Effects of brainstem lesions on tonic immobility in the rabbit (Oryctolagus cuniculus)

Brain Research

Bulktin,

Vol. 10, pp. 127-135, 1983.Printed in the

U.S.A.

Effects of Brainstem Lesions on Tonic Immobility in the Rabbit (Oryctolagus cuniculus) CLAUDE School of Psychology

and Department

M. J. BRAUN AND R. T. PIVIK’ of Psychiatry, Received

University of Ottawa, Ottawa, Ontario, Canada

12 April 1982

BRAUN, C. M. J. AND R. T. PIVIK. Effects of brainstem lesions on tonic immobility in the rabbit (Oryctolagus cuniculus). BRAIN RES BULL IO(l) 127-135, 1983.-Lesions were placed in discrete brainstem areas implicated in the generation of both tonic immobility (TI) and paradoxical sleep (PS) to examine postulated state and event correspondences between these states in the rabbit. Lesions were concentrated in the region of the nucleus locus coeruleus (LC)-an area implicated in the mediation of muscular atonia during PS-but also included other reticular (pontine gigantocellular tegmental field: FTG), and nonreticular (vestibular, cerebellar, central grey, collicular) areas. Polygraphic recordings of EEG, EMG and EOG activities were taken during sleep-waking states and measures of the TI response were obtained before (1 day prior) and after (5 and 14 days) lesions were made. None of the lesions was followed by a sustained, significant variation in either frequency of induction or duration of TI. Following LC lesions, and to a lesser extent after FTG lesions, sleep patterns were fragmented, with a reduction or absence of PS and the occurrence of phasic motor activation at times when PS periods might be expected to occur. The absence of PS and persistence of TI following specific brainstem lesions indicate a fundamental difference in mechanisms underlying these states. It is suggested that a major determinant of these results is the activation of phasic activity during PS but not TI, and that the possibility remains that both states may share a common mechanism of tonic motor control. Tonic immobility

Paradoxical sleep

Brainstem lesions

TONIC immobility (TI) is a spontaneously reversible state of inactivity characterized by a loss of righting reflexes and decreased responsiveness to sensory stimulation. The re-

sponse has been described as a hypnotic state of sedation [8] or an innate fear reaction [ll, 12, 381. The widespread phylogenetic representation of the TI response [lo, 13, 161 would seem to attest to its biological significance, yet other than the suggestion that, in nature, immobility has survival value accruing from the lifeless appearance of the organism [ 16,351, no generally accepted explanation of the biological significance of this behavior has been advanced. In an effort to localize brain structures responsible for this phenomenon, lesions, generally involving extensive tissue destruction, have been placed in a variety of central nervous system (CNS) structures. These lesion studies have indicated that only structures caudal to the pons are required for the TI response to occur [6, 27, 361. Klemm [21,23], on the basis of stimulation and multiple-unit recordings, designated the ponto-medullary reticular formation as the probable site for TI control. It is notable that this same brainstem region contains structures (gigantocellular tegmental field: FTG; nucleus locus coeruleus: LC) implicated in the generation of paradoxical sleep (PSta state which, in addition to requir-

ing the integrity of this brainstem area for state occurrence [5,19], shares with TI characteristics of high cortical arousal [ 1,7] and tonic motor activity [33]. Among these state correspondences, similarities in motor phenomena are particuimpressive. For example, homonymous and larly heteronymous monosynaptic and polysynaptic reflexes are markedly depressed or absent in both states [3, 4, 341. Furalthough previous reports [3,3 1] indicated thermore, hypotonia during both PS and TI, a recent study of quantified nuchal EMG in rabbits activity failed to reveal sustained atonia in either state [33]. There are, as well, important dissimilarities between PS and TI. These consist largely of the absence of phasic muscular and autonomic variations of PS during TI [3,4,22], higher frequency hippocampal theta activity during PS [ 141, and the spontaneous ultradian periodicity of PS but not TI. Although the noted dissimilarities rule out state identity between PS and TI, they do not exclude the possibility of a mechanism of tonic muscle control common to these states. This possibility seems all the more plausible in view of the demonstrated involvement of the LC in tonic motor phenomena of PS [15, 18, 20, 371 and the presence of this nucleus in the brainstem region essential to TI occurrence.

