Spinal segmental sympathetic outflow to cervical sympathetic trunk, vertebral nerve, inferior cardiac nerve and sympathetic fibres in the thoracic vagus

The spinal segmental localization of preganglionic neurons which convey activity to the sympathetic nerves, i.e. vertebral nerve, right inferior cardiac nerve, sympathetic fibres in the thoracic vagus and cervical sympathetic trunk, was determined on the right side in chloralose anaesthetized cats. For that purpose the upper thoracic white rami were electrically stimulated with a single pulse, suprathreshold for B and C fibres, and the evoked responses were recorded in the sympathetic nerves. The relative preganglionic input from each segment of the spinal cord to the four sympathetic nerves was determined from the size of the evoked responses. It was found that each sympathetic nerve receives a maximum preganglionic input from one segment of the spinal cord (dominant segment) and that the preganglionic input gradually decreased from neighbouring segments. The spinal segmental preganglionic outflow to the cervical sympathetic trunk, thoracic vagus, right inferior cardiac nerve and vertebral nerve gradually shifted from the most rostral to the most caudal spinal cord segments. In some cases, a marked postganglionic component was found in the cervical sympathetic trunk. It was evoked by preganglionic input from the same spinal cord segments which transmitted activity to the vertebral nerve. These results indicate that there is a fixed relation between the spinal segmental localization of preganglionic neurons and the branch of the stellate ganglion receiving the input from these neurons.     

Localization of sympathetic postganglionic neurons of physiologically identified cardiac nerves in the dog

Cardiac nerves were identified physiologically and injected with horseradish peroxidase in 38 dogs. Retrogradely labeled neurons were present in the greatest number in the middle cervical ganglion, whereas fewer labeled neurons were present in the stellate ganglion. Only occasional neurons in the superior cervical ganglion were labeled, and no labelphysiologically and injected with horseradish peroxidase in 38 dogs. Retrogradely labeled neurons were present in the greatest number in the middle cervical ganglion, whereas fewer labeled neurons were present in the stellate ganglion. Only occasional neurons in the superior cervical ganglion were labeled, and no labelphysiologically and injected with horseradish peroxidase in 38 dogs. Retrogradely labeled neurons were present in the greatest number in the middle cervical ganglion, whereas fewer labeled neurons were present in the stellate ganglion. Only occasional neurons in the superior cervical ganglion were labeled, and no labeled cells were found in the T3 to T6 paravertebral ganglia or in the ganglia contralateral to the nerve injected. following injections into specific cardiac nerves, retrograde labeling was widespread within the middle cervical ganglion, and the distributions of labeled neurons from different nerves overlapped considerably. In the middle cervical ganglion there was little or no regional grouping of cells projecting to specific cardiac nerves. within the stellate ganglion, however, te cardiac-sympathetic cells were clustered primarily at the cranial pole near toe origin of the ventral and dorsal ansae. Mediastinal ganglia and ganglia located in cardiac nerves were frequently as heavily labeled as the ipsilateral stellate ganglion. The occurrence of heavy labeling in mediastinal and cardiac nerve ganglia indicates that these hitherto unreported ganglia play a significant role in cardiac neural regulation. These data imply that the organization of sympathetic neurons controlling the heart is much more complex than has previously been considered.     

The orthograde labeling of postganglionic sympathetic cardiac nerves in the dog and cat as demonstrated by autoradiography

Previous functional and anatomical techniques have characterized the cardiac nerves and plexuses. They cannot, however, determine the course of fibers arising from a specific ganglion. This study has found that the intraaxonal orthograde labeling of axons can be used to determine the course of postganglionic sympathetic cardiac fibers in the dog and cat. The canine left caudal cervical ganglion and the feline right stellate ganglion were exposed through appropriate thoracotomies. Each ganglion received multiple injections of tritiated leucine (500 muCi/animal). Following a 3--14-day survival period the anesthetized animals were sacrificed by vascular perfusion. The injected ganglia, extracardiac nerves and selected portions of the heart were processed for autoradiography. Autoradiographs from the dog demonstrated labeled postganglionic sympathetic nerves in the extracardiac plexus, left atrial epicardium and the epicardium beneath the coronary sulcus. Labeled nerves in the cat heart were found within the epicardial layers and associated with blood vessels in the left ventricular myocardium. Neither myelinated fibers traveling through the injection site nor intrinsic cardiac ganglion cells were labeled, although the latter were often closely approximated to heavily labeled fibers.     

