Brain Research, 104 (1976) 341-346
341
© Elsevier ScientificPublishing Company, Amsterdam - Printed in The Netherlands
Powerful inhibition of pontine respiratory neurons by pulmonary afferent activity
JACK L. FELDMAN, MORTON I. COHEN AND PAUL WOLOTSKY Department o f Physiology, Albert Einstein College of Medicine, Bronx, N.Y. 10461 (U.S.A.)
(Accepted December 2nd, 1975)
The abrupt cessation of phrenic nerve discharge, i.e. the end of the inspiratory phase, which is characteristic of a normal respiratory pattern, is produced by interaction of pulmonary afferent (PA) activity, derived from lung stretch receptors, with the activity of brain stem respiratory neuronsT,9,11,14. In the cat, the centrally determined lung volume threshold for production of inspiratory cutoff decreases as the inspiratory phase progressesT, 14. The region of the nucleus parabrachialis medialis (NPBM) in the rostral pons, commonly referred to as the pneumotaxic center (PC) a, 10,20, has been shown to play an important role in determining the volume threshold 14. Previous studies of brain stem respiratory unit activity that were designed to ascertain the central effects of PA activity~,Z,9,16 suffered from certain limitations: (1) unit recording was usually restricted to the medulla and (2) the timing of imposed lung inflation, which produced PA activation, was not coincident with inspiratory discharge. This is in contrast to the situation during normal breathing, in which the timing of events during inspiration leading to PA activity can be described as follows: inspiratory discharge; contraction of the diaphragm and external intercostals; expansion of the lungs; activation of the pulmonary stretch receptors. This sequence can be mimicked in the paralyzed cat by using a respiratory cycle triggered pump (CTP) ~4. The CTP is a phrenic triggered pressure system (using logic circuits and a solenoid valve) that inflates the lungs from a constant pressure source (3-10 mm Hg) during the period of phrenic burst activity and allows the lungs to deflate passively after the cessation of phrenic activity (tracheal pressure trace, Fig. 1). The effect of PA activity on the brain stem respiratory centers can be studied using the CTP by comparing the firing patterns of respiratory neurons during: (a) a respiratory cycle with the CTP on and (b) a cycle with the CTP off. In the latter case there is no inflation and, therefore, no phasic PA activity. Experiments were performed on decerebrate, gallamine-paralyzed cats with pneumothorax. Under halothane or methoxyflurane anesthesia, midcollicular decerebration and partial decerebellation were performed and the C5 phrenic root was dissected. Recording began at least 2 h after the anesthesia was lifted. Efferent phrenic discharge served as an indicator of central respiratory outflow. The phrenic neuro-
342
Phr
Phr
~ 1 sec. Unit Spikes IIIJUII[I
Troth
Jill[ill[
da.
IJ[[l~l~lqtllllllIHL~l
5/~Hg
i ~ 1 sec Unit Spikes I[lllJ H
LillLIlllll
I I
:."
]
Trach ~r ^
:I
I
,,
iJ I " ' ~
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a
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Fig. 1. Polygraph traces of phrenic responses and responses of two units (A and B), located in NPBM, to preventing inflation by the cycle triggered pump (CTP) for one test cycle. Phr: integrated phrenic discharge (leaky integrator, time constant = 0.1 sec). Unit spikes: standard pulses derived from unit spikes. E and I: rectangular steps corresponding to expiratory (E) and inspiratory (I) phases; inflation was applied during I phase. Trach Pr: pressure measured through a transducer attached to the tracheal cannula. gram was used to derive pulses marking the onset of the inspiratory phase (I pulse) and the expiratory phase (E pulse) s. Stainless steel or tungsten microelectrodes were inserted into the brain stem and extracellular recordings were taken of spike activity of isolated units, mainly in two regions: (1) the N P B M in the rostral pons4,12 and (2) the region of the nucleus tractus solitarius (NTS) in the dorsal portion of the rostrai medulla 5,1a. A standard pulse was derived for each spike by use of amplitude and waveform discrimination. At the end of each experiment, the brains were perfused with l0 ~o formalin and the electrode tracks were later located in histological sections. When a brain stem neuron was found which changed its discharge upon removal of inflation in a preliminary test, an experimental series was taken. Each series began with 9 cycles in which lung inflation was controlled by the CTP. In the 10th cycle, the CTP was shut offand no inflation was applied (Fig. 1). This sequence (9 control cycles, 1 test cycle) was repeated 10-20 times. During each series, unit and phrenic activities, tracheal pressure, femoral arterial blood pressure, the I and E pulses, and pulses marking the test cycles, were recorded on magnetic tape. The data were analyzed with an averaging computer (CAT 1000), by deriving cycle triggered histograms (CTHs) a,s of both phrenic and unit activities during (a) test cycles and (b) the control cycles immediately preceding the test cycles. The effect of preventing inflation was to increase the duration of inspiration without changing the slope of the directly integrated (via the averaging computer) phrenic discharge (Fig. 3). This response represented the classical Breuer-Hering reflex, since by not inflating the lungs the inspiratory inhibitory effect of stretch receptor activation, which ordinarily shortens the inspiratory duration, was removed 11.
