Vasoconstrictor Neurons Research Articles

Somatic depressor reflexes: results of specific ‘depressor’ afferents' excitation or an epiphenomenon of general anesthesia and certain decerebrations?

In chloralose-urethane anesthetized cats and unanesthetized decerebrate cats graded electrical stimulation of the tibial nerve A-afferents was performed and the resulting changes in the tibial nerve compound action potentials, heart rate and systemic arterial pressure were recorded. Three subgroups of the tibial nerve Aδ-afferents were distinguished and their excitability, conduction velocity and relation to the circulatory reflexes were characterized. Stimulation of the same A-afferents evoked only tachycardic reflexes in high-mesencephalic unanesthetized cats while both tachy- and bradycardic reflexes developed in anesthetized brain-intact cats. The volleys of Aβ-afferents elicited depressor reflexes in 50% of anesthetized cats but were ineffective in the other anesthetized brain-intact cats and in all the unanesthetized decerebrate cats. In anesthetized cats, the volleys of two low-threshold subgroups of Aδ-afferents evoked only depressor reflexes and volleys of high-threshold Aδ-afferents evoked both depressor and pressor reflexes in dependence on the deepness of anesthesia. In unanesthetized cats, effects of Aδ-stimulation depended on the level of decerebration, being exclusively pressor when the most high-threshold Aδ-fibers were stimulated in high-mesencephalic cats, both pressor and depressor when only low-threshold subgroups of Aδ-fibers were stimulated in these cats, and exclusively depressor in prebulbar cats. The dependence of the direction of reflex blood pressure changes on the level of decerebration and anesthesia is incompatible with the classical concept of the so-called somatic depressor afferents. Moreover, general anesthesia is shown to suppress and invert not only excitatory effects of spinal A-afferents' volleys on sympathetic vasoconstrictor and cardioaccelerator neurones but the inhibitory effects of these afferents' signals on the vagal cardioinhibitory neurones, too. Contrary to this concept, we regard the ‘somatic depressor reflexes’ and accompanying bradycardia not as a result of ‘specific’ afferents excitation, but as an epiphenomenon of general anesthesia and certain decerebrations. This hypothesis is founded: (1) on the results of electrophysiological investigations of somato-sympathetic and somato-vagal reflexes indicating the existence of parallel excitatory and inhibitory interneuronal pathways between the spinal afferents and sympathetic and vagal neurones; and (2) on the assumption of unequal sensitivity of these pathways to certain anesthetics. The dependence of the reflex effects of the spinal A-afferents' volleys on the level of decerebration suggests the existence of a suprabulbar system which performs a tonic control of the excitability of these excitatory and inhibitory somato-autonomic pathways.

Characteristics of phasic and tonic sympathetic ganglion cells of the guinea‐pig.

Intracellular recording techniques have been used to determine the electrophysiological properties of sympathetic neurones in ganglia of the caudal lumbar sympathetic chain (l.s.c.) and in the distal lobes of inferior mesenteric ganglia (i.m.g.) isolated from guinea-pigs. Passage of suprathreshold depolarizing current initiated transient bursts of action potentials in 97% of l.s.c. neurones, but only 13% of i.m.g. cells ('phasic' neurones). Most i.m.g. neurones fired continuously during prolonged depolarizing pulses ('tonic' neurones). Passive membrane properties varied; mean cell input resistance was similar between groups, but phasic neurones had smaller major input time constants on average than had tonic cells. Current-voltage relations determined under both current clamp and voltage clamp were linear around resting membrane potential (approximately 60 mV), where membrane conductance was lowest. Instantaneous and time-dependent rectification varied in the different neurone types. The current underlying the after-hyperpolarization following the action potential was significantly larger on average in tonic i.m.g. cells than in phasic neurones, although its time course (tau = 100 ms) was similar. Phasic neurones fired tonically when depolarized after adding the muscarinic agonist, bethanechol (10(-5) M to 10(-4) M), to the bathing solution. Bethanechol blocked a proportion of the maintained outward current (presumably the M-current, IM, Adams, Brown & Constanti, 1982) in phasic neurones; this current was small or absent in tonic neurones. Transient outward currents resembling the A-current (IA, Connor & Stevens, 1971 a) were evoked in tonic but not in phasic neurones by depolarization from resting membrane potential. IA could only be demonstrated in phasic neurones after a period of conditioning hyperpolarization. After a step depolarization to approximately --50 mV, IA reached peak amplitude at about 7 ms and then decayed with a time constant of about 25 ms in both neurone types. Activation characteristics of IA were similar for phasic and tonic neurones, but inactivation curves, although having the same shape, were shifted to more depolarized voltages in tonic neurones. That is, IA was largely inactivated at resting membrane potential in phasic, but not tonic neurones. It is concluded that the discharge patterns of the two populations of sympathetic neurones result from differences in the voltage-dependent potassium channels present in their membranes. The anatomical occurrence of the different cell types suggests that phasic neurones are vasoconstrictor and tonic neurones are involved with visceral motility.

