THE RETICULAR FORMATION 



I 291 



these agents when administered to man in appropriate 

 doses have the common property of altering percep- 

 tive experience. 



It is possible that the 'psychogenic' properties of 

 drugs such as LSD relate in general to actions which 

 tend to excite reticular function just as do such stimu- 

 lant substances as epinephrine, acetylcholine, and 

 5-hydroxytrytamine. Amphetamine and other ex- 

 citatory drugs are known to exert a facilitating effect 

 upon the reticular formation (12, 60). LSD, a com- 

 pound somewhat similar in structure and effect to 

 5-hydroxytrytamine induces symptoms characterizing 

 psychotic behavior rather than sleeplessness. Yet 

 LSD dcsynchronizes the EEG as do other excitants 

 such as amphetamine (29). Leake (147) suggests that 

 the direct effect of epinephrine upon the brain is de- 

 pressant, and Marrazzi (173) has demonstrated that 

 it is a powerful synaptic inhibitor when injected into 

 the cerebral circulation. Leake feels that its excitant 

 action upon central ner\ous structures stems from its 

 peripheral action and is .secondary to proprioceptive 

 feedbacks into the Ijrain stem. 



It was proposed initially that chlorpromazine and 

 reserpine exerted an anesthetic-like effect upon re- 

 ticular function (116, 117). Recent evidence, how- 

 ever, indicates that EEG activation to reticular forma- 

 tion stimulation is only slightly altered by these drugs 

 (28, 138), although behavioral arousal from excita- 

 tion of the thalamic portion of the reticular system is 

 somewhat more depressed. The relative inattentive- 

 ness displayed by animals given chlorpromazine may 

 relate principally to its action upon sensory modulat- 

 ing functions of the reticular formation to be described 

 later (11, 138). The increased reticular inputs which 

 are known to attend chlorpromazine administration 

 are thought to enhance caudally-directed inhibitory 

 influences exerted upon afferent conduction (138). 

 This inhibition, coupled with a depressed cephalic 

 influence exerted upon cerebral structures (arousal 

 response), would appear to contribute importantly to 

 'tranquility.' 



The fact that Parkinson-like tremor may be mani- 

 fested following excess chlorpromazine and reserpine 

 ingestion suggests that an action upon the reticular 

 formation may relate to this toxic symptom. Tremor 

 is known to arise when lesions are made (227) or when 

 stimulation is applied (284) to the central brain stem. 

 Drugs such as scopolamine may inhibit tremor by 

 diminishing the cholinergic excitability of the reticu- 

 lar formation. 



DESCENDING INFLUENCES 



It is probable that all motor acti\ity is accomplished 

 through modulation of segmental reflex patterns by 

 inter- and suprasegmental influences (71). Discharges 

 are elicited in the motoneuron, the instrument of the 

 final common path, in response to local .sensory driv- 

 ing, but the primitive purposes subserved by pure 

 reflex activity have required amendment to permit 

 the addition of postural modification and volitional 

 direction to this local phenomenon. Implicit in the 

 process of encephalization is the requirement that a 

 major portion of these calibrating and driving in- 

 fluences emanate from the cephalic or direction end 

 of the modified neuraxis. It is now known tliat the 

 brain mechanisms concerned with postural regula- 

 tion exert their influences in large part through the 

 reticular formation. (See Chapter XLI of the Handbook 

 in which Eldred discusses postural mechanisms.) 



Orthodox concepts concerning the influences of the 

 brain upon tonic muscle function stemmed from the 

 observation that an animal is rendered spastic by a 

 transection of its neuraxis in the midljrain and re- 

 mains .so as more caudally located transections are 

 successively made until the region of the vestibular 

 nuclei is reached. Division of the brain stern just below 

 this level results in the disappearance of spasticity, 

 and following the explanation by Magnus, it was held 

 that the enhancement of tone observed in the decere- 

 brate preparation was maintained by vestibulospinal 

 activity. In 1932, Allen (8) offered an alternative sug- 

 gestion. "On the other hand, it might be explained 

 that the section below Deiters nucleus eliminated all 

 or practically all of the connections of the formatio 

 reticularis of the brain stem." In 1946, documentation 

 of this proposal began to be provided by Magoun and 

 his associates who found that the reticular formation 

 was capable of exerting pronounced facilitation and 

 inhibition upon spinal motor activity. 



Inhibition 



Magoun & Rhines (171, 172) described experi- 

 ments upon decerebrated or anesthetized cats in which 

 movements induced by evoking reflexes or exciting 

 the motor cortex were immediately inhibited or abol- 

 ished when the reticular formation was stimulated. 

 Clearly this inhibition was transmitted by rapidly 

 conducting neurons as its effect reached a maximum 

 after 9 msec. (15). Furthermore, it could be evoked 

 by brief low-threshold shocks of wide frequency range. 

 The descending reticulospinal fibers invoUed are 



