Inferior Cardiac Sympathetic Nerve Discharge Research Articles

The posterior vermis of the cerebellum selectively inhibits 10-Hz sympathetic nerve discharge in anesthetized cats

We studied the changes in inferior cardiac sympathetic nerve discharge (SND) and mean arterial pressure (MAP) produced by aspiration or chemical inactivation (muscimol microinjection) of lobule IX (uvula) of the posterior vermis of the cerebellum in baroreceptor-denervated and baroreceptor-innervated cats anesthetized with urethane. Autospectral analysis was used to decompose SND into its frequency components. Special attention was paid to the question of whether the experimental procedures affected the rhythmic (10-Hz and cardiac-related) components of SND. Aspiration or chemical inactivation of lobule IX produced an approximately three-fold increase in the 10-Hz rhythmic component of SND (P < or = 0.05) in baroreceptor-denervated cats. Total power (0- to 20-Hz band) was unchanged. Despite the absence of a change in total power in SND, there was a statistically significant increase in MAP. In baroreceptor-innervated cats, neither aspiration nor chemical inactivation of the uvula caused a significant change in cardiac-related or total power in SND or MAP. These results are the first to demonstrate a role of cerebellar cortical neurons of the posterior vermis in regulating the frequency composition of naturally occurring SND. Specifically, these neurons selectively inhibit the 10-Hz rhythm-generating network in baroreceptor-denervated, urethane-anesthetized cats. The functional implications of these findings are discussed.

A Selective Inhibitory Effect of the Posterior Cerebellar Vermis on 10‐Hz Sympathetic Nerve Discharge

We compared the changes in inferior cardiac sympathetic nerve discharge (SND) and mean arterial pressure (MAP) produced by aspiration of portions of lobule IX and in some cases lobule X of the posterior cerebellar vermis with those produced by chemical inactivation (muscimol microinjection) or electrical stimulation of the same regions. The experiments were performed on 13 baroreceptor‐denervated and vagotomized cats anesthetized with urethane. Autospectral analysis was used to decompose SND into its frequency components. Special attention was paid to the question of whether the experimental procedures differentially affected the rhythmic and aperiodic components of SND. Aspiration or chemical inactivation with muscimol of lobule IX produced an approximately three‐fold increase in the 10‐Hz rhythmic component of SND (P = 0.05). In contrast, wideband SND at lower frequencies (= 6 Hz) was either slightly reduced or unaffected. Total power (0‐ to 20‐Hz band) was unchanged. Despite this, there was a statistically significant increase in MAP. High frequency (50‐Hz) electrical stimulation of depressor sites in lobule IX of the posterior vermis selectively and significantly reduced 10‐Hz power in SND. The lower frequency components of SND were unchanged. These results demonstrate for the first time a role of cerebellar cortical neurons of the posterior vermis in regulating the frequency composition of naturally occurring SND. The functional implications of these findings are discussed.(Supported by NIH HL33266.)

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 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.

Pathways involved in synchronization of sympathetic nerve discharge to lung inflation

In urethane-anesthetized cats, we tested the hypothesis that sympathetic nerve discharge (SND) is synchronized to lung inflation, in part, over a vagal afferent pathway that bypasses the central respiratory oscillator. For this purpose, partial coherence analysis was used to mathematically remove the portion of the relationship between intratracheal pressure (ITP; index of lung inflation) and inferior cardiac SND that was common to that between ITP and phrenic nerve activity (PNA; index of central respiratory cycle). ITP-SND partial coherence (PNA-related component removed) at the frequency of breathing should be significantly different from zero if a bypass pathway exists. This was found to be the case in paralyzed, artificially ventilated cats when lung inflation and rhythmic PNA were coupled in various ratios (e.g. 1:1, 3:1) and in spontaneously breathing cats. As expected, surgical vagotomy eliminated ITP-SND coherence in artificially ventilated cats. These findings support the view that a portion of the relationship between ITP and SND is independent of the influences of pulmonary stretch receptors on central respiratory networks.