‘Requests for reprints should be addressed to R. T. Pivik, Psychophysiology Hospital, 501 Smyth Road, Ottawa, Ontario, Canada KlH 8L6.

Copyright 0 1983 ANKHO International

Laboratory,

Department

of Psychiatry,

Inc .-0361-9230/83/010127-09$03.00/O

Ottawa General

BRAUN AND PlVIK

12x

The present study was therefore conducted to determine the effects of localized brainstem lesions in the region of the LC on TI and PS in the rabbit. METHOD

Thirty-two adult male New Zealand White rabbits ((irvt,tola~us cupzicths; 2.7-3.8 kg) were housed in a temperature (22°C) and humidity (54%) controlled holding area. Lighting (100 lux) was maintained on a 12-hr cycle and food and water were provided ad lib. Polygraphic recordings were obtained under conditions identical to those maintained in the holding area.

Rabbits were implanted with electrodes for chronic recording of cortical EEG, EGG, and nuchal EMG activities using a modified stereotaxic apparatus and anesthetic procedures previously described [32,33]. Stainless steel cannuiae (24 mm long, 1.2 mm outside diameter), through which the radio frequency lesion probe was to be lowered, were stereotaxically aimed at brainstem nuclei and implanted with cannulae tips Positioned 2 mm above each target. Animals were routinely administered antibiotics during recovery from surgery and recuperated at least I week prior to pre-lesion recordings. Lesions were effected by a single descent of an electrode (David Kopf, Model RFG-4 lesion generator) through which a 500,000 Hz sinusoidal pulse was passed for 60 set under thermal regulation (60°C). The presence of previously implanted cannulae as guide tubes for the radio frequency elcctrode permitted the placement of lesions without anesthesia. Following this procedure the cannulae were capped and animals recovered for 5 days with 5% dextrose and Ringer lactate solutions injected subcutaneously as required.

Tonic immobiiity responses were elicited following sl~e~w~efulness recordings at approximately 5:Qo p.m. 1 day prior to, and 5 and 14 days after placement of lesions. In a subsample of 15 rabbits, polygraphit recordings of TI were obtained simultaneously with the behavioral measurements mentioned above. Tonic immobility was induced in the manner described by Klemm 1221. Specifically. the forelimbs were held in one hand, the hind~imbs in the other, and the anirn~s abruptly dorsoflexed (180” whole-body rotation in a dorsal direction) and gently deposited into a level V-shaped trough. The trough, routinely used to stabilize the animal during TI, does not restrict movement, and TI episodes always terminated with spontaneous righting. Each TI episode was timed and silence was maintained during TI testing. Ten episodes of TI were induced per session except when unusu~y lo~-l~ti~ TI episodes occurred. In such instances a ~nimum of five episodes was induced. Since repetitive induction of TI may stress the animals [26], a S-min rest period was given each time 5 min had elapsed regardless of whether one or several episodes had been induced. No episode was ever interrupted. During the 5-min rest period the animal was returned to the recording cage. Six-hour poiygraphic recordings (from IO:00 to 16:OOhrf of spontaneous sleep and waking were scored independently by two individuals. one blind with respect to recording con-

dition (interscorer agreement: ~195%). Records were categorized by visual analysis of .?o-set epochs into four states: waking(W). drowsiness (II), slow wave sleep (SWS). and paradoxical sleep (PS). A fifth behavioral category occurring in post-lesion records and termed phasic activation (P) was also scored. This state occurred predominantly following episodes of SW sleep and was cha~ct~~~e(i by de synchronized EEG and abrupt, intense outbursts of motet activity. Wakefulness, SWS and PS were scored according to generally accepted criteria [33]. Drowsiness was defined by the presence of isolated spindles (less than three per epoch). stable EMG, and absence of phasic EGG activity.

Subsequent to completion ot‘ data acquisition, animals were perfused (intercardiac) with 0.9% sodium chloride and 10% Formahn solutions, and brains were removed and scc-

tioned (frozen 28 F coronal sections stained with cresyi violet). Localization and evaluation of the lesions were based on three atlases, namely those of Fifkova and Marsala 191. M&ride and Klemm [27]. and Meesen and Qlszewskii [2X].

