Rhythm In Sympathetic Nerve Discharge Research Articles

Role of the medullary lateral tegmental field in sympathetic control.

The sympathetic nervous system maintains and regulates arterial pressure and tissue perfusion, via control of cardiac output and vasomotor tone. Sympatho-vascular-mediated increases in blood pressure are effected by arterioloconstriction, which causes an increase in afterload, and/or venoconstriction, which increases venous return, left ventricular preload, and consequently, the force of cardiac contraction via Frank-Starling mechanisms; withdrawal of sympathetic drive elicits reciprocal effects. Spinalization reduces mammalian arterial pressure to 40-50mm Hg consequent to the elimination of descending medullary pre-sympathetic bulbospinal drive to preganglionic sympathetic fibers in the intermediolateral cell column of the spinal cord. Beyond agreement that sympathetic tone is generated supraspinally, there is only controversy. One hypothesis posits that pre-sympathetic medullary regions, such as the rostral ventrolateral medulla (RVLM) and caudal raphé group, possess intrinsic tonic activity. Alternatively, pre-sympathetic medullary regions may receive tonic excitation from other areas in the brainstem. Neurons in the lateral tegmental field (LTF), an exclusively propriobulbar entity (cf. pre-Bötzinger complex- the propriobulbar inspiratory rhythmogenic kernel of the respiratory network), fire before and project to pre-sympathetic units in RVLM and caudal raphé and exhibit activity correlated to the cardiac-related rhythm in sympathetic nerve discharge, making the LTF a likely candidate for the primary source of basal sympathoexcitation. The LTF is additionally involved in a variety of cardiovascular and sympathetic reflexes (i.e., baroreflex, Bezold-Jarisch reflex). As it receives descending afferents from the infralimbic cortex and associated limbic structures, suggesting a role in the sympathetic response to fear, as well as vestibular inputs, consistent with a role in coordinating the sympathetic response with emesis proper, the LTF appears to play an extensive integrative role. In this review, we discuss the LTF, a once mysterious, poorly-characterized, and ill-defined region, the contribution of which to cardiovascular reflexes and basal sympathoexcitation has been more thoroughly elucidated in recent years and any model of central control of sympathetic output must take into consideration the contribution of this important region.

Role of serotonergic input to the ventrolateral medulla in expression of the 10-Hz sympathetic nerve rhythm

We studied the changes in inferior cardiac sympathetic nerve discharge (SND) produced by unilateral microinjections of 5-hydroxytryptamine (5-HT) receptor agonists and antagonists into the ventrolateral medulla (VLM) of urethane-anesthetized, baroreceptor-denervated cats. Microinjection of the 5-HT2 receptor antagonist LY-53857 (10 mM) into either the rostral or caudal VLM significantly reduced (P < or = 0.05) the 10-Hz rhythmic component of basal SND without affecting its lower-frequency, aperiodic component. The selective depression of 10-Hz power was accompanied by a statistically significant decrease in mean arterial pressure (MAP). Microinjection of LY-53857 into the VLM also attenuated the increase in 10-Hz power that followed tetanic stimulation of depressor sites in the caudal medullary raphé nuclei. Microinjection of the 5-HT2 receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)2-amino-propane (DOI; 10 microM) into the VLM selectively enhanced 10-Hz SND, and intravenous DOI (1 mg/kg) partially reversed the reduction in 10-Hz SND produced by 5-HT2 receptor blockade in the VLM. Microinjection of the 5-HT1A receptor agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OHDPAT; 10 mM), into either the rostral or caudal VLM also selectively attenuated 10-Hz SND and significantly reduced MAP. The reduction in 10-Hz SND produced by 8-OHDPAT was partially reversed by intravenous WAY-100635 (1 mg/kg), which selectively blocks 5-HT1A receptors. These results support the view that serotonergic inputs to the VLM play an important role in expression of the 10-Hz rhythm in SND.