Long-term correlations in the spike trains of medullary sympathetic neurons.

Fano factor analysis was used to characterize the spike trains of single medullary neurons with sympathetic nerve-related activity in cats that were decerebrate or anesthetized with Dial-urethan or urethan. For this purpose, values (Fano factor) of the variance of the number of extracellularly recorded spikes divided by the mean number of spikes were calculated for window sizes of systematically varied length. For window sizes < or =10 ms, the Fano factor was close to one, as expected for a Bernoulli process with a low probability of success. The Fano factor dipped below one as the window size approached the shortest interspike interval (ISI) and reached its nadir at window sizes near the modal ISI. The extent of the dip reflected the shape (skewness) of the ISI histogram with the dip being smallest for the most asymmetric distributions. Most importantly, for a wide range of window sizes exceeding the modal ISI, the Fano factor curve took the form of a power law function. This was the case independent of the component (cardiac related, 10 Hz, or 2--6 Hz) of inferior cardiac sympathetic nerve discharge to which unit activity was correlated or the medullary region (lateral tegmental field, raphe, caudal and rostral ventrolateral medulla) in which the neuron was located. The power law relationship in the Fano factor curves was eliminated by randomly shuffling the ISIs even though the distribution of the intervals was unchanged. Thus the power law relationship arose from long-term correlations among ISIs that were disrupted by shuffling the data. The presence of long-term correlations across different time scales reflects the property of statistical self-similarity that is characteristic of fractal processes. In most cases, we found that mean ISI and variance for individual spike trains increased as a function of the number of intervals counted. This can be attributed to the clustering of long and short ISIs, which also is an inherent property of fractal time series. We conclude that the spike trains of brain stem sympathetic neurons have fractal properties.

Medullary lateral tegmental field: an important source of basal sympathetic nerve discharge in the cat.

We used blockade of excitatory amino acid (EAA) neurotransmission in the medullary lateral tegmental field (LTF) and rostral ventrolateral medulla (RVLM) to assess the roles of these regions in the control of inferior cardiac sympathetic nerve discharge (SND) and mean arterial pressure (MAP) in urethan-anesthetized, baroreceptor-denervated cats. Bilateral microinjection of a non-N-methyl-D-aspartate (NMDA)-receptor antagonist [1,2,3, 4-tetrahydro-6-nitro-2,3-dioxobenzo-[f]quinoxaline-7-sulfonamide (NBQX)] into the LTF significantly decreased SND to 46 +/- 4% of control (as demonstrated with power-density spectral analysis) and MAP by 16 +/- 6 mmHg. In contrast, bilateral microinjection of an NMDA-receptor antagonist [D(-)-2-amino-5-phosphonopentanoic acid (D-AP5)] into the LTF did not decrease SND or MAP. These results demonstrate that the LTF is an important synaptic relay in the pathway responsible for basal SND in the cat. Bilateral microinjection of NBQX or D-AP5 into the RVLM significantly decreased power in SND to 48 +/- 5 or 61 +/- 5% of control, respectively, and reduced MAP by 15 +/- 2 or 8 +/- 4 mmHg, respectively. These data indicate that EAA-mediated synaptic drive to RVLM-spinal sympathoexcitatory neurons accounts for a significant component of their basal activity.

Rostral dorsolateral pontine neurons with sympathetic nerve-related activity.