Spinal origin of sympathetic preganglionic neurons in the rat

The segmental distribution of sympathetic preganglionic neurons (SPNs) and dorsal root ganglion cells (DRGs) was studied after Fluoro-gold injections into the major sympathetic ganglia and adrenal gland in rats. A quantitative assessment of the segmental and nuclear locations was made. Four general patterns of innervation were apparent: (1) a large number of SPNs (1000–2000/ganglion) innervate the sympathetic ganglia which control head or thoracic organs and a relatively small number of SPNs (100–400/ganglion) innervate the sympathetic ganglia controlling the gut, kidney, and pelvic organs; this difference in density of innervation probably relates to the level of fine control that can occur in these end organs by the SPNs; (2) the reverse pattern is seen in the DRG labeling where a large number of DRGs were labeled after Fluoro-gold injections into the preaortic ganglia (celiac, superior, and inferior mesenteric) and a small number were labeled after injections into the cervical sympathetic ganglia; (3) the intermediolateral cell column is the main source of SPNs except for the inferior mesenteric ganglion which is innervated predominantly by SPNs originating in the central autonomic nucleus (75%); the lateral funiculus is a source of SPNs mainly for the cervical sympathetic ganglia; and (4) each sympathetic ganglion and the adrenal gland receives a multisegmental SPN and DRG input with one segment being the predominant source of the innervation. The adrenal gland shows an intermediate position in terms of the density of SPN input (800 cells) and dorsal root input (300 cells); it has a widespread segmental input (T₄-T₁₂) with the T₈ segment being the major source.     

Hypoventilation recruits preganglionic sympathetic fibers with inspiration-related activity in the superior cervical trunk of the rat.

Activity in preganglionic sympathetic neurons projecting in the cervical sympathetic trunk (CST) of rats was analysed with respect to changes in the pattern of the respiratory modulation during a long lasting hypoventilation. Under normal acid-base status (pH: 7.36+/-0.04, pCO2: 42.1+/-6.1 mm Hg, pO2: 135.8+/-43 mm Hg) a maximum of activity during expiration (expiration-related activity) was observed in all nerve recordings (n = 27). No other pattern of respiratory modulation was observed under this condition. Under a hypoventilation a dissociation between the duration of phrenic nerve activity and that of the inspiratory inhibition in neurons with expiration-related activity was observed as the inhibition was significantly prolonged by 49+/-24.9% and outlasted inspiration in 5/7 multifibers. When acid-base status was systematically changed (pH: 7.15+/-0.05, pCO2: 80.4+/-11.8 mm Hg, pO2: 62.8+/-17.5 mm Hg [n = 7]) by a hypoventilation lasting for several hours activity with a maximum peak during central inspiration (inspiration-related activity) emerged and disappeared when control conditions were reestablished. Neurons with expiration-related activity showed a cardiac rhythmicity (CR) of 62.5+/-14.6% (n = 27) and were inhibited to baroreceptor stimulation whereas neurons with inspiration-related activity showed no discernible CR (23.1+/-5.1%; n = 7) and were not inhibited to baroreceptor stimulation. Furthermore, expiration-related neurons were inhibited by 32.5+/-18.3% (n = 27) during noxious cutaneous stimulation while neurons with inspiration-related activity were activated by 21.5+/-12.1% (n = 7). These findings suggest that the respiratory modulation of preganglionic sympathetic activity in the CST consists of expiration-related activity in normal acid-base status. During hypoventilation neurons with inspiration-related activity are recruited. These neurons show reflex patterns distinct from expiration-related neurons and probably constitute a subgroup of sympathetic neurons which is activated under increased respiratory drive.     

The ratio of preganglionic axons to postganglionic cells in the sympathetic nervous system of the rat

Previously reported preganglionic-postganglionic ratios for the sympathetic system are a major part of the evidence for the widely accepted idea that the sympathetic innervation of the viscera is diffuse. Unfortunately, the previous reports did not assess the non-preganglionic fibers in the nerves examined, and the limitations of light microscopy precluded accurate unmyelinated fiber counts. Thus, a recalculation of these ratios is necessary. The present study recalculates these ratios for the cervical sympathetic system of the rat. All fiber counts are done with the electron microscope which has the resolution necessary for accurately determining axon numbers. Selective surgical procedures establish that 84% of the axons in the cervical sympathetic trunk are preganglionic, 11% are postganglionic, and 5% are sensory. Thus, the numbers of preganglionic fibers can now be accurately assessed and compared to the number of postganglionic neurons in the superior cervical ganglion. When this is done, a preganglionic/postganglionic ratio of approximately 1:4 is obtained. This ratio differs considerably from those previously published.     

