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Vagal Preganglionic Neurons Innervating the Heart

K. Michael Spyer

10.1002/cphy.cp020105

Source: Supplement 6: Handbook of Physiology, The Cardiovascular System, The Heart

Originally published: 2002

Published online: January 2011

Full Article on Wiley Online Library



Abstract

The sections in this article are:

1 Chronotropic Actions of Activating Vagal Efferent Fibers
2 B‐Fibers and C‐Fibers: Effect of Electrical Stimulation
3 The Location of the Somata of Preganglionic Vagal Neurons
4 Physiological Mapping
5 Biophysical Properties of Cardiac Vagal Motoneurons
6 Physiological Properties of Cardiac Vagal Motoneurons
7 Baroreceptor Input
8 Respiratory Influences on Cardiac Vagal Motoneuron Discharge
9 Mechanisms of Respiratory Patterning
10 Arterial Chemoreceptor Inputs
11 Pulmonary and Airway Inputs
11.1 Slowly Adapting Pulmonary Inputs
11.2 Rapidly Adapting Pulmonary Inputs
12 Pulmonary C‐Fibers
13 Upper Airway Receptors
14 Cardiac Receptors
15 CNS Organization of Reflex Control
16 CNS Pathways Impinging on the Dorsal Ventral Nucleus and the Nucleus Ambiguus
17 Reflex Interactions: CNS Organization
18 Synaptic Effects Elicited by Baroreceptor Inputs in the Nucleus Tractus Solitarii
19 Synaptic Effects of Arterial Chemoreceptor Inputs
20 Central Modifications of Reflex Function
21 The Role of the Nucleus Tractus Solitarii in Reflex Adjustments
22 Respiratory Influences of Reflex Transmission Through the Nucleus Tractus Solitarius
23 Conclusions
Figure 1. Figure 1.

Traces show the heart rate responses produced by electrical stimulation of the cervical vagus (1 msec, 10 V, 10 Hz). Responses to stimulating B + C fibers were evoked with the cathode facing the heart and no anodal block. Responses to stimulating C fibers alone were evoked with the anode facing the heart and the anodal block technique applied.

Reprinted with permission from Jones, Wang, and Jordan 111
Figure 2. Figure 2.

A: Schematic representation of the position of retrogradely labeled neurons 1, at four levels of the medulla, after the application of cholera toxin conjugated to horseradish peroxidase (CT‐HRP) into the myocardium. AP‐area postrema; DVN‐dorsal motor nucleus of the vagus nerve; LRN‐lateral reticular nucleus; NA‐nucleus ambiguus; XII‐hypoglossal motonucleus; NTS‐nucleus tractus solitarii. B,C: Light micrographs showing cardiac vagal preganglionic motoneurones (CVMs) in the ventral regions of the nucleus ambiguus retrogradely labeled after the application of CT‐HRP into the myocardium (long arrows), the positions of which are represented in A by asterisks. Often the dendrites (arrowheads) of labeled neurons in this region extended as far as the ventral surface of the medulla (C). After some of the cardiac injections, a diffuse labeling of the compact group resulted (broad arrow), similar to that observed in control injections into the thoracic cavity (B). Scale bar: 50 mm.

Published with permission from Izzo and Spyer 104
Figure 3. Figure 3.

Distribution of cell somata labeled with HRP following microiontophoretic application to the cardiac branch of the vagus nerve. All HRP‐labeled cells in one animal were collectively plotted on the nearest of the four representative sections. A, B, C, and D: sections at the level of the obex, 420 m, 780 m, and 1,080 m rostral to it, respectively.

Published with permission from Nosaka et al. 186
Figure 4. Figure 4.

