Effects of state of arousal on click responses in the mesencephalic reticular formation

EFFECTS OF STATE OF A R O U S A L O N CLICK RESPONSES IN THE MESENCEPHALIC RETICULAR F O R M A T I O N P. R. HUTrENLOCHER,M.D. Laboratories of Clinical Science and Neurophysiology, National Institute of Mental Health, National Institutes of Health, Public Health Service, U.S. Department of Health, Education, and Welfare, Bethesda, Maryland

(Received for publication: November 30, 1959) N e u r o n e s located in the nleseneephaiie r,,tieular f o r m a t i o n have been shown to respond to S(qlsory stimuli of various modalities (Anlassian c t a l . 1954; I[ernfindez-Pedn and I l a ? ' b a r l h 1955, Mancia (t al. 1!)57; Ncheib(q r/ ¢/!. 1!)55). W h e n ma(,roeh, etrodes are used slow wave p()tentials are recorded in response t() a u d i t o r y , visual, or somesthetic stimuli ( i,'r(,m,h r! al. 1!)53a). Fren(,h ('l al. (1!)53b), A r d u i . i a.(l A r d u i n i (1954). and Ran(It c! a/. (195S) hay(, shown t h a t these brain stem r~>~})DilNPN ~tFe g r e a t l y diminished followinv' the a(hni.istrati(m ()f various auesthetic a~'e.ts. It Jl;l':, [!oell I)rol)()sud l h a t the sele(.tivo (h'lwessi(m of medial brain stem aetivily by anesth,'ti(, a~'ents forms lhe neural basis (,f lhe ~!nesthetie state. A similar depression of I)rai. stem activity has been postulated Io o.(.ur du]'inv nalural sleep ( F r e n c h ( t al. 1!)52: ,\I()ruzzi a . d Ma~'oun 1949). M~lehne ;ively. Casl)ers (,l al. (1958), in a s t u d y on the habituation of {he arousal reaction in the r , t with i m p l a n t e d electrodes, noted t h a t ltl)pt'r m e s e n e e p h a l i e and t h a l a m i c brain stem rusp(mses at the start of s i m p l e tones persist(.I mwhang'ed a f t e r the tones no lon~er

l)rodue.~d veneral arousal. I n the h)wer mes(,m'cl)halon similar responses generally de(.r(,ased in amplitude.

The present experiments were u n d e r t a k e n 1o stu(|y in (tetail the effects of sleep ()n reSl)Onses to sensory stimuli in the meseneephali(' reticular formation, l'nam,sthetizetl eats wilh implanted electrodes were used. Short clicks were used as s , n s o r y stimuli. Resl)onse:~ to ('lick were recorded f r o m the mesem.(q)hali(, rutieular formation, ( 1 ) clurin~' lhe w a k i . - ' state; (2) during' sh'ep with E E ( I slowing; and (3) d u r i n g sleep wilh h)w voltave fagt E E G activity as described by ])emen~ /I!tSS), Responses i . the u..hh,ar .u('leus wure recorded s i m u l t a . e o u s l y in (.r(h,r t(, oblaiu a measure of lhe variability (.f seusory input (turin~' sleep a.(I arousal. The e h . ' t r o e o r t i c o g r a m was h,d f r o m the aud i t o r y cortex, ihus 1)ermitting (~l)set'vati.)ns o . (wok('d cortical responses (luring' n . t u r a l sh.el). MET [I OI)S A d u l t male eats weighing 2.5 1o 3.5 k~'. were used. Steel electrodes 0.25 ram. in diameter were i m p l a n t e d u n d e r l)entot)arbilal anesthesia, using S h e a t z ' s technique (Sh(,alz, in l)ress',. ] ; i p o l a r recording' (,lectr(.h,s whose tips were 2 ram. al)arl were plae(,d in The meseneel)halic reticular formation at It(,'shg~-(~larke uom'(linates ?k 1 to A4, [~l to I~::, and 1). to l):;. B i p o l a r electrodes were i . s e r i e d into the eochh,ar mleleus al an angle 35 ~) posterior to the vertieal axis, thus enterin~ the skull just a n t e r i o r to lhe insertion . f 1he neck muscles and posterior lo ~he bmiy tentorture. A eortieal l)late electrode was l)laeed on the d u r a overlying' the superior portion (.f the sylvian gyrus. Cortical aetivity was recorded against a reference eleetro(le which was fastened on the occipital erest. E x p e r i m e n t s were s t a r t e d about one week postoperatively. D u r i n g the ni~'ht |)rior Io a

[ 819 ]

