THE NEURAL CONTROL OF RESPIRATION 



III7 



speak unequivocally for the existence of a rhythinicalK 

 active inspiratory center. Therefore, the conception of 

 an inherent rhythmicity of a narrowly circumscribed 

 and relatively simply constructed respiratory center 

 has, in general, been abandoned. 



The second possibility — periodic inhibition of a 

 tonically active inspiratory center — represents a 

 plausible working hypothesis. The intervention of an 

 inhibitory or expiratory- center also permits a better 

 explanation of how, under certain circumstances, not 

 only an inspiratory arrest but also an active expiration 

 can take place. Pitts (155) and Wyss (208) have de- 

 veloped, in their detailed review articles, more or less 

 similar conceptions of this intrinsic neuronal mecha- 

 nism of respiration which are also in agreement with 

 newer neurophysiological concepts. 



The inspiratory center in the medulla is tonically 

 active and emits impulses continuously. This would 

 explain why, after a hypocapnic apnea, a tonic base 

 activity develops in the phrenic nerve before any 

 rhythinic activity is observed (206). The apneusis oc- 

 curring after transverse section of the pons can be 

 interpreted as a liberation of the automatically active 

 inspiratory center from inhibitory influences. To sup- 

 port the theory of a primary inspiratory autonomy, 

 stimulation experiments have also been carried out 

 in the nucleus reticularis ventralis (inferior) of the 

 medulla with the result that a strong inspiratory 

 tetany, or a direct facilitation of the phrenic moto- 

 neurons, has been obtained (7, 18, 43, 151, 152, 154). 

 From injection experiments with solutions of bicar- 

 bonate containing carbon dioxide (43), one may con- 

 clude that the nervous substrate with maximal 

 sensitivity for carbon dioxide lies in the region of the 

 inspiratory center. Slow potential waves can be ob- 

 tained from this region under the influence of carbon 

 dioxide (6.5 per cent in the inspired air), even in the 

 fully denervated medulla. These potentials have been 

 designated as 'slow medulla chemopotentials' (124, 

 190, 191). 



This locally originating inspiratory tonus is then 

 modulated through two (155, 163, 164) or three (208) 

 inhibitory processes and transformed into a series of 

 rhythmic events. To begin with, an intramedullary 

 control mechanism must be assumed, since the 

 apneusis which occurs after bilateral vagotomy and 

 transverse section through the pons is transformed into 

 rhythmic respiration by an additional transection 

 through the striae acusticae, caudal to the trapezoid 

 bodies (27, loi, 130). The inspiratory center, as 

 postulated, sends out impulses, descending not only to 

 the motoneurons of the inspiratory muscles but also 



to the bulbar expiratory center, and excites this 

 through as yet undefined connections. Since this ex- 

 piratory center requires a high degree of summation, 

 it takes a certain amount of time before it is suffi- 

 ciently activated. During this time the inspiration is 

 completed. As soon, however, as the expiratory center 

 begins to discharge, the inspiratory center (through 

 an intramedullary process) and the inspiratory moto- 

 neurons (through a bulbospinal tract) become 

 blocked. With a sufficiently high excitation of the ex- 

 piratory center, the expiratory muscles are also 

 excited. For the inspiratory motoneurons this can be 

 looked upon as a form of reciprocal inhibition. With 

 the decrease in the activity of the inspiratory center, 

 the excitatory influence on the expiratory center dis- 

 appears, the inhibitory influences of this center di- 

 minish, and the inspiratory center begins again to 

 send out impul.ses in rapidly increasing succession. 



An experimental proof for such an intrinsic self- 

 regulating loop mechanism as has been described is, up 

 to the present, lacking; and the two assumptions made 

 in the concept of an interneuronic genesis of respira- 

 tory rhythmicity are defined by Wyss (208) as follows: 

 "The one refers to the time lag inherent to the postu- 

 lated interneuronic control, the other is concerned 

 with what may be called the "characteristic" of this 

 control. The latter apparently does not follow a steady 

 course hm shows somewhere a critical level for the 

 inhibition of, as well as for the release from, tonic 

 inspiratory activity. Variations of the rate and depth 

 of breathing would then be accounted for by changes 

 in the reaction time of such as intrinsic control in 

 either direction." 



Corresponding to this intermedullary control 

 mechanism is a second, pontobulbar inhibitory mecha- 

 nism. The pneumotaxic center is believed to be ex- 

 cited either from the inspiratory center in the medulla 

 (155) or from the apneustic center in the pons. Here 

 also it can be assumed that tiie influenceof the pneumo- 

 taxic center inhibits inspiratory activity, but that the 

 influence lasts only so long as a maximal excitatory 

 state prevails in the center. The inhibition of in- 

 spiratory activity can then result either from a block- 

 ing of the apneustic center, so that an activating in- 

 fluence on inspiration is suppressed, or from an 

 intensification of the activity of the inhibitory (ex- 

 piratory) center in the medulla. 



This point of view is supported, above all, b\ the 

 occurrence of apneusis after removal of the pneumo- 

 taxic center through a transection in the cranial third 

 of the pons. Not fitting in with this scheme, however, 

 is the assertion that electrical stimulation of the locus 



