142
Brain Research, 96 (1975) 142-146 © Elsevier Scientific Publishing Company, Amsterdam - Printed in The Netherlands
The probabilistic behavior of central 'vasomotor' neurons
GERARD L. GEBBER Department of Pharmacology, Michigan State University, East Lansing, Mich. 48824 (U.S.A.,)
(Accepted May 28th, 1975)
Bursts of activity recorded from pre- and postganglionic sympathetic nerve bundles usually are coupled in a 1:1 relation to the cardiac cycle2,3,9,11,13,zl. Yet, with the exception of neurons in the vicinity of the nucleus of the solitary tract 6,8,12, 15,1s,19 which receive direct input from the baroreceptor nerves, attempts to locate brain stem units whose spontaneous discharge is locked to the cardiac cycle have failed 6-8,14,15,19. This observation can be interpreted in at least two ways. First, the failure to locate neurons within the pressor region of the medulla which exhibit a cardiac rhythm in their discharge might be related to a microelectrode sampling problem. Second, absence of a cardiac rhythm in the spontaneous discharges of medullary units might signify that only a small percentage of the total population of brain stem vasomotor neurons participates in each cardiac related burst of activity recorded from peripheral sympathetic nerve bundles; and that the active subpopulation changes from heart beat to heart beat. In this case, it might be possible to identify single vasomotor neurons in the brain stem by determining the probability of their discharge during the phases of the cardiac cycle. This possibility was studied by constructing post-R wave time interval histograms of spontaneously occurring unitary discharge. Experiments were performed on cats anesthetized by the intraperitoneal injection of sodium diallylbarbiturate (70 mg/kg), urethan (280 mg/kg) and monoethylurea (280 mg/kg). The animals were immobilized with gallamine triethiodide (4 mg/kg, i.v.) and artificially respired. Pneumothoracotomy was performed to minimize respiratory related movements. The dorsal surface of the medulla was exposed after removal of portions of the occipital bone and cerebellum. Platinum-coated stainless steel microelectrodes (Transidyne General Corp.) with 1 #m tip diameters and exposed tip lengths of 5 #m were used for extracellular recording of unit discharges from the lateral portions of nucleus reticularis gigantocellularis (R.gc.) and nucleus reticularis ventralis (R.v.). These reticular structures form part of the classical medullary pressor region 2°. Microelectrode tracks were identified upon microscopic examination of 30/zm thick medullary sections prepared with a freezing microtome. Unit discharges were amplified with a capacitance-coupled Grass P511 preamplifier (100-1000 Hz bandpass) and recorded on magnetic tape. Blood pressure, and a timing pulse derived from the R wave of the E K G also were placed on tape. The data on magnetic tape
143
40-!
Z
o
iJ
u
,,
0
POST- R WAVE
I
z
§ ,i C
I N T, m s e c
5OO
' •
u,,Ll L jtJll .LII l i •
| 10
0
INTER,SPIKE
INl,sec
Fig. 1. Spontaneous discharge pattern of medullary unit located in R. v. of medulla (stereotaxic coordinates: P12.0, L2.0, H-8.2). A: phase relations between arterial pulse wave (top) and post-R wave Till of unitary discharge (bottom). Sample run was 8.5 rain. Address bin was 4 msec. Mean blood pressure was 150 mm Hg. B: imerspike interval histogram of unitary discharge (200 spikes).
was fed to a Nicolet computer (Model 1070) and analyzed in the following manner. The sweep of the computer was triggered by the timing pulse derived from the R wave. The computer was programmed to average the arterial pulse wave and to build a unitary post-R wave time interval histogram (TIH). Unit recordings were subjected to window discrimination before presentation to the computer. Single preganglionic sympathetic neurons within the seventh thoracic spinal segment were identified antidromically by stimulation of the splanchnic nerve in a second series of experiments using the method described by Taylor and Gebber 20. Post-stimulus histograms (PSH) of unitary discharge to single shock stimulation of pressor sites in R.gc. and R.v. were constructed. The medulla was stimulated with square wave pulses (10V; 0.5 msec) passed from a Grass $88 stimulator through a stimulus isolation unit to bipolar concentric semimicroelectrodes (David K o p f Instruments, model SNE-100). The phase relations between the arterial pulse and the spontaneous discharges of a single neuron in R.v. are shown in Fig. 1A. The probability of unitary discharge was considerably higher during early and middiastole than during the rest of the cardiac cycle. It is evident from the interspike interval histogram shown in Fig. 1B that the unitary discharge pat'tern was quite irregular. Indeed, the neuron remained quiescent for as long as 18 heart beats. The modal interspike interval was 1.12 sec.