Spike-triggered averaging, arterial pulse-triggered analysis, and coherence analysis were used to classify rostral dorsolateral pontine (RDLP) neurons into groups whose naturally occurring discharges were correlated to only the 10-Hz rhythm (n = 29), to only the cardiac-related rhythm (n = 15), and to both rhythms (n = 15) in inferior cardiac sympathetic nerve discharge (SND) of urethan-anesthetized cats. Most of the neurons with activity correlated to only the cardiac-related rhythm were located medial to the other two groups of neurons. The firing rates of most RDLP neurons with activity correlated to only the 10-Hz rhythm (9 of 12) or both rhythms (7 of 8) were decreased during baroreceptor reflex-induced inhibition of SND produced by aortic obstruction; thus, they are presumed to be sympathoexcitatory. The firing rates of four of seven RDLP neurons with activity correlated to only the cardiac-related rhythm increased during baroreceptor reflex activation; thus, they may be sympathoinhibitory. We conclude that the RDLP contains a functionally heterogeneous population of neurons with sympathetic nerve-related activity. These neurons could not be antidromically activated by stimulation of the thoracic spinal cord.

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.

Bispectral analysis of complex patterns of sympathetic nerve discharge.

Bispectral analysis was used to demonstrate quadratic nonlinear coupling (i.e., phase locking) of different frequency components in inferior cardiac sympathetic nerve discharge (SND) of urethan-anesthetized rats. The complex patterns of SND analyzed included mixtures of 1) the cardiac-related and 10-Hz rhythms, 2) the 10-Hz rhythm and irregular 2-to 6-Hz oscillations, and 3) the 10-Hz rhythm and a lower frequency non-cardiac-related rhythm near 4 Hz. In some cases, the bicoherence function (normalized bispectrum) showed no phase locking of these frequency components. Cases of nil bicoherence are equated with linear superposition of frequency components, which implies the existence of multiple and noninteractive central circuits. Increased complexity of SND was observed in other cases, as evidenced by significant phase locking of different frequency components with or without frequency locking. Frequency locking (higher frequency rhythm is a multiple of lower) was confirmed by constructing Lissajous orbital plots showing covariation of voltages in selectively filtered bands of SND. We equate frequency locking with nonlinear coupling of the central generators of different sympathetic nerve rhythms and phase locking without frequency locking possibly with nonlinearities arising at levels below noncoupled central rhythm generators.

Presence of vasomotor and respiratory rhythms in the discharge of single medullary neurons involved in the regulation of cardiovascular system

We analyzed the discharges of 77 single neurons located in the rostral ventrolateral medulla (RVLM, n = 25), caudal ventrolateral medulla (CVLM, n = 18), lateral tegmental field (LTF, n = 190) and caudal raphe nuclei ( n = 15). These recordings were made from 36 vagotomized and sinoaortic denervated cats that were either decerebrate ( n = 27) or anesthetized with urethane ( n = 9) and from 3 decerebrate cats with intact sinoartic and vagal nerves. These neurons were classified as sympathetic-related ( n = 61) if spike triggered averaging showed that their naturally occurring discharges were correlated to either the cardiac related (2–6 Hz) or a faster (10 Hz) oscillation in inferior cardiac sympathetic nerve discharge. Neurons were classified as sympathetic-unrelated ( n = 16) if they lacked these characteristics. We used autoregressive spectral techniques to detect additional slower oscillations hidden in the variability of neuronal discharge and possibly correlated to the oscillations of systolic arterial pressure (SAP). This analysis revealed the existence of a low frequency (LF) oscillation (0.12 ± 0.02 Hz) in the discharges of 36 sympathetic-related and 9 sympathetic-unrelated neurons. In relation to 35 neurons in 21 animals there was also an LF component in SAP variability. In 29 instances the LF neuronal discharges and SAP variabilities were significantly correlated. In addition, there was a high frequency (HF) oscillation (0.34 ± 0.06 Hz) in the discharges of 59 medullary neurons. In 56 cases the HF in neuronal discharge variability cohered to that in SAP variability. These data are the first to demonstrate the existence of an LF component in the discharges of individual medullary neurons, at least some of which were likely to be involved in the regulation of the cardiovascular system. Since these oscillations were evident in cats with section of sinoaortic and vagal nerves, they likely reflect central rhythmogenic properties.

