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G L Gebber

Publications and source records attributed to G L Gebber.

At least 73 records · Page 4Linked to original sources

Electrophysiological evidence for the modular organization of the reticular formation: sympathetic controlling circuits.

Cross-correlation analysis revealed that the discharges of cat medullary reticular neurons located in the recording field of a single microelectrode were synchronized on a time scale of a few ms. The incidence of short time scale interactions was significantly greater when both members of a neuronal pair had activity temporally related to postganglionic inferior cardiac sympathetic nerve discharge than when only one member had sympathetic nerve-related activity. The data support the view that the reticular formation is organized into functionally distinct modules that are potentially interactive.

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Forebrain contribution to sympathetic nerve discharge in anesthetized cats.

We tested the hypothesis that the forebrain is responsible for a component of basal sympathetic nerve discharge (SND) in the anesthetized cat. For this purpose integrated postganglionic inferior cardiac SND and blood pressure were measured before and after serial transections of the midbrain at stereotaxic planes A3 and AP0. In the first series of experiments on baroreceptor-denervated cats anesthetized with alpha-chloralose, A3 transection significantly reduced SND to 62 +/- 7% of control. Blood pressure was reduced 33 +/- 4 mmHg. SND and frontal-parietal cortical activity were temporally related prior to A3 transection in many of these animals. Recovery of SND and blood pressure to control levels occurred within 30 min after A3 transection. A second midbrain transection at AP0 failed to affect SND and blood pressure at this time. This observation suggests that the effects of A3 transection were due to the loss of a component of SND of forebrain origin rather than to generalized trauma. The effects of A3 transection were not attributable to cataleptic anesthesia with alpha-chloralose, since SND and blood pressure were significantly reduced by midbrain transection in baroreceptor-denervated cats anesthetized with diallylbarbiturate-urethan. A3 transection also reduced SND and blood pressure in some baroreceptor-innervated cats. Finally, medial diencephalic ablation prevented the effects of A3 transection. We conclude that the forebrain is responsible for a significant component of sympathetic tone in anesthetized cats. Recovery from the loss of this component, however, occurs rapidly even in animals deprived of their compensatory baroreceptor reflex mechanisms.

Anesthesia↗

Lateral tegmental field neurons of cat medulla: a source of basal activity of ventrolateral medullospinal sympathoexcitatory neurons.

We tested the hypothesis that neurons of the lateral tegmental field (LTF) of the cat medulla exert their sympathoexcitatory actions over a pathway that includes rostral ventrolateral medullospinal neurons innervating the spinal intermediolateral nucleus (IML). Thirty-one LTF neurons with sympathetic nerve-related activity [as demonstrated with spike-triggered averaging of inferior cardiac postganglionic sympathetic nerve discharge (SND)] were antidromically activated by microstimulation of the rostral ventrolateral medulla (VLM). The threshold current required to elicit the longest latency antidromic response was increased when the stimulating microelectrode was moved to more dorsal or medial sites in the rostral medulla. This observation suggests that the axons of LTF neurons projected to the rostral VLM. The firing rate of LTF neurons with sympathetic nerve-related activity was decreased during baroreceptor reflex activation. This observation is consistent with the view that these neurons subserved a sympathoexcitatory function. Twenty-five VLM neurons with sympathetic nerve-related activity were synaptically activated by microstimulation of the LTF. The modal onset latency of synaptic excitation (25.6 +/- 2.6 ms) compared favorably with the difference (31 ms on the average) between the firing times of LTF and VLM neurons relative to the peak of the cardiac-related sympathetic nerve slow wave. The firing rate of these VLM neurons decreased during baroreceptor reflex activation. Of nine VLM neurons tested, seven were antidromically activated by microstimulation of the second thoracic (T2) IML. These data are consistent with the view that LTF neurons are a source of the basal discharge of VLM-spinal sympathoexcitatory neurons. Sixteen VLM neurons with sympathetic nerve-related activity were antidromically activated by microstimulation of both the LTF and the T2 IML. In some cases, LTF stimulation activated an axonal branch rather than the main axon. This was demonstrated using time-controlled collision of the VLM neuronal action potentials initiated by LTF and T2 IML stimulation. These data raise the possibility that individual VLM neurons influence SND by actions mediated at both spinal and supraspinal levels.