144 SPLANCHNIC ANTIDROMIC
ORTHODROMIC
~;~ o
15
25
o
20
ONSET LATENCY, msec
14o
Fig. 2. Poststimulus histograms (PSH) of the discharges of a single preganglionic splanchnic sympathetic neuron. PSH of unitary responses evoked by antidromic stimulation (8 V; 0.1 msec) of splanchnic nerve is shown on the left. PSH of unitary discharges evoked by single shocks (10 V; 0.5 msec) applied once every 2 sec to a pressor site in R. v. of the medulla (200 trials) is shown on the right. The unit discharged no more than once for each shock applied to the medulla.
The shortest interspike interval was approximately 0.4 sec while the longest interval was 9.6 sec. Six of 38 cells sampled in R.gc. and R.v. (8 cats) showed a relationship between the probability of unitary discharge and the cardiac cycle similar to that depicted in Fig. 1. Although many more than 38 cells were encountered, computer analysis was performed only on those cells whose mean frequency of discharge was below 3/sec (average heart rate). The spontaneous discharges of the 6 cells showing a positive correlation between the post-R wave TIH and the cardiac cycle were inhibited during the rise in blood pressure produced by the intravenous injection (1-2 #g/kg) of norepinephrine (i.e., baroreceptor reflex activation). This observation further suggested that the neurons were contained within a vasopressor circuit. Using cross-correlation analysis, Gootman et al. 4 recently reported on 2 medullary neurons whose spontaneous discharge patterns were similar to those of the whole splanchnic nerve of the cat. The discharge characteristics of one of these neurons suggested that it was functionally located near the efferent outflow of the medullary sympathetic driving network. The discharge frequency of this unit was considerably higher than those of the neurons reported upon in the present investigation. The small samples in both studies, however, precludes a decision on whether the low and high frequency discharging neurons were part of the same or different brain stem sympathetic circuits. The identification of neurons whose spontaneous discharges were not locked in a 1 : 1 relation to the cardiac cycle, but whose probability of discharge was related to the phases of the cardiac cycle supports the contention that only a small and continuously changing segment of the total population of brain stem vasomotor neurons participates in each cardiac related burst of activity recorded from groups
145 of peripheral sympathetic nerve fibers. This observation also raises the possibility that individual preganglionic sympathetic neurons serve as the final common pathway for a large number of brain stem neurons. Although it is difficult as well to find preganglionic neurons which discharge during each cardiac cycleS,10,17,~0, the redundancy of brain stem input would function to enhance the probability of cardiac-related preganglionic unitary discharge. The possibility that individual preganglionic neurons receive excitatory input from many descending pathways was tested on the following assumption. Redundancy, in combination with a continually changing population of brain stem neurons responsive to excitation, should lead to a degree of unpredictability regarding the latency of preganglionic unitary discharge to successive stimuli applied to the same pressor site in the medulla; providing that impulses can be transmitted to the spinal cord over a number of different routes, each having a different conduction time. This assumption seems reasonable in view of the extensive interconnections known to exist between large numbers of reticulospinal neurons at medullary and pontine levels1,16. The preganglionic unitary response patterns produced by stimulation of the splanchnic nerve (antidromic activation) and a medullary pressor site (orthodromic activation) are shown in Fig. 2. The PSH of unitary responses evoked antidromically is shown on the left. The onset latency of the antidromically elicited spike varied less than 1 msec. The spike followed frequencies of antidromic stimulation in excess of 100 Hz. The unitary response pattern to 10 V shocks applied once every 2 sec to