Habituation of aversive reticular stimulation effects on evoked potentials

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Brain Research, 56 (1973) 340- 344 © Elsevier Scientific Publishing Company, Amsterdam

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Habituation of aversive reticular stimulation effects on evoked potentials

JOEL D. KNISPEL* hYD J E R O M E SIEGEL

Department of Psychology, University of Delaware, Newark, Del. 1971l (U.S.A.) (Accepted April 5th, 1973)

It has been known for some time that peripheral somatic and autonomic responses to aversive conditions habituate10,13,14,19, 22. This report is concerned with habituation of a central neural response to aversive stimulation. We have previously described specific changes in visual evoked potentials (EPs) concomitant with aversion 11. Compared to relaxed arousal, intense aversive levels of stimulation to the mesencephalic reticular formation augmented cortical EPs produced by light flash and attenuated responses produced by a single shock to the visual pathway. Such contrasting effects on EPs have been attributed to the greater ability of the centrally delivered visual stimulus to evoke a well synchronized volley of corticipetal impulses 2,2z,24. The increased amplitudes of flash-EPs during aversive reticular stimulation were comparable to click-EP amplitude increases seen by other authors during foot shock 6 and fear s,15, but were quite distinct from the effects of moderate arousal or lower non-aversive levels of reticular stimulation. Taken together, these findings suggest that aversive conditions exert a specific but widespread influence on cortical sensory functions and that this influence may be mediated by brain stem reticular mechanisms classically involved in cortical activation processes9,16,17. The current study employed 3 chronically implanted cats and was essentially similar to the previous experiment 11, except that these animals were examined for the effect on the EP of repeated experience with aversive stimulation. Test sessions began with a 15 min adaptation period. Control EPs were then recorded from primary visual cortex while animals were in a state of relaxed waking. The visual stimulus was either a 10/~sec light flash or a 0.1 msec shock to the optic tract and was presented at a rate of 1/4 sec. Following the collection of control data, a 2 sec bipolar reticular stimulation pulse train (0.1 msec monophasic pulses, 150 pulses/sec) was introduced. The reticular stimulation pulse train terminated 25 msec before the presentation of the visual stimulus. In the first test session, reticular stimulation intensity was raised in small increments until animals displayed an obvious aversion as indicated by pilo* Present address: Laboratory of Neurophysiology, UCLA Mental Retardation Center, 760 Westwood Plaza, Los Angeles, Calif. 90024, U.S.A.

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Fig. 1. Habituation of flash-EP responses to aversive stimulation. B-C component amplitude is plotted as a function of experience with aversive reticular stimulation. In this and the next figure, each successive average EP consists of 3 single sweeps. The interflash interval was 4 sec. The control ranges (vertical brackets) represent 4 average EPs from each session recorded during pre-stimulation pzriods of quiet waking. The insert illustrates an average EP consisting of 3 single sweeps. Positivity is up. The start of the trace is coincident with the light flash. Calibration: 25/tV, 50 msec. erection, miaowing and, in some cases, escape oriented behavior. The thresholds for aversion, so determined, were 0.15 mA for all 3 animals. These determinations were subsequently validated by monitoring 2 of the 3 animals in a shuttle box preference situation3,11. After the first test session animals were readapted to the sensory stimulatingrecording situation over the course of 1-2 weeks. When animals showed a return of control (pre-aversive stimulation) EP amplitudes and a tendency towards sleep, readaptation was considered complete and they were again tested with the same intensity of reticular stimulation. Later in the second test session, animals were also tested with a higher intensity of reticular stimulation. As in our earlier experiment, the ftash-EP initial component was unresponsive to aversive reticular stimulation. In Fig. 1, this is the baseline to A component. Consistent changes were limited to the later occurring components indicating that the effects were intracortical in nature and not merely a reflection of changes taking place in the lower visual pathway. Fig. I shows late component (B-C) changes recorded from an animal during the first experience with aversive reticular stimulation and during a second session with the same intensity of stimulation. Aversive reticular stimulation effects on the A - B negative-going late component followed the same time course. In session 1, late components were potentiated and this effect was sustained throughout the session. In session 2, however, late components showed a decreased tendency to respond to aversive stimulation. After an initial increase in amplitude similar to that of session 1, but of lower magnitude, the late component amplitudes of successive average evoked potentials fell close to or within the control range. To test whether late components were still capable of responding, a higher intensity of aversive reticular stimulation was presented later during session 2. This