343 B I00F
20
60 40 20 0
I0
0
O_
~'_
0
~HN..H~.H..,
4 0 0 MSEC
40
C
- -
INFLATION
- -
N O INFLATION
~
INSPIRATION
~
EXPIRATION
~
2001-n,.-n ~,,~q...
~- !
_
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0
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Fig. 2. Cycle triggered histograms (CTHs) of activity of 4 pontine units (A, B, C and D) in the region of the NPBM for two conditions: with inflation (thin lines, lower trace of each pair) and without inflation (thick lines, upper trace of each pair). In this and the subsequent figure, traces were derived from computer averages (bin width = 50 msec) using the I pulses as triggers. Number of cycles averaged A, 15; B, 6; C, 20; and D, 12. A and B correspond to Fig. 1A and B, respectively.
A very dramatic effect of preventing inflation was seen in units of the region of the NPBM (Fig. 1, traces; Fig. 2, CTHs). During control cycles, most of these units had tonic discharges with very weak or no respiratory modulation. In fact, almost none of the tonically firing units recorded in the pons during ventilation with the CTP had a respiratory modulation that could be detected by listening to the audiomonitor, in contrast to the readily audible respiratory modulation of medullary units. During the test cycles, when no inflation was applied, a small fraction of the pontine units (23 of hundreds which were monitored) exhibited a respiratory modulation, i.e., an increase of frequency, often quite marked, above the tonic level. The most common type of modulation seen was of the inspiratory augmenting type (Fig. 2A, B); less commonly, the modulation was of the inspiratory-expiratory (Fig. 2C) or early-expiratory (Fig. 2D) type. In addition, increases of inflation pressure did not produce changes in the pattern of tonic, non-modulated discharge during control cycles. Moreover, the modulation usually started well before the time in the prolonged inspiratory phase corresponding to the time of inspiratory cutoff (dotted lines in Fig. 2) during the control cycles. Since the slope of integrated phrenic activity was the same in control and test cycles, this meant that the modulation in the test cycles began when the value of the integrated phrenic amplitude was significantly less than the peak (end-inspiratory) value during the control cycles. This rules out the possibility of the effect being simply a case of 'recruitment', i.e. that the units recorded were below threshold for modulation when the phrenic amplitude was below the peak control value but were above threshold only when the phrenic amplitude was greater during
344 INFLATION
A Phrj~
- -
NO
INFLATION
B
2oo~sEc~Phr~
t,o
6012,
,-~ Unit
v
30 0
o
h
Fig. 3. CTHs of activity of phrenic (Phr) and of two units (A and B). With inflation: thin lines; without inflation: thick lines. Number of cycles averaged: A, 20 and B, 17. A: unit with a-type response; B: unit with fl-type response.