Role of 5‐hydroxytryptamine (5‐HT2) receptors in the ventrolateral medulla (VLM) in the expression of the 10‐Hz rhythm in sympathetic nerve discharge (SND)

We have shown that chemical inactivation (muscimol or 8‐OHDPAT microinjections) of the medullary raphe selectively reduces the 10‐Hz rhythmic component in SND of baroreceptor‐denervated, urethane‐anesthetized cats. These data suggest that raphe serotonergic neurons play a role in expression of the 10‐Hz rhythm. The current study was designed to identify the brainstem regions and 5‐HT receptor type acted on by these raphe neurons. For this purpose, power in the 10‐Hz band of left and right inferior cardiac SND was measured before and after unilateral microinjections (50 nl/injection) of a 5‐HT2 receptor antagonist (10 mM LY‐53,857) or agonist (10 uM DOI) into the caudal or rostral VLM, 3.8 − 4.2 mm lateral to the midline. LY‐53,857 significantly (p ≫ 0.05) reduced 10‐Hz power (ipsilateral to the injection site) to 32 +/− 8% and 22 +/− 8% of control when injected into the caudal and rostral VLM, respectively. The 10‐Hz power recorded contralateral to the injection site was reduced to a lesser extent. Power at lower frequencies (&lt; 6 Hz) was not significantly changed in either nerve recording. DOI microinjection into either the caudal or rostral VLM produced a change in 10‐Hz power (an increase) opposite to that produced by the 5‐HT2 receptor antagonist. These results support the view that raphe neurons selectively enhance 10‐Hz SND by activating 5‐HT2 receptors on VLM neurons that comprise the rhythm generator. (Supported by HL‐33266.)

Role of ventrolateral medulla in generating the 10-Hz rhythm in sympathetic nerve discharge

We recorded changes in right inferior cardiac and either left inferior cardiac or left vertebral sympathetic nerve discharge (SND) produced by unilateral microinjections of GABA-A and excitatory amino acid (EAA) receptor antagonists into the ventrolateral medulla (VLM) of urethane-anesthetized, baroreceptor-denervated cats. Unilateral microinjections of GABA-A receptor antagonists, SR-95531 or bicuculline, into single tracks in VLM anywhere between 1 and 5 mm rostral to the obex eliminated or markedly reduced 10-Hz power in SND on both sides of the body. Low-frequency components (<6 Hz) of SND were unaffected. Complete blockade of the 10-Hz rhythm occurred with a dose of SR-95531 as low as 6.25 pmol in a 50-nl volume. Unilateral microinjections of the nonselective EAA receptor antagonist, kynurenate (KYN; 7.5 nmol), into the caudal or rostral VLM significantly reduced, but did not eliminate, 10-Hz SND ipsilateral to the injection sites, while 10-Hz SND contralateral to the injection sites was not significantly changed. These observations suggest that 1) GABAergic transmission in VLM is critical for generation of the 10-Hz rhythm, 2) the caudal and rostral portions of VLM act together to generate the 10-Hz rhythm, and 3) 10-Hz rhythm generation depends, at least in part, on tonic or phasic excitatory drive to GABAergic interneurons in caudal VLM and presympathetic neurons in rostral VLM. The data also suggest that pathways interconnecting the two halves of the brain stem play an important role in promoting 10-Hz rhythm generation.

Role of GABA in generating the 10‐Hz rhythm in sympathetic nerve discharge

The 10-Hz rhythm in SND of the cat is dependent on neurons located in the caudal and rostral ventral lateral medulla (VLM) and medullary raphe (Barman and Gebber, J Biol Rhythms 15: –379, 2000). We sought to determine whether GABA-mediated synaptic transmission in these regions is involved in 10-Hz rhythm generation. For this purpose, we recorded the discharges of the left and right inferior cardiac or the left vertebral and right inferior cardiac postganglionic sympathetic nerves in baroreceptor-denervated cats anesthetized with urethane. Unilateral microinjection of GABA-A receptor antagonists (50 nl of 1- mM solution of either SR-95531 or bicuculline) into the VLM eliminated the 10-Hz rhythm bilaterally. This was the case for injections made in single or multiple tracks in the VLM between the obex and 6 mm rostral. Recovery occurred within 3 h, and 10-Hz SND was unchanged after microinjection of vehicle (phosphate buffered saline). In contrast, the 10-Hz rhythm in SND was enhanced by multiple microinjections of the GABA antagonists into the raphe from 0 to 6 mm rostral to the obex. These results indicate that GABA-mediated synaptic inhibition in the VLM is critical for 10-Hz rhythm generation. Moreover, the data support the view that networks of neurons located bilaterally throughout the VLM act as a unit to generate the 10-Hz rhythm in SND. (Supported by NIH grant HL33266.)