Intracellular recording from CVM. A: Stimulating cervical vagus (0.1 ms, 6 V) at 1 Hz. Five superimposed sweeps. B: Three consecutive sweeps illustrating the collision of an othodromic spike, in the middle trace, with the antidromic spike. D: Lower Trace: electrocardiogram‐(ECG) triggered histogram of ongoing discharge of the CVM identified in A, B, C, D (110 sweeps, 10 ms bins). Upper trace: femoral arterial waveform averaged over the same course and triggered from ECG (100 sweeps). C: stimulation of the cardiac branches of the right vagus (0.1 mecs, 3 V). Three consecutive sweeps, collision with orthodromic spike in tower trace. Stimulus marked by (l) in A, B, C, E: Intracellular recording from a CVM showing respiratory‐related changed in membrane potential. The cell stopped firing action potentials 5 min after the cell was penetrated. In each panel traces from above; high and low gain d.c. recordings of membrane potential, phrenic nerve activity, arterial blood pressure, and tracheal pressure.

Modified and reproduced with permission from Gilbey et al. 79
Figure 5. Figure 5.

Location. The positions of forty‐six cardiac efferent neurons are shown on four standard sections of the medulla taken at obex level, and at 1 mm intervals rostrally. Inserts, 2 mm square, show details of their relation to the structure of the nucleus ambiguus. Abbreviations: TS, tractus solitarius; DNV, dorsal motor nucleus of the vagus; NA, nucleus ambiguus.

Published with permission from McAllen and Spyer 158
Figure 6. Figure 6.

A: Antidromically evoked action potential in the dorsal vagal nucleus (DMV) neuron upon vagal stimulation. B: Orthodromically evoked epsp and action potential in a DMV neuron upon perivagal stimulation. C: Orthodromic mixed epsp‐ipsp in a DMV neuron during steady current injection to hold the cell resting membrane potential at a depolarized level of −35 m V. Action potentials were often triggered after the ipsps. D: At a holding potential of −40 m V, spontaneous miniature epsps and spontaneous miniature ipsps were observed as inward (downward) and outward (upward) currents, respectively, and were not abolished by the presence of 1 mM TTX.

Reproduced with permission from Travagli and Gillis 244
Figure 7. Figure 7.

The cardiac rhythm of a c.v.m. (aortic baroreceptors denervated). Pulse‐triggered histogram of c.v.m. activity (lower trace) and pulse‐triggered average of femoral pulse wave (upper trace). 128 super‐imposed cycles, 10 msec bin width. A: both common carotid arteries open; B: contralateral carotid occluded; C, ipsilateral carotid occluded; D, bilateral carotid occlusion. Unit firing in response to 8 nA DLH.

Reproduced with permission from McAllen and Spyer 161
Figure 8. Figure 8.

A: extracellular recording from a c.v.m. (see ref. 189) B: intracellular recording from a c.v.m. (see ref. 73) Traces, from top to bottom: low gain recording of c.v.m. activity, phrenic nerve activity (p.n.a.), femoral arterial blood pressure (B.P.), and tracheal pressure (T.P.).

Reproduced with permission from Gilbey et al. 79
Figure 9. Figure 9.

Respiratory modulation of pulse‐rhythmic epsps. Recording in a cell in which ipsps had been reversed previously by C1− injection (3 nA for 5 min). Further details in text. Traces from top to bottom: high and low gain d.c. recordings of membrane potential, phrenic nerve activity, femoral arterial blood pressure, and tracheal pressure.

Reproduced with permission from Gilbey et al. 79
Figure 10. Figure 10.

Dog, anaesthetized with chloralose and paralyzed with D‐tubocurarine. Upper and lower panels show heart rate, integrated phrenic activity, intratracheal pressure, and carotid sinus blood pressure, recorded during periods of temporary cessation of artificial ventilation. The effects of chemoreceptor stimuli (intracarotid injections of CO2‐saline at markers) on heart rate are seen. When the vagi are intact (upper panel), chemoreceptor stimuli evoke bradycardia, except when delivered during period of inspiration (second of the stimuli shown) or while the lungs are expanding in response to a rise in intratracheal pressure (third stimulus). After denervation of the lungs (lower panel), the stimuli remain ineffective during periods of central inspiratory activity (second stimulus), but now evoke a large bradycardia when delivered while the lungs are expanding in response to a rise in intratracheal pressure.