Axonal projections of caudal ventrolateral medullary and medullary raphe neurons with activity correlated to the 10-Hz rhythm in sympathetic nerve discharge.

1. This is the first study to map the axonal projections of medullary neurons that are elements of the network responsible for the 10-Hz rhythm in sympathetic nerve discharge (SND) of urethan-anesthetized cats. Spike-triggered averaging and coherence analysis were used to identify caudal ventrolateral medullary (CVLM) and medullary raphe neurons with activity correlated to this component of SND. Spike-triggered averaging showed that CVLM neurons fired significantly earlier (17 ms on the average) than raphe neurons during the 10-Hz slow wave in inferior cardiac postganglionic SND. This observation raised the possibility that CVLM neurons are a source of the discharges of raphe neurons that are correlated to SND. 2. Nineteen of 47 CVLM neurons with activity correlated to the 10-Hz rhythm in SND were antidromically activated by micro-stimulation of the raphe. The longest onset latency of antidromic activation was 19.9 +/- 2.8 (SE) ms, a value comparable with the difference in firing times of CVLM and raphe neurons during the naturally occurring 10-Hz slow wave in inferior cardiac SND. In most cases the response likely reflected activation of an axonal branch of the CVLM neuron, because the onset latency of antidromic activation could be changed dramatically by moving the stimulating microelectrode as little as 0.2 mm within the raphe. Also, the onset latency of antidromic activation of nine CVLM neurons was significantly shortened (25.0 +/- 2.5 vs. 16.7 +/- 2.7 ms) when the stimulus intensity was raised above threshold. 3. The hypothesis that the axons of CVLM neurons with activity correlated to the 10-Hz rhythm in SND terminated on and excited raphe neurons was supported by the following observations. First, CVLM neurons could not be antidromically activated by stimuli applied to sites in tracks located 1.5-2 mm lateral to the midline, contralateral to the neuronal recording site; thus their axons did not cross the midline. Second, some CVLM neurons could be antidromically activated by stimuli applied to sites in only one of the tracks through the midline; thus it is unlikely that their axons were destined for more rostral or caudal portions of the brain stem. Third, 37% of the raphe neurons with activity correlated to the 10-Hz rhythm were synaptically activated by microstimulation of the CVLM, with a minimum onset latency of 18.1 +/- 2.6 ms. This value was not significantly different than the longest onset latency of antidromic activation of CVLM neurons by raphe stimulation. 4. CVLM neurons with activity correlated to the 10-Hz rhythm in SND could not be antidromically activated by microstimulation of the rostral ventrolateral medulla (RVLM) or thoracic spinal cord. Thus CVLM neurons are not a direct source of the 10-Hz discharges of RVLM or preganglionic sympathetic neurons. 5. Eight of 41 raphe neurons with activity correlated to the 10-Hz rhythm in SND were antidromically activated by microstimulation of the CVLM. The latency of the antidromic response of six raphe neurons was shortened from 15.2 +/- 3.1 to 11.9 +/- 3.1 ms by raising stimulus current above threshold, implying the existence of local axonal branching. The onset latency of antidromic activation of five raphe neurons was changed by moving the stimulating microelectrode within the CVLM. 6. The axons of at least some of these raphe neurons likely terminated in the CVLM, because higher current was required to antidromically activate these neurons from sites in a track located 0.5 mm further laterally, and they were not antidromically activated by microstimulation of the RVLM. Also 32% of the CVLM neurons were either excited or inhibited by microstimulation of the raphe. The minimum onset latency of synaptic activation (18.3 +/- 4.2 ms) or inhibition (10-20 ms) of CVLM neurons by raphe stimulation was similar to the longest onset latency of antidromic activation of raphe neurons by CVLM microstimulation. 7. These data are consistent with the view

A modulatory role of central cholinergic transmission in control of the 10-Hz rhythm in sympathetic nerve discharge

