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G L Gebber

Publications and source records attributed to G L Gebber.

At least 55 records · Page 3Linked to original sources

Role of the brain stem in generating the 2- to 6-Hz oscillation in sympathetic nerve discharge.

We tested the hypothesis that brain stem circuits normally generate a 2- to 6-Hz oscillation in sympathetic nerve discharge (SND). Experiments were performed on baroreceptor-denervated decerebrate cats and urethan-anesthetized rats in which renal or splanchnic SND was recorded along with field potentials (population activity) from sites in the rostral ventrolateral medulla, medullary raphe, or medullary lateral tegmental field. Our major findings were as follows. 1) Population activity recorded from the three medullary regions contained a 2- to 6-Hz oscillation. 2) The 2- to 6-Hz oscillation in population activity recorded from some medullary sites was correlated to that in SND. Peak coherence in the 2- to 6-Hz band approached a value of 1 in some cases. 3) Whereas cervical spinal cord transection abolished or markedly reduced SND, the 2- to 6-Hz oscillation in medullary activity was essentially unchanged. These results support the view that the 2- to 6-Hz oscillation in SND can be generated in the brain stem of cats and rats.

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The 10-Hz rhythm in sympathetic nerve discharge.

Frequency-domain analysis was used to characterize the relationships among the rhythmic discharges recorded simultaneously from two to four sympathetic nerves in unanesthetized decerebrate cats. The major new findings were as follows. 1) The 10-Hz rhythmic discharges of different nerves cohered strongly in baroreceptor-innervated and -denervated cats. 2) The interval between the discharges of two nerves was frequency dependent in the 10-Hz band in some cats, supporting the view that the 10-Hz rhythm is generated by multiple central circuits that are coupled. 3) In some cases the central circuits responsible for the 10-Hz rhythms nonuniformly affected different nerves. 4) In baroreceptor-innervated cats the coherence values for the cardiac-related discharges of any two nerves were significantly higher than those for the 10-Hz rhythms. 5) In baroreceptor-denervated cats the 10-Hz rhythmic discharges of different nerves cohered more strongly than the 2- to 6-Hz rhythms. 6) The 10-Hz rhythm usually was not a harmonic of the 2- to 6-Hz or cardiac-related rhythm. Thus these rhythms are generated independently.

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Effects of brain stem lesions on 10-Hz and 2- to 6-Hz rhythms in sympathetic nerve discharge.

We studied the effects of brain stem lesions or transection on the 10-Hz and 2- to 6-Hz rhythms in sympathetic nerve discharge (SND) in baroreceptor-denervated unanesthetized decerebrate cats. The results indicate that these two rhythms depend in part on different brain stem regions. The 10-Hz rhythm was eliminated by ablation of the rostral ventrolateral medulla (RVLM), medullary raphe complex, or pontine parabrachial and Kölliker-Fuse complex (PB/KF) or by pontomedullary border transection. Except for RVLM lesions, these procedures did not disrupt the 2- to 6-Hz rhythm in SND. In fact the power in SND at frequencies less than 6 Hz was increased by raphe or PB/KF lesions. Total power in SND was not significantly affected by raphe or PB/KF lesions, but mean arterial pressure was significantly reduced. Field potentials recorded from the RVLM (11 of 26 sites) and raphe (10 of 20 sites) were correlated to the 10-Hz rhythm in SND, further supporting a role of these areas in either generating or relaying this rhythm to sympathetic nerves. In contrast, field potentials recorded from the PB/KF were not correlated to the 10-Hz rhythm in SND. Thus this region may provide a tonic drive to the 10-Hz generator located elsewhere in the brain stem.

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Forced oscillations in sympathetic nerve discharge.

Periodic electrical stimulation of the medullary raphe or lateral tegmental field in baroreceptor-denervated cats was used to force the central systems responsible for the 10-Hz and 2- to 6-Hz rhythms in post-ganglionic sympathetic nerve discharge (SND). The 10-Hz rhythm in SND could be entrained either to the frequency of medullary stimulation or to harmonics of the stimulus frequency. The harmonic of the stimulus frequency to which the 10-Hz rhythm was entrained in one postganglionic nerve could be different from that in another nerve. On this basis, we propose that the circuits responsible for the 10-Hz rhythms in SND may be modeled as a system of coupled nonlinear oscillators, each of which either influences one postganglionic nerve or nonuniformly affects different postganglionic nerves. The relatively wide band 2- to 6-Hz component in SND could be forced into a stable oscillatory state by medullary stimulation at frequencies between 3 and 5 Hz. This observation is consistent with the view that the 2- to 6-Hz component reflects the complex behavior of a nonlinear oscillator rather than the output of a physiological noise generator.