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P. tl. HUTTENLOCHER

sleep experiment the eat was kept awake by being plaeed in a slowly revolving drum. The experimental room was partially soundproofed and equipped with a one-way mirror through which the behavior of the animal was observed. During the experiment the eat was u n r e s t r a i n e d in a 2 x 11/2 x 3 foot cage. Pulses p r o d u c e d by a T e k t r o n i x t y p e 161 pulse generator were a m p l i f i e d a n d led to a small loudspeaker which was f a s t e n e d on the top of the cage. The i n t e n s i t y of the r e s u l t i n g elieks was 40-50 db above the threshold of the cochlear nucleus response. A m p l i t u d e was v a r i e d by means of a H e w l e t t - P a e k a r d 350 B attemtator. Click responses were r e e o r d e d on a Grass i n k w r i t i n g oscillograph a n d were also led throuo'h conventional amplifie, rs (time c o n s t a n t 0.1. see.) to a dual beam oscilloscope. ~'[easurements of responses in the eoehlear nucleus were made on p h o t o g r a p h e d oscilloscope traces, since the i n k w r i t i n g oscillograph r e p r o d u c e d these fast responses with considerable rc(luetion in amplitude. P e a k to peal( a m p l i t u d e of responses in the r e t i c u l a r f o r m a tion was m e a s u r e d f r o m i n k w r i t t e n records. B y use of closely spaced bipolar eleeirodes whi~q~ reduced s p o n t a n e o u s b r a i n waves it was possible to obtain i n k w r i t t e n records with easily measurable responses (fig. 3). Clicks were presented in g r o u p s of 50 or more at :/.2 see. intervals. A period of silence lasting for at least 15 rain. was allowed to elapse before a n o t h e r series of clicks was presented. Records of responses d u r i n g the w a k i n g state, d u r i n g sleep with slow waves a n d d u r i n g sleep with low voltage fast activit.v w e r e u s u a l l y obtained on the same (lay, in order to avoid d a y to d a y variations in resp(mse a m p l i t u d e which were occasionally observed. Click responses d u r i n ~ the \vakin~' state u s u a l l y were r e c o r d e d a f t e r the sleep reeords had been obtained. RESULTS [.

Click rc.~po~tses i n the m e s e n c e p h a l i c reticular f o r m a t i o m

Records f r o m w a k i n g animals were taken while the E E G showed low voltage fast activity. a n d while the animals were sitting quietly. U n d e r these conditions click responses in the

reticular f o r m a t i o n consisted of slow waves of 50 to 100 msee. d u r a t i o n a n d of u p to 150 ~V. a m p l i t u d e (fig. 1). I u 7 eats ('licks were presented at 3.2 see. intervals for o . e hour. I n these eats m e a n a m p l i t u d e ot' 50 responses at the b e g i n n i n g of the period ,,f clicks was 61.9 ~V. The mean a m p l i t u d e ,,f 50 responses a f t e r (me hem' of clicks was (;2.!) /,~V. Thus, no h a b i t u a t i o n of responses was observed a f t e r more t h a n ore, lh()usa.(l successive clicks had been presented. W a k i n g eats h a d consistently large b r a i n stem responses to (dicks only whih: sitlin~' quietly. Bo(ty mowmwnts, vocalizing, and licking <)fh,n were a c c o m p a n i e d by marke(l re(h~ction ~)t' these I)otentials. Records ()f sleep with slow waves w('r(' taken while the animals were lying' q u i d l y , and after t h e y ha(t shown larlz(' aml)litmh' sh)w E E G activity for at least 5 m i , . (!li~,ks of the intensity used in the present s i m l y usually did not pr()duee I~E(~ arousal. 1, a few instam,es E E ( I arousal .('(,urred . n presentati,m of the first elicl( ,)t' a seri(,s. I . these eases, habituati(m of lhe arousal re~,,tion (Nharpless a.(l .Jasper 1!)55) I(,o1( pla('e within one t() 3 series ()f (.li(d(s. 1)m'in~' sh,w wave sleep - - in eonlrast to the (luiet waki.,,,' state --- only the firs1 5 to 1l) clicks afler a period of silence eonsiste.tly pr,)(h..ed lara'(, brain stem responses. .~,ubseqm'llt (.li(.ks r~'sultc,d in variabh' a . d ~'em'raIIy smalh'r r,'%pl}/lses,

i [ [ ( ) \ v c v e r , re,~l)O]lSeS \ v e r e i i ( ' v e r ,~e(,i,

to d i s a p p e a r eomplet('ly, ('v~'n at'h'r s~'veral h u n d r e d (~o.seeutiv(. (.li(.ks. l"i~'llr(' 2 shows mean a m p l i t u d e of resp,mse~ lo 50 ('o.~e(-lltive clicks in (g animals. In em'h (,ase, l/l(' first (.li(.k was presented ~,t't(,r a period of silem'e lastin~z 15 rain. or h)nger. The meal, aml)liiude of response to lhe t'irs~ 5 ('li(.ks is .~een to be ahnost as lar~'(, ;~ duriHK ih,, (lui,l waking' state, but r(,sp(ms(,s l(, ~ut)se(tu(uM (.li(.ks show r a p i d lmbituali()n, alld al'l('r 10 elieks the a m p l i t u d e of r(,~l)(m,~(,s has (h,(,reased to about 50 per (.('nl of r('slmns(' size iu wal
The d i f f e r , ' , . . ( '

