THE RETICULAR FORMATION 



1289 



60, 123, 124). The critical contributions sucii sub- 

 stances make to visceral mechanisms are well es- 

 tablished. Chemoreceptors in great vessels and brain 

 mechanisms regulating respiratory and cardiovascular 

 phenomena have long been recognized to be sensitive 

 to variations in circulating carbon dioxide. Only 

 lately, however, has it been recognized that this 

 metabolite exerts a prominent stimulating effect upon 

 the reticular formation (60) and an enhancing effect 

 upon cerebral circulation (124). That the influence 

 is direct rather than reflex is indicated by the ob- 

 servations of von Euler & Soderberg (273) who 

 noted that vigorous discharge was elicited in units 

 of the deafferentiated caudal brain stem by ventilat- 

 ing the animals with 6.5 per cent carbon dioxide. 

 Moreover, Dell (60) described augmented firing 

 in reticular units of a brain stem completely isolated 

 by transections at the postmammillary and pre- 

 trigeminal levels, and presumably this metabolic 

 excitation is exerted upon the entire reticular forma- 

 tion. By contrast, oxygen was found to have an in- 

 hibiting effect upon the reticular formation and this 

 influence appeared to be mediated exclusively through 

 carotid body reflexes (60). 



The role of epinephrine and of acetylcholine has 

 long been studied in the peripheral autonomic system, 

 but adrenergic and cholinergic mechanisms have only 

 recently been found to participate importantly in 

 functions subserved by the reticular formation. It has 

 been demonstrated that EEG arousal can be induced 

 by administrations both of acetylcholine and cholin- 

 ergic and anticholinesterase drugs {26, 28, 60) and 

 of epinephrine as well as adrenergic drugs (24, 26-28, 

 60). The fact that adrenergic and cholinergic sub- 

 stances both excite the reticular formation has led 

 Rothballer to suggest that separate brain-stem mecha- 

 nisms respond to each agent (232) and Vogt has been 

 able to find epinephrine and acetylcholine in differ- 

 ential amounts at various loci in the neuraxis (269). 

 These agents appear to act directly upon the reticular 

 formation (24, 60) as well as upon structures repre- 

 senting more cephalic extensions of it, for Porter 

 has described EEG activation of the posterior hypo- 

 thalamus in response to circulating epinephrine (216). 

 Moreover, Sawyer has reported that anticholinergic 

 and antiadrenergic agents each block neurogenic 

 stimulation of the release of pituitary gonadotrophic 

 hormone (236). 



There can be little doubt that these neurohumors 

 act directly upon reticular systems and hence upon 

 structures which are activated alternatively or ad- 

 ditionally through neural pathways. Reticular unit 



discharges have been induced equivalently by in- 

 jections of epinephrine, by hypoxia (through the 

 carotid chemoceptor reflex) and by stimulation of 

 the lingual nerve (60), indicating convergence from 

 both neural and humoral sources. Arousal of the 

 EEG evoked by neurohumors is the consequence of 

 their action upon the brain stem rather than the 

 cortex, for desynchronization to epinephrine does not 

 occur in animals with intercoUicular decerebration 

 (60). Bonvallel el al. (24) suggest that arousal to 

 noxious stimuli has a dual .source: the initial rapid 

 desynchronization is thought to be mediated by 

 neural excitation of the reticular formation, while 

 slower epinephrine activation serves to perpetuate 

 arousal. Thus, reticular stimulation by either neural 

 or humoral agencies is capable of inducing cortical 

 activation through common reticulocortical path- 

 ways. Perhaps such corticipetal conduction can itself 

 be mediated by humoral mechanisms for, following 

 reticular formation stimulation, Ingvar has ob- 

 served EEG desynchronization in the cortex com- 

 pletely isolated from the rest of the brain. Caudally- 

 oriented reticular formation influences are equally 

 sensitive to humoral excitation, for Dell has shown 

 that the myotatic reflex in decerebrate animals is 

 facilitated by epinephrine administration and in- 

 hibited by carotid sinus stimulation (60). Also Sigg 

 et al. (248) demonstrated that adrenal medullary 

 substances can excite or inhibit cortically induced 

 movement through action on the reticular formation. 

 Clearlv, then, these dual excitatory influences must 

 compliment each other in eliciting all of the responses 

 which result from reticular formation activation. 



Drug Effects 



ANESTHESIA. When the reticular formation is de- 

 stroyed or injured either in animal or in man, the 

 subject is rendered comatose, insensitive to stimuli 

 and, except for reflex responses, immobile (76, 78, 

 81). Because the administration of anesthetic agents 

 induces such behavioral changes reversibly, it might 

 be presumed that these drugs exert a selective effect 

 upon the reticular formation. In general, available 

 information has shown this postulate to be true, 

 although depressant drugs are known to affect other 

 neural regions as well as the central brain stem. 



Evidence has been presented by Larrabee & 

 Posternak (145) and reviewed extensively by Brazier 

 (31) which indicates that anesthetic agents exert 

 a blocking effect upon synaptic transmission to a much 

 greater extent than upon nerve fiber conduction 