The origin of postganglionic and sensory axons in the cervical sympathetic trunk of the cat: A horseradish peroxidase study

The composition of the cervical sympathetic trunk (CST) in the cat is still not completely understood. The present study investigates, by the horseradish peroxidase (HRP) method of tracing neuronal connections, the presence of postganglionic and sensory neurons projecting via the CST. Following sympathectomy at the midcervical level and the application of HRP crystals to the cut ends of the CST which had been isolated from the surrounding by a 1.5% solution of agar-agar, labelled neurons were seen in the superior cervical (SCG), stellate (SG), inferior vagal ganglia (IVG), and spinal ganglia C₈–T₈. The maximum number of labelled nuerons was 536 in the SCG, 460 in the SG, 180 in the IVG, and 104 in spinal ganglia C₈–T₈.     

Decreased sympathetic outflow to muscles in patients with cervical spondylosis

To clarify the pathogenesis of neurologic symptoms of a vascular nature that may accompany cervical spondylosis (CS), we measured the sympathetic outflow to muscles (muscle sympathetic nerve activity: MSNA) in 8 ambulatory patients with CS and 10 healthy volunteers (controls). The burst rate and incidence of MSNA at rest were significantly lower in patients with CS than in controls ( P < 0.01). There were no differences between the 2 groups in either resting heart rate or blood pressure. During a head-up tilting, the changes in MSNA were slightly greater in CS patients than controls due to reduced baseline levels of MSNA in CS patients. The burst incidence of MSNA in CS was significantly negatively correlated with the severity of pyramidal tract symptoms ( P < 0.05). The decreased MSNA at rest in CS patients may be due to spinal cord compression resulting from posterior spondylotic changes in the cervical spine.     

Responses of cardiac vagus and sympathetic nerves to excitation of somatic and visceral nerves

Somato-vagal and somato-sympathetic reflex responses were studied by recording simultaneously the activity of cardiac vagal and sympathetic efferents following excitation of various somatic (and 1 visceral) nerves in chloralose-anesthetized dogs.Stimulation of pure cutaneous (infraorbital, superficial radial, sural nerves), muscle (gastrocnemius, hamstring nerves) and mixed nerves (sciatic, brachial, intercostal, spinal) with short trains of pulses inhibited the activity of cardiac vagus nerve and excited that of cardiac sympathetic nerve after a latency of approximately 40–60 ms, depending on the nerve stimulated. These responses were followed by the opposite response, i.e. excitation of vagus and long-lasting inhibition (`silent period') of sympathetic nerve activity. These biphasic reflex responses recorded from both autonomic nerves had similar latencies so that a clear reciprocal relationship was observed. In addition to the above reflex responses which were observed in most instances, two peaks of excitation of short duration were recorded from the vagus nerve, in some instances, and an ‘early (spinal) reflex’ in sympathetic nerve was also observed. Both excitatory and inhibitory responses described above in either nerve were readily evoked by excitation of Group II (Aβ), but not Group I (Aα), afferent fibers and increased in magnitude when Group III (Aδ) afferents were also excited. Group IV (C) afferent contributed insignificantly to the somato-vagal reflex. The vagus nerve discharge evoked by sinus nerve stimulation was inhibited during reflex inhibition produced by somatic nerve stimulation. The latency of such inhibition was less than 20 ms and lasted for 100 ms after sural nerve stimulation. We conclude that, as in case of the baroreceptor reflex and autonomic component of the ‘defense reaction’, the somato-vagal and somato-sympathetic reflex responses are reciprocal in nature.     

Reactions of cardiac postganglionic sympathetic neurons to movements of normal and inflamed knee joints

The effects of passive movements of normal and inflamed knee joints on unitary activity in filaments of the inferior cardiac nerve (ICN) were studied in cats anesthetized with chloralose and urethane. The effects were compared with those obtained by electrical stimulation of afferent A- and C-fibers in the medial articular nerve, in muscle and in cutaneous hind limb nerves. The vagus nerves were cut and the right carotid artery was tied off. The left carotid sinus was intact. All ICN units used in this study displayed spontaneous activity which was usually related to the cardiac and respiratory rhythms. The ICN units were regularly excited by electrically evoked single or short repetitive A-volleys in articular, cutaneous and muscle nerves. The excitation was followed by a silent period. Inclusion of C-fibers in the afferent volleys gave a second, long-latency burst of impulses which was seen only with short repetitive stimulation. Passive movements in the normal working range of the joint did not influence the activity of ICN units. However, noxious joint movements, particularly of inflamed joints, led to pronounced excitation of ICN units accompanied by rises in blood pressure. Most of these effects could still be seen after all nerves to the hind limbs, except the medial articular nerve, were cut. It is proposed (a) that ICN units form a homogeneous population of sympathetic postganglionic units whose reaction pattern to somatovisceral input is distinctly different from that of other sympathetic subsystems, and (b) that articular receptors make a substantial contribution to the ICN input particularly when many fine afferent units are sensitized to mechanical stimulation by an acute joint inflammation.     