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

1. The current study is the first to identify medullary neurons whose naturally occurring discharges were correlated to the 10-Hz rhythm in sympathetic nerve discharge (SND). Spike-triggered averaging showed that 44 of 164 rostral ventrolateral medullary (RVLM) and 44 of 174 caudal medullary raphe neurons had activity correlated to the 10-Hz rhythm in inferior cardiac postganglionic SND of 23 baroreceptor-denervated, decerebrate cats. 2. When the frequency of the rhythm in SND was decreased by lowering body temperature, the discharges of the 10 neurons tested (6 RVLM and 4 raphe) remained locked to the peak of the next 10-Hz sympathetic nerve slow wave rather than to the peak of the preceding slow wave. This observation supports the contention that the 10-Hz rhythm in basal SND was generated in the brain stem rather than in the spinal cord. 3. Frequency-domain analysis was used to characterize further the relationship between the 10-Hz rhythm in SND and the discharges of 30 RVLM and 24 raphe neurons. The autospectra of the discharges of eight RVLM and four raphe neurons contained a sharp peak near 10 Hz, although the mean firing rates of these neurons were lower than the frequency of the rhythm in SND. Coherence values as high as 0.76 characterized the relationship between the discharges of these "rhythmically firing neurons" and the 10-Hz rhythm in SND. A coherence value of 1.0 indicates a perfect correlation. The autospectra of the discharges of the 22 RVLM and 20 raphe neurons did not contain a peak near 10 Hz. The mean firing rates and coherence values relating the discharges of these "nonrhythmically firing neurons" and the 10-Hz rhythm in SND were significantly lower than those for the rhythmically firing neurons. Because the frequency of the population rhythm recorded from the inferior cardiac nerve was higher than the firing rates of individual medullary neurons, the 10-Hz rhythm in SND appears to be an emergent property of a network of neurons whose discharges are probabilistically related to the population rhythm. 4. In addition to the peak near 10-Hz, the autospectrum of SND often contained considerable power at frequencies < 6 Hz. This component of SND is called the 2- to 6-Hz rhythm.(ABSTRACT TRUNCATED AT 400 WORDS)

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High power, low frequency components of cardiac, renal, splenic and vertebral sympathetic nerve activities are uniformly reduced by spinal cord transection.

Others have reported that spinal cord transection non-uniformly affects the activities of the cardiac, renal and splenic nerves. We were unable to confirm this finding while recording the wide band (1-1000 Hz) discharges of these sympathetic nerves in baroreceptor-denervated, chloralose-anesthetized cats. Most of the power in nerve discharges was below 6 Hz. There was high coherence between the low frequency discharges of different nerves, and power below 15 Hz was essentially eliminated by spinal transection. Evidence is presented that the disparities between this and past studies are, in part, due to the use of a 30-Hz high-pass filter in the earlier studies.

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Differential relationships among discharges of postganglionic sympathetic nerves.

The relationships among the simultaneously recorded discharges of as many as four postganglionic sympathetic nerves were studied with coherence and phase spectral analyses in baroreceptor-denervated cats. Discharges were recorded from the inferior cardiac (CN), vertebral (VN), and renal (RN) nerves. Most of the power in sympathetic nerve discharge was less than 6 Hz, and the discharges of any two nerves coherred over a frequency band generally between 0 and 15 Hz. Peak coherence occurred between 2 and 6 Hz in most cases. Our most important observations are as follows. 1) Coherence values were significantly higher in chloralose-anesthetized than in unanesthetized decerebrate cats. 2) Coherence values were higher for near ipsilateral nerves (e.g., CN and VN) than for widely separated ipsilateral nerves (e.g., CN and RN). 3) Coherence values for most pairs were higher when the nerves were located on the same side (ipsilateral nerves) rather than on opposite sides (contralateral nerves) of the body. 4) Coherence values were higher for some functionally complementary nerves (e.g., CN and RN) than for noncomplementary nerves (e.g., VN and RN). These results support the hypothesis that the central circuits responsible for the basal discharges of different postganglionic sympathetic nerves are selectively coupled.

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Relationships between activity of sympathetic nerve pairs: phase and coherence.