the test cycles. Therefore, this response represents inhibition of those units by PA activity. The effects of preventing inflation on inspiratory units in the NTS were, in contrast, quite different (Fig. 3). These effects were of two types. (1) Some units responded with changes in firing pattern that resembled the changes in phrenic activity, i.e. when there was no inflation these inspiratory units fired for a longer time and reached a greater maximum frequency, although there was no change in the slope of the CTH (Fig. 3A). These units correspond to those designated as u by earlier workers2,~aJ 6 and which presumably project to respiratory motor neurons in the spinal cord. (2) Other units, in response to the stopping of inflation, commenced firing later in the inspiratory phase and showed a decrease in slope of the CTH, though they reached approximately the same maximum frequency (Fig. 3B). These units correspond to those designated as fl by earlier workers2,13,16, i.e., they have an inspiratory discharge pattern and are also excited by lung inflation; they are thought to be involved in the production of inspiratory cutoff. Since it had been reported that electrical stimulation of the afferent vagi in vagotomized cats produced no change in the activity of respiratory modulated units in the PC (Fig. 13 in ref. 3), the very strong inhibition by the PA of such units found in our study was quite unexpected. It was striking how few respiratory modulated units were seen in the pons of vagally intact cats during respiration by the CTP, in contrast to the large numbers seen in the pons of the vagotomized cat4,1~. Indeed, the respiratory modulation ofpontine units only became apparent by preventing inflation, which eliminated phasic vagal afferent activity. This effect of PA activity perhaps explains the inability of investigators who recorded in cats with intact vagi 6,18 to confirm the findings by Cohen and Wang 12, who recorded many respiratory modulated units in the pons of vagotomized cats.
345 Although the pathway for this inhibition of respiratory modulation in PC units is unknown, the results seem to indicate that the site of the PA generated inhibition is presynaptic to these neurons, in the sense that it lies in an afferent pathway to the PC neurons. This conclusion is based on the finding that we never observed a decrease in the tonic discharge during the time of PA activity in the control cycles. Even when the inflation pressure was increased, there was no reduction of discharge frequency during the inflation. I f the inhibition was acting postsynaptically on these neurons, we would expect to see such a reduction. In the region of the NPBM, lesions result in a significant weakening of the inspiratory cutoff mechanism in cats with intact vagi14,15 and produce apneusis in vagotomized catsSAS,17,19,~0; and electrical stimulation in the N P B M can produce premature inspiratory cutoffa, 10. Moreover, in the vagotomized cat, unit recordings in this region have shown the presence of large numbers of respiratory modulated units 4, 12. Therefore, it is likely that in the vagotomized cat these units play a significant phasic (i.e. respiratory modulated) role in the timing of the respiratory cycle, particularly in the inspiratory cutoff. In the present study, it has been shown that there is a strong inhibition of the respiratory modulation of PC units by PA activity. Therefore, the phasic contribution of PC activity to inspiratory cutoff mechanisms is significantly diminished in cats with intact vagi. Nevertheless, since in this state these units have tonic discharge patterns (with weak or no respiratory modulation), they could still exert a tonic influence on the timing of inspiratory cutoff. This conclusion is supported by the observation that even in cats with intact vagi lesions of the PC result in increases of the volume threshold for the Breuer-Hering reflex 14. Thus, the major extramedullary phasic influence on the inspiratory cutoff mechanism differs between cats with and without vagi, i.e. it is the PA in the former case and the PC in the latter case. However, since cats do not normally exhibit spontaneous vagotomy, the question remains: in what physiological conditions does the potentially phasic activity of PC units become important in the regulation of respiration? This research was supported by U S P H S G r a n t NS-03970. Thanks are given to Keith Benjamin for technical assistance.