In 43 urethane-anesthetized or decerebrate, baroreceptor-denervated cats, spectral analysis showed that most of the power in sympathetic nerve discharge (SND) was at frequencies < 6 Hz. In 18 of these cats, physostigmine (100 μg/kg i.v.) induced a 10-Hz rhythm in inferior cardiac SND that was eliminated by atropine sulfate (0.25 mg/kg i.v.; n = 6). In contrast, the naturally occurring 10-Hz rhythm that appeared in SND in other experiments was atropine-insensitive ( n = 6). The data indicate that central muscarinic cholinergic transmission is not essential for the naturally occurring 10-Hz rhythm. Nonetheless, facilitation of cholinergic transmission can induce a 10-Hz rhythm.

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

1. This is the first study to show that caudal ventrolateral medullary (CVLM) neurons play an important role in governing the 10-Hz rhythm in sympathetic nerve discharge (SND). Spike-triggered averaging showed that the naturally occurring discharges of 66 of 246 CVLM neurons located 0-2.5 mm rostral to the obex, 4-4.25 mm lateral to the midline, and within 2 mm of the ventral surface were correlated to the 10-Hz rhythm in inferior cardiac SND of 17 urethan-anesthetized cats. 2. Frequency domain analysis was used to characterize further the relationships between SND and the discharges of 45 CVLM neurons with activity correlated to the 10-Hz rhythm in inferior cardiac nerve activity. The autospectra of the discharges of 22 of these neurons contained a sharp peak near 10 Hz (corresponding to the peak in the autospectra of SND), although the mean firing rate of these neurons was only 5.9 +/- 0.5 (SE) spikes/s. The peak coherence value relating the 10-Hz discharges of these CVLM neurons and the inferior cardiac nerve was 0.42 +/- 0.03. The autospectra for the other 23 CVLM neurons did not contain a peak near 10 Hz. Their mean firing rate was 2.3 +/- 0.5 spikes/s, and the peak coherence value relating their discharges to the 10-Hz rhythm in SND was 0.08 +/- 0.01. The coherence value was significantly different than zero in all but three cases. 3. Importantly, spike-triggered averaging and coherence analysis demonstrated that CVLM neurons with activity correlated to the 10-Hz rhythm did not have activity correlated 1:1 to the cardiac-related rhythm in SND of baroreceptor-innervated cats. Also, their discharges were not correlated to the irregular 2- to 6-Hz oscillations in SND of baroreceptor-denervated cats. These data support the hypothesis that different pools of brain stem neurons generate the 10-Hz rhythm and the 2- to 6-Hz oscillations (or cardiac-related rhythm) in SND. 4. Despite the fact that CVLM neurons with activity correlated to the 10-Hz rhythm did not have activity correlated 1:1 to the cardiac-related rhythm in SND, these neurons were influenced by baroreceptor afferent nerve activity. First, their firing rates could be decreased (n = 12) or increased (n = 2) during the pressor response induced by inflating a balloon in the aorta (aortic obstruction). Second, on occasion, the discharges of CVLM neurons and the 10-Hz rhythm in SND were entrained to a harmonic of the heart rate.(ABSTRACT TRUNCATED AT 400 WORDS)

Lateral tegmental field neurons play a permissive role in governing the 10-Hz rhythm in sympathetic nerve discharge.