1)(.lw~',,.

the curve of re~ponse~ (luring' tl., waki.-" state a n d t h a t of sleep wiih sl()w waves i~ statistically significant (1) <0.()1, using 1t,(, sign test).

STATE OF AROUSAL AND CLICK R E S P O N S E S

I n 6 cats, click responses in the mesencephalic reticular f o r m a t i o n were studied during sleep with low voltage fast E E G activity. All 6 animals readily demonstrated this phase of sleep. The E E G d u r i n g " f a s t activity s l e e p " was indistinguishable f r o m a waking E E G (fig. 3), but behaviorally the cats a p p e a r e d deeply asleep with head resting on forepaws and eyes closed. R h y t h m i e move-

821

shows that mean responses to the first 5 clicks a f t e r a period of silence are only about 55 per eeut of responses in waking animals. The difference between these two points is statistically significant (p ~ 0.025, using a one tailed t-test). Mean responses to subsequent clicks are seen to decrease r a p i d l y to about 20 per cent of response size in waking animals. F i g u r e 4 shows response amplitudes during

Fig. 1 Ten superimposed traces of click responses in auditory cortex (first vertic:d row~, in mesenceplmlic reticular formation (second vertic~d row) ~Jnd in cochlear nm.leus (third vertical row); A. Responses during the quiet waking state; P,. Responses during sleep with slow waves; C. Responses during sleep with low voltage fast EEG activity. In each case many clicks had been presented before the record was taken. Cortical responses :,re re(.orde,I unipohlrly, positive up. t/rain stem and e~chlear responses ;ire reeorde(1 with closely Sl,:lc(',l bipolar electrodes.

m e a t s of limbs were occasionally noted. During sl,,ep with low voltage fast E E G activity suppr,,ssion of ,dick responses in the mesencephalic reticular formation was considerably more marked than during sleep with slow waves. This is illustrated in the superimposed traces of figure 1, and in the g r a p h of mean responses for 6 eats in figure 2. F i g u r e 2

sleep with low voltage fast aetiviiy in one cat. I t is seen that several large responses occur during the first 10 elicks, hut therea f t e r m a n y clicks result in no nieasurable responses, or in responses of small amplitude. Arousal of the animal (at arrow) is accompanied by immediate r e t u r n of large (dick responses. A u d i t o r y stimuli were llsually

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v . R . HUTTENLOCHER

used for arousal, but the same effect was seen on several occasions during spontaneous awakening. All cats used in the above experilnents were also studied under pentobarbital anesthesia. Pentobarbital (30 m g / k g . ) produced depression of click responses in the mesencephalic reticular formation comparable lo that reported by other authors ( F r e n c h c t a l . 1953b). Responses to new stinmli were depressed as well as responses to repeated stimuli.

on any one day) no evidence of habituation of cochlear nucleus responses was obtained. Habituation of these responses after several hours or days of clicks has been reported hy tlernhndez-Pe6n and Scherrer (1955), IIern~ndez-Pe6n, Jouvet and Schcrrer (1957) and (]alambos ctal. (1956). I n the l)resent sludy,

A

II. Click responses in the cochlear nucleus. Click responses in the cochlear nucleus consisted of several fast spikes up to about 1.5 inV. in amplitude. F i g u r e 1 shows superimposed oscilloscope traces of cochlear nu90

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I n k w r i t t e n records of a c t i v i t y on a u d i t o r y c ort e x ( u p p e r t r a c e s ) a n d in m e s e n c e p h a l i c r e t i c u l a r forma t i o n (lower t r a c e s ) . A Record is t a k e n d u r i n g (inlet w a k i n g s t a t e ; B. D u r i n g sleep w i t h slow w a v e s ; (?. D u r i n g sleep w i t h low v o l t a g e f a s t E E G a c t i v i t y . Clicks a re r e p r e s e n t e d by m a r k e r on lower line. I n t e r v a l between clicks is 3.2 see.