1 BATSEL, H., Some functional properties of bulbar respiratory units, Exp. Neurol., 11 (1965)
341-366. 2 BAUMGARTEN,R. VON,AND KANZOW, E., The interaction of two types of inspiratory neurons in
the region of the tractus solitarius of the cat, Arch. ital. Biol., 96 (1958) 361-373. 3 BERTRAND,F., AND HUGELIN, A., Respiratory synchronizing function of nucleus parabrachialis medialis: pneumotaxic mechanisms, J. NeurophysioL, 34 (1971) 189-207. 4 BERTRAND,F., HUGEHN,A., AND Vm~RT, J. F., A stereologic model of pneumotaxic oscillator based on spatial and temporal distributions of neuronal bursts, J. NeurophysioL, 37 (1974) 91-107. 5 BIANCm,A. L., Localisation et 6tude des neurones respiratoires bulbaires. Mise en jeu antidromique par stimulation spinale ou vagale, J. PhysioL (Paris), 63 (1971) 5--40. 6 CAaREGAL,E. J. A., WILUAMS,B., A~D BmzIS, L., Respiratory centers in the dog and squirrel monkey: a comparative study, Respirat. PhysioL, 3 (1967) 333-348.
346 7 CLARK, F. J., AND EULER, C. VON, On the regulation of depth and rate of breathing, J. Physiol. (Lond.), 222 (1972) 267-295. 8 COHEN, M. I., Discharge patterns of brain-stem respiratory neurons in relation to carbon dioxide tension, J. Neurophysiol., 31 (1968) 142-165. 9 COHEN, i . I., Discharge patterns of brain-stem respiratory neurons during Hering-Breuer reflex evoked by lung inflation, J. Neurophysiol., 32 (1969) 356-374. 10 COHEN, M. 1., Switching of the respiratory phases and evoked phrenic responses produced by rostral pontine electrical stimulation, J. PhysioL (Lond.), 217 (1971) 133-158. 11 COHEN, M. I., Phrenic and recurrent laryngeal discharge patterns and the Hering-Breuer reflex, ,4mer. J. Physiol., 228 (1975) 1489-1496. 12 COHEN, M. I., AND WANG, S. C., Respiratory neuronal activity in pons of cat, J. Neurophysiol., 22 (1959) 33-50. 13 EULER, C. VON, HAYWARD,J. N., MARTTILA,I., AND WYMAN,R. J., Respiratory neurones of the ventrolateral nucleus of the solitary tract of the cat: vagal input, spinal connections and morphological identification, Brain Research, 61 (1973) 1-22. 14 FELDMAN,J. L., AND GAUTIER,S., The interaction of pulmonary afferents and pneumotaxic center in control of respiratory pattern in cats, J. NeurophysioL, 39 (1976) 31-44. 15 GAUTIER, O., AND BERTRAND, F., Respiratory effects of pneumotaxic center lesions and subsequent vagotomy in chronic cats, Respirat. Physiol., 23 (1975) 71-85. 16 NESLAND,R., AND PLUM, F., Subtypes of medullary respiratory neurons, Exp. Neurol., 12 (1965) 337-348. 17 ST. JOHN, W. M., GLASSER,R. L., AND KING, R. A., Apneustic breathing after vagotomy in cats with chronic pneumotaxic center lesions, Respirat. Physiol., 12 (1971) 239-250. 18 SALMOIRAGHI,G. C., AND BURNS, B. D., Localization and patterns of discharge of respiratory neurones in brain stem of cat, J. Neurophysiol., 23 (1960) 2-13. 19 TANG, P. C., Brain stem control of respiratory depth and rate in the cat, Respirat. Physiol., 3 (1967) 349-366. 20 WANG, S. C., NGA1, S. H., AND FRUMIN, M. J., Organization of central respiratory mechanisms in the brain stem of the cat: genesis of normal respiratory rhythmicity, Amer. J. PhysioL, 190 (1957) 333-342.
341
© Elsevier ScientificPublishing Company, Amsterdam - Printed in The Netherlands
Powerful inhibition of pontine respiratory neurons by pulmonary afferent activity
JACK L. FELDMAN, MORTON I. COHEN AND PAUL WOLOTSKY Department o f Physiology, Albert Einstein College of Medicine, Bronx, N.Y. 10461 (U.S.A.)
