitatory vagal influences. These interactions help to explain the physiology of esophageal peristalsis, gastric motility, lower esophageal sphincter, and pyloric sphincter. Vagal secretory pathways are predominantly excitatory and involve ACh and VIP as the postganglionic excitatory neurotransmitters. Vagal effects on secretory functions are exerted either directly or via release of local mediators or circulating hormones.


2018 ◽  
Author(s):  
Isamu Aiba ◽  
Jeffrey L. Noebels

AbstractCholinergic vagal nerves projecting from neurons in the brainstem nucleus ambiguus (NAm) play a predominant role in cardiac parasympathetic pacemaking control. Central adrenergic signaling modulates the tone of this vagal output; however the exact excitability mechanisms are not fully understood. We investigated responses of NAm neurons to adrenergic agonists using in vitro mouse brainstem slices. Preganglionic NAm neurons were identified by Chat-tdtomato fluorescence in young adult transgenic mice and their cardiac projection confirmed by retrograde dye tracing. Juxtacellular recordings detected sparse or absent spontaneous action potentials (AP) in NAm neurons. However bath application of epinephrine or norepinephrine strongly and reversibly activated most NAm neurons regardless of their basal firing rate. Epinephrine was more potent than norepinephrine, and this activation largely depends on α1-adrenoceptors. Interestingly, adrenergic activation of NAm neurons does not require an ionotropic synaptic mechanism, since postsynaptic excitatory or inhibitory receptor blockade did not occlude the excitatory effect, and bath-applied adrenergic agonists did not alter excitatory or inhibitory synaptic transmission. Instead, adrenergic agonists significantly elevated intrinsic membrane excitability to facilitate generation of recurrent action potentials. T-type calcium current (ICaT) and hyperpolarization-activated current (Ih) are involved in this excitation pattern, while not required for spontaneous AP induction by epinephrine. In contrast, pharmacological blockade of persistent sodium current (INaP) significantly inhibited the adrenergic effects. Our results demonstrate that central adrenergic signaling enhances the intrinsic excitability of NAm neurons, and persistent sodium current is required for this effect. This central balancing mechanism may counteract excessive peripheral cardiac excitation during increased sympathetic tone.New & NoteworthyCardiac preganglionic cholinergic neurons in the Nucleus ambiguus (NAm) are responsible for slowing cardiac pacemaking. This study identified that adrenergic agonists can induce rhythmic action potentials in otherwise quiescent cholinergic NAm preganglionic neurons in brainstem slice preparation. The modulatory influence of adrenaline on central parasympathetic outflow may contribute to both physiological and deleterious cardiovascular regulation.


1982 ◽  
Vol 243 (1) ◽  
pp. R92-R98 ◽  
Author(s):  
S. Nosaka ◽  
K. Yasunaga ◽  
S. Tamai

In chloralose- and urethan-anesthetized rats, the cardiac branch (CB) of the vagus nerve was electrically stimulated, and antidromic responses of medullary cells were recorded. The cells identified as the vagal cardiac preganglionic neurons (VCPN) were localized in the dorsal motor nucleus (ND group, 8 cells), a region in and around the nucleus ambiguus (NA group, 7 cells) and an intermediary zone (IM group, 2 cells) lying in between. Latencies of the antidromic responses were distinctly different among the three groups, and calculated conduction velocities indicated that the VCPN of the ND group possess C-fiber axons whereas those of the NA group and probably of the IM group, B-fiber axons. In another series of experiments, the right carotid sinus nerve (CSN) or the left cervical vagus nerve was stimulated, and efferent fiber group(s) mediating reflexly evoked discharges to the CB was determined by means of two-point recordings. Among reflex discharges evoked by stimulation of the CSN the shortest latency reflex was proved to be mediated by B-efferent fibers. In contrast, among reflex discharges evoked by stimulation of the vagus nerve, the greatest reflex component was found to be conveyed by C-efferent fibers. It was concluded that the VCPN consist of two types of cells, each located in a different region of the medulla oblongata and contributing to vagal cardiac reflex mechanisms in a different manner.


1998 ◽  
Vol 810 (1-2) ◽  
pp. 251-256 ◽  
Author(s):  
Karen J.L. Blinder ◽  
Linda W. Dickerson ◽  
Alrich L. Gray ◽  
Jean-Marie Lauenstein ◽  
Joseph T. Newsome ◽  
...  

1999 ◽  
Vol 79 (3) ◽  
pp. 855-916 ◽  
Author(s):  
Edwin W. Taylor ◽  
David Jordan ◽  
John H. Coote

This review explores the fundamental neuranatomical and functional bases for integration of the respiratory and cardiovascular systems in vertebrates and traces their evolution through the vertebrate groups, from primarily water-breathing fish and larval amphibians to facultative air-breathers such as lungfish and some adult amphibians and finally obligate air-breathers among the reptiles, birds, and mammals. A comparative account of respiratory rhythm generation leads to consideration of the changing roles in cardiorespiratory integration for central and peripheral chemoreceptors and mechanoreceptors and their central projections. We review evidence of a developing role in the control of cardiorespiratory interactions for the partial relocation from the dorsal motor nucleus of the vagus into the nucleus ambiguus of vagal preganglionic neurons, and in particular those innervating the heart, and for the existence of a functional topography of specific groups of sympathetic preganglionic neurons in the spinal cord. Finally, we consider the mechanisms generating temporal modulation of heart rate, vasomotor tone, and control of the airways in mammals; cardiorespiratory synchrony in fish; and integration of the cardiorespiratory system during intermittent breathing in amphibians, reptiles, and diving birds. Concluding comments suggest areas for further productive research.


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