Pr+Lt~.siott kklinys Mean pre-lesion TI duration was 144 set (SD=63 set). Ot the total number of attempted TI inductions in intact (preof failures (<8 set Tf lesion) rabbits. the mean percent duration) was 17.25% (SD= 15.32%). Physical restraint is known to potcntiate Tl duration, and since the cable attachments required for polygraphic recordings during TI might facilitate such restraint, comparisons of TI duration with and without cable attachments were made. However, for the 15 animals in which such re~ordjn~s were made, mean values for the presence or absence of cables (160.36 and 187.38 set, respectivety) were not significantly different (pbO.25, Friedman test). Pre-lesion polygraphic measurements and behavioral aspects of TI in this investigation resembled data from previous reports in intact animals [3,24]. except that in the present investigation nuchal muscle tonus remained elevated during TI (Fig. 1). An analysis of the relationships between sleep-waking states and TI conducted on pre-lesion data indicated that the amounts of time spent in different states of sleep and waking were not significantly correlated with mean durations of TI (Table 1). However, animals which spent more time in slow wave sleep and less time awake did tend to manifest longer episodes of TI.

On the basis of histological locahxation of lesions animals were grouped into four categories, namely: (a) an “LC” group (n= I tf with H?W%bitateraI ~~~~~~on of the IX: (b) a partial-LC (“PLC”) group (n= i 1) in which only a portion (3040%) of the LC nuclei, namely the caudal tn=S1, later4 (n-2), lateral-caudal (n=2), dorsal (n= 1) and dorsalcaudal LC (n= I) were destroyed; (c) a reticular(R) group (n=S in which bilateral lesions were lociflized to the nucleus reticular& pontis caudalis (NRPC. n-3) or &he nucleus reticularis pontis orahs (NRP0, n= 1) or both (n- f). Ali five lesions completely spared the LC; and, (di a non_~ticular (NR) group (n=5) in which lesions were centered on nonreticular structures, namely the vestibular nuclei (n-2). the

129

6

SECS

FIG. I. Continuous poiygraphic recordings of an episode of tonic immobility. Note that nuchal EMC activity is sustained throughout the episode. A 2-Hzotfactory rhythm is present in the anterior derivations. The isolated deflections occurring in the SEOG channels (upper tracings) and alte~at~~g in both EGG channels in the rower-tidings may represent a rare occurrence of eye movement during TX. At the time these ~e~ec~~o~~occurred the animal was not under direct visual observation and consequently the deviations could not be verified as eye movement. W=waking; TI=tonic immobility; A-EEG=anterior electroencephalo~r~; C-EEG=central EEG; P-EEG==posterior EEG; A-EOG=anterior electrooculogram; S-EOG=superior EOG; ~~G~nucka~ ele~tromyog~m. Two sets af nuckal EMG derivatjons art: represented. TI onset and spontaneous termination are indexed by vertical arrows in upper and lower tracings, respectively. Verticat calibration bars==50 gv.

BKAUN

P 13

AND PIVLK

P 13

P 14

P

13

Pl4

FIG. 2. Schematic tracings of brainstem lesions categorized in the reticular(R) gruup. Abbreviations for this figure and Fig. 3 are as follows: BC, brachium ~o~~cti~m: BP, b~bium pbntis; CC, central gXey:.C_TEG, centrai tegmen~al tract; IXQC, floccubnodular tobe; 10, inferior olive: IX, Ioeus coeruIcUs: LX lateral ~stl~~~ar nucleus: RA, raphe nuclei; RGC, reMRF, m~ull~ reticular fo~a~on; MV, rn~~~ vestibule nucleus; PY, putrid; tic&-is pontis gig~to-ce~ul~s; RX, ~et~c~~ pontis caudalis, * RPO, ~etjcut~s Tpontis oralis; SC, superioi nucleus: T, t~a~~o~~ IV. c~Iliculus; So, superior olive; SpV, spinal ves~u~~ Lucius; SV, superior ves~~I~ trochiear nucleus: V. trigeminal nucleus: VII. facial nerve: GVII, genu of facial nerve: WI. auditcrry nerve.

BRAINSTEM

LESIONS

131

AND TONIC IMMOBILITY

sm

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FIG. 3. Schematic tracings of brainstem lesions categorized in the nonreticular (NR) group. See Fig. I caption for identification of structure abbreviations.