Functional characterization of preganglionic neurons projecting in the lumbar splanchnic nerves: vasoconstrictor neurons

Lumbar preganglionic neurons, which project in the lumbar splanchnic nerves and which probably have a vasoconstrictor function (visceral vasoconstrictor, VVC neurons), were analyzed for their discharge patterns. The responses of these neurons to the following natural stimuli were tested: stimulation of arterial baroreceptors, arterial chemoreceptors and visceral afferents from the urinary bladder, the colon and the mucosal skin of the anus. Forty-nine preganglionic neurons were classified as VVC neurons. They showed the following characteristics: (1) the ongoing activity of the VVC neurons exhibited pronounced cardiac rhythmicity and correlated with the cycle of the artificial ventilation. Stimulation of arterial baroreceptors, produced by increase of blood pressure or by increase of pressure in an isolated carotid blind sac, led to inhibition of activity in VVC neurons. Unloading of arterial baroreceptors, produced by decrease of blood pressure, led to an increase in VVC neuron activity. (2) Stimulation of arterial chemoreceptors by bolus injections of CO 2-enriched saline solution, close to a carotid glomus, led to a weak excitation of VVC neurons. Stimulation of arterial chemoreceptors by systemic hypoxia led to weak excitation and/or to depression of activity in VVC neurons. (3) Stimulation of visceral afferents from urinary bladder and colon by isovolumetric contractions and distensions of the organs had no effect on most VVC neurons. Anal stimulation also did not induce reflexes in the majority of the VVC neurons. (4) Some 14% of the VVC neurons (7 from 49) were excited by at least one of the visceral stimuli in the same manner as the motility-regulating (MR) neurons (see ref. 1). (5) This investigation shows that preganglionic neurons, probably involved in regulation of vascular resistance in colon and pelvic organs, are functionally a distinct population of neurons with some interesting functional overlap with the motility-regulating neurons (see ref. 1).

Secondary functional properties of lumbar visceral preganglionic neurons

Preganglionic visceral vasoconstrictor (VVC) neurons and motility-regulating (MR) neurons and other visceral preganglionic neurons, which project in the lumbar splanchnic nerves, were analyzed for their segmental distribution, the conduction velocity of their axons, ongoing activity and reflexes elicited by electrical stimulation of visceral afferents in white rami and of somatic afferents in spinal nerves. (1) Identified preganglionic neurons and neurons without ongoing and reflex activity were distributed over segments L1–L5. VVC neurons were distributed over segments L1–L4 and MR neurons over segments L3–L5. (2) VVC axons conducted at 2.8 ± 2.5 m/s (mean ± 1 S.D., n = 49), MR axons at 8.1 ± 4.7 m/s (n = 131). (3) The ongoing activity of VVC neurons was 1.6 ± 0.7 imp/s (n = 46), that of MR neurons 0.8 ± 0.7 imp/s (n = 91). There was no correlation between the conduction velocity of preganglionic axons and the rate of ongoing activity for VVC and MR neurons. (4) Electrical stimulation of visceral afferents in white rami and of somatic afferents in spinal nerves elicited short-latency (< 50 ms) and long-latency (> 50 ms) reflexes in practically all VVC neurons, but preferentially short-latency reflexes in only 50 to 60% of the MR neurons. These results show that VVC and MR neurons are not only different in their reflex patterns, elicited by stimulation of visceral receptors and of arterial baro- and chemoreceptors, but also in the 4 properties analyzed in this paper.