Role of medullary excitatory amino acid receptors in mediating the 10-Hz rhythm in sympathetic nerve discharge of cats

We tested the hypothesis that excitatory amino acid (EAA)-mediated transmission plays a role in generating the 10-Hz rhythm in sympathetic nerve discharge (SND) of baroreceptor-denervated, urethane-anesthetized cats. Microinjection of either an N-methyl- d-aspartate (NMDA) or non-NMDA receptor antagonist into any one of three medullary regions (lateral tegmental field, rostral, or caudal ventrolateral medulla) essentially eliminated the 10-Hz rhythm in inferior cardiac SND. We conclude that EAA receptors in the medulla are critical for generation of the 10-Hz rhythm.

Coupling of arterial pulse and 10-Hz rhythm in sympathetic nerve discharge

We used time series analysis to characterize the relationships among the arterial pulse (AP) and the cardiac-related and 10-Hz rhythms in sympathetic nerve discharge (SND) of urethane-anesthetized cats. We found that 10-Hz activity was more tightly coupled to the AP than to the cardiac-related rhythm. These data support the view that the dynamic coupling of AP and the 10-Hz rhythm in SND involves a direct influence of baroreceptor activity on the 10-Hz oscillator.

"Rapid" rhythmic discharges of sympathetic nerves: sources, mechanisms of generation, and physiological relevance.

Like virtually all other physiological control systems, the sympathetic nervous system controlling cardiovascular function is characterized by the presence of rhythmic activity. These include slow rhythms with frequencies at or below that of the respiration and rapid rhythms with frequencies at or above that of the heart beat. The rapid rhythms are the subject of this review. The specific questions entertained are as follows: (1) Are the rapid cardiac-related and 10-Hz rhythms inherent to central sympathetic networks, or are they imposed on sympathetic nerve discharge (SND) by extrinsic periodic inputs? (2) Does basal SND arise from an anatomically circumscribed "vasomotor center" composed of pacemaker neurons in the rostral ventrolateral medulla or from an anatomically distributed network oscillator composed of different types of brainstem neurons, none of which necessarily have intrinsic pacemaker properties? (3) Are the rapid rhythms generated by single circuits or by systems of coupled oscillators, each with a separate target? (4) Are the rapid rhythms in SND simply by-products of the sympathetic generating mechanisms, or do they subserve selective and special functions, such as the formulation of differential patterns of spinal sympathetic outflow that support particular behaviors? The controversial aspects of these issues and the state-of-the-art analytical methods used to study them are stressed in this review.

Partial spectral analysis of cardiac-related sympathetic nerve discharge.

We have studied the relationship between pulse synchronous baroreceptor input (represented by the arterial pulse, AP) and the cardiac-related rhythm in sympathetic nerve discharge (SND) of urethan-anesthetized cats by using partial autospectral and partial coherence analysis. Partial autospectral analysis was used to mathematically remove the portion of SND that can be directly attributed to the AP, while partial coherence analysis was used to removed the portion of the relationship between the discharges of sympathetic nerve pairs that can be attributed to linear AP-SND relationships that are common to the nerves. The ordinary autospectrum of SND (AS(SND)) and coherence functions relating the discharges of nerve pairs (Coh(SND-SND)) contained a peak at the frequency of the heart beat. When the predominant mode of coordination between AP and SND was a phase walk, partialization of the autospectra of SND with AP (AS(SND/AP)) left considerable power in the cardiac-related band. In contrast, when the predominant mode of coordination between AP and SND was phase-locking, there was virtually no cardiac-related activity remaining in AS(SND/AP). Partialization of Coh(SND-SND) with AP reduced the peak coherence within the cardiac-related band in both modes of coordination but to a much greater extent during phase-locking. After baroreceptor denervation, Coh(SND-SND) at the cardiac frequency remained significant, although a clear peak above background coherence was no longer apparent. These results are consistent with a model in which the central circuits controlling different sympathetic nerves share baroreceptor inputs and in addition are physically interconnected. The baroreceptor-sympathetic relationship contains both linear and nonlinear components, the former reflected by phase-locking and the latter by phase walk. The residual power in AS(SND/AP) during phase walk can be attributed to the nonlinear relationship, and the residual peak in partialized nerve-to-nerve coherence (Coh(SND-SND/AP)) arises largely from nonlinearities that are common to the two nerves. During both phase walk and phase-locking, in addition to common nonlinear AP-SND relationships, coupling of the central circuits generating the nerve activities may contribute to Coh(SND-SND/AP) because significant Coh(SND-SND) was still observed following baroreceptor denervation.