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Axonal branching patterns and funicular trajectories of raphespinal sympathoinhibitory neurons.

We studied axonal branching patterns and funicular trajectories of cat medullary raphespinal neurons with spontaneous activity related to inferior cardiac postganglionic sympathetic nerve discharge (as demonstrated with spike-triggered averaging). These neurons were excited by raising carotid sinus pressure. We have classified these neurons as sympathoinhibitory in function and refer to them here as RS neurons. Microstimulation of the second thoracic spinal segment (T2) antidromically activated RS neurons (as determined with time-controlled collision of spontaneous and evoked action potentials). The longest-latency antidromic responses were elicited with the lowest-threshold current from sites in the intermediolateral nucleus (IML). This observation suggests that RS neurons innervated IML. Most RS neurons activated from T2 were also antidromically activated by stimulation of a more caudal thoracic spinal segment (T6 or T12). Time-controlled collision of action potentials evoked by stimulation at two thoracic levels allowed us to distinguish activation of an axonal branch in T2 from that of the main axon coursing through T2 to the more caudal thoracic level. Of those RS axons that branched in T2, 78% descended at least as far caudal as T6, whereas 65% reached T12. The axonal projections of other RS neurons that innervated T2 were restricted to no more than two consecutive thoracic spinal segments (as determined by stimulation in T3). Antidromic mapping of T2 further revealed that the axons of RS neurons coursed through the dorsolateral, ventral, or ventrolateral funiculus to innervate the ipsilateral and/or contralateral IML. The conduction velocities of dorsolateral and ventral RS axons indicated that they were finely myelinated. The data demonstrate the existence of RS neurons with restricted and widespread axonal branching patterns, thereby supporting the view that the medullary raphe complex is capable of regional as well as global inhibitory control over spinal sympathetic outflow.

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Axonal projection patterns of ventrolateral medullospinal sympathoexcitatory neurons.

We studied the following properties of cat ventrolateral medullary (VLM) neurons that projected to the thoracic spinal cord: the relationship between their spontaneous activity and that in the inferior cardiac postganglionic sympathetic nerve, their responses to baroreceptor-reflex activation, their axonal conduction velocities, the funicular trajectories of their axons, the likely sites of termination of their axons, and their axonal branching patterns. Microstimulation in the second thoracic spinal segment (T2) antidromically activated 67 VLM neurons (as determined with time-controlled collision of spontaneous and evoked action potentials), whose activity was correlated to inferior cardiac sympathetic nerve discharge (as determined with spike-triggered averaging). We tested the effect of baroreceptor-reflex activation on the firing rate of 20 of these VLM-spinal neurons. Because the firing rate decreased in each instance, these neurons apparently subserved a sympathoexcitatory function. The axonal branching patterns of 51 VLM-spinal sympathoexcitatory neurons were studied. Thirty-four neurons were antidromically activated by stimulation in the T2 gray matter and in more caudal thoracic spinal segments (T11 and/or T6). In each case, the antidromic response evoked by stimulation in the T2 gray matter was due to activation of an axonal branch rather than the main axon (via current spread to the white matter). This was demonstrated with tests that included time-controlled collision of the action potentials initiated by stimulation in T2 and a more caudal thoracic spinal segment. Some VLM-spinal axons that projected to T11 branched in T6 as well as in T2. These data indicate that some VLM-spinal neurons exerted widespread excitatory influences on sympathetic outflow. Seventeen VLM sympathoexcitatory neurons that innervated the T2 gray matter could not be antidromically activated by stimulation in T5, T6, and T11 despite an extensive search at each level. Thus the axonal projections of some VLM-spinal neurons were restricted to upper thoracic segments. Antidromic mapping in T2 revealed that the axons of VLM sympathoexcitatory neurons coursed through the dorsolateral or ventrolateral funiculus to innervate the region of the intermediolateral nucleus. Mean axonal conduction velocity was 3.5 +/- 0.3 m/s. Those VLM-spinal axons restricted to upper thoracic segments generally were located dorsally and/or medially to those that innervated widely separated thoracic segments. The discharges of 35 other VLM neurons that were antidromically activated by T2 stimulation were not related to sympathetic nerve activity.(ABSTRACT TRUNCATED AT 400 WORDS)

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Lateral tegmental field neurons of cat medulla: a potential source of basal sympathetic nerve discharge.