a pressor site in R.v. is shown on the right side of Fig. 2. As reported previously by Taylor and Gebber 20 for cervical preganglionic neurons, the splanchnic preganglionic unit responded no more than once to each shock applied to the medullary pressor site. The onset latency of the single spike, however, was quite variable ranging from 37 to 104 msec. The probability of discharge of the unit to medullary stimulation was approximately 80 ~. Similar results were obtained from I0 antidromically identified preganglionic units in 3 cats. The variability of preganglionic unitary discharge onset latency in response to medullary stimulation can be explained in at least two ways. First, stimulation of a medullary site might activate a number of different pathways converging onto the same preganglionic unit. The variability of preganglionic unitary discharge onset latency in this case would reflect the number of pathways receptive to activation at any given time as well as conduction time in these pathways. In this regard, the data presented in Fig. 1 suggest that during any given cardiac cycle, a significant number of the individual components of the brain stem vasopressor system and hence a significant proportion of the available pathways to the spinal cord fail to transmit impulses. Alternatively, or in addition, it is possible that the observed variability resulted from random summation of electrically evoked and spontaneously occurring activity transmitted to the preganglionic neuron over a number of different pathways. In this case, the latency of spike initiation would be dependent upon the relationship between the timing of the shock applied to the medulla and the phase of the cycle of spontaneously occuring activity. This investigation was supported by USPHS Grant HL-13187.
146 1 BRODAL, A., The Reticular Formation of the Brain Stem. Anatomical Aspects and Functional Correlations, Oliver and Boyd, London, 1957, 87 pp. 2 BRONK, D. W., FERGUSON, L. K., MARGARIA, R., AND SOLANDT, D. Y., The activity of the cardiac sympathetic centers, Amer. J. Physiol., 117 (1936) 237-249. 3 DOWNING, S. E., AND SIEGEL, J. H., Baroreceptor and chemoreceptor influences on sympathetic discharge to the heart, Amer. J. Physiol., 204 (1963) 471-479. 4 GOOTMAN, P. M., COHEN, M. I., PIERCEY, M . P . , AND WOLOTSKY, P., A search for medullary neurons with activity patterns similar to those in sympathetic nerves, Brain Research, 87 (1975) 395-406. 5 GREEN, J. H., AND HEFFRON, P. F., Studies upon patterns of activity in single post-ganglionic sympathetic fibres, Arch. int. Pharmacodyn., 173 (1968) 232-243. 6 HELLNER, K., UND BAOMGARTEN, R. VON, Uber ein Endigungsgebiet afferenter Kardiovascul~irer Fasern des Nervus vagus im Rautenhirn der Katze, Pfliigers Arch. ges. Physiol., 273 (1961) 223-234. 7 HUMPHREY, P. R., Neuronal activity in the medulla oblongata of cat evoked by stimulation of the carotid sinus nerve. In P. KEZDI (Ed.), Baroreeeptors and Hypertension, Pergamon, New York, 1967, pp. 131-167. 8 KOEPCHEN, H.P., LANGHORST, P., SELLER, H., POLSTER, J., UND WAGNER, P.H., Neuronale Aktivit~t im unteren Hirnstam mit Beziehungen Kreislauf, Pfliigers Arch. ges. Physiol., 294 (1967) 40-64. 9 KOlZUMI, K., SELLER, H., KAUFMAN, A., AND BROOKS, C. McC., Pattern of sympathetic discharges and their relation to baroreceptor and respiratory activities, Brain Research, 27 (1971) 281-294. 10 MANNARD, A., AND POLOSA, C., Analysis of background firing of single sympathetic preganglionic neurons of the cat cervical nerve. J. Neurophysiol., 36 (1973) 398-408. 11 MCCALL, R.B., AND GEBBER, G . L . , Brain stem and spinal synchronization of sympathetic nervous discharge, Brain Research, 89 (1975) 139-143. 12 MIDDLETON, S., WOOLSEY, C. N., BURTON, H., AND ROSE, J. E., Neural activity with cardiac periodicity in medulla oblongata of cat, Brain Research, 50 (1973) 297-314, 13 PITTS, R. F., LARRABEE, M. G., AND BRONI~, D. W., An analysis of hypothalamic cardiovascular control, Amer. J. Physiol., 134 (1941) 359-383. 14 PRZYBYLA,A. C., AND WANG, S. C., Neurophysiological characteristics of cardiovascular neurons in the medulla oblongata of the cat, J. Neurophysiol., 30 (1967) 645-660. 