BEHAVIORAL BIOLOGY, 14,489-498 (1975), Abstract No. 4324

Normal Jump Avoidance Performance in Rats with the Hippocampa! Theta Rhythm Selectively Disrupted I

TROND MYHRER

Institute of Neurophysiology, University of Oslo, Oslo, Norway The purpose of the present study was to investigate whether the hippocampal theta activity is necessary for the appearance of behavior with which it is normally correlated. Rats were trained in a one~way active avoidance test (jump test) a performance which is usually accompanied by clear theta waves. The theta activity was then disrupted by a medial fornical lesion leaving the major hippocampal input and output systems functionally intact. By comparing pre- and postoperative jump avoidance latencies no statistically significant difference was revealed. Thus, the occurrence of theta activity was not necessary for normal jump avoidance behavior. It is suggested that the theta rhythm reflects internal hippocampal processes, and it may not be a reliable measure of the influence which the hippocampal formation exerts upon other parts of the neuronal network.

Considerable interest has been focused on the relation between the hippocampal rhythmic slow activity (theta) and behavior in recent years. However, an increasing controversy appears to exist with respect to the behavioral correlates of the theta activity. Among the hypotheses advanced is theta associated with arousal (e.g., Green and Arduini, 1954), attention or orienting responses (Grastyn'n, Lissn'k, Madar~sz, and Donhoffer, 1959; Bennett, H~bert, and Moss, 1973), Darning (e.g., Elazar and Adey, 1967), frustration (Gray, i 9 7 2 ) , and voluntary movements (e.g., Vanderwolf, 1971; Whishaw and Vanderwolf, 1973). In a recent study the necessity of theta accompanying behavior was questioned (Bennett, 1973). The purpose o f the present study was to investigate the performance of a task, normally accompanied with clear theta r h y t h m , following surgical elimination o f the theta activity without interference w i t h other,vise i m p o r t a n t hippocampal fiber connections.

1This study was supported by the Norwegian Research Council for Science and the Humanities. 489 Copyright © 1975 by Academic Press, Inc. All rights of reproduction in any form reserved.

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The theta activity is assumed to be initiated by a group of cells in the dorsal part of the nucleus of the diagonal band of Broca (cf., Apostol and Creutzfeldt, 1974). In a recent study it was discovered that the fibers necessary for the theta rhythm do not course in the fimbria, as might be expected. The pacemaker cells in the septum send their axons in the medial fornix and then directly into the hilus of the fascia dentata (Andersen, Bland, Myhrer, and Schwartzkroin, 1975). Accordingly, it appears possible to abolish the theta activity by transecting the relevant fibers and leave the hippocampus otherwise functionally intact. Since the theta waves seem closely related to certain movements in the rat (e.g., Vanderwolf, 1971), a jump avoidance task was used in the present study. This task has several advantages: (a) the initiation of muscular activity can be defined accurately; (b) a large movement is required, ensuring large amplitude theta; (c) the use of shock reinforcement suppresses irrelevant spontaneous motor activity (Vanderwolf, 1971). In the present study the rats were trained in the jump avoidance test at f'Lxed times concurrently with EEG recording and measurement of the avoidance latency. The procedure was then repeated after elimination of the theta activity in order to compare the p r e - a n d postoperative avoidance performance.

METHODS

Subjects. Eight rats of the M6ll-Wistar strain weighing 350-430 g at the time of implantation were used. They were housed in groups of two or three and fed commercial rat pellets and water ad lib. Implantations. Under sodium pentobarbital anesthesia, bipolar electrodes were implanted stereotaxically in both dorsal hippocampi and fixed with steel screws and dental cement. The electrodes were made from nichrome wire (250 tam diam.) each soldered to a female pin component (Ultra Electronics Components Ltd. 2 5 0 0 - S - 2 - A - 22). The electrodes were cut so that one tip was 0.5 mm shorter than the other. Only the tips were bared of insulation and they were spaced 1.5 mm from one another. Placement of such electrodes with one in the subfield CA1 and the other in the granular layer of the fascia dentata use to permit the recording of clear large amplitude theta activity with very little artifact. The rats were grounded to the recording polygraph (Grass model III C) from a screw in the skull. Lesions. The surgery was carried out under anesthesia as described above, 13 days after implantations. The lesions were made mechanically with the sharp edges of a cannula that was mounted to a syringe and provided with a small adjustable collar. The cannula was inserted through a small hole in the flat skull (0.7 mm behind bregrna and 0.5 mm lateral to the midline) to the