60 ~ 5o

a transient decrease in the amplitude of cochlear nucleus responses was often seen during body movemeuts, vocalizing and licking. Cochlear nucleus responses recorde(1 durlug slow wave sleep and during sleep with low voltage fast aetivily did not differ in

30 20 I0 0

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CLICKS

Fig'. 2 M e a n : m q ) l i l u d e of click responses in the mese n c e p h a l i c r e t i c u l a r f o r m a t i o n to 50 consecutive clicks a f t e r a p e r i o d of silence. Solid circles = awake, 8 cp.ts. T r i a n g l e s = sleep w i t h slow waves, 8 cats. Open circles = sleep w i t h low v o l t a g e f a s t E E G a c t i v i t y , 6 c'tts. V e r t i c a l b a r s r e p r e s e n t ___ one s t a n d a r d ('rror of ln(~l/ll.

cleus responses in one cat. Similar spikes were obtaincd in all seven cats in which cochlear nucleus electrodes had been implanted successfully. Responses from the cochlear nucleus were very constant in the quiet waking state. D u r i n g the relatively short runs of clicks employed in the present study (up to about one hour of clicks at 3.2 see. intervals

I

A m p l i t u d e of click responses in the cochlear nucleus (in #V.) d u r i n g the w a k i n g s t a t e a nd d u r i n g sleep. E a c h f i g u r e ret)resents tile me a n of 50 c(tnsecutive resI)o uses.

Cat No.

11288 259 429 479 559 5159 659 Me a n

Awake Control

Sleep With Slow Waves

14(i! °48 837 1130 1040 234 818

155 207 721 1320 1060 242 822

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8.6 16.5 13.9 16.8 1.9 3.4 o5

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Sleep W'ith I~lsl Activi:v

131 :215 S13 115[) 102() 231 .q(15

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0.2

STATE OF AROUSAL AND (HACK R E S P O N S E S

amplitude or form from those recorded during the quiet waking state (fig. 1, table l). Small unexplained day to day variations in resl)ouse size oecurred in some of the cats. Sim.e in several instances it was impossible to obtain records of all three states of arousal within a short period of time, some of these hmg-h,rm variations appear in table I. For instance, the slow wave record of eat 479 (table 1) was obtained several days after the waking and " f a s t activity sleep" records. I t is evident from table [ that these small varialions in response size are unrelated to the stale of arousal of the animal. 120

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D u r i n g the quiet waking state, the first few clicks after a period of silence usually resulted in a cortical response consisting of two fast positive spikes followed by a t)iphasie, (negative then positive) slow wave. The slow wave components often showed habituation when several hundred successive clicks were presented, althongh this was not invariably the case. Furthermore, after habituation had occurred there often was " s p o n t a n e o u s " r~'appearance of slow wave components durin~ the same series of clicks. Iiabitualion of the slow w a v e c o m p o n e n t s o f tile cortical resl)(ms~' to click has recently been reported by (b~lamI

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Fig. 4 Amplitude of click responses in the meseneephalic reticular formation during sleep with low voltage fast activity and daring arousal. First click was presented after :t period of silence, nnd while the ear's EEG and behavior were characteristic of sleep with low voltrm'e fast activity. Animal was aroused at arrow.

] [[. (!lick rcspo~tses on auditory cortex. Aualysis of the effect of sleep on cortical responses was made difficult by the fact that these responses showed marked variations during the waking state. There was no "typi~,al" control response in waking animals with which responses d u r i n g sleep could be compared. The late slow wave components of the response showed the greatest variability. Therefore, only rough qualitative comparisons were nlade.

bos and Sheatz (1959). Figure 1 straws the slow wave components during the wakiug state. ]n the same figure it is seen that during sleep with E E G slowing there is inem'ased variability of the two fast positive spikes of tile eortical response. The late slow waves are reduced in amplitude. I)uring sleep with low voltage fast E E G activity, the fast positive spikes resemble those seen in tile waking animals, but there is absence of the slow waw, components of the response. Marked redue-

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P. R. HUTTENLOCHER

t i o n or absence of the slow w a v e c o m p o n e n t s d u r i n g sleep was observed i n all 8 animals. ANATOMICAL FINDINGS

Electrode location was verified aimtomically in all cats. The brain stem electrodes were located in the u p p e r meseneei)halie reticular formation in all 8 cats from which large brain stem responses to click had been recorded (fig. 5). Several cats had two electrode positions in the reticular formation, and in these cases both are included in the figure.