Modes of baroreceptor-sympathetic coordination.

We tested the hypothesis that the cardiac-related rhythm in sympathetic nerve discharge (SND) results from the forcing of a central oscillator to the frequency of the heart beat by pulse-synchronous baroreceptor afferent nerve activity. For this purpose, time series analysis was used to examine the phase relations between the brachial arterial pulse (AP) and cardiac-related activity recorded from the postganglionic inferior cardiac sympathetic nerve (CN) in urethan-anesthetized cats. Specifically, we made cycle-by-cycle measurements of peak systolic blood pressure, heart period, CN burst amplitude, and the phase angle (and corresponding interval) between peak systole and the next peak of CN activity. As the steady-state level of systolic blood pressure was raised by increasing the rate of a constant intravenous infusion of phenylephrine, we observed transitions from no phase-locking of CN activity to the AP to either phase-locking of variable strength or phase walk through part of the cardiac-cycle on the time scale of respiration. Phase walk is defined as a progressive and systematic change in the phase lag of cardiac-related CN activity relative to peak systole. Raising blood pressure strengthened phase-locking and either increased or decreased the mean interval between peak systole and the next peak of CN activity even when the change in heart period was small. CN burst amplitude and the interval between peak systole and the next peak of CN activity were inversely related, but the strength of the relationship varied considerably with experimental conditions. The relationship was strongest during phase walk. Step-wise increases in blood pressure induced by abdominal aortic obstruction led to an abrupt increase in the phase lag of CN activity relative to peak systole even when heart rate was not changed. We refer to such changes as sharp phase transitions that are a general property of dynamical nonlinear systems. The results support the view that the cardiac-related rhythm in SND is a forced nonlinear oscillation rather than the consequence of periodic inhibition of randomly generated activity.

Lateral tegmental field neurons with activity correlated to the 10-Hz rhythm in sympathetic nerve discharge

Neurons in the lateral tegmental field (FTL) has been previously reported to have activity only minimally correlated (<1% of neurons tested) with the 10-Hz rhythm of the slow wave of the sympathetic nerve discharge. We report here that 10% of the neurons recently tested in the FTL could be shown to correlate with the 10-Hz rhythm. The neuron-to-nerve coherence is weaker than in other medullary areas, but is nonetheless significant.

Classification of caudal ventrolateral pontine neurons with sympathetic nerve-related activity.