(Accepted December 2nd, 1975)
The abrupt cessation of phrenic nerve discharge, i.e. the end of the inspiratory phase, which is characteristic of a normal respiratory pattern, is produced by interaction of pulmonary afferent (PA) activity, derived from lung stretch receptors, with the activity of brain stem respiratory neuronsT,9,11,14. In the cat, the centrally determined lung volume threshold for production of inspiratory cutoff decreases as the inspiratory phase progressesT, 14. The region of the nucleus parabrachialis medialis (NPBM) in the rostral pons, commonly referred to as the pneumotaxic center (PC) a, 10,20, has been shown to play an important role in determining the volume threshold 14. Previous studies of brain stem respiratory unit activity that were designed to ascertain the central effects of PA activity~,Z,9,16 suffered from certain limitations: (1) unit recording was usually restricted to the medulla and (2) the timing of imposed lung inflation, which produced PA activation, was not coincident with inspiratory discharge. This is in contrast to the situation during normal breathing, in which the timing of events during inspiration leading to PA activity can be described as follows: inspiratory discharge; contraction of the diaphragm and external intercostals; expansion of the lungs; activation of the pulmonary stretch receptors. This sequence can be mimicked in the paralyzed cat by using a respiratory cycle triggered pump (CTP) ~4. The CTP is a phrenic triggered pressure system (using logic circuits and a solenoid valve) that inflates the lungs from a constant pressure source (3-10 mm Hg) during the period of phrenic burst activity and allows the lungs to deflate passively after the cessation of phrenic activity (tracheal pressure trace, Fig. 1). The effect of PA activity on the brain stem respiratory centers can be studied using the CTP by comparing the firing patterns of respiratory neurons during: (a) a respiratory cycle with the CTP on and (b) a cycle with the CTP off. In the latter case there is no inflation and, therefore, no phasic PA activity. Experiments were performed on decerebrate, gallamine-paralyzed cats with pneumothorax. Under halothane or methoxyflurane anesthesia, midcollicular decerebration and partial decerebellation were performed and the C5 phrenic root was dissected. Recording began at least 2 h after the anesthesia was lifted. Efferent phrenic discharge served as an indicator of central respiratory outflow. The phrenic neuro-
342
Phr
Phr
~ 1 sec. Unit Spikes IIIJUII[I
Troth
Jill[ill[
da.
IJ[[l~l~lqtllllllIHL~l
5/~Hg
i ~ 1 sec Unit Spikes I[lllJ H
LillLIlllll
I I
:."
]
Trach ~r ^
:I
I
,,
iJ I " ' ~
|llJll
II
1
a
:
__
Fig. 1. Polygraph traces of phrenic responses and responses of two units (A and B), located in NPBM, to preventing inflation by the cycle triggered pump (CTP) for one test cycle. Phr: integrated phrenic discharge (leaky integrator, time constant = 0.1 sec). Unit spikes: standard pulses derived from unit spikes. E and I: rectangular steps corresponding to expiratory (E) and inspiratory (I) phases; inflation was applied during I phase. Trach Pr: pressure measured through a transducer attached to the tracheal cannula. gram was used to derive pulses marking the onset of the inspiratory phase (I pulse) and the expiratory phase (E pulse) s. Stainless steel or tungsten microelectrodes were inserted into the brain stem and extracellular recordings were taken of spike activity of isolated units, mainly in two regions: (1) the N P B M in the rostral pons4,12 and (2) the region of the nucleus tractus solitarius (NTS) in the dorsal portion of the rostrai medulla 5,1a. A standard pulse was derived for each spike by use of amplitude and waveform discrimination. At the end of each experiment, the brains were perfused with l0 ~o formalin and the electrode tracks were later located in histological sections. When a brain stem neuron was found which changed its discharge upon removal of inflation in a preliminary test, an experimental series was taken. Each series began with 9 cycles in which lung inflation was controlled by the CTP. In the 10th cycle, the CTP was shut offand no inflation was applied (Fig. 1). This sequence (9 control cycles, 1 test cycle) was repeated 10-20 times. During each series, unit and phrenic activities, tracheal pressure, femoral arterial blood pressure, the I and E pulses, and pulses marking the test cycles, were recorded on magnetic tape. The data were analyzed with an averaging computer (CAT 1000), by deriving cycle triggered histograms (CTHs) a,s of both phrenic and unit activities during (a) test cycles and (b) the control cycles immediately preceding the test cycles. The effect of preventing inflation was to increase the duration of inspiration without changing the slope of the directly integrated (via the averaging computer) phrenic discharge (Fig. 3). This response represented the classical Breuer-Hering reflex, since by not inflating the lungs the inspiratory inhibitory effect of stretch receptor activation, which ordinarily shortens the inspiratory duration, was removed 11.