Fig. 5 Cross section of brain stem at level of superior colliculus. Electrode positions are indicated by triangles. All positions were within -± 2 ram. anterior or posterior to the section. S.C. superior collieulus. C.P. cerebral peduncle. R.N. red nucleus. M.L. medial lemniseus. Electrode tips located in the superior colliculus, near the medial lemniscus and in the substantia nigra, did not yield slow wave responses to clicks. Cochlear nucleus electrodes were in the ventral cochlear nucleus in 2 eats a n d in the dorsal cochlear nucleus in one cat. F o u r eats had bipolar electrodes in both dorsal and ventral nuclei. Cortical electrodes were placed near the superior border of the sylvian c y r u s in all eats. DISCUSSION

These experiments indicate that the response of the meseneephalie reticular formation to sensory stimuli varies with the state of arousal of the animal. D u r i n g natural sleep there is a significant decrease in amplitude of brain stem responses to repeated clicks. A t the same time, cochlear nucleus responses remain constant, while alterations of the evoked

cortical potentials are confined to the late slow wave components. These results confirm the suggestions of Magoun and coworkers ( F r e n c h et al. 1952; Moruzzi and Magoun 1949) that during sh, e p - - a s d u r i n g the anesthetic s t a t e - - t h e r e is selective depression of activity in the nonspecific afferent system. Behaviorally, natural sleep differs from the anesthetic state in m a n y respects. Most important, is the fact that during natural sleep the animal can be aroused. ()he would therefore expect differences between the effects of sensory stimuli on activity in the mesencephalie reticular formation during natural sleep and during anesthesia. Several such differences were found in the present study. I)uring natural sleep, the first few (dicks after a period of silence consistently evoked large brain stem potentials. Rapid habituation of responses occurred when repeated clicks were presented. Anesthesia, on the other hand, depressed resl)onses to both m,w and repeated stimuli. D u r i n g slow wave sleep suplu'ession of brain stem potentials was never as complete as it was during moderately deep anesthesia. Responses were variable during sleep, while during anesthesia the)" were uniformly depressed. Almost eonlplete suppression of evoked brain stem potentials was found to occur during sleel) with low volta~'e fast E E G activily. The oeeurrem, e of h)w voltage fast E E G m,tivity durino" behavioral sleep in eats has r('(~ently been described by 1)ement (1!)58). A similar E E G pattern is t're(luen|ly observed during slee 1) in man, where it is asso(date(t with a higql incident[, of dreamin,.,' (Dement and Kleitman 1!)57). [)ur data show that during sleep with low w)lta,z'e fast E E G m,tivity, gross responses to sensory stimuli in uOnSl)eeific afferent 1)athways are considerably decreased. A decrease in ~'ross responses probably indicates that nero'(real discharge in response to the sensory stimuli is diminished; lhe me~,hanism of such decrease in evoked dis(,har~es (-mmot be definitely inferred from nm(,roelectrode reeordimz's. The possit)ili~y exists that during sleep with low v()llage fast EE~I activity there is generalized depression ()f neuronal activity in nonspecifie afferent pathways, similar to that ocenrin~" durin~ the ate-

STATE OF AROUSAL AND CLICK RESPONSES esthetic state and t ) r e s u m a b l y d u r i n g sleep w i t h slow w a v e s (Machne ct al. 1955). H o w ever, depression of activity in the nonspecifie

a f f e r e n t system is generally thought to be associated with E E G slow waves, and the " a r o u s e d " E E G d u r i n g sleep with low w)ltagc fast activity therefore remains unexplai,ed. A second possibility deserves to be eonsidered. D u r i n g sleep with low voltage fast a(,tivity, neurones in the nonspecific a f f e r e n t system m a y discharge at a high rate and r , sponses to sensory stimuli m a y be suppressed by occlusion. On anatomical gromlds, one would expect occlusion to p l a y a considerable role in the functioning of the ascendin-' reti(-ular system si.ee there seems to he considerabh, convergcnee of a f f e r e n t input of various modalities on single cells (Seheib~q r! al. 1955). ()eehlsi(m p r o b a b l y operates duri . g l h . suppression of brain stem respons,s 1(~ s,,nsory stimuli in excited and attentive waking' animals as reported by Hern[mdezl ' e d , ~t al. (1!)57) -rod as also seen in the I)res,,nl experiments. ('li('k responses in tile cochlear nueleus wore similar in form, amplitude and duration to those reported in acute p r e p a r a t i o n s b y Rosmd)lith (1!)54) and by J u n g e r t (1,()58}. The.~e responses persisted ulmhanged din'in/ mttural sleep, suggesting' that ill the a u d i t o r y syst(,m sensory input does not v a r y with (,hanges in state of arousal. A decrease in the size of ~'ochlear mwleus responses was often ,(m,d while the animals were moving about, vocalizing, or licking'. This finding is similar to ohservations made by IIernfindez-Pedn, ,%.horr.,r and Jouvet (1956). ('li(,k responses ()n p r i m a r y a u d i t o r y c o t rex showed redm,tio, in the late slow wave emnponents duri,o' sleep. According to Marshall cl al. (1943~ and B r e m e r (1953) the negative slow wave of the cortical response is a measm'e of efferent impulses which activate secon(lary sensory areas and motor nuelei inm,rvating e a r nluseles. I t therefore a p p e a r s that (lurin~ sleep there is a decrease in the spread of activity f r o m p r i m a r y a u d i t o r y cortex to association and motor areas. Buser and Borenstein (1959) have recently r(,corded a long latency slow wave response to eli(d( from s u p r a s y l v i a n association cortex