This study was designed to answer three questions concerning caudal ventrolateral pontine (CVLP) neurons whose naturally occurring discharges are correlated to sympathetic nerve discharge (SND). 1) What are the proportions of CVLP neurons that have activity correlated to both the cardiac-related and 10-Hz rhythms in SND, to only the 10-Hz rhythm, and to only the cardiac-related rhythm? 2) Do CVLP neurons with activity correlated to the cardiac-related and/or 10-Hz rhythm in SND subserve a sympathoexcitatory or sympathoinhibitory function? 3) Do CVLP neurons with activity correlated to the cardiac-related and/or 10-Hz rhythm in SND project to the thoracic spinal cord? To address these issues we recorded from 476 CVLP neurons in 24 urethan-anesthetized cats. Spike-triggered averaging, arterial pulse-triggered analysis, and coherence analysis revealed that the discharges of 66 of these neurons were correlated to inferior cardiac postganglionic SND. For 39 of these neurons, we were able to determine whether their discharges were correlated to one or both rhythms. The results showed that the CVLP contained a heterogeneous population of neurons with sympathetic nerve-related activity. The discharges of 21 neurons were correlated to both the 10-Hz and cardiac-related rhythms in SND, 9 neurons had activity correlated to only the 10-Hz rhythm, and 9 neurons had activity correlated to only the cardiac-related rhythm. The firing rates of CVLP neurons with activity correlated to both rhythms or to only the 10-Hz rhythm were decreased during the inhibition of SND induced by baroreceptor reflex activation (rapid obstruction of the abdominal aorta). These neurons are presumed to exert sympathoexcitatory actions. The time-controlled collision test verified that 11 of 12 CVLP neurons with activity correlated to both rhythms were antidromically activated by stimulation of the first thoracic segment of the spinal cord. Antidromic mapping at this level showed that the site requiring the least stimulus current to elicit the longest latency response (nearest the terminal) was in the vicinity of the intermediolateral nucleus (IML). In contrast, only 1 of 13 CVLP neurons with activity correlated to only one of the rhythms in SND could be antidromically activated by spinal stimulation. These data demonstrate for the first time that there is a direct pathway from the CVLP to the IML that is comprised almost exclusively of sympathoexcitatory neurons whose discharges are correlated to both the 10-Hz and cardiac-related rhythms in SND.

Nonlinear interactions of slow and rapid rhythms in sympathetic nerve discharge.

We used bispectral analysis to characterize the nonlinear interactions of the respiratory-related (RR), cardiac-related (CR), or 10-Hz rhythms in sympathetic nerve discharge (SND) of urethan-anesthetized cats. Bispectral analysis investigates relationships among frequency triples in the same signal (inferior cardiac postganglionic SND) where the third frequency is the sum of the other two due to quadratic nonlinear coupling. Coupling of the RR and CR rhythms leading to the generation of new components (i.e., modulated frequencies) in SND occurred in 84% of the total cases, whereas the incidence was 71% for the RR and 10-Hz rhythms. The occurrence of such nonlinear interactions implies that the RR, CR, and 10-Hz rhythms are carried to common targets by the same postganglionic sympathetic neurons. Furthermore, we suggest that nonlinear interactions leading to the generation of new frequencies in SND may affect end-organ function beyond the level expected in simple cases of linear superposition of the primary rhythms. This suggestion is supported by our observation that strong coupling of the RR and CR rhythms resulted in appreciable power at the modulated frequencies.

Nonlinear dynamics of the frequency locking of baroreceptor and sympathetic rhythms.

We used phase plane analysis to identify modes of frequency locking of the 10-Hz rhythm in sympathetic nerve discharge (SND) to the cardiac cycle in urethan-anesthetized, baroreceptor-innervated cats. Frequency locking occurred in rational ratios predicted by a generic mathematical construct called the Farey tree. Both simple harmonic ratios (e.g., 1:3) and complex ratios (e.g., 2:5) comprised of relatively prime integers (no common divisor) were identified under natural conditions. Frequency locking in such ratios is attributed to forcing of the 10-Hz oscillator by pulse-synchronous baroreceptor afferent nerve activity (BNA). Ventricular pacing changed the frequency of the 10-Hz rhythm as well as heart rate so as to maintain or change the ratio of frequency locking in a predictable way. Intriguingly, frequency locking of the 10-Hz rhythm to medullary raphe sympathoinhibitory stimuli in simple harmonic ratios was accompanied by increased power in the 10-Hz band of SND, whereas locking in complex ratios led to decreased 10-Hz power. These findings raise the possibility that pulse-synchronous BNA also exerts divergent actions on the 10-Hz rhythm depending on the ratio of frequency locking. Augmented 10-Hz power can be attributed to the resonant properties of oscillators that are periodically forced at the same phase in their cycle.

Pontine neurons are elements of the network responsible for the 10-Hz rhythm in sympathetic nerve discharge.