15 SALMOIRAGHI,G. C., 'Cardiovascular' neurones in brain stem of cat, J. Neurophysiol., 25 (1962) t82-197. 16 SCHEIBEL, M. E., AND SCHEIBEL, A. B., Structural substrates for integrative patterns in the brain stem reticular core. In H. H. JASPER, L. D. PROCTOR, R. S. KNIGHTON, W. C. NOSHAY AND R. T. COSTELLO (Eds.), Reticular Formation of the Brain, Little, Brown, Boston, Mass., 1958, pp. 31-55. 17 SELLER, H., The discharge pattern of single units in thoracic and lumbar white rami in relation to cardiovascular events, Pfliigers Arch. ges. Physiol., 343 (1973) 317-330. 18 SELLER, H., AND ILLERT, M., The location of the first synapse in the carotid sinus baroreceptor reflex pathway and its alteration of the afferent input, Pfliigers Arch. ges. Physiol., 306 (1969) 1-19. 19 SMITH, R. S., AND PEARCE, J. W., Microelectrode recordings from the region of the nucleus solitarius in the cat, Canad. J. Biochem., 39 (1961) 933-939. 20 TAYLOR, D. G., AND GERBER, G. L., Sympathetic unit responses to stimulation of cat medulla, Amer. J. Physiol., 225 (1973) 1138-1146. 21 TAYLOR, D. G., AND GEBBER, G. L., Baroreceptor mechanisms controlling sympathetic nervous rhythms of central origin, Amer. J. Physiol., 228 (1975) 1002-1013.
Brain Research, 96 (1975) 142-146 © Elsevier Scientific Publishing Company, Amsterdam - Printed in The Netherlands
The probabilistic behavior of central 'vasomotor' neurons
GERARD L. GEBBER Department of Pharmacology, Michigan State University, East Lansing, Mich. 48824 (U.S.A.,)
(Accepted May 28th, 1975)
Bursts of activity recorded from pre- and postganglionic sympathetic nerve bundles usually are coupled in a 1:1 relation to the cardiac cycle2,3,9,11,13,zl. Yet, with the exception of neurons in the vicinity of the nucleus of the solitary tract 6,8,12, 15,1s,19 which receive direct input from the baroreceptor nerves, attempts to locate brain stem units whose spontaneous discharge is locked to the cardiac cycle have failed 6-8,14,15,19. This observation can be interpreted in at least two ways. First, the failure to locate neurons within the pressor region of the medulla which exhibit a cardiac rhythm in their discharge might be related to a microelectrode sampling problem. Second, absence of a cardiac rhythm in the spontaneous discharges of medullary units might signify that only a small percentage of the total population of brain stem vasomotor neurons participates in each cardiac related burst of activity recorded from peripheral sympathetic nerve bundles; and that the active subpopulation changes from heart beat to heart beat. In this case, it might be possible to identify single vasomotor neurons in the brain stem by determining the probability of their discharge during the phases of the cardiac cycle. This possibility was studied by constructing post-R wave time interval histograms of spontaneously occurring unitary discharge. Experiments were performed on cats anesthetized by the intraperitoneal injection of sodium diallylbarbiturate (70 mg/kg), urethan (280 mg/kg) and monoethylurea (280 mg/kg). The animals were immobilized with gallamine triethiodide (4 mg/kg, i.v.) and artificially respired. Pneumothoracotomy was performed to minimize respiratory related movements. The dorsal surface of the medulla was exposed after removal of portions of the occipital bone and cerebellum. Platinum-coated stainless steel microelectrodes (Transidyne General Corp.) with 1 #m tip diameters and exposed tip lengths of 5 #m were used for extracellular recording of unit discharges from the lateral portions of nucleus reticularis gigantocellularis (R.gc.) and nucleus reticularis ventralis (R.v.). These reticular structures form part of the classical medullary pressor region 2°. Microelectrode tracks were identified upon microscopic examination of 30/zm thick medullary sections prepared with a freezing microtome. Unit discharges were amplified with a capacitance-coupled Grass P511 preamplifier (100-1000 Hz bandpass) and recorded on magnetic tape. Blood pressure, and a timing pulse derived from the R wave of the E K G also were placed on tape. The data on magnetic tape
143
40-!