~25

which is most p r o m i n e n t during drowsiness and which disappears during strong arousal and during E E G slowing. This finding provides f u r t h e r cvidence that spread of activity f r o m p r i m a r y a u d i t o r y areas varies with the state of arousal of the animal. SUMMARY

Click responses hi the mesencephalic reticular formation, the cochlear nucleus and the p r i m a r y a u d i t o r y cortex were studi~d during sleep and wakefulness in eats with implanted electrodes. The following observations were made : 1. D u r i n g the quiet waking state, click responses in the nlesencephalic reticular formation consisted of slow waves of up to 150 /~\*. anlplitude which persisted undiminished after more t h a n one thousand eonseeutivc clicks. 2. During sleep with E E G slow waves, habitnatitm of responses in the mcseneephalie reticular t'ornmtion oeenrred a f t e r only 5-10 clicks, llesponses became variable and mean amplitn(le of responses deereased to about 50 per ~'ent of response size in waking animals. 3. l ) u r i n g sleel) with low voltage l'asl E E ( I activity, there was ahnost e(m~plete suppression of brain stem responses to repeated eli('ks. 4. II~'sponse in the cochlear nucleus did not v a r y with (,hanges in state of arousal. 5. Click responses on p r i m a r y au(lilory ('ortex persisted during sleep except fro" a decrease in the late slow w a v e ~.ol~llmlle~ltS o f the response. The results suggest that during natm'al sleep there is depression of activity in lhe tmnspeeifie a f f e r e n t system, while activity in prim a r y auditory p a t h w a y s remains unehano'ed. The depressi(m of aetivity in the nonspe('ific afferent systenl d u r i n g sleep differs in several respects f r o m that ohserved d u r i n ~ the anesthetic state. ~g:SL'g~:: Des r6p()nses ti des elies enregist%es dans la formation r6ticul6e m6senc6phalique, le noyau eoehl6aire et dans le eortex auditif primaire ont 6t6 ~tudi6es p e n d a n t le sommeil et l'~veil chez des ehats p o r t e u r s d'61eetrodes implan%es. Les observations suivantes ont (~t~ faites :

826

P. R. tIUTTENLOCHER

1. P e n d a n t l'6tat d'6veil au repos, les r6ponses ?~ des clies enregistr6es dans la formation r6ticul6e m6sene6phalique consistent en des ondes lentes d ' u n e amplitude, j u s q u ' h 150 ~V. qui persistent d ' u n e faeon non-diminu6e aprbs une %p6tition de plus d ' u n mille elies eons6cutifs. 2. P e n d a n t le somnleil earact6ris6 p a r un E E G eontenant des ondes lentes, l ' h a b i t u a t i o n des r6ponses dans la f o r m a t i o n r6tieul6e m6sene6phalique se produisait aprhs seulement 5 h 10 clies. Les r6ponses devenaient variables et l ' a m p l i t u d e moyenne des r6ponses diminuait jus(tu'i~ une valeur eorrespondant '~ 50 per cent de l ' a m p l i t u d e des r6ponses enregistr6es ehez les animaux 6veill6s. 3. P e n d a n t le sommeil caraet6ris6 p a r un E E G de bas voltage contenant de l'aetivit6 rapide, la r6ponse aux elies enregistr6e darts le trone e6r6bral 6tait presque eompl~tement supprim6e. 4. Les %ponses enregist%es (tans le noyau (!oehl6aire ne variaient pas en raison de l%tat (1 '6veil. 5. l~es r6ponses aux elics enregisir6es dans le cortex auditif primaire persistaient pend a m le sommeil exception faite p o u r m~e dimimltion de l'onde lente tt longue latence faisant p a r t de la r@onse. Ces r & u l t a t s sugg6rent que p e n d a n t le sommeil naturel il y a d6pression de l'aetivi% dn systbme aff6rent non-sp6cifique tandis que l'aetivi% dans le systbme auditif sp&ifique demem'e inehang6e. Cette d6pression d'aetivit6 dans le systbme aff6rent non-sp6cifique pr6sente p e n d a n t le sommeil diffbre dans plu.qeurs aspects de la d6pression observ6e pendant l ' O a t d 'anesth6sie. ZUSAMMENFASSUNG

Katzen mit implantierten Elektroden zur Re~istrierun~ von A n t w o r t e n auf Klieks im Mittelhirn-Retikulum, im Nucleus eochlearis und in der primiiren HSrrinde, wurden im ,%~hlaf und W a c h z u s t a n d untersueht. Polgendes wurde ge~ehen : 1. h n ruhitzen W a e h z u s t a n d bestanden die Antworten anf Klieks im Mittelhirn-RetikuInto arts langsamen ~Vellen mit A m p l i t u d e n bis zu 150 /.V., welehe selbst naeh iiber tausend Klicks, persistierten ohne kleiner zu werden.