The current study was designed to test the hypothesis that pontine neurons are elements of the network responsible for the 10-Hz rhythm in sympathetic nerve discharge (SND). The first series of experiments tested whether chemical inactivation of neurons in the rostral dorsolateral pons (RDLP) or caudal ventrolateral pons (CVLP) affected inferior cardiac postganglionic SND of urethan-anesthetized cats. Muscimol microinjections into either region eliminated the 10-Hz rhythm in SND, supporting the view that pontine neurons are involved in the expression of this rhythm. Additional experiments were designed to determine if pontine neurons have activity correlated to the 10-Hz rhythm in SND or whether they merely provide a tonic (nonrhythmic) driving input to the rhythm generator. Coherence analysis revealed that local field potentials recorded from the RDLP or CVLP had a 10-Hz component that was significantly correlated to SND. Also, spike-triggered averaging and coherence analysis showed that the naturally occuring discharges of individual RDLP or CVLP neurons were correlated to the 10-Hz rhythm in SND. Taken together, these data support the hypothesis that RDLP and CVLP neurons are essential for the expression of the 10-Hz rhythm in SND and that they are elements of or receive input from the rhythm generator.

Neurons of the rostral para-ambiguual field have activity correlated to the 10-Hz rhythm in sympathetic nerve discharge of urethane-anesthetized cat

Using the techniques of time domain correlation (mid-signal spike-triggered averaging) and frequency domain correlation (neuron-to-nerve coherence), 24% (54) of a sample of 229 neurons of the rostral para-ambiguual field have shown to have activity correlated to the 8- to 13-Hz rhythm in the inferior cardiac sympathetic nerve discharge (SND) of urethane-anesthetized cat. This correlation existed in both baroreceptor-innervated and -denervated animals. Of the correlated neurons, 37% (20) were non-rhythmically firing and displayed flat autospectra, while 63% (34) fired rhythmically and contained well-defined peaks in their autospectra. The group firing rate of these neurons was 4.3±0.4 spikes/s, indicating that they are not pacemaker neurons for the 10-Hz SND rhythm. The group time of firing of these neurons to the next peak of the SND slow wave was 52±4 ms. Correlation of the activity of medullary neurons with the 8–13-Hz rhythm of the SND was previously claimed only for rostral ventrolateral medulla, caudal raphe, and rostral caudal ventrolateral medulla. This present finding suggests that this behavior may be more widely spread throughout the medulla.

Coupled oscillators account for the slow rhythms in sympathetic nerve discharge and phrenic nerve activity.

Phase-locked slow rhythms in sympathetic nerve discharge (SND) and phrenic nerve activity (PNA) are generally thought to arise from a common brain stem "cardiorespiratory" oscillator. The results obtained in vagotomized and baroreceptor-denervated cats anesthetized with pentobarbital sodium do not support this view. First, partial coherence analysis revealed that the discharges of pairs of sympathetic nerves remained correlated at the frequency of the central respiratory cycle after mathematical removal of the portion of these signals common to PNA. The residual coherence suggests that the slow rhythm in SND is dependent on central mechanisms in addition to those responsible for rhythmic PNA. Second, the rhythms in SND and PNA became coupled in a 2:1 relationship during either moderate systemic hypocapnia or hypercapnia. Third, the slow rhythm in SND was maintained when rhythmic PNA was eliminated during extreme hypocapnia. Fourth, during extreme hypercapnia, coherence of the rhythms in SND and PNA was drastically reduced. These results suggest that the slow rhythms in SND and PNA arise from separate oscillators that are normally coupled.

Subgroups of Rostral Ventrolateral Medullary and Caudal Medullary Raphe Neurons Based on Patterns of Relationship to Sympathetic Nerve Discharge and Axonal Projections