Published with permission from Gandevia, McCloskey, and Potter 70
Figure 11. Figure 11.

Control of CVM activity: inspiratory and reflex inputs. Diagrammatic representation of the inputs to CVM (C) that determine their sensitivity to baroreceptor and chemoreceptor inputs. Inspiratory neurons (In) directly or via interneurons (e.g. PI, postinspiratory neurons) or inhibitory interneurons (shown in black) control of the excitability of CVM. Baroreceptor and chemoreceptor inputs are processed initially in the nucleus tractus solitarii (NTS) and send excitatory connections to CVM localized in the nucleus ambiguus, but these inputs act differentially on inspiratory neurons. Open symbols: excitatory: filled symbols: inhibitory.
Figure 12. Figure 12.

Additional evidence for HDA inhibitory actions on SLN‐evoked responses. Intracellular recording of a cell within the NTS (membrane potential, −62 mV). A: this neuron responded to stimulation of the HDA (5 pulses, 500 Hz, 0.1 mA, given at 1 Hz) with an ipsp (upper traces). The unit was baroreceptive, as shown in the lower left panel, since inflation of the ipsilateral carotid sinus (Barotest) evoked a burst of action potentials. B, SLN stimulation (1 pulse, 0.1 ms, 7 V at 1 Hz) evoked an excitatory response. C: epsp and action potentials evoked on stimulation of the SN (2 pulses, 0.1 ms, 1 kHz, 9V at 1 Hz). D: simultaneous stimulation of both nerves (Sn + SLN) evoked an enhanced response. The latency was shortened and a third spike was evoked in 80% of the stimulations. Stimulating parameters as in B and C. E: conditioning stimulus to the hypothalamus (HDA) suppressed the combined effects of SLN + SN stimulation (compare with D). Neuronal recordings in A (upper traces) B, C, D, and E are shown as 2 superimposed traces.

Reproduced with permission from Dawid‐Milner et al. 50
Figure 13. Figure 13.

Schematic diagram of the connections within the nucleus tractus solitarii (NTS) that mediate arterial chemoreceptor inputs and interaction with the arterial baroreceptors. Inputs to NTS from baroreceptors, chemoreceptors and HDA are shown. Exclusively baroreceptor‐sensitive neurons are shown as ○; chemoreceptors are ☆. Excitatory inputs are shown as ▴ and inhibitory as ⁁. Neurons receiving convergent baroreceptor and chemoreceptor inputs are shown as combined symbols: when baroreceptor influence is excitatory, when inhibitory.

Reproduced with permission from Silva‐Carvalho et al. 227


Figure 1.

Traces show the heart rate responses produced by electrical stimulation of the cervical vagus (1 msec, 10 V, 10 Hz). Responses to stimulating B + C fibers were evoked with the cathode facing the heart and no anodal block. Responses to stimulating C fibers alone were evoked with the anode facing the heart and the anodal block technique applied.

Reprinted with permission from Jones, Wang, and Jordan 111


Figure 2.

A: Schematic representation of the position of retrogradely labeled neurons 1, at four levels of the medulla, after the application of cholera toxin conjugated to horseradish peroxidase (CT‐HRP) into the myocardium. AP‐area postrema; DVN‐dorsal motor nucleus of the vagus nerve; LRN‐lateral reticular nucleus; NA‐nucleus ambiguus; XII‐hypoglossal motonucleus; NTS‐nucleus tractus solitarii. B,C: Light micrographs showing cardiac vagal preganglionic motoneurones (CVMs) in the ventral regions of the nucleus ambiguus retrogradely labeled after the application of CT‐HRP into the myocardium (long arrows), the positions of which are represented in A by asterisks. Often the dendrites (arrowheads) of labeled neurons in this region extended as far as the ventral surface of the medulla (C). After some of the cardiac injections, a diffuse labeling of the compact group resulted (broad arrow), similar to that observed in control injections into the thoracic cavity (B). Scale bar: 50 mm.