The coherence function and phase spectrum were used to study the relationships between the discharges of sets of two postganglionic or preganglionic sympathetic nerves in baroreceptor-denervated cats anesthetized with either 5,5-diallylbarbiturate-urethan or alpha-chloralose. Most of the power in sympathetic nerve discharge was contained between 2 and 6 Hz. The coherence values relating the activity of two nerves were significantly different from zero within this frequency band. The phase spectrum was either linear or complex (i.e., showed changes in slope) within the coherent frequency band. We observed three patterns of relationship. The first pattern was characterized by a constant interval between activity in different sympathetic nerves within the coherent frequency band. The second pattern was characterized by a frequency-dependent interval. The third pattern was characterized by uncoupling of the 2- to 6-Hz rhythms in the discharges of different nerves. Switching between these patterns was observed. We suggest that the three patterns reflect different functional states of the central system responsible for the 2- to 6-Hz rhythm. Two models of this system are entertained. The first model is one of a system of coupled oscillators while filtering circuits that receive common inputs are the elements of the second model.

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Coherence of medullary unit activity and sympathetic nerve discharge.

Analyses in the frequency and time domains were used to study the relationships between the discharges of single brain stem neurons and postganglionic sympathetic nerves in baroreceptor-innervated and -denervated cats anesthetized with 5,5-diallylbarbiturate-urethan. Spike-triggered averaging was used initially to identify single neurons with sympathetic nerve-related activity in the medullary lateral tegmental field, rostral ventrolateral medulla, and medullary raphe. The discharges of such neurons were correlated to the 2- to 6-Hz rhythm in sympathetic nerve discharge (SND). Frequency-domain analysis revealed that the relationship between medullary unit activity and the sympathetic nerve rhythm was not fixed from cycle to cycle. First, the coherence values relating the activity of these neurons to SND were closer to zero than to unity in most cases. Second, whereas most of the power in the autospectra of SND was contained between 2 and 6 Hz, that in the autospectra of medullary unit activity was more evenly distributed over a much wider frequency band. These and other observations indicate that the 2- to 6-Hz rhythm is an emergent property of a network of brain stem neurons whose discharges are probabilistically rather than strictly related to the phases of the population rhythm.

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Forebrain rhythm generators influence sympathetic activity in anesthetized cats.

Autospectral and coherence analyses were used to study the frequency-domain relationships between frontal-parietal cortical activity [electroencephalogram (EEG)] and the discharges of the interior cardiac and renal sympathetic nerves of baroreceptor-denervated and vagotomized cats anesthetized with either alpha-chloralose or pentobarbital sodium. Delta slow-wave activity in the EEG was correlated to sympathetic nerve discharge (SND) as shown by sharp peaks between 0.5 and 4 Hz in the coherence function. The relationship was stronger in chloralose- than in pentobarbital-anesthetized cats. Coherence of the two signals could be attributed to descending influences of forebrain delta slow-wave generators on sympathetic circuits, since midbrain transection preferentially reduced the power in SND at frequencies that cohered to the EEG before transection. In contrast, the power in the EEG was not reduced by midbrain transection. The relationship between cortical delta slow-wave activity and SND was stronger during than between cortical spindlelike events that lasted 1-3 s and recurred once every 5-10 s. These events were similar to cortical spindles observed during the early stages of sleep and under light barbiturate anesthesia. These observations raise the possibility that the influences of forebrain delta slow-wave generators on SND are gated by thalamic mechanisms normally involved in the sleep-wake cycle.

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Basis for the naturally occurring activity of rostral ventrolateral medullary sympathoexcitatory neurons.

This chapter entertains two theories (network oscillator vs. intrinsic pacemaker) on the generation of the major component of SND - the 2- to 6-Hz rhythm in the cat and the 2- to 10-Hz rhythm in the rat. Evidence from experiments on cats strongly supports the hypothesis that the 2- to 6-Hz rhythm is an emergent property of a network oscillator located in the brain stem. Specifically, we propose that the 2- to 6-Hz component in SND arises from an ensemble of neurons of different types interconnected in such a way to generate the rhythm. There is no evidence for the existence of intrinsic pacemaker neurons in this network. Our experiments on cats also indicate that the rhythm is generated by neurons in the brain stem that are antecedent to RVLM-spinal SE and raphespinal-SI neurons. Our experiments on rats are not consistent with the hypothesis of Sun et al. (1988b) that "vasoconstrictor and cardioaccelerator sympathetic tone is due in large part to the intrinsic pacemaker activity of a small group of reticulospinal excitatory neurons located at the extreme anterior tip of the ventrolateral medulla". Rat RVLM pacemaker neurons act independently of each other following i.c. injection of the glutamate-receptor antagonist, KYN (Sun et al., 1988a). Thus, they would as a group provide white noise input to spinal neurons. It follows that i.c. KYN should have desynchronized SND if, as proposed by Sun et al., RVLM pacemakers are primarily responsible for SND in the rat. This was found not to be the case. The most likely explanation is that the 2- to 10-Hz rhythm in rat SND is not generated by intrinsic pacemaker neurons in the RVLM.

