THE CEREBELLUM 



255 



various sources may occur at precerebellar levels. 

 There is also ample evidence that a high degree of 

 convergence occurs within the cerebellar cortex 

 itself (108, 140, 177, 179, 320). Bremer & Bonnet 

 have devoted a series of studies to the manner of 

 interaction between the surface negative v^'aves 

 which may be recorded from the unanesthetized 

 animal in good general condition following stimula- 

 tion of many afferent sources (28, 38, 39, 41). The 

 negative wave of the test responses is completely 

 occluded at very short test intervals, is facilitated at 

 slightly longer intervals and undergoes subnormality 

 at still longer intervals, whether the initiating sensory 

 volleys come from similar sources or from sources as 

 widely different as cutaneous and auditory. Con- 

 vergence and interaction of impulses initiated by 

 sensory and cerebral corte.x stimulation have also 

 been demonstrated by Albe-Fessard & Szabo using 

 surface leads (3, 321) and intracellular leads {4). 



Cerebellar Activity as Allerrd by Drug Actions 



Since cerebellar neurons, seemingly to a greater 

 extent than other neurons, are susceptible to nar- 

 cotics, anesthetics and other depressing agents, the 

 following section will emphasize the actions of ex- 

 citatory agents. 



TOPic.'>iL .APPLICATION. The high-voltage synciironized 

 spikelike potential wave produced by strychnine 

 topically applied to the cerebral cortex is a dramatic 

 and easily reproducible event which has been studied 

 and utilized as an investigative tool by many. The 

 original observation of KornmuUer (175), confirmed 

 by Dow (106) and all subsequent investigators, that 

 strychnine applied to the surface of the cerebellar 

 cortex does not produce hypersynchronous dis- 

 charges cannot be regarded as evidence that strych- 

 nine does not stimulate cerebellar neurons. The most 

 direct evidence of the excitant effect of strychnine 

 has been furnished by the records of single cerebellar 

 neurons in convulsive activity as a result of strych- 

 nine (51, 52). Cerebellar neurons, normally in tonic 

 discharge, alter their pattern of activity under the 

 influence of strychnine. The affected units go into an 

 interrupted burst of discharge in which the frequency, 

 initially within normal limits, rises progressively to 

 abnormally high values of 400 to 500 per sec. before 

 the termination of the burst. The diminution of spike 

 amplitude at the higher frequency near the termina- 

 tion of the burst suggests that the interval between 

 impulses becomes shorter than the refractory period. 



The abrupt cessation of the burst with very small 

 spikes suggests that the burst is self-terminating by 

 virtue of hyperdepolarization. After a variable re- 

 covery period, the sequence is repeated and con- 

 tinues to be repeated until the strychnine is removed. 

 Less direct evidence of the stimulant effect of strych- 

 nine is supplied by the observation that the negative 

 component of the evoked surface potential, related 

 to the discharge of Purkinje cells, is augmented by 

 strychnine (28, 42, 44). And finally. Miller's observa- 

 tion (207, 208) that muscular tonus and posture may 

 be altered by local application of strychnine to the 

 surface of the cerebellum has been confirmed many 

 times (200, 286, 297). It has also been recorded that 

 the discharge frequency of cerebellar neurons may be 

 augmented by the local application of acetylcholine 

 after pretreatment with physostigmine (90). Surface- 

 negative responses of the cerebellar cortex, which 

 Grundfest & Purpura ascribe to dendritic activity, 

 are said to be eliminated by (/-tubocurarine (141 J. 



SYSTEMIC .ADMiNisTR.\TioN. Although the local appli- 

 cation of strychnine to the cerebellar cortex does not 

 produce the surface potential changes characteristic 

 of convulsive activity, the intravenous administration 

 of strychnine to curarized animals is followed by the 

 dramatic appearance of low-frequency (10 to 30 per 

 sec.) high-voltage (o.i to 0.4 mv) rhythms which 

 have been termed cerebellar convulsions or cerebellar 

 tetanus (42, 44, 143, 170, 171, 201-203, 289). Al- 

 though it was first considered that these outbursts 

 were truly representative of cerebellar convulsions, 

 it has been conclusively demonstrated by Bremer and 

 his colleagues that they are, in fact, the result of af- 

 ferent volleys impinging on the cerebellar cortex 

 from the convulsing spinal cord and brain stem (42, 

 44). The.se conclusions are derived from the follow- 

 ing considerations. The effect of intravenous strych- 

 nine on the spinal cord is the initiation of outbursts 

 of rhythmic convulsive activity of frequency of 10 to 

 30 per sec. Each tetanic wave at the cerebellar sur- 

 face has a time course which is similar to that pro- 

 duced by an afferent volley arriving at the cerebellar 

 cortex. The tetanic waves are localized to the bulbo- 

 spinal projection areas of the anterior portion of the 

 cerebellum. Evoked potentials and tetanic waves 

 show mutual interaction. The phase reversal upon 

 leading from the depths of the cerebellar cortex is 

 similar for tetanic waves and evoked potentials. Local 

 pentobarbital and asphyxia may abolish the negative 

 components of both the tetanic waves and evoked 

 potentials without affecting the positive components 