Published with permission from Izzo and Spyer 104


Figure 3.

Distribution of cell somata labeled with HRP following microiontophoretic application to the cardiac branch of the vagus nerve. All HRP‐labeled cells in one animal were collectively plotted on the nearest of the four representative sections. A, B, C, and D: sections at the level of the obex, 420 m, 780 m, and 1,080 m rostral to it, respectively.

Published with permission from Nosaka et al. 186


Figure 4.

Intracellular recording from CVM. A: Stimulating cervical vagus (0.1 ms, 6 V) at 1 Hz. Five superimposed sweeps. B: Three consecutive sweeps illustrating the collision of an othodromic spike, in the middle trace, with the antidromic spike. D: Lower Trace: electrocardiogram‐(ECG) triggered histogram of ongoing discharge of the CVM identified in A, B, C, D (110 sweeps, 10 ms bins). Upper trace: femoral arterial waveform averaged over the same course and triggered from ECG (100 sweeps). C: stimulation of the cardiac branches of the right vagus (0.1 mecs, 3 V). Three consecutive sweeps, collision with orthodromic spike in tower trace. Stimulus marked by (l) in A, B, C, E: Intracellular recording from a CVM showing respiratory‐related changed in membrane potential. The cell stopped firing action potentials 5 min after the cell was penetrated. In each panel traces from above; high and low gain d.c. recordings of membrane potential, phrenic nerve activity, arterial blood pressure, and tracheal pressure.

Modified and reproduced with permission from Gilbey et al. 79


Figure 5.

Location. The positions of forty‐six cardiac efferent neurons are shown on four standard sections of the medulla taken at obex level, and at 1 mm intervals rostrally. Inserts, 2 mm square, show details of their relation to the structure of the nucleus ambiguus. Abbreviations: TS, tractus solitarius; DNV, dorsal motor nucleus of the vagus; NA, nucleus ambiguus.

Published with permission from McAllen and Spyer 158


Figure 6.

A: Antidromically evoked action potential in the dorsal vagal nucleus (DMV) neuron upon vagal stimulation. B: Orthodromically evoked epsp and action potential in a DMV neuron upon perivagal stimulation. C: Orthodromic mixed epsp‐ipsp in a DMV neuron during steady current injection to hold the cell resting membrane potential at a depolarized level of −35 m V. Action potentials were often triggered after the ipsps. D: At a holding potential of −40 m V, spontaneous miniature epsps and spontaneous miniature ipsps were observed as inward (downward) and outward (upward) currents, respectively, and were not abolished by the presence of 1 mM TTX.

Reproduced with permission from Travagli and Gillis 244


Figure 7.

The cardiac rhythm of a c.v.m. (aortic baroreceptors denervated). Pulse‐triggered histogram of c.v.m. activity (lower trace) and pulse‐triggered average of femoral pulse wave (upper trace). 128 super‐imposed cycles, 10 msec bin width. A: both common carotid arteries open; B: contralateral carotid occluded; C, ipsilateral carotid occluded; D, bilateral carotid occlusion. Unit firing in response to 8 nA DLH.

Reproduced with permission from McAllen and Spyer 161


Figure 8.

A: extracellular recording from a c.v.m. (see ref. 189) B: intracellular recording from a c.v.m. (see ref. 73) Traces, from top to bottom: low gain recording of c.v.m. activity, phrenic nerve activity (p.n.a.), femoral arterial blood pressure (B.P.), and tracheal pressure (T.P.).

Reproduced with permission from Gilbey et al. 79


Figure 9.