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Sympathetic activity remains synchronized in presence of a glutamate antagonist.

Sun et al. like activity in the rostral ventrolateral medulla (RVLM) of the rat after an intracisternal injection of the glutamate receptor antagonist, kynurenate (KYN). They proposed that these neurons are primarily responsible for sympathetic nerve discharge (SND). The fact that RVLM pacemaker neurons discharge independently of each other after intracisternal KYN leads to the prediction that SND will be desynchronized by this drug. The results of the current study show that this is not the case. Postganglionic SND was recorded in rats and cats before and after intracisternal injection of KYN in doses that blocked the baroreceptor reflexes. Whereas the background level of SND was unchanged in rats, KYN markedly reduced SND in cats. Independent of this difference, KYN failed to desynchronize SND in either species. Power density spectra of SND in rats and cats contained sharp peaks between 2 and 10 Hz before and after intracisternal KYN. These results require a reassessment of the pacemaker hypothesis on the origin of SND. Moreover, KYN-induced depression of SND in the cat points to the importance of brain stem synaptic mechanisms in the genesis of sympathetic tone in this species.

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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)

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The axons of raphespinal sympathoinhibitory neurons branch in the cervical spinal cord.

This study shows that the axons of some raphespinal sympathoinhibitory neurons projecting to the third thoracic spinal segment emit branches in the third-fourth cervical spinal segments of cats. This was demonstrated by using time-controlled collision of neuronal action potentials initiated by stimuli applied at these spinal levels. Antidromic mapping revealed that the cervical branches of these neurons likely terminated in Rexed's lamina VII. In contrast to these raphe neurons, the axons of ventrolateral medullospinal sympathoexcitatory neurons did not emit cervical branches.

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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.

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Cat diencephalic neurons with sympathetic nerve-related activity.

In a companion paper, we demonstrated that hypothalamic or medial thalamic lesions attenuate the reduction in inferior cardiac postganglionic sympathetic nerve discharge (SND) produced by decerebration in the anesthetized cat [Huang et al., Am. J. Physiol. 254 (Regulatory Integrative Comp. Physiol. 23): R249-R256, 1988]. This raised the possibility that these diencephalic regions contain the cell bodies of neurons that contribute to SND. The current study tested this possibility in cats anesthetized with alpha-chloralose. Spike-triggered averaging of inferior cardiac SND revealed the existence of two types of hypothalamic and medial thalamic neurons with sympathetic nerve-related activity. Recordings were made from the soma-dendritic region of these neurons, since an inflection often appeared on the rising phase of the unit action potential. The activity of type 1 neurons was synchronized to an aperiodic spikelike event in SND, whereas that of type 2 neurons was synchronized to a 2- to 6-Hz rhythmic component. Some of the type 2 neurons but none of the type 1 neurons had cardiac-related activity. Microstimulation at type 1 and type 2 unit recording sites increased SND. Our results are consistent with the possibility that hypothalamic and medial thalamic neurons contribute to the rhythmic and aperiodic components of SND in the anesthetized cat.

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Studies on the origin and generation of sympathetic nerve activity.

This paper summarizes the efforts of our laboratory to define the substrates and mechanisms for generation of one of the primary components in sympathetic nerve discharge (SND) of the cat, the 2- to 6-Hz rhythm. Using spike-triggered averaging, we have identified single brain stem neurons with naturally occurring activity correlated to the 2- to 6-Hz rhythm in SND. Such neurons were found in three regions--the rostral ventrolateral medulla (RVLM), medullary raphe (R) and medullary lateral tegmental field (LTF). RVLM neurons were inhibited in parallel to SND when carotid sinus pressure was raised while R neurons were excited. These observations suggest that RVLM neurons exert sympathoexcitatory (SE) actions while R neurons mediate sympathoinhibitory (SI) effects. Both SE and SI neurons were found in the LTF. Antidromic mapping revealed that the axons of RVLM-SE and R-SI neurons innervate the thoracic spinal intermediolateral nucleus. In contrast, LTF neurons do not project to the spinal cord. Rather, the axons of LTF-SE neurons project to the RVLM while those of LTF-SI neurons project to R. We hypothesize that the aforementioned cell groups comprise a network oscillator responsible for the 2- to 6-Hz rhythm in SND.

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