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depth permitted by the collar. The entire medial fornix could be reached from one side and was transected in two steps by moving the cannula back and forth in the frontal plane in depth of 4 and 5 ram, respectively, from the top of the calvarium. Avoidance apparatus. Testing took place in a box of black plywood (30 × 30 × 28 cm), previously described (Myhrer, 1975b). The box was placed on a grid, which could be electrified with 0.35 mA. A plywood shelf, 6 cm wide, was located around the outside of the box 1.3 cm below the upper edge. The rats could jump out of the box, catch the raised edge with their forepaws, and pull themselves up onto the outside shelf. Avoidance procedure. Training was started by allowing a rat to explore the apparatus for 5 min. On the succeeding training trials the rat was placed on the grid and given shock (to a maximum of 5 sec) after 10 sec had elapsed. The intertrial interval was 1 min during which the rat stayed on the shelf. Care was taken to avoid overtraining which may mask lesion effects (cf., Rosner, 1970). On the first 2 days the subjects were trained to a criterion of nine correct avoidance responses out of ten consecutive trials. On the third day trials were given until the occurrence of two avoidance responses. Then, six to eight avoidance responses with concomitant EEG recording was undertaken. Since no shock can be applied during recording, five subsequent trials with the leads disconnected formed the basis of preoperative performance in terms of total avoidance latency. The postoperative testing was carried out 2 days following lesions. This relatively short interval was chosen in order to reduce interference from memory impairment. The interval also appeared justified in view of the gentle lesion procedure applied and the apparently good postoperative condition of the animals. The total latency during five trials with shock available formed the postoperative scores. Subsequently, EEG recording was made during avoidance performance. Upon completion of the experiments the brains were removed, fixed in formalin, and embedded in paraffin. Serial sections ( 1 6 # m thick) were prepared and every twentieth section was stained with thionin. RESULTS

Histology. The electrode locations were nearly always found placed with one tip in the CA 1 pyramidal layer and the other in the granular layer of the fascia dentata (Fig. 1A). The lesions were restricted to the aorsomedial portion of the fornix (Fig. 1B). Additional damage was made in the dorsal fornix, the hippocampal commissural fibers, the corpus callosum, and the neocortex. Recording. Initially, clear large amplitude theta activity was obtained bilaterally in all subjects. As previously described for the rat (e.g., Vanderwolf,

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Fig. 1. A. Diagrara of a frontal section showing electrode placements. Electrode 1 is located in the CA 1 pyramidal cell layer (1.5 mm rostral to the plane of the section shown). Electrode 2 is located in the granular cell layer of the fascia dentata. B. Representative example of dorsomedial fomical lesion.

1971) the theta waves accompanied certain types o f movements like walking, running, rearing, and struggling (Fig. 2A). As seen from Fig. 3A the occurrence of theta preceded the jump response. Between 1 and 2 sec before the jump the frequency rose to 8-10 Hz. However, it was noticed that the occurrence of theta associated with the jump response declined as a function of training, particularly if the intertrial interval was only 5-10 sec. In some rare instances no clear theta at all correlated with the jump response. Following lesions no theta rhythm was seen during behaviors with which it previously was correlated (Fig. 2B). The jump responses were associated with small and large irregular activity (Fig, 3B). However, large amplitude irregular activity was more pronounced when the rats moved than when they were immobile (Fig. 2B).

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L. Hipp.