343 B I00F
20
60 40 20 0
I0
0
O_
~'_
0
~HN..H~.H..,
4 0 0 MSEC
40
C
- -
INFLATION
- -
N O INFLATION
~
INSPIRATION
~
EXPIRATION
~
2001-n,.-n ~,,~q...
~- !
_
~,oo~sE,c
30°
f
3O 20 10
I0 1
2c F
vrc~. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
0
~
~F
n
i i i
Fig. 2. Cycle triggered histograms (CTHs) of activity of 4 pontine units (A, B, C and D) in the region of the NPBM for two conditions: with inflation (thin lines, lower trace of each pair) and without inflation (thick lines, upper trace of each pair). In this and the subsequent figure, traces were derived from computer averages (bin width = 50 msec) using the I pulses as triggers. Number of cycles averaged A, 15; B, 6; C, 20; and D, 12. A and B correspond to Fig. 1A and B, respectively.
A very dramatic effect of preventing inflation was seen in units of the region of the NPBM (Fig. 1, traces; Fig. 2, CTHs). During control cycles, most of these units had tonic discharges with very weak or no respiratory modulation. In fact, almost none of the tonically firing units recorded in the pons during ventilation with the CTP had a respiratory modulation that could be detected by listening to the audiomonitor, in contrast to the readily audible respiratory modulation of medullary units. During the test cycles, when no inflation was applied, a small fraction of the pontine units (23 of hundreds which were monitored) exhibited a respiratory modulation, i.e., an increase of frequency, often quite marked, above the tonic level. The most common type of modulation seen was of the inspiratory augmenting type (Fig. 2A, B); less commonly, the modulation was of the inspiratory-expiratory (Fig. 2C) or early-expiratory (Fig. 2D) type. In addition, increases of inflation pressure did not produce changes in the pattern of tonic, non-modulated discharge during control cycles. Moreover, the modulation usually started well before the time in the prolonged inspiratory phase corresponding to the time of inspiratory cutoff (dotted lines in Fig. 2) during the control cycles. Since the slope of integrated phrenic activity was the same in control and test cycles, this meant that the modulation in the test cycles began when the value of the integrated phrenic amplitude was significantly less than the peak (end-inspiratory) value during the control cycles. This rules out the possibility of the effect being simply a case of 'recruitment', i.e. that the units recorded were below threshold for modulation when the phrenic amplitude was below the peak control value but were above threshold only when the phrenic amplitude was greater during
344 INFLATION
A Phrj~
- -
NO
INFLATION
B
2oo~sEc~Phr~
t,o
6012,
,-~ Unit
v
30 0
o
h
Fig. 3. CTHs of activity of phrenic (Phr) and of two units (A and B). With inflation: thin lines; without inflation: thick lines. Number of cycles averaged: A, 20 and B, 17. A: unit with a-type response; B: unit with fl-type response.
the test cycles. Therefore, this response represents inhibition of those units by PA activity. The effects of preventing inflation on inspiratory units in the NTS were, in contrast, quite different (Fig. 3). These effects were of two types. (1) Some units responded with changes in firing pattern that resembled the changes in phrenic activity, i.e. when there was no inflation these inspiratory units fired for a longer time and reached a greater maximum frequency, although there was no change in the slope of the CTH (Fig. 3A). These units correspond to those designated as u by earlier workers2,~aJ 6 and which presumably project to respiratory motor neurons in the spinal cord. (2) Other units, in response to the stopping of inflation, commenced firing later in the inspiratory phase and showed a decrease in slope of the CTH, though they reached approximately the same maximum frequency (Fig. 3B). These units correspond to those designated as fl by earlier workers2,13,16, i.e., they have an inspiratory discharge pattern and are also excited by lung inflation; they are thought to be involved in the production of inspiratory cutoff. Since it had been reported that electrical stimulation of the afferent vagi in vagotomized cats produced no change in the activity of respiratory modulated units in the PC (Fig. 13 in ref. 3), the very strong inhibition by the PA of such units found in our study was quite unexpected. It was striking how few respiratory modulated units were seen in the pons of vagally intact cats during respiration by the CTP, in contrast to the large numbers seen in the pons of the vagotomized cat4,1~. Indeed, the respiratory modulation ofpontine units only became apparent by preventing inflation, which eliminated phasic vagal afferent activity. This effect of PA activity perhaps explains the inability of investigators who recorded in cats with intact vagi 6,18 to confirm the findings by Cohen and Wang 12, who recorded many respiratory modulated units in the pons of vagotomized cats.