Functional characterization of preganglionic neurons projecting in the lumbar splanchnic nerves: neurons regulating motility

Lumbar preganglionic neurons, which projected in the lumbar splanchnic nerves and were probably involved in regulating motility of colon and pelvic organs (motility-regulating, MR neurons), were analyzed for their discharge patterns. The responses of the neurons to the following stimuli were tested: stimulation of arterial baro- and chemoreceptors and of afferents from the urinary bladder, colon, mucosal skin of the anus and perianal hairy skin. The following findings were made: (1) a total of 131 preganglionic neurons were classified as MR neurons; these reacted to natural stimulation of at least one of the afferent inputs from the urinary bladder, colon and anal and perianal skin. (2) The ongoing activity of these neurons did not correlate with the cardiac cycle or the cycle of the artificial ventilation. Most of them did not respond to an increase of blood pressure produced by i.v. injection of adrenaline or noradrenaline; some showed a weak depression or weak excitation which, in the time course, was untypical for visceral vasoconstrictor neurons (see ref. 4). (3) Stimulation of arterial chemoreceptors either did not influence MR neurons or produced only a secondary response owing to contraction of the urinary bladder. (4) Ninety-seven preganglionic MR neurons could be subclassified: MR 1 neurons were excited by distension and contraction of the urinary bladder and/or inhibited by distension and contraction of the colon (n = 61), a few were excited from both organs (n = 4); MR 2 neurons were inhibited by distension and contraction of the urinary bladder and/or excited by distension and contraction of the colon (n = 32). (5) Ninety-five out of 121 MR neurons (78.5%) were excited, 10 (8%) were inhibited and 16 (13%) not influenced by mechanical shearing stimuli applied to the mucosal skin of the anus. (6) Most neurons which were excited by anal stimulation were not influenced by mechanical stimulation of the perianal (perigenital) skin. Twenty-eight per cent of the MR neurons (18 out of 64) were excited or inhibited upon stimulation of perianal skin. A few of these (7 out of 64 neurons, 11%) were involved in reflex responses which were different from those elicited from anal skin. (7) At present no further consistent subclassification of MR 1 and MR 2 neurons appears possible on the basis of the excitatory and inhibitory anal and perianal reflexes. (8) The results show that the population of visceral preganglionic neurons, which are probably involved in regulation of motility of colon and pelvic organs, is not homogeneous and probably consists of several subpopulations.

Reflex patterns in postganglionic vasoconstrictor neurons following chronic nerve lesions

Lesions of limb nerves in man may be associated with a variety of painful disorders with trophic changes described by the generic term ‘reflex sympathetic dystrophy’. Our hypothesis is that pain and trophic changes are produced by an abnormal discharge pattern in postganglionic neurons supplying the limb (see refs. 3,24). In relation to this hypothesis, reflex patterns in postganglionic vasoconstrictor neurons supplying the skin (CVC) and the skeletal muscle (MVC) of the cat hindlimb were investigated at various times after a peripheral nerve lesion had been produced. These reflex patterns were compared with those in animals without nerve lesions (control preparations). The following lesions were made; (a) cutting and ligating the superficial peroneal nerve (skin nerve) with subsequent neuroma formation, (b) suturing the central stump of the superficial peroneal nerve to the peripheral stumps of muscle branches of the deep peroneal nerve, (c) suturing the central stumps of muscle branches of the deep peroneal nerve to the peripheral stump of the superficial peroneal nerve, (d) cutting and resuturing the superficial peroneal nerve, (e) deafferentation of the whole hindlimb. The responses of vasoconstrictor neurons to stimulation of arterial chemoreceptors, arterial baroreceptors (cardiac rhythmicity of postganglionic activity) and cutaneous nociceptors were tested. In the animals with nerve lesions, the following groups of postganglionic vasoconstrictor neurons were analyzed: neurons projecting to the lesioned nerve, neurons projecting to hairy skin through an intact skin nerve (sural nerve) and neurons projecting to skeletal muscle through intact muscle nerves. (1) In control preparations without nerve lesions, MVC neurons were excited by stimulation of arterial chemoreceptors and cutaneous nociceptors and inhibited by stimulation of arterial baroreceptors. Most CVC neurons were inhibited by stimulation of chemoreceptors and nociceptors and weakly inhibited by stimulation of baroreceptors. (2) In animals with nerve lesions a and b, many CVC neurons in the lesioned nerves, as well as in the non-lesioned cutaneous nerve nearby, behaved in the same manner as MVC neurons. With respect to the control, this difference proved to be statistically significant. In preparations with lesions a, b and c, MVC neurons did not change their reflex patterns. (3) After nerve lesions d and e, no major changes of reflex patterns were observed in CVC and MVC neurons. The inhibitory influence of arterial baroreceptors on CVC activity decreased in deafferented preparations (lesion c). (4) The results indicate that lesions of cutaneous nerves of an extremity may lead to changes in the response pattern in CVC neurons to certain afferent stimuli, in the sense that this pattern becomes similar to that in MVC neurons.