A study was made of 170 neurons of the lateral tegmental field (LTF) of the cat medulla with spontaneous activity temporally related to the 2- to 6-Hz slow wave in inferior cardiac postganglionic sympathetic nerve discharge (as demonstrated with spike-triggered averaging). LTF neurons were excited by the iontophoresis of L-glutamate, and an inflection on the rising phase of their action potentials was observed. Thus, the site of extracellular unit recording presumably was in the region of the cell body. The lag between LTF unit spike occurrence and the peak of the 2- to 6-Hz slow wave in sympathetic nerve discharge (SND) was unchanged when blood pressure and, thus, baroreceptor nerve activity were lowered to a level at which the phase relationship between the slow wave and the cardiac cycle was disrupted. Thus, the discharges of LTF neurons apparently were more closely associated with those of elements of "efferent" brain stem networks controlling SND than with those of interneurons in the afferent limb of the baroreceptor reflex arc. LTF neurons with sympathetic nerve- and cardiac-related activity were classified into three types depending on their responses to elevated carotid sinus pressure (i.e., baroreceptor reflex activation). Of the 82 neurons tested, 33 were inhibited, 16 were excited, and 33 were unaffected by baroreceptor reflex activation. Using data collected in this and previous studies from our laboratory, we compared the firing times of neurons in the LTF, rostral ventrolateral medulla, and medullary raphe nuclei relative to the peak of the sympathetic nerve slow wave. LTF neurons that were inhibited by baroreceptor reflex activation are presumed to subserve a sympathoexcitatory function. These neurons fired significantly earlier during the sympathetic nerve slow wave than their counterparts in the rostral ventrolateral medulla and medullary raphe nuclei. LTF neurons classified as sympathoinhibitory (i.e., excited by baroreceptor reflex activation) fired significantly earlier than their counterparts in the medullary raphe nuclei. These data raise the possibility that LTF neurons are closer (at least in a temporal sense) to the region of origin of the 2- to 6-Hz component of SND than are ventrolateral medullary and raphe neurons. The firing times of sympathoexcitatory and sympathoinhibitory LTF neurons were not significantly different. These data are discussed relative to potential mechanisms involved in generating SND. Microstimulation of the second thoracic spinal segment was used to determine whether the axons of LTF neurons with sympathetic nerve-related activity projected to this level.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

Baroreceptor influences on cardiac-related sympathetic nerve activity.

We studied the effect of a dropped ventricular beat (i.e. loss of one cycle of pulse synchronous baroreceptor nerve activity) on the centrally generated 2-6 Hz oscillation in postganglionic sympathetic nerve discharge (SND) in cats anesthetized with Dial-urethane. The results indicate that in each cardiac cycle baroreceptor nerve activity can: (1) decrease the rate of recruitment and number of postganglionic fibers that become active and (2) advance the onset of central inhibition responsible for the abrupt decline of SND. These effects are independent of baroreceptor-mediated entrainment of the 2-6 Hz oscillation of SND to the cardiac cycle.

Adrenergic Fibers↗

Raphe neurons with sympathetic-related activity: baroreceptor responses and spinal connections.