2. lm Schlaf mit langsamer E E G - A k t i v i tiit t r a t eine H a b i t u a t i o n im Mittelhirn-Retikulum bereits nach 5 bis 10 Klieks auf. l)ic Antworten wurden veriinderlieh und die mittlere Amplitude verkleinerte sM1 auf etwa 5 0 G derjenigen bet wachen Tieren. 3. Im Sehlaf mit niedergespannter, sehneller E E ( , - A k t l ~ l t a t versehwanden die I l i r n stamm-Reizantworten auf wiederhollc Klieks fast viillig. 4. Antworten im Nucleus coehlearis w~riinderten sieh nieht mit ver:dnderten Waehzustan(t. 5. Antworten auf Klieks in der primiiren Hih'rinde persistiert(m im Sehlaf, die sp:d|e lantzsame Komponente wurde jedoeh ldeiner. Die Ergebnisse leg'en nahe, dass im natiirliehen Schlaf eine I:nterdriiekmlg yon Aktivitht im unspezifis(qwn afferenten System stattfindet, wiihrend (tie Aktivitiit im prim:,iren IISrsystem unver'hndert bMbt. ]lie Unterdriiekun~ der Aktivit:,it im niehtspezifis('hen afferenten System im %l,hlaf isl in mehrfaeher Ilinsieht vers('hieden yon (h'rj(,nitzen w,q('he in Narkose gesehen wird. T h e a u t h o r wishes to t h n n k ])r. E d w a r d V. E v a r t s for his advice a n d i n t e r e s t t h r o u g h o u t the stud.v, nnd for his review of tile manus('ript. R E F E R E N(~E.~ AMASSIAN, V. E. a n d DEVVPO, R. V. U n i t activity in r e t i c u l a r f o r m a t i o n "had n e ' t r b y s t r u c t u r e s , d. Ne,trophysiol., 1954, 17:575 ~03. ARDUINI, A. a n d ARDUIXI, M. G. E f f e c t of d r u g s and metabolic a l t e r a t i o n s on b r a i n stem a r o u s a l m e c h a n i s m . J. Pharmaeol., 1954, 11!9: 76-85. BREMER, F. SO?}IC P r o b b ' m x of Nc~trophy.~iology. L o n d o n Univ. P r e s s , 1953. BUSER, P. et ~ORENSTEIN, P. Rdponses somesthdsiques, visuelles et :/u,litivcs, reeueillies ,'tu nivenu du cortex <> s u p r n s y l v i e n ehez le chat curaris6 non anesth6si6. EEG Clin. Nc,roph?/siol., 1:959, 1 I : 2 8 5 - 3 0 4 .

CASPER,q, H., LERCI1E, E. lind GRUETER, ][. Adal*tions e r s c h e i n u n g e n der a k u s t i s c h ausgelSsten ~Veekrcaktion bet R e i z u n g m i t d e f i n i e r t e n T o n i m p u l s e n . Pfliiger's Archiv, 1958, 267 : 128-141. DEMENT, W. The occurrence of low v o l t a g e f a s t eh.etroeneephalogram patterns d u r i n g behavioral sleep in tlle eat. EEG Clin. Ne~lrophyxiol., 1958, 10: 291-296. I')EMENT, W. a n d KLEITMAN, N. Cyclic v a r i a t i o n s of E E G d u r i n g sleep mid their relation to eye movem e n t s , body motility and d r e a m i n g . EE(; Clin. Ne~wophysiol., 1957, 9: 673-690.

STATE

OF AROUSAL

AND CLI(!K RESPONSES

FRENCH, g. D., VON AMERONGEN, F. K. and MAGOUN, 1t. W. A n a c t i v a t i n g s y s t e m in b r a i n s t e m of monkey. A.M.A. Arch. Neurol. Psychiat., 1952, 65 : 577-590. ]~'I/EXCI[, J. D., VERZEANO, M. a n d MAGOUX, H. W. An e x t r a l e m n i s c a l s e n s o r y s y s t e m in t h e brMn. A.M.A. Arch. Neurol. Ps)eh+iat., 1953a, 6.9: 505,51~.