R. Hipp.

--Moving

~St illJf-~Wal k i n g

I Immobile-

IIOO pv I sec

R. Hip;).

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Immobile.--

Fig. 2. Electrical activity in the hippocampal formation of the same rat during movements and immobility before lesion (A) and after lesion (B).

THETA BLOCKING AND ACTIVE AVOIDANCE ,~

493

L. Hipp.

R. Hipp.

Placed on grid

3

Jump

L. Hipp.

.._._3 leO pV I sec

R~ Hipp.

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Fig. 3. Simultaneous recording of hippocampal activity in a rat performing a jump avoidance response before lesion (A) and after lesion (B). Avoidance performance. Mean pre- and postoperative latency based on the total number of seconds during five trials did not differ substantially (Fig. 4). T test for dependent data revealed no significant differences (t = 0.18, d f = 14, P > 0.10).

DISCUSSION The present results showed that the~theta activity was not necessary for the occurrence of normal jump avoidance response with which it is usually correlated. Neither was the coordination of spontaneous motor activities noticeably interfered with following disruption of theta, since the rats displayed no difficulties in maneuvering on the comparatively narrow shelf of the jump apparatus. These data may imply that the hippocampal theta rhythm 50

to C~ 2 0 Z 0 o t,J I0 03

PR E O P .

POS TOP.

Fig. 4. Mean pre- and postoperative jump avoidance latency based on the total number of seconds during five trials. Bars represent _+ SEM.

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is more an indicator than an activator p e r se. However, it cannot be ruled out that more sensitive tests might reveal behavioral changes after selective theta disruption. Furthermore, it cannot be maintained that theta was absent in the entire hippocampus, but at the electrode sites only. The present data only show that the theta rhythm is unnecessary for performance of a well-trained response. Whether theta is necessary for acquisition of the jump task remains to be investigated. Such an investigation appears pertinent since theta has been related to memory processes (Landfield and McGaugh, 1972; Landfield, McGaugh, and Tusa, 1972; Landfield, Tusa, and McGaugh, 1973). In a recent lesion study it was suggested that the hippocampal formation may be involved in relating new stimuli to previous experience, based on the assumption that the septohippocampal projection system probably mediates sensory information of subcortical origin and the perforant paths likely mediate sensory information of cortical origin (Myhrer, 1975c). Collaterals to the reticular formation of the brain stem from afferent pathways subserving all the sensory modalities have been demonstrated (cf., Deutsch and Deutsch, 1966). A variety of external sensory stimulation or direct excitation of the brain stem are associated with theta waves in the hippocampus (Green and Arduini, 1954). Since primarily the granule cells of the fascia dentata and to some extent the C-A I pyramidal cells most likely generate the theta rhythm (Andersen, Bland, and Ganes, 1975; Winson, 1974), it might be suggested that the theta activity indicates when the granule cells and the CA 1 pyramids receive sensory information by way of the reticular activating system. Interestingly, the theta is mediated by an input pathway of its own (see introduction), whereas the main projection from the medial septum is located in the fimbria (Daitz and Powell, 1954; McLardy, 1955; Raisman, Cowan, and Powell, 1965; Raisman, 1966). Noteworthy, the disruption of theta in the present study did not interfere with the fimbria. Presumably important sensory information to the hippocampus is mediated through the fimbria, inasmuch as medial septal lesions produce a large number of behavioral changes (e.g., Donovick, 1968; Clody and Carlton, 1969; Hamilton, Kelsey, and Grossman, 1970; Gray, Quint~o, and Araujo-Silva, 1972). Therefore, no or very few behavioral changes may actually be expected following selective removal of the theta waves. It must be borne in mind that lesions in the medial septal area destroy far more neurons than the relatively few cells which probably initiate the hippocampal theta waves (cf., Apostol and Creutzfeldt, 1974). It has been suggested that the theta rhythm reflects a functionally active hippocampus (Gray, 1972) or an inhibited hippocampus (e.g., Bennett e t al., 1973). According to the hypothesis proposed in the present study theta presumably only gives information of afferent input and not of functional activity in an executive way. This notion appears reconcilable with the lack of