Chemoreceptor and baroreceptor inputs to ventrolateral medullary neurons.

Recording experiments were done in chloralose-anesthetized, paralyzed, and artificially ventilated cats to identify single units in the ventrolateral medulla (VLM) projecting directly to the region of the intermediolateral nucleus of the spinal cord (T2) and responding to selective activation of peripheral chemoreceptors (sodium cyanide, 20-60 micrograms in 0.1-0.3 ml saline into medial thyroid artery) and baroreceptors (phenylephrine, 2 micrograms/kg iv). The firing frequency of 49 of the 81 antidromically identified single units was altered by activation of the peripheral cardiovascular receptors. Of these responsive units, 25 responded only to activation of chemoreceptors (17 excited and 8 inhibited), 20 responded in various combinations to activation of both chemo- and baroreceptors, and 4 responded only to activation of baroreceptors. In addition, units that altered their firing frequency during baroreceptor activation (n = 24) responded in the opposite direction to baroreceptor unloading (carotid arterial occlusion). These results suggest that neurons in the VLM are components of bulbospinal sympathoexcitatory and -inhibitory pathways that receive cardiovascular afferent information and in turn influence vasoconstrictor and cardioacceleratory neurons in the intermediolateral nucleus of the upper thoracic cord.

Vasoconstrictor systems supplying skeletal muscle, skin, and viscera.

Stimulation of afferent inputs from the body surface and from the interior of the body elicits distinct reflex patterns in post- and preganglionic vasoconstrictor neurons supplying skeletal muscle, skin and viscera of the cat. These patterns are due to characteristic organizations of the vasoconstrictor systems in the neuraxis and may serve as functional labels for the neurons but also as conceptual leads in experimental investigations of the vasoconstrictor systems in the neuraxis. These systems may be generally organized in a hierarchical manner. The lowest level of the hierarchy consists of separate common final sympathetic pathways, the pre-postganglionic channels, with some integrating processes in the ganglia. Then there is the spinal level with the spinal sympathetic motor units. Different functional motor units overlap and receive their inputs from the periphery via primary afferents and from brain stem and hypothalamus via spinal descending systems. Brain stem and hypothalamus organize spinal motor units into global functional units.

Direct pathway from cardiovascular neurons in the ventrolateral medulla to the region of the intermediolateral nucleus of the upper thoracic cord: an anatomical and electrophysiological investigation in the cat

Horseradish peroxidase (HRP) and single unit recording experiments were done in cats to identify neurons in the ventrolateral medulla (VLM) projecting directly to the intermediolateral nucleus (IML) of the thoracic cord and relaying cardiovascular afferent information from the buffer nerves and hypothalamus. In the first series, HRP was allowed to diffuse from a micropipette into the region of the IML at the level of T2. After a survival period of 30–138 h, transverse and horizontal sections of the brainstem were processed according to the tetramethyl benzidine method. Labeled neurons were found in the VLM 1–5 mm rostral to the obex, bilaterally, but with an ipsilateral predominance. The majority were observed in sections 2–4 mm rostral to the obex, clustered in an area lateral to the inferior olivary nucleus around the intramedullary rootlets of the hypoglossal nerve. Additional labeled neurons were found scattered along the ventral surface of the medulla; most of these neurons were oval in shape, 15–30 μm in diameter, and had dendritic processes which lay parallel to the ventral surface. In the second series, the region of the VLM shown to contain labeled neurons was systematically explored for single units antidromically activated by electrical stimulation of the IML in chloralosed, paralyzed and artificially ventilated animals. These antidromically identified units were then tested for their responses to electrical stimulation of the carotid sinus (CSN) and aortic depressor (ADN) nerves, and the paraventricular nucleus (PVH). Ninety-four single units in the VLM were antidromically activated with latencies corresponding to a mean conduction velocity of 19.1 ± 1.5 m/s. Of these units 52% (49/94) were orthodromically excited by stimulation of buffer nerves; 12 by stimulation of the CSN only (mean latency, 16.0 ± 3.6 ms), 5 by stimulation of the ADN only (mean latency, 9.5 ± 2.0 ms), 7 by both buffer nerves, and the remaining 25 units responded to at least one of the buffer nerves and to PVH. Stimulation of PVH excited orthodromically 42 of the 94 units (45%), of which 17 responded only to stimulation of PVH (mean latency, 17.9 ± 3.5 ms). These experiments provide anatomical and electrophysiological evidence for the existence of a direct cardiovascular pathway from the VLM to the region of the IML and suggest that neurons in the VLM are involved in the integration of cardiovascular afferent inputs from buffer nerves and the hypothalamus to provide an excitatory input to vasoconstrictor neurons in the IML.