345 Although the pathway for this inhibition of respiratory modulation in PC units is unknown, the results seem to indicate that the site of the PA generated inhibition is presynaptic to these neurons, in the sense that it lies in an afferent pathway to the PC neurons. This conclusion is based on the finding that we never observed a decrease in the tonic discharge during the time of PA activity in the control cycles. Even when the inflation pressure was increased, there was no reduction of discharge frequency during the inflation. I f the inhibition was acting postsynaptically on these neurons, we would expect to see such a reduction. In the region of the NPBM, lesions result in a significant weakening of the inspiratory cutoff mechanism in cats with intact vagi14,15 and produce apneusis in vagotomized catsSAS,17,19,~0; and electrical stimulation in the N P B M can produce premature inspiratory cutoffa, 10. Moreover, in the vagotomized cat, unit recordings in this region have shown the presence of large numbers of respiratory modulated units 4, 12. Therefore, it is likely that in the vagotomized cat these units play a significant phasic (i.e. respiratory modulated) role in the timing of the respiratory cycle, particularly in the inspiratory cutoff. In the present study, it has been shown that there is a strong inhibition of the respiratory modulation of PC units by PA activity. Therefore, the phasic contribution of PC activity to inspiratory cutoff mechanisms is significantly diminished in cats with intact vagi. Nevertheless, since in this state these units have tonic discharge patterns (with weak or no respiratory modulation), they could still exert a tonic influence on the timing of inspiratory cutoff. This conclusion is supported by the observation that even in cats with intact vagi lesions of the PC result in increases of the volume threshold for the Breuer-Hering reflex 14. Thus, the major extramedullary phasic influence on the inspiratory cutoff mechanism differs between cats with and without vagi, i.e. it is the PA in the former case and the PC in the latter case. However, since cats do not normally exhibit spontaneous vagotomy, the question remains: in what physiological conditions does the potentially phasic activity of PC units become important in the regulation of respiration? This research was supported by U S P H S G r a n t NS-03970. Thanks are given to Keith Benjamin for technical assistance.
1 BATSEL, H., Some functional properties of bulbar respiratory units, Exp. Neurol., 11 (1965)
341-366. 2 BAUMGARTEN,R. VON,AND KANZOW, E., The interaction of two types of inspiratory neurons in
the region of the tractus solitarius of the cat, Arch. ital. Biol., 96 (1958) 361-373. 3 BERTRAND,F., AND HUGELIN, A., Respiratory synchronizing function of nucleus parabrachialis medialis: pneumotaxic mechanisms, J. NeurophysioL, 34 (1971) 189-207. 4 BERTRAND,F., HUGEHN,A., AND Vm~RT, J. F., A stereologic model of pneumotaxic oscillator based on spatial and temporal distributions of neuronal bursts, J. NeurophysioL, 37 (1974) 91-107. 5 BIANCm,A. L., Localisation et 6tude des neurones respiratoires bulbaires. Mise en jeu antidromique par stimulation spinale ou vagale, J. PhysioL (Paris), 63 (1971) 5--40. 6 CAaREGAL,E. J. A., WILUAMS,B., A~D BmzIS, L., Respiratory centers in the dog and squirrel monkey: a comparative study, Respirat. PhysioL, 3 (1967) 333-348.
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