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theta rhythm in the subfield CA 3 and the sparse occurrence in the CA 1 area (Andersen et al., 1975), since these subfields give rise to the two major hippocampal outputs (e.g., Andersen, Bland, and Dudar, 1973). Furthermore, blocking of fimbrial CA 3 output produces far more behavioral changes than blocking of the CA 1 output (Myhrer, 1975a). The theta rhythm probably reflects internal hippocampal processes, and it may not be a reliable measure of the degree to which the hippocampal formation exerts influence upon other parts of the neuronal network. It has previously been claimed that theta is not necessary for the occurrence, during learning, of behaviors with which it is normally correlated (Bennett, 1973). Unfortunately, in the study of Bennett a test in which even hippocampectomized subjects perform normally was employed (see Bennett, 1973). In the present jump test rats with hippocampal perforant paths sections display impaired performance (Myhrer, 1975b). Furthermore, a jump avoidance retention deficit in seen in hippocampectomized rats (Rich and Thompson, 1965). Accordingly, intact hippocampal function but not the theta rhythm appears necessary for normal jump avoidance. In addition to interruption of fibers responsible for theta, the present lesions also destroyed the dorsal fornix which is not considered a hippocampal output (cf., Myhrer and Kaada, 1975). However, transection of the dorsal fornix does not change avoidance behavior (Van Hoesen, Wilson, MacDougall, and Mitchell, 1972; Myhrer and Kaada, 1975). Furthermore, medial fornix lesions sparing the fimbrial component have no effect upon a DRL task (MacDougall, Van Hoesen, and Mitchell, 1969). Thus, there are few reasons to expect that the present lesions actually improved the jump avoidance, in such a way that a possible impairment of theta disruption was counteracted and subsequently masked. On the other hand, the failure to demonstrate a lesion effect was probably not due to overtraining, since five of the rats in fact needed shock reinforcement during postoperative testing. The hypotheses which relate theta to information transaction (Adey, 1966), information processing (Routtenberg, 1968, 1971), and memory storage (Landfield and McGaugh, 1972; Landfield et al., 1972, 1973) presumably require some integration of sensory input. However, the present hypothesis suggests that the theta rhythm may be a correlate of internal information processing rather than of some overt behavior. If tile hypothesis advanced in the present paper is valid, a possibility for resolving the apparent controversy concerning the behavioral correlates of the theta rhythm cited in the introduction might be accessible. The arousal or attention notion is in accord with the present view, apart from the present attempt to put the arousal concept in a context of subcortical sensory information. Both orienting responses and learning are likely associated with hippocampal input of sensory information as well, in particular, since the hippocampus is suggested to relate new stimuli to previous experience

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(Myhrer, 1975c). The idea o f Gray (1972) might be explained b y attention shift or increased need for sensory information to compensate for frustrative nonreward. As with the theory o f Vanderwolf it might be suggested that lower animals unlike higher animals are more dependent upon sensory information of subcortical origin for their performance of voluntary movements. In agreement with the results o f other authors (cf., Feder and Ranck, 1973) it was noticed in the present study that the occurrence o f theta associated with the avoidance response gradually declined as training proceeded. This might mean that the performance of a task becomes less dependent on direct sensory information and more associated with previous experience as a function o f training. Moreover, the sparse appearance of theta waves in higher animals (cf., Green and Arduini, 1954; Winson, 1972) may imply that these animals have a better ability to utilize previous experience in coping with the environment than lower animals.

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Winson, J. (1972). Interspecies differences in the occurrence of theta. Behav. Biol. 7, 479-487. Winson, J. (1974). Patterns of laippocampal theta rhythm in the freely moving rat. Electroencephalogr. Clin. Neurophysiol. 36, 291-301.

Normal jump avoidance performance in rats with the hippocampal theta rhythm selectively disrupted.

BEHAVIORAL BIOLOGY, 14,489-498 (1975), Abstract No. 4324 Normal Jump Avoidance Performance in Rats with the Hippocampa! Theta Rhythm Selectively Disr...
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