Discharge patterns of sympathetic neurons supplying skeletal muscle and skin in man and cat

Skeletal muscle and skin of humans and cats are supplied by various sympathetic systems: vasoconstrictor neurons, sudomotor neurons, vasodilator neurons and pilomotor neurons. Only vasoconstrictor and sudomotor neurons have resting activity in both species. Discharge patterns of spontaneous activity in postganglionic neurons with resting activity as well as their reflex responses to various stimuli have been compared for both species: (1) muscle vasoconstrictor neurons react similarly in both species; they are under dominant control of arterial baroreceptors; (2) in both species cutaneous vasoconstrictor neurons are under no or weak control of arterial baroreceptors and they are influenced in similar ways by thermal stimuli. In contrast, other (somatic and visceral) stimuli elicit largely inhibition in these neurons in cats but excitation in humans. This may be due to the different experimental situations (anesthesia, etc.); (3) sudomotor neurons in humans are involved in thermoregulation, in cats they are not. The differences in the reflexes may also be due to the different experimental situations and to species differences; (4) the implications of studies on sympathetic neurons in humans and animals for the progress of research in this field have been discussed.

Changes of reflexes in vasoconstrictor neurons supplying the cat hindlimb following chronic nerve lesions: a model for studying mechanisms of reflex sympathetic dystrophy?

The generic term ·reflex sympathetic dystrophy’ describes a clinical syndrome which sometimes develops after traumata at the extremities with lesions of nerves or — more rarely — after other events. The syndrome consists of the following components: pain (hyperpathia, allodynia), trophic changes of skin and deep tissues, dysregulation of sweating and cutaneous blood flow of the extremity concerned. It is assumed that all symptoms are produced by abnormal sympathetic activity. Interruption of the sympathetic activity to the affected extremity abolishes most of the pain and may lead to remission of the trophic changes. The hypothesis is that the trauma with lesion of the primary afferent axons leads subsequently to an abnormal state of the primary afferent neurons and to distorted processing of information in the spinal cord. As a consequence of this abnormal central state the activity in the sympathetic (vasomotor and sudomotor) supply to the affected extremity is distorted. The results are pain, trophic changes and dysregulations of autonomic effector organs. In some yet unknown way a vicious circle between periphery and spinal cord is established (afferent → spinal cord → sympathetic → afferent). This hypothesis was the starting point for analysis of the reflex pattern in postganglionic vasoconstrictor neurons supplying the cat hindlimb after chronic nerve lesions performed in the same limb (cutting and ligating a skin nerve; suturing the central stump of a skin nerve to the peripheral stump of a muscle nerve). The results obtained show that the reciprocity of the reflex pattern which is normally observed between cutaneous and muscle vasoconstrictor neurons is lost in many animals. Cutaneous vasoconstrictor neurons are very similar to muscle vasoconstrictor neurons in their reactions to stimulation of arterial baroreceptors and chemoreceptors. If the same sequence of events also occurs in patients with reflex sympathetic dystrophy, it could explain the dysregulation of blood flow through skin and also the occurrence of trophic changes in the limb.