We have previously used spike-triggered averaging to identify cat medullary raphe neurons with activity locked to the 2- to 6-cycles/s rhythm in sympathetic nerve discharge (SND) [Am. J. Physiol. 243 (Regulatory Integrative Comp. Physiol. 12): R49-R59, 1982]. In the present study, we classified such cat raphe neurons on the bases of their spinal connections and responses to baroreceptor reflex activation. Type I neurons, comprising 139 of 190 raphe units with activity related to inferior cardiac SND, were excited when carotid sinus pressure was elevated. The majority of these neurons were located in nucleus raphe pallidus. A time-controlled collision test for antidromic activation revealed that the axons of approximately one-third of type I neurons terminated in the sympathetic intermediolateral nucleus (IML) after coursing through the dorsolateral funiculus (DLF) of the spinal cord. The axons of the remaining type I neurons did not project to the spinal cord. It is suggested that type I raphe neurons are involved in mediating sympathoinhibition at spinal and supraspinal levels. Importantly, type I unit discharge remained locked to SND when the phase relationship between baroreceptor afferent and sympathetic efferent activities was disrupted. Thus type I neurons are not simple interneurons in the afferent limb of the baroreceptor reflex arc. Apparently they also receive input from the generator of the 2- to 6-cycles/s rhythm in SND. Type II raphe neurons (n = 51) were inhibited when carotid sinus pressure was elevated. Although the axons of these neurons coursed through the spinal DLF, they did not terminate in IML. Whether type II neurons subserve a sympathoexcitatory function remains to be determined.

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Differential control of sympathetic nerve discharge by the brain stem.

This investigation was designed to test the hypothesis that the brain stem differentially controls the basal discharges of postganglionic sympathetic nerves distributed to different organs. Previous studies have shown that the 2- to 6-Hz activity pattern in sympathetic nerves of the baroreceptor-denervated cat originates in the brain stem. In the current study, autocorrelation and power spectral analyses were used to compare the 2- to 6-Hz frequency components of the simultaneously recorded discharges of postganglionic sympathetic nerve pairs (inferior cardiac and renal; external carotid and renal) in baroreceptor-denervated cats anesthetized with sodium diallylbarbiturate and urethan (Dialurethane). In addition, spike-triggered averaging was used to compare the relative strengths of coupling of the basal discharges of single ventrolateral medullary reticular or medullary raphe neurons to activity in postganglionic sympathetic nerve pairs. The major findings of the study are as follows: 1) the predominant 2- to 6-Hz frequency component in the basal discharges of one sympathetic nerve often was different from that in the discharges of a second nerve, and 2) the activity of approximately one-third of ventrolateral medullary reticular neurons and one-half of medullary raphe neurons (with sympathetic-related activity) was differentially related to the discharges of postganglionic nerve pairs. These results support the view that the brain stem reticular formation and raphe complex exert their influences on different sympathetic nerves in a nonuniform fashion.

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Spinal interneurons with sympathetic nerve-related activity.

This study tested the hypothesis that at least some brain stem and reflex control of sympathetic outflow is mediated over pathways containing spinal interneurons. The vicinity of the intermediolateral nucleus (IML) of the third thoracic spinal segment was searched for neurons with spontaneous activity correlated to that in the inferior cardiac post-ganglionic sympathetic nerve of 16 baroreceptor-denervated cats anesthetized with Dial-urethane. Section of the carotid sinus, aortic depressor, and vagus nerves prevented the coupling of sympathetic and nonsympathetic networks by pulse synchronous baroreceptor activity. Spike-triggered averaging revealed the existence of two types of spinal neurons with sympathetic nerve-related activity. Preganglionic sympathetic neurons (PSN; n = 33) were antidromically activated by electrical stimulation of their axons in the third thoracic white ramus. Four observations suggest that the second group of neurons with sympathetic nerve-related activity (n = 18) were spinal interneurons (SIN) in pathways that excite PSN. First, these neurons could not be antidromically activated by stimulation of the segmental white ramus. Second, the intervals between spontaneous unit spike occurrence and inferior cardiac nerve activity were similar for SIN and PSN. Third, SIN and PSN were activated with nearly identical onset latencies by electrical stimulation of medullary sympathoexcitatory sites. Fourth, SIN were excited by intensities of cardiac sympathetic afferent stimulation that also activated PSN and the inferior cardiac nerve. SIN and PSN were distinguished on the basis of their spontaneous firing patterns; i.e., interspike intervals of SIN were significantly shorter than those of PSN.(ABSTRACT TRUNCATED AT 250 WORDS)

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Sequence of activation of ventrolateral and dorsal medullary sympathetic neurons.