Recordings from sympathetic nerves in decerebrate cats show a variable mixture of 10-Hz and 2- to 6-Hz discharges. Although medullary lateral tegmental field (LTF) neurons are considered to be a source of the 2- to 6-Hz oscillation in sympathetic nerve discharge (SND), their role in the control of the 10-Hz rhythm has not been critically evaluated. This issue served as the focus of the current study. In the first series of experiments, spike-triggered averaging of inferior cardiac SND was used in an attempt to identify LTF neurons with activity correlated to the 10-Hz rhythm in SND. The discharges of only one of the 120 LTF neurons studied were correlated to this component of SND. In contrast, 17 of 79 neurons had activity correlated to the 2- to 6-Hz oscillation in experiments in which this component of SND was prominent. These data indicate that LTF neurons neither receive input from nor are components of the 10-Hz rhythm generator. In a second series of experiments, muscimol was microinjected into the LTF bilaterally. Chemical inactivation of the LTF either eliminated the 10-Hz rhythm or reduced the power and peak frequency in this band of SND. These data support the view that LTF neurons have a permissive role in governing the 10-Hz rhythm in SND, probably by acting on elements of the rhythm generator located elsewhere. As expected, muscimol microinjections reduced the power in the 2- to 6-Hz band in SND in some experiments.

The 10-Hz sympathetic rhythm is dependent on raphe and rostral ventrolateral medullary neurons

We studied the effects of brain stem and spinal lesions on the 10-Hz rhythms in left and right inferior cardiac sympathetic nerve discharge (SND) of baroreceptor-denervated, decerebrate cats. Unilateral medullary lesions [parasagittal section 1.5 mm lateral to midline, radiofrequency lesion of the rostral ventrolateral medulla (RVLM), or chemical inactivation (muscimol) of the RVLM] dramatically reduced the 10-Hz rhythmic discharges in the two nerves. Power in the 10-Hz band of ipsilateral inferior cardiac SND was reduced more than that in contralateral SND. In contrast, bilateral parasagittal medullary sections or microinjection of muscimol into the medullary raphe uniformly reduced the 10-Hz rhythmic discharges of both nerves. Unlike unilateral medullary lesions, rostral pontine or cervical spinal hemisection reduced the 10-Hz discharges of only the ipsilateral inferior cardiac nerve. The chemical inactivation experiments demonstrate that the 10-Hz rhythm in SND is dependent on medullary raphe and RVLM neurons. Moreover the experiments with unilateral lesions demonstrate a mutually facilitatory interaction of medullary circuits that are responsible for the 10-Hz rhythmic discharges in sympathetic nerves located on opposite sides of the body.

Lateral tegmental field neurons of cat medulla: a source of basal activity of raphespinal sympathoinhibitory neurons.

1. We tested the hypothesis that sympathoinhibitory (SI) neurons in the lateral tegmental field (LTF) of the cat medulla exert their actions over a pathway that includes raphe neurons whose axons innervate the thoracic intermediolateral nucleus (IML). 2. We recorded from 32 LTF neurons with sympathetic nerve-related activity [as demonstrated with spike-triggered averaging of inferior cardiac sympathetic nerve discharge (SND)] whose firing rate increased during the inhibition of SND produced by baroreceptor reflex activation. These neurons were classified as SI in function. 3. Twenty-three of these 32 LTF-SI neurons were antidromically activated by microstimulation of the raphe nuclei, 2-4 mm rostral to the obex and 3-4.5 mm below the dorsal surface of the medulla. The threshold current for eliciting the longest-latency antidromic responses [18.9 +/- 2.4 (SE) ms] was increased when the stimulating microelectrode was moved more dorsally in the midline. With one exception, these neurons could not be antidromically activated by stimulation of sites either 1.5-2.0 mm lateral to the midline, contralateral to the site of unit recording or raphe sites caudal to the obex. Threshold stimuli applied 2-4 mm rostral to the obex and 1 mm lateral to the midline, ipsilateral to the site of unit recording, elicited antidromic responses whose onset latencies were shorter than those produced by raphe stimulation. These data support the view that the axons of LTF-SI neurons terminated in the region of the raphe that contains SI neurons whose axons innervate the IML. 4. We recorded from 32 raphe neurons with sympathetic nerve-related activity whose firing rate increased during baroreceptor reflex activation. These neurons were classified as SI in function. Twenty-five of the 32 raphe-SI neurons were antidromically activated by microstimulation of the third thoracic (T3) IML. Seven (including 5 with spinal axons) of 24 raphe-SI neurons tested were synaptically activated by microstimulation of the region of the LTF containing SI neurons. The modal onset latency of synaptic activation was 22.8 +/- 8.4 ms. This value is close to the difference in spontaneous firing times (26 ms on the average) of LTF-SI and raphe-SI neurons, relative to the peak of the cardiac-related burst of SND. 5. Taken together, these data are consistent with the hypothesis that LTF-SI neurons are a source of the background discharges of raphespinal-SI neurons. 6. Thirteen raphe-SI neurons were antidromically activated by stimulation of both the medulla and T3 IML.(ABSTRACT TRUNCATED AT 400 WORDS)