Activity in sympathetic neurons supplying skin and skeletal muscle in spinal cats

In anesthetized cats with intact neuraxis, vasoconstrictor neurons supplying skeletal muscle (MVC) and hairy and hairless skin (CVC), and sudomotor neurons innervating sweat glands (SM), exhibit distinct reflex patterns. MVC and SM are largely under excitatory, CVC under inhibitory control of various afferent input systems from the body surface and from the viscera. In chronic spinal animals all 3 types of sympathetic neurons exhibit some resting activity without cardiac and respiratory modulation. Sixty to 150 days after isolation of the neural circuits within the spinal cord from their descending control systems by spinalization, these reflex patterns are very similar to those in animals with intact neuraxis. Important changes which do occur after spinalization are the following: CVC neurons are excited by stimulation of visceral afferents in spinal animals but inhibited in animals with intact neuraxis; noxious stimulation of skin leads to long-lasting after-effects in CVC and SM neurons in spinal animals. Comparison of reflexes among spinal animals and animals with intact neuraxis indicates that spinal circuits are probably important for the functioning of the sympathetic systems. It is possible that these circuits determine the typical reaction patterns seen in the sympathetic systems by integrating multisensory information from primary afferents and information from spinal descending fiber tracts.

Reflex activation of postganglionic vasoconstrictor neurones supplying skeletal muscle by stimulation of arterial chemoreceptors via non-nicotinic synaptic mechanisms in sympathetic ganglia.

Postganglionic sympathetic neurones supplying skeletal muscle and skin can be activated from the preganglionic site via cholinergic nicotinic, muscarinic and noncholinergic synaptic mechanisms. The experiments described in this paper were designed in order to show that postganglionic vasoconstrictor neurones supplying skeletal muscle can be activated by the naturally occurring discharge pattern in preganglionic axons when the nicotinic transmission is blocked. For this purpose, the activity was recorded simultaneously from postganglionic vasoconstrictor axons supplying skeletal muscle and vasoconstrictor axons supplying hairy skin. The preganglionic neurones were driven reflexly by stimulation of the arterial chemoreceptors. 1) During blockade of nicotinic transmission muscle vasoconstrictor neurones were activated via the CNS during stimulation of arterial chemoreceptors. This activation is either generated by muscarinic action of released acetylcholine or by a noncholinergic synaptic mechanism. 2) Postganglionic cutaneous vasoconstrictor neurones were inhibited during stimulation of arterial chemoreceptors. During blockade of cholinergic nicotinic transmission these neurones were not activated reflexly by stimulation of arterial chemoreceptors although they received inputs via cholinergic muscarinic and noncholinergic synaptic mechanisms. 3) The results illustrate that postganglionic vasoconstrictor neurones supplying skeletal muscle can not only be activated via non-nicotinic synaptic mechanisms through synchronous repetitive electrical stimulation of preganglionic axons but also by the discharge pattern produced in preganglionic neurones during stimulation of arterial chemoreceptors.

Enhancement of resting activity in postganglionic vasoconstrictor neurones following short-lasting repetitive activation of preganglionic axons.

Resting activity in postganglionic neurones supplying the cat hindlimb was enhanced after activation of preganglionic axons in the lumbar sympathetic trunk with short trains of stimuli (50 stimuli at 25 Hz). The characteristics of this enhancement were as follows: 1) It has values of 120 to 600% and lasts for 4 to more than 40 min. 2) It can be elicited heterosynaptically by repetitive stimulation of the peripheral end of a cut white ramus. 3) It is dependent on the activation of thin, probably unmyelinated, preganglionic axons. 4) It is probably produced by non-nicotinic (muscarinic and non-cholinergic) synaptic mechanisms in the sympathetic chain ganglia. 5) Vasoconstrictor neurones can be activated in this way, but not sudomotor neurones. The results argue that nicotinic transmission of activity from pre- to postganglionic vasoconstrictor neurones can be modulated heterosynaptically by slow non-nicotinic synaptic processes.

Transmission of impulses from pre- to postganglionic vasoconstrictor and sudomotor neurons

Transmission of impulses from pre- to postganglionic neurons supplying skeletal muscle and skin of the cat's hindlimb and tail was investigated. The objective of the study was to determine whether these postganglionic neurons can be influenced from the preganglionic side by non-nicotinic synaptic mechanisms in the lumbar sympathetic chain ganglia. The activity of the postganglionic neurons was recorded from their axons being isolated from peripheral skin and muscle nerves. 1. (1) Vasoconstrictor neurons can be activated by muscarinic action of released acetylcholine and by a non-cholinergic synaptic mechanism. This type of non-nicotinic excitation of postganglionic vasoconstrictor neurons requires the activation of thin, probably unmyelinated preganglionic axons and considerable summation. Postganglionic sudomotor and pilomotor neurons cannot be activated in this way. 2. (2) Ongoing activity in postganglionic vasoconstrictor neurons, but not in sudomotor neurons, can be enhanced for up to 60 min by brief trains of stimuli applied to the preganglionic site. Also this enhancement requires the activation of thin preganglionic axons. 3. (3) Stimulation of thin preganglionic axons leads to an activation of muscle vasoconstrictor neurons via non-nicotinic synaptic mechanisms in the ganglia after complete block of nicotinic transmission. 4. (4) Postganglionic vasoconstrictor neurons and sudomotor neurons may be inhibited by a catecholaminergic autogenic mechanism in the ganglia. 5. (5) The results indicate that integration may take place in the sympathetic chain ganglia by other than divergent and convergent processes. In this integration muscarinic actions of released acetylcholine and non-cholinergic synaptic mechanisms may be involved.