A unique approach to the problem of evaluating potential regions of origin of the cardiac-related component in basal sympathetic nerve discharge (SND) is described in the present investigation. Specifically a comparison was made of the firing times of cat ventrolateral and dorsal medullary neurons with sympathetic nerve-related activity. These two medullary regions are known to play a role in the maintenance of blood pressure. Spike-triggered averaging and post-R wave interval analysis were used to identify single medullary neurons with spontaneous discharges temporally related to those in the renal or inferior cardiac sympathetic nerve. The results obtained using a ventricular pacing test previously developed in our laboratory allowed us to classify some of these neurons as elements of networks that control SND (i.e., medullary sympathetic neurons). The test is based on the assumption that brain stem sympathetic neurons should exhibit discharges that remain locked in time to the peak of the cardiac-related component of SND during changes in heart rate that shift the phase relations between baroreceptor and sympathetic nerve activity. Electrical stimulation of sites from which the discharges of such units were recorded elicited increases in SND, thus suggesting that these neurons subserved a sympathoexcitatory function. On the average, ventrolateral medullary neurons fired 48 ms later than dorsal medullary neurons during the cardiac-related component in SND. This observation does not support the previous suggestion [R. A. L. Dampney and E. A. Moon. Am. J. Physiol. 239 (Heart Circ. Physiol. 8): H349-H358, 1980] that basal sympathetic tone originates exclusively in circuits of ventrolateral medullary neurons. Possibilities concerning the interconnections of dorsal and ventrolateral medullary neurons involved in maintaining blood pressure are discussed.

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Short time scale interactions between brain stem neurons with sympathetic nerve-related activity.

Cross-correlation analysis revealed short time scale (ms) interactions between closely adjacent cat brain stem neurons with sympathetic nerve-related activity. The incidence of such interactions was significantly greater for reticular neurons than for raphe neurons. Shared input and/or interconnection via mono- or oligosynaptic pathways are considered as mechanisms for synchronization of the discharges of elements of the brain stem network which controls sympathetic nerve activity.

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Brain stem neurons governing the discharges of sympathetic nerves.

Recent work from our laboratory revealed that the brain stem is inherently capable of generating a 2-6 cycles/s rhythm in sympathetic nerve discharge (SND) of the baroreceptor denervated cat. It is believed that this rhythm is representative of the fundamental organization of those brain stem networks responsible for the background discharges in sympathetic nerves. As a consequence, an attempt was made to identify brain stem neurons with activity patterns related to the 2-6 cycles/s rhythm in inferior cardiac SND of the baroreceptor denervated cat. Specifically, the relationships between the spontaneous discharges of single brain stem neurons and the inferior cardiac nerve were analyzed with the technique of spike-triggered averaging. Neurons whose discharges were synchronized either to the rising or falling phase of inferior cardiac SND were located in the classic pressor region of the lateral medullary reticular formation. These neurons may comprise or receive inputs from the oscillator responsible for the 2-6 cycles/s rhythm in SND. In addition, neurons which reset the 2-6 cycles/s rhythm were identified. These neurons may provide inputs to the 2-6 cycles/s oscillator in the brain stem.

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Sympathetic nerve discharge in chronic spinal cat.

A study was made of external carotid, renal, and splanchnic sympathetic nerve discharge (SND) in chloralose-anesthetized cats subjected to transection of the sixth cervical spinal segment 2-37 days earlier. Minimal activity was observed under normocapnic conditions 2 days after spinal transection, and ganglionic blockade failed to lower blood pressure. Moderate hypercapnia increased SND and led to synchronization of activity into 1-6 cycle/s slow waves. Such slow-wave activity was present under normocapnic conditions in cats 9-37 days after spinal transection. Ganglionic blockade significantly reduced blood pressure in these preparations. The interval between successive 1-6 cycle/s slow waves was variable. Thus, unlike the case in baroreceptor-denervated cats with an intact neuraxis [Barman and Gebber, Am. J. Physiol. 239 (Regulatory Integrative Comp. Physiol. 8): R42-R47, 1980], chronic spinal cats are incapable of rhythm generation in the 1-6 cycle/s frequency range. Crosscorrelation analysis revealed that the discharges of pairs of segmental (but not intersegmental) sympathetic nerves were related in the chronic spinal cat. This situation differs from that in the baroreceptor-denervated cat in which the discharges of pairs of intersegmental as well as segmental sympathetic nerves are related. Thus coordination of activity in sympathetic nerves that arise from different spinal segments requires the integrity of bulbospinal connections. Finally, no evidence was obtained for the existence of a baroreceptor-like reflex mechanism acting to control SND in the chronic spinal cat.