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Fig. 2. Habituation of central shock-EPs responses to aversive stimulation in 2 different animals. A-B component amplitudes are plotted as a function of experience with aversivereticular stimulation. Each insert illustrates an average EP consisting of 3 single sweeps. The occurrence of the optic tract shock is indicated by the stimulus artifact which is the first upward deflection of the baseline. Calibration: 25 ~V, 10 msec.

higher intensity produced a sustained enhancement which was virtually identical to that of session 1 ; i.e., the B-C late component exhibited a 42 ~ increase in amplitude. Fig. 2 illustrates the central shock-EP changes recorded from 2 other animals. As with the flash-EP, consistent changes were limited to the late A - B and B-C components. Within each animal, the responses of both late components followed the same time course. The course of habituation of the central shock-EP response recorded from the second animal (Fig. 2, top) closely resembles the course of habituation of the flash-EP response in the first animal (Fig. 1); in session 1 late components showed a sustained dramatic response to aversive reticular stimulation, but in session 2 after an initial responsiveness, late components showed a decreased tendency to respond to aversive reticular stimulation. The second animal was also tested with a higher intensity of reticular stimulation later in session 2. This resulted in a sustained attenuation of late components which was similar to that of session 1. Decrements of the A-B late component amounted to 65 ~ of the mean control value. In the third animal, the course of habituation was faster (Fig. 2, bottom). Late components showed a decreased tendency to respond to aversive reticular stim-

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ulation even during session 1. In both sessions, after an initial responsiveness to aversive stimulation, late component amplitudes returned to control levels. When this animal was tested with a higher intensity of aversive reticular stimulation, late components were attenuated to the same extent as they were initially with the lower intensity, but this decrement lasted through 2 successive average evoked potentials before returning to control levels. That the response endured longer at the higher intensity rules out the possibility that the response decrement at the lower intensity was due to fatigue. These results are not without precedent. Gerkin and Neff 6 observed that potentiation of cortical click-EP late components during aversive conditioning procedures was eliminated by prior pseudo-conditioning. Although these authors did not refer to habituation, their observations do support such an interpretation. As with the present findings, Gerkin and Neff also observed subject-to-subject variability in their study. It should be noted that other individual differences in cats relating to EP changes and 'personality' variables have been describedL In addition to the relatively permanent plastic changes that are supposed to underlie various forms of habituation4, ~1, several other processes could play a role in habituation of the EP response to aversive stimulation. These include well known negative feedback regulatory systems that serve to dampen excessive levels of reticular activation. Dell et al. 5 have demonstrated that active reticular deactivation is accomplished by descending cortical influences and by interoceptor afferent activity. There is also evidence that the hippocampus is and other forebrain areaslA2,20, 25 can exert inhibitory effects on reticular arousal processes. In concluding we would like to suggest that the consistent and dramatic changes in the cortical EP represent sensitive indicators of aversion and subtle changes in the course of aversion. By virtue of their specificity and fidelity these centrally generated neural responses may prove to be considerably more useful than the second order peripheral indicators such as heart rate and galvanic skin response. This work was completed while J. D. Knispel was a doctoral candidate at the University of Delaware. The research was supported by N S F Grant GB-8429 to J. Siegel. 1 BREMER,F., Preoptic hypnogenic focus and mesencephalic reticular formation, Brain Research, 21 (1970) 132-134. 2 BREMER, F., ET STOUPEL,N., Facilitation et inhibition des potentiels 6voqu6s corticaux dans l'6veil c6r6bral, Arch. int. Physiol., 67 (1959) 240-275. 3 CAMPBELL,B. A., AND MASTERSON,F. A., Psychophysics of punishment. In B. A. CAMPBELLAND R. M. CHURCH(Eds.), Punishment and Aversive Behavior, Appleton-Century-Crofts, New York, 1969, pp. 3-42. 4 CASTELLUCHI,V., PINSKER,H., KUPFERMAN,L, AND KANDEL,E., Neuronal mechanisms of habituation of the gill-withdrawal reflex in Aplysia, Science, 167 (1970) 1740-1748. 5 DELL, P., BONVALLET,M., AND HUGELIN, A., Mechanisms of reticular deactivation. In G. W. WOLSTENHOLMEAND M. O'CONNER(Eds.), The Nature of Sleep, Churchill, London, 1960, pp. 86-102. 6 GERKIN,G. M., ANDNEFF, W. D., Experimental procedures affecting evoked responses recorded from auditory cortex, Electroenceph. din. Nearophysiol., 15 (1963) 947-957.