A spinal cord pathway connecting primary afferents to the segmental sympathetic outflow system

The sympathetic innervation of lumbar dorsal root ganglia (DRGs) and the possible presence of spinal cord circuits connecting primary sensory afferents to the sympathetic outflow to DRGs were investigated. We used simultaneous tracing of the sympathetic input to and sensory output from DRGs. Adult male rats received unilateral microinjections of the Bartha strain of pseudorabies virus into four lumbar DRGs. At 24 h post-inoculation, productive infection was detected in both DRG neurons and sympathetic postganglionic neurons. Infection of spinal cord neurons was first observed in sympathetic preganglionic neurons of the intermediolateral column. Subsequently, the infection spread to the contralateral intermediolateral column, the area around the central canal and the superficial dorsal horn layers. To investigate the relationship between infected spinal cord neurons and primary afferents from the corresponding DRGs, we injected pseudorabies virus for retrograde tracing together with cholera toxin B for anterograde tracing. We found that infected LIV/LV and LX neurons were in close apposition to cholera toxin B labeled afferents. Importantly, immunohistochemical detection of bassoon, a pre-synaptic zone protein, identified such contacts as synapses. Together, this suggests synaptic contacts between primary sensory afferents and neurons regulating sympathetic outflow to corresponding DRGs.     

Acetylcholine-induced back-firing in the preganglionic trunk of the rat superior cervical ganglion

ACh (5 × 10⁻⁴ M), when applied to isolated ganglion preparations elicited an apparently antidromic discharge in the cervical sympathetic trunk. The intensity of this back-firing was found to be about 10 times lower than that of the postganglionic discharge evoked by ACh in the internal carotid nerve. Both responses, however, displayed a similar time course and consisted of an early and a late component. In the back-firing the early component died out in a few seconds, while the late one lasted for 20–30 s. The two components were cancelled by d-tubocurarine (5 × 10⁻⁶ M) and atropine (10⁻⁶ M), respectively, suggesting that both nicotinic and muscarinic cholinoceptive sites are involved. In chronically decentralized preparations ACh evoked a clear back-firing response not substantially different from that elicited in normal ganglia. Therefore it is likely that the back-firing phenomenon is not due to antidromic activation of preganglionic fibers. The back-firing observed in the rat superior cervical ganglion was interpreted as being due to activation of sympathetic neurons known to give rise to recurrent axons in the cervical sympathetic trunk.     

Descending pathways to sympathetic and parasympathetic preganglionic neurons

In this review a summary of some of the neural pathways that appear to be involved in central cardiovascular control is given. The efferent connections of the nucleus tractus solitarius are described. Particular emphasis is placed on those projections that go to nuclei that have direct connections with the intermediolateral cell column (viz. paraventricular hypothalamic nucleus, Kölliker—Fuse nucleus, A5 catecholamine cell group, the chemosensitive region of the ventral medulla, and possibly the region of the A1 catecholamine cell group). In addition, some of these nuclei also have direct or indirect connections with the paraventricular and/or supraoptic hypothalamic nuclei. This suggests that some of the pathways that project to the cardiovascular preganglionic neurons may also influence the release of vasopressin.     

Multifiber efferent activity in postganglionic sympathetic and parasympathetic nerves related to the latency of spontaneous and evoked pupillary dilation

Spontaneous and peripherally evoked multifiber potentials were recorded from the sympathetic and parasympathetic pupillomotor fibers of the acutely prepared, pharmacologically immobilized cat. The onset latency of change in axonal activity was compared to the onset latency of pupillary dilation of the contralateral iris. Spontaneous pupillary dilations were accompanied by inhibition of parasympathetic and excitation of sympathetic pupillomotor activity. However, parasympathetic inhibition precedes sympathetic excitation. As with spontaneous changes, evoked changes in parasympathetic discharge rate occurred with a shorter onset latency than changes in sympapathetic discharge. In addition, the onset latency of change in sympathetic and parasympathetic nerve discharge was not related to the onset latency of evoked pupillary dilation by a constant factor. The difference in latency of the neural and pupillary response was found to increase systematically as a function of the latency of pupillary dilation.     

The proportions of sympathetic postganglionic and unmyelinated afferent axons in normal and regenerated cat sural nerves

Electrophysiological experiments have been carried out to see if the proportions of sympathetic postganglionic and unmyelinated afferent axons in a cutaneous nerve were changed after injury and regeneration. It seemed possible that an alteration in the relative numbers of the two groups of axons could contribute to the aetiology of reflex sympathetic dystrophy, but the experiments provided no evidence for such a change. There were, however, signs of a decrease in axon numbers in the regenerated nerves.