HRAUN

132

P 13

P 13

P 14

P 14

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LC OROUP. LC

4. Schematic

tracings

of brainstem

lesions

categorized

Gmuf? in the locus

coeruleus

P 13

P 13

P 13

P 14

P 14

P 14

FIG.

5. Schematic

tracings

LLC (LC) group.

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AND PIVIK

BRAINSTEM

LESIONS

133

AND TONIC IMMOBILITY TABLE

1

CORRELATIONS (PEARSON r) BETWEEN THE SUMMED SPENT IN EACH STATE PER RECORDING

TIMES

1 Day Pre-Lesion (N=32) State

D

SW

PS

TI

W D SW PS

-.16

-.87* ~ .06

-.07 -.38; -.26

-.29 -.08 2s .14

W=waking, D=drowsiness, SW=slow wave sleep, PS= paradoxical sleep, TI=tonic immobility; *p
I I

3

200

z 5 n

100

LC central grey matter (n= I), the colliculi (n= 1) and the cerebellum (n= 1). None of these lesions involved the LC. Examples of lesions from these groupings are illustrated in Figs. 2-5.

A temporary syndrome of adipsia, aphagia and diarrhea was observed following lesion placement in all animals. In two NR animals diarrhea persisted until the time of sacrifice. Animals with LC lesions lost approximately one kilogram of weight during the first post-lesion week, and remained at that level for the survival period. Animals with other reticular and nonreticular lesions had regained normal weight levels by the 14th post-lesion day. Vegetative functions behaviorally monitored in this study (respiration, micturition, defecation, eating and drinking) appeared normal 4-5 days following the lesions in all cases except two (NR-I and PLC-1 I) in which respiration remained labored but not apneustic until sacrifice I4 days post-lesion. No dystonias, ataxias, or other abnormal movements were observed during waking in animals with LC lesions. Not unexpectedly, these behaviors were present in animals with lesions involving the vestibular system and cerebellum. Lesions centered on the NRPC produced persistent motor abnormalities. Spastic neck dystonia was present in two animais, and dystaxia was observed in a third. The lesion involving the NRPO and the rostra1 part of the NRPC did not produce obvious motor abnormalities. Though rabbits with LC lesions were less well kempt than they were prior to the procedure, grooming was observed in all LC animals by the 14th day post-lesion. In only one animal (NR-I) with lesions involving all four colliculi, was grooming not observed post-lesion. All animals became relatively inactive immediately following the lesions, but activity levels returned to pre-lesion levels within the first week post-lesion. Lesion Effwts

$

5 DAYS POST

on Slerp- Wukefdnccw Patterns

A detailed consideration of variations in sleep patterns after LC lesions is presented elsewhere [2]. However, a brief summary statement of the effects of the various lesions on PS will be presented to provide a basis for PS-TI comparisons. Lesions of areas included in the NR group did not significantly alter PS. but post-lesion PS was reduced or absent after LC and NRCP (“R” group) lesions. The degree of PS

PLC

R

NR

GROUP FIG. 6. Duration of tonic immobility response before and after brainstem lesions. The broken-line tracings in R group data represent the addition of data from one animal with unusually long TI episodes at the 5-day post-lesion interval.

60, g

50. PLC LC

R I

I DAY PRE-LESION

5 DAYS 14 DAYS POST-LESION

FIG. 7. Tonic immobility induction failure rates (percentage of total induction attempts) before and after lesions in each group.

reduction after LC lesions was proportional to the amount of LC destroyed. Intense phasic motor behavior occurred in post-lesion recordings of animals with lesions localized to both LC and R lesion categories, but only minimally in the latter group. Effwts

of Lesions on Tonic Immobilit>

No signi~cant changes in TI duration were observed in any group post-lesion [group by interval repeated measures analysis of variance (UCLA Medical School BMDP2V program) conducted after logarithmic transformation of data]. Although there was a marked increase in mean duration of TI 5 days post-lesion in the reticular group (Fig. 6), these effects were not statistically significant. This increase in mean TI duration was due entirely to the results of one animal, (R-31),