This study was designed to answer three questions concerning rostral ventrolateral medullary (RVLM) and caudal medullary raphe (CMR) neurons with activity correlate to sympathetic nerve discharge (SND). 1) What are the proportions of RVLM and CMR neurons that have activity correlated to both the cardiac-related and 10-Hz rhythms in SND, to only the 10-Hz rhythm, and to only the cardiac-related rhythm? 2) Which of these cell types project to the spinal cord? 3) Do the outputs of the cardiac-related and 10-Hz rhythm generators converge at the level of bulbospinal neurons or their antecedent interneurons? To address these issues we recorded from 44 RVLM and 48 CMR neurons with sympathetic nerve-related activity in urethan-anesthetized cats with intact carotid sinus nerves, but sectioned aortic depressor and vagus nerves. Spike-triggered averaging, arterial pulse-triggered analysis, and coherence analysis revealed that the naturally occurring discharges of 24 of these RVLM neurons and 41 of these CMR neurons were correlated to both the 10-Hz and cardiac-related rhythms in inferior cardiac postganglionic SND. The discharges of the other neurons were correlated to only the 10-Hz rhythm (15 RVLM and 6 CMR neurons) or to only the cardiac-related rhythm (5 RVLM neurons and 1 CMR neuron) in SND. The time-controlled collision test verified that 16 of 18 RVLM and 31 of 34 CMR neurons with activity correlated to both rhythms were antidromically activated by stimulation of the white matter of the first thoracic (T1) segment of the spinal cord. In contrast, only 1 of 10 RVLM neurons and 0 of 4 CMR neurons with activity correlated to only the 10-Hz rhythm could be antidromically activated by stimulation at T1. Also 0 of 3 RVLM neurons with activity correlated to only the cardiac-related rhythm in SND were antidromically activated by spinal stimulation. These data show for the first time that bulbospinal sympathetic pathways emanating from the RVLM and CMR are comprised almost exclusively of neurons whose discharges are correlated to both the cardiac-related and 10-Hz rhythms in SND. Moreover, the data support the hypothesis that the outputs of the cardiac-related and 10-Hz rhythm generators converge on RVLM and CMR bulbospinal neurons rather than on their antecedent interneurons. Finally, the data demonstrate that a substantial proportion of RVLM neurons and a small group of CMR neurons with activity correlated to SND do not project to the thoracic spinal cord. Their discharges were correlated to only one of the rhythms in SND. Their axonal trajectories and functions are unknown.

Comparison of results obtained with time- and frequency-domain analysis when searching for the 10-Hz rhythm in sympathetic nerve discharge

Kubota et al. (Neurosci. Lett., 196 (1995) 173–176) constructed distributions of the intervals between successive bursts of sympathetic nerve discharge (SND) in three mammalian species. The mode in such interburst interval histograms (IBIHs) was near 100 ms in most cases. This interval was equated with the 10-Hz rhythm in SND identified by others using power density autospectral analysis. However, in the current study we found a modal interval near 100 ms independent of whether the autospectrum showed a peak near 10 Hz. A 10-Hz rhythm appeared in the autospectrum of SND only when counts in the IBIH were normally distributed around 100 ms and the coefficient of variation was <0.25. We conclude that a modal interval of 100 ms, by itself, is not a predictor of a 10-Hz rhythm in SND. As such, the conclusions of Kubota et al. on the spinal origin and ubiquity of the 10-Hz rhythm are open to question.

Central catecholaminergic neurons are involved in expression of the 10-Hz rhythm in SND

We studied the effects of adrenoceptor agonists and antagonists on sympathetic nerve discharge (SND) of urethan-anesthetized, baroreceptor-denervated cats. In cats in which a 10-Hz rhythm coexisted with irregular 2- to 6-Hz oscillations in SND, intravenous clonidine, an alpha 2-adrenoceptor agonist, blocked the 10-Hz rhythm without affecting power at lower frequencies. In contrast, power at frequencies < or = 6 Hz was depressed by clonidine in cats in which the 10-Hz rhythm was absent. These effects were reversed by intravenous administration of alpha 2-adrenoceptor antagonists, idazoxan and rauwolscine. Rauwolscine is devoid of affinity for imidazoline receptors. Furthermore, in cats untreated with clonidine, idazoxan and rauwolscine enhanced or induced the 10-Hz rhythm without affecting power at lower frequencies. Prazosin, an alpha 1-adrenoceptor antagonist, selectively blocked the 10-Hz rhythm in SND. Finally, the 10-Hz rhythm in SND was blocked by microinjection of clonidine into the rostral or caudal ventrolateral medulla. The results support the view that central catecholaminergic neurons play a role in expression of the 10-Hz rhythm in SND.