Z
o
iJ
u
,,
0
POST- R WAVE
I
z
§ ,i C
I N T, m s e c
5OO
' •
u,,Ll L jtJll .LII l i •
| 10
0
INTER,SPIKE
INl,sec
Fig. 1. Spontaneous discharge pattern of medullary unit located in R. v. of medulla (stereotaxic coordinates: P12.0, L2.0, H-8.2). A: phase relations between arterial pulse wave (top) and post-R wave Till of unitary discharge (bottom). Sample run was 8.5 rain. Address bin was 4 msec. Mean blood pressure was 150 mm Hg. B: imerspike interval histogram of unitary discharge (200 spikes).
was fed to a Nicolet computer (Model 1070) and analyzed in the following manner. The sweep of the computer was triggered by the timing pulse derived from the R wave. The computer was programmed to average the arterial pulse wave and to build a unitary post-R wave time interval histogram (TIH). Unit recordings were subjected to window discrimination before presentation to the computer. Single preganglionic sympathetic neurons within the seventh thoracic spinal segment were identified antidromically by stimulation of the splanchnic nerve in a second series of experiments using the method described by Taylor and Gebber 20. Post-stimulus histograms (PSH) of unitary discharge to single shock stimulation of pressor sites in R.gc. and R.v. were constructed. The medulla was stimulated with square wave pulses (10V; 0.5 msec) passed from a Grass $88 stimulator through a stimulus isolation unit to bipolar concentric semimicroelectrodes (David K o p f Instruments, model SNE-100). The phase relations between the arterial pulse and the spontaneous discharges of a single neuron in R.v. are shown in Fig. 1A. The probability of unitary discharge was considerably higher during early and middiastole than during the rest of the cardiac cycle. It is evident from the interspike interval histogram shown in Fig. 1B that the unitary discharge pat'tern was quite irregular. Indeed, the neuron remained quiescent for as long as 18 heart beats. The modal interspike interval was 1.12 sec.
144 SPLANCHNIC ANTIDROMIC
ORTHODROMIC
~;~ o
15
25
o
20
ONSET LATENCY, msec
14o
Fig. 2. Poststimulus histograms (PSH) of the discharges of a single preganglionic splanchnic sympathetic neuron. PSH of unitary responses evoked by antidromic stimulation (8 V; 0.1 msec) of splanchnic nerve is shown on the left. PSH of unitary discharges evoked by single shocks (10 V; 0.5 msec) applied once every 2 sec to a pressor site in R. v. of the medulla (200 trials) is shown on the right. The unit discharged no more than once for each shock applied to the medulla.