RRAUN AND PIVlK

134

in which the lesion involved the caudal NRPO and the rostra1 NRPC. The cont~bution of data from this animal to the group data is indicated in Fig. 6. The effect, moreover. was transient and TI duration in R-31 dropped below baseline level 14 days fallowing the lesion. Tonic immobility-industion failure rates (Fig. 7) clustered between 10 and 20% at baseline for each group, increased five days post-lesion in all but the R group (comb~ued group mean=38. I groups SDS ~gi~ from 33.21 to 43.22%) and became qdite variable by 14 days post-lesion (combined group mean=34.11%, groups SDS ranging from 14.5 to 40.3(X%). None of these effects was statistically significant. Pre-lesion TI was ch~~te~~d by the absence of phasic activity (i.e., bursts of eye movements, muscle twitches. cortical spikes, etc.) and by cortical EEG syn~b~ni~tion except in unusuaUy long episodes in which high voltage slow waves appeared. These phenomena persisted following LC lesions except in two cases (LC-6, LX-8) in which a few ~xception~y long episodes of TI lasting more than 20 min contained episodes of syn~hron~~d EEG followed by phasic muscular activation. These brief moments of abrupt motor activation were a~comp~ied by low voltage cortical EEG activity, but eye movements were not observed. These phasic episodes did not result in termination of the TI state (i.e., initiation of righting reflexes), but were followed by EEG slow waves and tonic motor activity. In general a~eement with previaus reports based on less specific lesions, [6,25] lesions of nonreticular cerebellar and vestibuiar areas did not have a marked effect on TI duration. However, since such lesions were foliowed by Ihe most marked increases in failure rate of all lesion areas, an involvement of neural elements in these NR areas may be indicated in the induction of TI.

The localized lesions of the pontine reticular formation (mG) and tegmentum (LC and PLC) have added new information regarding neural re~~iation of TI. The most marked reductions in all aspects of the TI response, includes induction failure, and duration and variability in episodes, were effected by FTG lesions. These findings provide empirical support for previous su~estions of core intone-reti~uIar control of TI [25]. Pontine tegmentai lesions, however. did not have great impact on TI duration, although again, as with NR structures, induction failure rate increased following these lesions. In reviewing results of transection studies in the rabbit, Klemm [25] reported an increase in nuchd EMG activity in association with lesions passing through the posterior pons-an area which would have included the LC region. However, since increased EMG activation was not apparent in our post-lesion LC or PLC TI recordings, the increased EMG activatjo~ Kiemm observed must involve st~~tures or pathways other than those compromised by lesions in the present study. It is well established that neurons in both the FTG and LC regions have extensive ascending and descending connections to central nervous system areas of motor control. and that dest~~tion of these pontine regions results in increased motoric activation. For example, following lesions of these regions in the cat there is increased waking motor activity, e~mination or reduction of p~dox~~ sleep, and disruption of sleep by intense outbursts of motor activity (17, 18, 20, 301. In view of these dramatic motoric consequences of le-

sions in these areas-effects which are largely present in the rabbit as well [2l---it is remarkable that such lesions do not have more severe consequences for the TI response than those observed. However. much of the difficulty in assessing the effects of manipulations on this state derives from the extreme response lability preseslt even under baseline conditions 1251. In this regard the effects of FTG lesions on global aspects of the TI response, altb~ugh not statistic~i~y . ‘ficant, may indeed indicate an irn~)~ant rote for this in TI control. The relative absence of effects of LC lesions on TI has implications reaping neur~hemi~~ regulation of this behavior. Since the LC is a major site of noradrenai~ne synthesis, lesions of this structure effect a marked decrease in CNS noradrenaline, The post-lesion survival period in the present ex~~ment was chosen to allow sufficient time for depletion of noradrenaline from LC terminals. However. since clusters of noradrenergic ceil bodies are present outside the LC (e.g., in the lateral t~entum~, even with complete LC destruction the involvement of a norad~en~~i~ rnech~~sm in TI cannot be excluded. It can be said, however, that cell bodies or fibers of passage in the LC regjon are not necessary for TI induction and maintenance. Finally, although the present results would appear to indicate a general absence of relationship between PS and TI, the possibility of a common rn~G~~isrn of tonic motor control is not excluded by these data. As previously indicated, the outstanding feature di~erentja~~ TI and PS is the absence of phasic activity during TX. Levels of tunic EMG activity are the same for both states- [33]. in the present study, LC and reticular lesions decreased or eliminated PS. resulted in phasic activation at times when PS periods would be expected to occur, but did not disrupt the TI response. It is notable that when pbasic activity did intrude du~ng Tf, it only occurred af%er EEG synchr&ni~.io+--that is, when PS might be expected to occur. The o~cul~ence of EEG synchronization during TI has been previously observed in intact animals (4,221, and although the relationship of this activity to similar EEG activity characteristic of slow www sleep has not been established, it is clear that toni coinponents ofTI occur and can be m~int~ned in ass with a variety of eiectrocortical ~~tte~n~. One interpretation of the present data not inconsis&e~t with these obse~ati~~s is that LC lesions do not eliminate the tonic motor component of either TI or PS, but rather that these lesions release a phasic motor mechanism normally inhibited during PS. Such an explanation has been advanded to explain the phenomenon of PS without atonia in cats with lesions in the LC’ region [29}. Apparently this phasic motor behavior is contingent upon a sleep-related mechanism- for activ~t~ori. and since TI is neither a state of sleep nor a state characterized by pbasic: activation, it may not be affected by these lesions as is PS. Consequently, despite the apparently discrepant effects of LX: and FTG Iesions upon TI and PS in the rabbit. the possibility of a mechanism of tonic motor control common and basic to these two states remains and ~v~~ants further investigatiotl. ACKNOWLEDCXMENT