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Hypothalamic neurons with activity patterns related to sympathetic nerve discharge.

Spike-triggered averaging was used to identify hypothalamic neurons with activity patterns related to inferior cardiac sympathetic nerve discharge (SND). Three neuronal types were identified in baroreceptor-innervated cats. The discharges of SR units were temporally related to SND and the R wave of the electrocardiogram. The discharges of SER units were in addition related to electroencephalogram (EEG) activity. SE unit discharges were related to SND and EEG activity but not to the R wave. Two neuronal types were identified in baroreceptor-denervated cats. The discharges of S units were temporally related to SND but not to EEG activity. The second neuronal type exhibited activity patterns similar to those for SE neurons in the baroreceptor-innervated cat. With the exception of SER neurons, all unit types could be subdivided into two groups depending on whether their discharges were followed by an increase or a decrease in SND. The discharges of SER units were followed by a decrease in SND. These data are discussed with regard to the role played by the hypothalamus in generating the basal discharges of sympathetic nerves.

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Classification of raphe neurons with cardiac-related activity.

The cardiac-related component of sympathetic nerve discharge (SND) results from entrainment of a rhythm of brain stem origin by the baroreceptor reflexes [Gebber, Am. J. Physiol. 239 (Heart Circ. Physiol. 8): H143-H155, 1980]. As a consequence, changes in heart rate are accompanied by shifts in the phase relations between SND and the arterial pulse wave. This observation presented us with the opportunity of distinguishing brain stem neurons whose discharges are locked to SND from other neuronal types that exhibit cardiac-related activity. Raphe neurons in the cat medulla with cardiac-related activity were identified using post-R wave interval analysis. The discharges of one group of these neurons remained locked to inferior cardiac SND during changes in ventricular rate which shifted the phase relations between SND and the arterial pulse wave. Most importantly, the lag between unit spike occurrence and the peak of the cardiac-related component of SND was unchanged during ventricular pacing (as demonstrated with cross-correlation analysis). It is suggested that these neurons were contained in brain stem networks which control SND. The discharges of two additional types of raphe neurons remained locked to the arterial pulse wave during ventricular pacing. Neurons of the first type exhibited an increase in discharge probability in late diastole and early systole. Neurons of the second type exhibited a period of reduced activity time-locked to systole.

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Problems associated with the identification of brain stem neurons responsible for sympathetic nerve discharge.

A study of the role of lower brain stem neurons generating sympathetic nerve discharge and reactions. A discussion of the problem and requirements for its resolution is followed by a description of approaches made and discussion of reported findings as well as new observations. There is a discussion of the possible origin of respiratory linked rhythms in sympathetic nerve discharge. Spike-triggered averaging was used to relate medullary neuron and inferior cardiac sympathetic nerve discharge under varying external and internal circumstance. Data obtained indicate that it is possible to identify and distinguish reticular neurons which govern sympathetic nerve discharge from other functional types.

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Brain stem neuronal types with activity patterns related to sympathetic nerve discharge.

The relationships among the spontaneous activity of single neurons in the cat medulla and inferior cardiac sympathetic nerve discharge (SND), electroencephalogram (EEG) activity, phrenic nerve activity, and the R wave of the electrocardiogram were studied with the methods of spike-triggered averaging and postevent interval analysis. Three categories of neurons (SR, SE, and S) with activity patterns related to SND wee identified. The activity of SR units was related in time to SND and the R wave but not to EEG activity. SE unit discharges were related to SND and EEG activity but not to the R wave. S unit activity was related only to SND. Each of the three categories of neurons could be subdivided into two groups depending on whether their discharges were followed by an increase or a decrease in SND. All unit types exhibited respiratory-related discharge patterns. These data are discussed with regard to the problems associated with the identification of neurons in brain stem networks that govern the discharges of sympathetic nerves.

Action Potentials↗