Respiratory modulation of pulse‐rhythmic epsps. Recording in a cell in which ipsps had been reversed previously by C1− injection (3 nA for 5 min). Further details in text. Traces from top to bottom: high and low gain d.c. recordings of membrane potential, phrenic nerve activity, femoral arterial blood pressure, and tracheal pressure.

Reproduced with permission from Gilbey et al. 79


Figure 10.

Dog, anaesthetized with chloralose and paralyzed with D‐tubocurarine. Upper and lower panels show heart rate, integrated phrenic activity, intratracheal pressure, and carotid sinus blood pressure, recorded during periods of temporary cessation of artificial ventilation. The effects of chemoreceptor stimuli (intracarotid injections of CO2‐saline at markers) on heart rate are seen. When the vagi are intact (upper panel), chemoreceptor stimuli evoke bradycardia, except when delivered during period of inspiration (second of the stimuli shown) or while the lungs are expanding in response to a rise in intratracheal pressure (third stimulus). After denervation of the lungs (lower panel), the stimuli remain ineffective during periods of central inspiratory activity (second stimulus), but now evoke a large bradycardia when delivered while the lungs are expanding in response to a rise in intratracheal pressure.

Published with permission from Gandevia, McCloskey, and Potter 70


Figure 11.

Control of CVM activity: inspiratory and reflex inputs. Diagrammatic representation of the inputs to CVM (C) that determine their sensitivity to baroreceptor and chemoreceptor inputs. Inspiratory neurons (In) directly or via interneurons (e.g. PI, postinspiratory neurons) or inhibitory interneurons (shown in black) control of the excitability of CVM. Baroreceptor and chemoreceptor inputs are processed initially in the nucleus tractus solitarii (NTS) and send excitatory connections to CVM localized in the nucleus ambiguus, but these inputs act differentially on inspiratory neurons. Open symbols: excitatory: filled symbols: inhibitory.



Figure 12.

Additional evidence for HDA inhibitory actions on SLN‐evoked responses. Intracellular recording of a cell within the NTS (membrane potential, −62 mV). A: this neuron responded to stimulation of the HDA (5 pulses, 500 Hz, 0.1 mA, given at 1 Hz) with an ipsp (upper traces). The unit was baroreceptive, as shown in the lower left panel, since inflation of the ipsilateral carotid sinus (Barotest) evoked a burst of action potentials. B, SLN stimulation (1 pulse, 0.1 ms, 7 V at 1 Hz) evoked an excitatory response. C: epsp and action potentials evoked on stimulation of the SN (2 pulses, 0.1 ms, 1 kHz, 9V at 1 Hz). D: simultaneous stimulation of both nerves (Sn + SLN) evoked an enhanced response. The latency was shortened and a third spike was evoked in 80% of the stimulations. Stimulating parameters as in B and C. E: conditioning stimulus to the hypothalamus (HDA) suppressed the combined effects of SLN + SN stimulation (compare with D). Neuronal recordings in A (upper traces) B, C, D, and E are shown as 2 superimposed traces.

Reproduced with permission from Dawid‐Milner et al. 50


Figure 13.

Schematic diagram of the connections within the nucleus tractus solitarii (NTS) that mediate arterial chemoreceptor inputs and interaction with the arterial baroreceptors. Inputs to NTS from baroreceptors, chemoreceptors and HDA are shown. Exclusively baroreceptor‐sensitive neurons are shown as ○; chemoreceptors are ☆. Excitatory inputs are shown as ▴ and inhibitory as ⁁. Neurons receiving convergent baroreceptor and chemoreceptor inputs are shown as combined symbols: when baroreceptor influence is excitatory, when inhibitory.

Reproduced with permission from Silva‐Carvalho et al. 227
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Article Title: Vagal Preganglionic Neurons Innervating the Heart
 

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K. Michael Spyer. Vagal Preganglionic Neurons Innervating the Heart. Compr Physiol 2011, Supplement 6: Handbook of Physiology, The Cardiovascular System, The Heart: 213-239. First published in print 2002. doi: 10.1002/cphy.cp020105