assistance. This work was supported by grace from the Medical Research Council and the Ontario Mental Me&h ~#u~d~tj~n. This research was presented in part at the 22nd Annual Meeting of the A~s~iat~~n for the Psychophysiological Study of Steep. March 17-22. 1980.

BRAINSTEM

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AND TONIC IMMOBILITY REFERENCES

I, Barratt, E. S. EEG correlates of tonic immobility in the oppossum, Electraenceph. clin. Neurophysiol. 18: 709-711, 1965. 2. Braun, C. M. J. and R. T. Pivik. Effects of locus coeruleus lesions upon sleeping and waking in the rabbit. Brain Res. 230: 133-151, 1981. 3. Carli, G. Depression of somatic reflexes during rabbit hypnosis. Brain Rcs. 11: 453-456, 1968. 4. Carli, G. Dissociation of electrocortical activity and somatic reflexes during rabbit hypnosis. Archs itaf Bioi. 107: 219-234. 1969. 5. Carli, G. Subcortical origin of rabbit hypnosis. Brain Res. 14: 7X3-75.5, 1969. 6. Carli, G. Subcortical mechanisms of rabbit hypnosis. Archs ital. Biof. 109: 15-26, 1971. 7. Dement, W. C. The occurrence of low voltage fast electroencephalogram patterns during behavioral sleep in the cat. Electroenceph. clin. Neurophysiol. 10: 291-296, 1958.

8. Draper, D. C. and W. R. Klemm. Behavioral responses associated with animal hypnosis. Psycho/. Rec. 17: 13-21, 1967. 9. F&ova, E. and J. Marsala. Stereotaxic atlas for the cat, rabbit, and rat. In: Electrophysiafogical Methods in Biofugical Research, edited by J. M. BDres and J. 2. Petran. New York: Academic Press, 1967. 10. Foley, J. P., Jr. Tonic jmmobiiity in the rhesus monkey (Macaca mulattu) induced by manipulation, immobili~tion, and experimental inversion of the visual field. J. camp. Psythof. 26: 515-526, 1938. 11. Gallup, G. G., Jr. Animal hypnosis; factual status of a fictional concept. Psychoi. Bull. 81: 836853, 1974. 12. Gallup, G. G., Jr., R. F. Nash, N. H. Donegan and M. D. McClure. The immobility response: A predator-induced reaction in chickens. Psvchol. Rec. 21: 513-519, 1971. 13. Gilman, T. and F. i. Marcuse. Animal hypnosis. Psycho/. Rec. 46: 151-165, 1949. 14. Harper, R. M. Frequency changes in hippocampal electrical activity during movement and tonic immobility. Physiof. Behav. 7: 5.5-58, 1971. 15. Henley, K. and A. R. Morrison. A re-evaluation

of the effects of lesions of the pontine tegmentum and locus coeruleus on phenomena of paradoxical sleep in the cat. Arta ~eur~~~iaf. exp. 34: 215-232, 1974. 16. Hoagland, H. On the mechanism of tonic immobility in vertebrates. J. gcn. fhysiaf. 11: 715-741, 1928. 17. Jones, B. E. Elimination of paradoxical sleep by lesions of the pontine gigantocellular tegmental field in the cat. Neurosci. Lett. 13: 285-293, 1979. 18. Jones, B. E., S. T. Harper and A. E. Halaris. Effects of locus coeruleus lesions upon cerebral monoamine content, sleepwakefulness states and the response to amphetamine in the cat. Brain Res. 124: 473-496,