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7 HALL,R. A., RAPPAPORT,M., HOPKINS,H. K., GRIFFIN,R., AND SILVERMAN,J., Evoked response and behavior in cats, Science, 170 (1970) 998-1000. 8 HALL, R. n., AND MARK, R. G., Acoustically evoked potentials in the rat during conditioning, J. Neurophysiol., 30 (1967) 875-892. 9 JONES, B., BOBILLIER,P., ET JOUVET, M., Effets de la destruction des neurones contenant des cat6cholamines du m6senc6phale sur le cycle veille-sommeil du chat, C. R. Soc. Biol. (Paris), 163 (1969) 176-181. 10 KELLOG, W. N., Electric shock as a motivating stimulus in conditioning experiments, d. gen. Psychol., 25 (1941) 85-96. ] 1 KNISPEL,J. D., AND SIEGEL,J., Tegmental stimulation: aversive effects on behavior and modulation of visual evoked potentials, Brain Research, 37 (1972) 317-321. 12 LINEBERRY,C. G., AND SIEGEL,J., EEG synchronization, behavioral inhibition and mesencephalic unit effects produced by stimulation of orbital cortex, basal forebrain and caudate nucleus, Brain Research, 34 (1971) 143-161. 13 MACDONALD,A., The effect of adaptation to the unconditioned stimulus upon the formation of conditioned avoidance responses, J. exp. Psychol., 36 (1946) 1-12. 14 McCuLLOCH,T. L., ANDBRUNER,J. S., The effect of electric shock on subsequent learning in the rat, J. Psychol., 7 (1939) 333-336. 15 MARK, R. G., AND HALL, R. n., Fear and the modification of acoustically evoked potentials during conditioning, J. Neurophysiol., 30 (1967) 893-910. 16 MORUZZI,G., AND MAGOUN,H. W., Brain stem reticular formation and activation of the EEG, Electroenceph. clio. Neurophysiol., 1 (1949) 455-473. 17 PIN, C., JONES,B., ET JOUVET,M., Topographie des neurones monaminergiques du tronc c6r6bral du chat: 6tude par histofluorescence, C. R. Soc. Biol. (Paris), 163 (1968) 2136-2142. 18 REDOING,F. K., Modification of sensory cortical evoked potentials by hippocampai stimulation, Electroenceph. clio. Neurophysiol., 22 (1967) 74-83. 19 SEWARD,J. P., AND SEWARD,G. H., The effects of repetition on reactions to electric shock: with special reference to the menstrual cycle, Arch. Psychol., 27 (1934) 103 pp. 20 SIEGEL,J., AND LINEBERRY,C., Caudate-capsular induced modulation of single unit activity in mesencephalic reticular formation, Exp. Neurol., 22 (1968) 444 463. 21 SOKOLOV,E. N., Neuronal models and the orienting reflex. In M. A. BRAZIER(Ed.), The Central Nervous System and Behavior, Josiah Macy, Jr. Foundation, New York, N. Y., 1960, pp. 187-276. 22 STECKLER,L. C., AND O~KELLY,L. T., Persistence of response as a function of thirst in terms of early experience with electric shock, J. camp. Psychol., 32 (1941) 1-10. 23 STERIADE,M., BELEKHOVA,M., AND APOSTOL,V., Reticular potentiation of cortical flash-evoked after discharge, Electroenceph. clio. Neurophysiol., 11 (1968) 276-280. 24 STERIADE,M., ANDDEMETRESCU,M., Stimulation of peripheral sensory input by electrical pulsetrain applied to specific afferent pathways, Exp. Neurol., 19 (1967) 265-277. 25 STERMAN,M. B., AND FAIRCHILD,M.D., Modification of locomotor performance by reticular formation and basal forebrain stimulation in the cat: evidence for reciprocal systems, Brain Research, 2 (1966) 205-217.