I'~REXCII, J. J).~ VERZEANO~ ~{. and ~IAGOUN~ H. V. A n e u r a l bqsis of t h e a n e s t h e t i c state. A.M.A. Arch. Neurol. Psyehiat., 1953b, 6 9 : 5 1 9 529. GALA51BOS, R. "rod SHEATZ, G. C. Evoked cortb;al q u d i t o r v rcst)onses. Fed. Proe., 1959, 18: 49.

{]ALAMBOS, ~/~.~ SHEATZ, (]. and VERNIER~ V. G. E]octrophysiological correlqtes of a conditioned sponse in cats. Science, 1956, 123: 37(;-377.

re-

HERN~.NDEZ-PEON, R., G['ZM.~_N-FLORES, C., ALCARAZ, M. till(1 }'ERN.~NDEZ-GUARDIOLA~A. S e n s o r y transmission in visual pathw-ty d u r i n g " a t t e n t i o n " in m m n e s t h e t i z e d eats. A cta Neurol. Lati~oamrr., 1957, 3: 1-8. IIEI~N.~NDEZ-PE(~N, R. qn(t IIAGI~ARTft, K . - E . I n t e r a c tion between a f f e r e n t a n d cortically indm-ed reticular responses. J. Ncurophysiol., 1955, 18: 54-55. I{EICN.;~Xl)EZ-I)E6N, }~., JOUVET, M. a n d SCItERRER, H. A u d i t o r y p o t e n t i a l s at cochlear n u c l e u s d u r i n g acm~stie h a b i t u ' l t i o n . Aeta Neurol. Latinoamer., 1957, 3: 144-156. I[ERN,(XDEZ-])EI~N, R. ~llld SCHERREI¢, H. " I l a b i t m l t i o n " to acoustic s t i m u l i in coeMear nucleus. F t d . Proc., 1955, 2-i: 71.

tIERN:~NDEZ-t)EdN, R., SCHERRER, H . . ' t n d JOUVET, M. M o d i f i c a t i o n of electric a c t i v i t y in cochlear nu-

~4~7

cleus d u r i n g " a t t e n t i o n " in u n a n e s t h e t i z e d eats. Science, 1956, 123 : 331-332. JUNGERT, S. A u d i t o r y p a t h w a y s in the brain stem. A neurophysiologieal study. Acta O~o-Laryngologica, Stockholm. Suppl. 133, 1958. MACHXE, X., (':XLXtA, I. a n d MAGOUN, It. W. U n i t activity of central cephalic brain s t e m in E E G qrousal. J. Neurophysiol., 1955. I3: 547-55,q. MANCI% M., MECHELSE, K. a n d MOLL1CA, A. Microelectrode recording f r o m m i d b r a i n reticular formqtion in the decerebrate cat. Arch. ital. bioh, 1957, 95:1 l w l l g . ~IARSIIALL, W. ]1., TALBOT, S. A. a n d ADEF,, I|. W. (!ortical resl)onse of the a n e s t h e t i z e d c'tt to tzross photic a n d electrical a f f e r e n t s t i m u l a t i o n . ,1. Nvurophysiol., 1943, 6: 1-15. ~IORUZZI, (i. and MAGOUN, H. W. Brain stem reticul:,r f o r n m t i u n a n d a c t i v a t i o n of the E E G . El';(; Clin. Nc,rophysiol., 1949, 1: 455-473. RAND'f, 1'. T., (JOLL1N*'Z,, W. P., DAVIS, I[. S. and I)ILI.ON, W. It. l ) i f f e r e n t i a l susceptibility ()f a f f e r e n t p a t h w a y s to a n e s t h e t i c q g e n t s in t h e cat. Amcr. J. I'hysiol., 1955, t92: 305-310. ~OSENI;LITI[, \¥. A. Electrical responses from au,litory nervous system. +Inn. Olol. Rhinol. Larjlngoh, 19514, 6d: 8:~9-861. SCHEIIIEL, M., SCItEIBEL~ A., MOLLICA, A. and MO: RITZZI, (}, (~onvergenee "/ll(l inter:,d:ion of qt'f e r e n t impulses on single u n i t s of reticular formation. ,l. Neurophysiol., 1955, 1S: :~()9 331. SHARPLESS, S. all(| JASPEg, t[. H a t ) i t u a t i o n of lhe a r o u s a l reaction. Brain, 1956, 79: q;55.6bl(k SH~:ATZ, G. In: Electrical Stimulation of the Brahe. U n i v e r s i t y of T e x a s Press, A u s t i n (in pr,,ss).

R~ference: tII;TTENLOC!IER, P. R. E f f e c t s of s t a t e of a r o u s a l on click responses in the mesencephalic reticul.,r formation.

EEG Clim Neurophysiol., 1960, 17,: 819-827.