20. Jouvet, M. and J. Delorme. Locus coeruleus et sommeil uaradoxal. C.r. SPanc. Sac. Biol. 159: 1599-1604. 1965. 21. Klemm, W. R. Potentiation of animal hypnosis with low levels of electrical current. Anim. Behav. 13: 551-574, 1965. 22. Klemm, W. R. Electroencephalographic-behavioral dissociations during animal hypnosis. Efectroenceph. clin. Neurophysiol. 21: 36.5-372, 1966.

23. Klemm, W. R. Mechanisms of the immobility reflex (animal hypnosis) II. EEG and multiple unit correlates in the brainstem. Communs Behav. Biol. 3: 43-52, 1969. 24. Klemm, W. R. Animal hypnosis, an experimental model of EEG-behavioral dissociations. Efectroencrph. cfin. Neuruphysiol. 26: 336-342, 1969. 25. Klemm, W. R. Identity of sensory and motor systems that are

26. 27.

28. 29. 30.

31. 32.

401-404, 1978. 33. Pivik, R. T., S. Sircarand

during sleep, wakefulness

35.

36. 37.

19. Jouvet, M. The role of monoamines Ph>kol.

64: 166-307,

1972.

C. M. J. Braun. Nuchal muscle tonus and tonic immobility in the rabbit.

Physiol. Behav. 26: 13-20, 1981. 34. Pompeiano, 0. Sensory inhibition during motor activity during sleep. In: N~uraphysiolagi~af Basis c?f Normal and Abnarmai Motur Activities (Proceedings of the 3rd Svmoosium of the

1977.

and acetylcholine containing neurons in the regulation of the sleep-waking cycle. Ergebn.

critical to the immobility reflex (“animal hypnosis”). J. Neurosci. RPS. 2: 57-69, 1976. Liberson, W. T. Prolonged hypnotic states with “local signs” induced in guinea-pigs. Science 108: 40-41, 1948. McBride, R. L. and W. R. Klemm. Stereotaxic atlas of rabbit brain, based on the rapid method of photography of frozen, unstained sections. Communs Behav. Biol. 12: 179-215, 1968. Meesen, H. and J. A. Olszewskii. A Cytoarchitectonic Atlas of the Rh~~m~encephuf~n ofrhe Rabbit. Basel: Karger, 1938. Morrison, A. R. Brainstem regulation of behavior during sleep and waking. Prog. ~sy~ho~~af. Psych~~physiol. 8: 91-135, 1979. Morrison, A. R., G. Mann and J. C. Hendricks. The relationship of excessive exploratory behavior in wakefulness to paradoxical sleep without atonia. Sleep 4: 247-258, 1981. Narebski, J., J. Tymicz and W. Lewosz. The circadian sleep of rabbits. Acta Biol. exp., Vars. 29: 185-200, 1969. Pivik, R. T. and C. M. J. Braun. A method for effective rabbit head restraint during stereotaxic surgery. Brain Res. Bull. 3:

38.

Parkinsons Disease Info~a~on and Researih Center), edited by M. D. Yahr and D. K. Purpura. New York: Raven Press, 1967. Sargeant, A. B. and L. W. Everhardt. Death feigning by chickens in response to predation by red foxes (Vulpes fifva). Am. Midl. Nai. 94: 108-119, 1975. Spiegel, E. A. and A. A. Goldbloom. Die Innervation der Korperhaltung im Zustande der sogenannten Hypnose bei Saugetieren. Pftigers Arch. ges. Physiol. 207: 361-369, 1925. Van Dongen, P. A. M., C. L. E. Broekkamp and A. R. Cools. Atonia after carbachol microinjections near the locus coeruleus in cats. Pharmac. Biochem. Bahav. 8: 527-532, 1978. Woodruff, M. L. Limbic modulation of contact defensive immobility (“animal hypnosis”). Psychof. Rec. 27: 161-175, 1977.