Identification of serotonergic and sympathetic neurons in medullary raphe nuclei

The purpose of the present study was to identify midline medullary serotonin (5-HT) neurons and to determine if these neurons were distinct from previously identified sympathoinhibitory and sympathoexcitatory neurons. Identification of medullary 5-HT neurons was based on electrophysiological and pharmacological similarities to dorsal raphe 5-HT neurons. Sympathoinhibitory and sympathoexcitatory neurons were characterized by an irregular discharge pattern which was temporally related to inferior cardiac sympathetic nerve discharge (SND) and to the cardiac cycle. Sympathoinhibitory neurons increased their discharge rate and the discharge of sympathoexcitatory neurons decreased during baroreceptor reflex activation. A third type of neuron fired in an extremely regular fashion (as judged by interspike interval analysis), fired at a rate of 1.1 spikes/s and had spike durations of approximately 2 ms. The discharges of regularly firing neurons were not temporally related to SND and were not affected during baroreceptor reflex activation. Regularly firing neurons and sympathoinhibitory neurons could be antidromically activated by electrical stimulation of the intermediolateral cell column of the spinal cord. Axonal conduction velocity of sympathoinhibitory neurons (2.4 m/s) was significantly greater than that for regularly firing neurons (1.3 m/s). Regularly firing neurons were completely inhibited by low doses of the 5-HT 1A agonist 8-hydroxy-dipropylamino-tetralin (8-OH-DPAT) (i.e. 2 μg/kg, i.v.) while much higher doses of the drug failed to affect the discharges of sympathoinhibitory and sympathoexcitatory neurons. Microiontophoretic application of 5-HT and 8-OH-DPAT profoundly depressed the firing of regularly discharging neurons. Based on the striking similarities between regularly firing medullary neurons and dorsal raphe 5-HT neurons it is concluded that the regularly firing neurons were 5-HT-containing neurons. Furthermore, these medullary 5-HT neurons are distinct from sympathoinhibitory and sympathoexcitatory neurons.

Diencephalic regions contributing to sympathetic nerve discharge in anesthetized cats.

We reported that the forebrain is responsible for a significant component (38%) of inferior cardiac postganglionic sympathetic nerve discharge (SND) in baroreceptor-denervated cats anesthetized with alpha-chloralose [Huang et al., Am. J. Physiol. 252 (Regulatory Integrative Comp. Physiol. 21): R645-R652, 1987]. The current study was initiated to assess the contribution of various diencephalic regions to the forebrain-dependent component of SND in this preparation. For this purpose, the reductions in inferior cardiac SND and blood pressure produced acutely by midbrain transection at stereotaxic plane A3 in nonlesioned control cats were compared with those in cats in which diencephalic lesions were made with radio-frequency current. Lesions of the anterior medial hypothalamus including the paraventricular nucleus failed to attenuate the decreases in SND and blood pressure produced by midbrain transection. In contrast, the effects of midbrain transection were significantly attenuated by lesions of the lateral hypothalamus (including medial forebrain bundle), posterior medial hypothalamus, or the medial thalamus. We conclude that both the hypothalamus and medial thalamus contribute to SND in anesthetized cats.