The shortest interspike interval was approximately 0.4 sec while the longest interval was 9.6 sec. Six of 38 cells sampled in R.gc. and R.v. (8 cats) showed a relationship between the probability of unitary discharge and the cardiac cycle similar to that depicted in Fig. 1. Although many more than 38 cells were encountered, computer analysis was performed only on those cells whose mean frequency of discharge was below 3/sec (average heart rate). The spontaneous discharges of the 6 cells showing a positive correlation between the post-R wave TIH and the cardiac cycle were inhibited during the rise in blood pressure produced by the intravenous injection (1-2 #g/kg) of norepinephrine (i.e., baroreceptor reflex activation). This observation further suggested that the neurons were contained within a vasopressor circuit. Using cross-correlation analysis, Gootman et al. 4 recently reported on 2 medullary neurons whose spontaneous discharge patterns were similar to those of the whole splanchnic nerve of the cat. The discharge characteristics of one of these neurons suggested that it was functionally located near the efferent outflow of the medullary sympathetic driving network. The discharge frequency of this unit was considerably higher than those of the neurons reported upon in the present investigation. The small samples in both studies, however, precludes a decision on whether the low and high frequency discharging neurons were part of the same or different brain stem sympathetic circuits. The identification of neurons whose spontaneous discharges were not locked in a 1 : 1 relation to the cardiac cycle, but whose probability of discharge was related to the phases of the cardiac cycle supports the contention that only a small and continuously changing segment of the total population of brain stem vasomotor neurons participates in each cardiac related burst of activity recorded from groups
145 of peripheral sympathetic nerve fibers. This observation also raises the possibility that individual preganglionic sympathetic neurons serve as the final common pathway for a large number of brain stem neurons. Although it is difficult as well to find preganglionic neurons which discharge during each cardiac cycleS,10,17,~0, the redundancy of brain stem input would function to enhance the probability of cardiac-related preganglionic unitary discharge. The possibility that individual preganglionic neurons receive excitatory input from many descending pathways was tested on the following assumption. Redundancy, in combination with a continually changing population of brain stem neurons responsive to excitation, should lead to a degree of unpredictability regarding the latency of preganglionic unitary discharge to successive stimuli applied to the same pressor site in the medulla; providing that impulses can be transmitted to the spinal cord over a number of different routes, each having a different conduction time. This assumption seems reasonable in view of the extensive interconnections known to exist between large numbers of reticulospinal neurons at medullary and pontine levels1,16. The preganglionic unitary response patterns produced by stimulation of the splanchnic nerve (antidromic activation) and a medullary pressor site (orthodromic activation) are shown in Fig. 2. The PSH of unitary responses evoked antidromically is shown on the left. The onset latency of the antidromically elicited spike varied less than 1 msec. The spike followed frequencies of antidromic stimulation in excess of 100 Hz. The unitary response pattern to 10 V shocks applied once every 2 sec to a pressor site in R.v. is shown on the right side of Fig. 2. As reported previously by Taylor and Gebber 20 for cervical preganglionic neurons, the splanchnic preganglionic unit responded no more than once to each shock applied to the medullary pressor site. The onset latency of the single spike, however, was quite variable ranging from 37 to 104 msec. The probability of discharge of the unit to medullary stimulation was approximately 80 ~. Similar results were obtained from I0 antidromically identified preganglionic units in 3 cats. The variability of preganglionic unitary discharge onset latency in response to medullary stimulation can be explained in at least two ways. First, stimulation of a medullary site might activate a number of different pathways converging onto the same preganglionic unit. The variability of preganglionic unitary discharge onset latency in this case would reflect the number of pathways receptive to activation at any given time as well as conduction time in these pathways. In this regard, the data presented in Fig. 1 suggest that during any given cardiac cycle, a significant number of the individual components of the brain stem vasopressor system and hence a significant proportion of the available pathways to the spinal cord fail to transmit impulses. Alternatively, or in addition, it is possible that the observed variability resulted from random summation of electrically evoked and spontaneously occurring activity transmitted to the preganglionic neuron over a number of different pathways. In this case, the latency of spike initiation would be dependent upon the relationship between the timing of the shock applied to the medulla and the phase of the cycle of spontaneously occuring activity. This investigation was supported by USPHS Grant HL-13187.