Effects of central thermal stimuli on activity in cutaneous and muscle vasoconstrictor neurones supplying the cat hindlimb

Cutaneous (CVC) and muscle vasoconstrictor neurones (MVC) exhibit characteristic reflex patterns upon somatic and visceral stimuli. Central thermal stimuli should be specific for CVC neurones and not affect MVC neurones. In the following the reactions of these sympathetic neurones to warming and cooling of hypothalamus and spinal cord are described. The hypothalamus was warmed and cooled by a water-perfused thermode which was positioned stereotaxically into the rostral part of the third ventricle, the spinal cord by a water-perfused U-shaped tubing positioned epidurally. Vasoconstrictor activity was recorded from postganglionic axons which have been isolated in bundles from peripheral skin and muscle nerves of the cat hindlimb. The following results were obtained: I) Hypothalamic and spinal cord wanning lead to a decrease of activity in CVC neurones in a graded manner. When both brain structures are warmed the decrease of activity is larger than the algebraic sLm~nation of the individual effects. 2) Central cooling leads to an increase of activity in the CVC neurones. This increase was very often transient and comparatively smaller than the effects upon central warming. 3) The activity in MVC neurones was either not influenced by central thermal stimuli or increased due to small decreases of systematic blood pressure (baroreceptor unloading). 4) During hypothalamic warming respiratory rhythmicity in the activity of many CVC neurones was enhanced.

Cardiac rhythmicity of skin sympathetic activity recorded from peripheral nerves in man

In previous microelectrode recordings of sympathetic impulse activity in human peripheral nerves a marked cardiac rhythmicity has been found in the spontaneous firing of vasoconstrictor neurones supplying the vascular bed of skeletal muscles. Evidence has been presented that this rhythmicity depends on a potent baroreflex control of these neurones which are significantly involved in blood pressure regulation. In contrast, no cardiac rhythmicity has previously been seen in the spontaneous firing of sympathetic fibres supplying vessels and sweat glands in the human skin. The present study shows that when strong sudomotor activity is induced in skin nerves by a rise in ambient temperature, the sudomotor impulses tend to occur in volleys time-locked to the cardiac cycle. A similar cardiac rhythmicity is not exhibited by the skin vasoconstrictor fibres which can be activated by lowering of the ambient temperature. Induced falls in blood pressure do not produce any baroreflex modulations of the sudomotor outflow, suggesting that the cardiac rhythmicity of the sudomotor impulses is not dependent on the action of this reflex.

The organization of lumbar preganglionic neurons.

The organization of pre- and postganglionic neurons supplying blood vessels of the skin (vasoconstrictor neurons) and of the skeletal muscle (vasoconstrictor neurons), sweat glands (sudomotor neurons) and erector pilimuscles (pilomotor neurons) of the cat's hind limb and tail is discussed. Each sympathetic subsystem has its own, though as yet unknown, central organization which is reflected in the reaction patterns typically seen. The conduction velocities of the pre- and postganglionic axons of each subsystem have their unique distributions. Postganglionic vasoconstrictor neurons supplying skeletal muscle and skin are influenced via cholinergic muscarinic and non-cholinergic synaptic mechanisms from thin, probably unmyelinated, preganglionic axons; postganglionic sudomotor and pilomotor neurons most likely do not receive this synaptic input. A high proportion of preganglionic neurons projecting with their axons onto postganglionic neurons which supply skin and skeletal muscle are silent and do not exhibit reflex activity. Some of these neurons synapse with postganglionic pilomotor, vasodilatator and sudomotor neurons; part of them may also synapse with vasoconstrictor neurons. However, the high proportion of preganglionic neurons without reflex and resting activity which cannot be classified on the basis of functional properties presents a considerable problem in the analysis of the central organization of the sympathetic nervous system. It is concluded that the 4 types of pre- and postganglionic neurons mentioned constitute 4 largely separate channels which transmit information from the spinal cord to the respective target organs.