146 1 BRODAL, A., The Reticular Formation of the Brain Stem. Anatomical Aspects and Functional Correlations, Oliver and Boyd, London, 1957, 87 pp. 2 BRONK, D. W., FERGUSON, L. K., MARGARIA, R., AND SOLANDT, D. Y., The activity of the cardiac sympathetic centers, Amer. J. Physiol., 117 (1936) 237-249. 3 DOWNING, S. E., AND SIEGEL, J. H., Baroreceptor and chemoreceptor influences on sympathetic discharge to the heart, Amer. J. Physiol., 204 (1963) 471-479. 4 GOOTMAN, P. M., COHEN, M. I., PIERCEY, M . P . , AND WOLOTSKY, P., A search for medullary neurons with activity patterns similar to those in sympathetic nerves, Brain Research, 87 (1975) 395-406. 5 GREEN, J. H., AND HEFFRON, P. F., Studies upon patterns of activity in single post-ganglionic sympathetic fibres, Arch. int. Pharmacodyn., 173 (1968) 232-243. 6 HELLNER, K., UND BAOMGARTEN, R. VON, Uber ein Endigungsgebiet afferenter Kardiovascul~irer Fasern des Nervus vagus im Rautenhirn der Katze, Pfliigers Arch. ges. Physiol., 273 (1961) 223-234. 7 HUMPHREY, P. R., Neuronal activity in the medulla oblongata of cat evoked by stimulation of the carotid sinus nerve. In P. KEZDI (Ed.), Baroreeeptors and Hypertension, Pergamon, New York, 1967, pp. 131-167. 8 KOEPCHEN, H.P., LANGHORST, P., SELLER, H., POLSTER, J., UND WAGNER, P.H., Neuronale Aktivit~t im unteren Hirnstam mit Beziehungen Kreislauf, Pfliigers Arch. ges. Physiol., 294 (1967) 40-64. 9 KOlZUMI, K., SELLER, H., KAUFMAN, A., AND BROOKS, C. McC., Pattern of sympathetic discharges and their relation to baroreceptor and respiratory activities, Brain Research, 27 (1971) 281-294. 10 MANNARD, A., AND POLOSA, C., Analysis of background firing of single sympathetic preganglionic neurons of the cat cervical nerve. J. Neurophysiol., 36 (1973) 398-408. 11 MCCALL, R.B., AND GEBBER, G . L . , Brain stem and spinal synchronization of sympathetic nervous discharge, Brain Research, 89 (1975) 139-143. 12 MIDDLETON, S., WOOLSEY, C. N., BURTON, H., AND ROSE, J. E., Neural activity with cardiac periodicity in medulla oblongata of cat, Brain Research, 50 (1973) 297-314, 13 PITTS, R. F., LARRABEE, M. G., AND BRONI~, D. W., An analysis of hypothalamic cardiovascular control, Amer. J. Physiol., 134 (1941) 359-383. 14 PRZYBYLA,A. C., AND WANG, S. C., Neurophysiological characteristics of cardiovascular neurons in the medulla oblongata of the cat, J. Neurophysiol., 30 (1967) 645-660. 15 SALMOIRAGHI,G. C., 'Cardiovascular' neurones in brain stem of cat, J. Neurophysiol., 25 (1962) t82-197. 16 SCHEIBEL, M. E., AND SCHEIBEL, A. B., Structural substrates for integrative patterns in the brain stem reticular core. In H. H. JASPER, L. D. PROCTOR, R. S. KNIGHTON, W. C. NOSHAY AND R. T. COSTELLO (Eds.), Reticular Formation of the Brain, Little, Brown, Boston, Mass., 1958, pp. 31-55. 17 SELLER, H., The discharge pattern of single units in thoracic and lumbar white rami in relation to cardiovascular events, Pfliigers Arch. ges. Physiol., 343 (1973) 317-330. 18 SELLER, H., AND ILLERT, M., The location of the first synapse in the carotid sinus baroreceptor reflex pathway and its alteration of the afferent input, Pfliigers Arch. ges. Physiol., 306 (1969) 1-19. 19 SMITH, R. S., AND PEARCE, J. W., Microelectrode recordings from the region of the nucleus solitarius in the cat, Canad. J. Biochem., 39 (1961) 933-939. 20 TAYLOR, D. G., AND GERBER, G. L., Sympathetic unit responses to stimulation of cat medulla, Amer. J. Physiol., 225 (1973) 1138-1146. 21 TAYLOR, D. G., AND GEBBER, G. L., Baroreceptor mechanisms controlling sympathetic nervous rhythms of central origin, Amer. J. Physiol., 228 (1975) 1002-1013.