Organization of the sympathetic innervation supplying the hairless skin of the cat's paw

The sympathetic outflow supplying the hairless skin of the cat's hind paw has been analyzed in brain-intact and chronic low spinal animals. For this purpose the activity of postganglionic axons in fascicles of the medial plantar nerve which innervate the central pad and the respective responses of the target organs (transient skin potentials, skin temperature) have been recorded. (1) Blood vessels and sweat glands in the hairless skin of the cat's hind paw are under efferent control of vasoconstrictor neurons, sudomotor neurons, and possibly vasodilatator neurons. (2) Vasoconstrictor neurons are largely under inhibitory control of various afferent input systems from the body surface and from the internal milieu, and sudomotor neurons under excitatory control in brain-intact as well as in chronic spinal cats. (3) The basic neuronal network or "machinery" for the this reciprocal organization is probably located in the spinal cord. (4) Effects of anesthetics on the sudomotor reflexes indicate that this spinal neuronal organization is controlled in a complex manner by descending spinal systems from the brain stem. (5) The existence of vasodilatator neurons, a third efferent control system supplying the hairless skin, which can only be activated by spinal cord warming in brain-intact as well as in chronic spinal cats is not very well established. Neurons with this property are rare and it is unclear whether they course through the sympathetic trunk or dorsal roots or through both. The axons of these neurons are unmyelinated. (6) The organization of the neuronal control of vessels and sweat glands in the hairless skin may be a paradigmatic model for studying the respective neuronal organization in the spinal cord and its descending control.

Functional properties of lumbar preganglionic neurones

Lumbar preganglionic neurones projecting through WRL 2 and L 3 to lumbar ganglia caudal to L 4 were investigated for those functional properties which are typical for postganglionic vasoconstrictor neurones supplying muscle and skin and for postganglionic sudomotor neurones. The properties tested were the cardiac rhythmicity of the activity and the reactions to systemic hypoxia, to noxious stimulation of skin and (in part of the experiments) to vibrational stimuli. Furthermore, resting activity and conduction velocities of the axons were measured. 426 neurones were investigated. 311 (73%) of them were silent and could — as far as tested — not be excited by the afferent stimuli used. The conduction velocities of the axons of these neurones ranged from 0.5 to about 16 m/sec. 115 neurones had resting activity of 0.1–4.6 impulses/sec. The conduction velocities of their axons ranged from 0.5 to about 12 m/sec. 80 preganglionic neurones with resting activity were classified on the basis of the reflexes in these neurones to afferent stimuli. Preganglionic neurones reacting like postganglionic vasoconstrictor neurones to muscle (excited by systemic hypoxia and/or by noxious stimulation of skin; with cardic rhythmicity) were classified as type 1 neurones (26 from 80 neurones tested). The resting activity of these neurones was 1.8 ± 1.3impulses/sec(mean ± 1S.D.). Their axons conducted with 3.9 ± 2.2m/sec. Preganglionic neurones reacting like the majority of the postganglionic vasoconstrictor neurones to hairy and hairless skin (inhibited by systemic hypoxia and/or noxious cutaneous stimuli) were classified as type 2 neurones (48 from 80 neurones investigated). In 40% of these neurones the activity had cardiac rhythmicity. The resting activity was 0.9 ± 0.6impulses/sec. The distribution of the conduction velocities of the axons of these neurones was bimodal. They conducted on the average with 1.3 ± 0.6m/sec and6.6 ± 2.2m/sec respectively. A neurones were found (6 fronm 80 neurones) which were activated by vibrational stimuli (activation of Pacinian corpuscles by tapping on the hindfoot). Since this type of activation is typical for postganglionic sudomotor neurobes they were classified as type 3 neurones. The activity of these neurones had no cardiac rhythmicity. Indirect measurements of the conduction velocities of preganglionic axons converging onto postganglionic neurones supplying skeletal muscle and hairy skin yielded values which were statistically not different from the conduction velocities of the axons of type 1 and type 2 neurones respectively. These measurements support the classification into type 1 and type 2 preganglionic neurones. The implications of this study are discussed.