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Effect of Fornical Stimulation Upon the Ca1 and Ca2 Apical Dendrite of Rabbit's Hippocampus

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Effect of Fornical Stimulation Upon the Ca1 and Ca2 Apical Dendrite of Rabbit's Hippocampus EFFECT OF FORNICAL STIMULATION UPON THE CA1 AND CA2 APICAL DENDRITE OF RABBIT'S HIPPOCAMPUS Yasuichiro FUJITA* AND Yoshio NAKAMURA** Section of Neurophysiology, Institute of Brain Research, School of Medicine University of Tokyo Since GREEN and ADEY7) found a post-synaptic response in hippocampus following fornical stimulation in 1956, the fact has been re-affirmed by von EULER et al.5). These workers all seem to regard this response as excitatory postsynaptic potential arising in or near the soma of the pyramidal cell. However, the authors of the present paper think that there have been no definite proofs to support such conclusion. FUJITA and SAKATA6)found a spike potential originating in the apical dendrite of the pyramidal cell of rabbit's hippo- campus following stimulation of CA3, CA4 or the Schaffer collaterals. On the other hand, by stimulating the neural structure within 200 micra from the alveus, FUJITA and NAKAMURArecorded a positive potential of 15 to 35 msec in duration in the apical dendrite layer, which inhibited the spike of the apical dendrite. The aims of the present paper are (1) to analyse precisely this inhibitory slow potential and (2) to know the nature of the postsynaptic response evoked by fornical stimulation, taking the spike of the apical dendrite as an indicator of the excitability change. METHODS Thirty two rabbits were used. The experimental methods were nearly the same as those described in the separate paper6). The chief difference was that in this experiment the hipocampus was usually not exposed, because the hipocampus easily succumbed to depression, if exposed. As the readings of a micromaniplator is not always reliable owing to many reasons, the change in the time course or polarity of the potential evoked by stimulation of the axon collaterals of deeply or laterally placed pyramidal cells as the recording electrode was moved along the apical dendrite of the pyramidal cells in the medial part of the Ammon's horn, was taken as an indicator of the position of the tip of the recording electrode (FIG. 1). Neural structures which generated this evoked potential was examined histologically in the separate paper6). For immobilization, curare or nembutal was used. As far as the present experi- Received for publication January 30, 1961 **藤 田安一郎,中 村嘉 男 *Present address: Departrnent of Physiology , Nippon Medical School, Bunkyoku, Tokyo. 357 358 Y. FUJITA AND Y. NAKAMURA FIG. 1. Laminar analysis of EPSP and action potential of the apical dendrite evoked by stimulation of the Schaffer collaterals. Downward deflection denotes negativity. Zero point is arbitrary. Numbers on the left show distances from zero point in micron. The pyramidal cell layer is considered to be located at 200 micra. A: weak stimulation; B: strong stimulation. Note the largest spike in the apical dendrite layer. ment was concerned, no essential difference was found between curarised rabbit and nembutalized one. Liquor cerebro-spinalis was sucked out to minimize the disturbance by respiratory movement. The stimulating and recording electrodes were 3 molar KCL filled mcro-pipettes with 10 to 40 micra and I micron in tip diameters respectively. Usually a negative pulse of 1 msec duration, the intensity of which was strong enough to generate a spike in the apical dendrite, was delivered to the Schaffer collaterals. For stimulation of the fornix and intrahippocampal structure which evoked an inhibitory process in the apical dendrite, the same pulse of different intensity was used. After the experiment was over, the structure surrounding the stimulating electrode for the fornix was gently sucked out, and by exposing the fornix, the localization of the tip was ascertained, under direct vision. CR coupled amplifiers with time constant of 0.1 and 0.3sec respectively were used to record electrical changes. Cathode followers were constructed as the input stages of the amplifiers. Photographs were taken with a long recording camera. The upward deflection in the records denotes positive sign. All records in this paper are superimposition of four to six traces. FORNICAL STIMULATION AND HIPPOCAMPUS 359 RESULTS Usually, two stimulating electrodes were inserted into the lateral part of the Ammon's horn. One was used for stimulating the Schaffer collaterals or deeper pyramidal cell layer. The other was used to stimulate the neural structure, which was located within 300 micra from the alveus. A recording electrode was in- troduced into the medial part (CA1) of the Ammon's horn. I. Stimulation of the neural structure within 300 micra from the alveus. When the stimulating electrode was placed at a point, which was located within 300 micra from the alveus, a positive potential of 15 to 35msec in duration was recorded in the apical dendrite layer (FIG. 3B). As the recording electrode was slowly withdrawn, the potential reversed its polarity and became negative in sign in the cell layer. Usually, the positive deflection in the apical dendrite layer was larger in amplitude than the negative deflection in the cell layer. The phase reversal took place 100 to 200 micra above the point, at which the phase- reversal of EPSP of the apical dendrite evoked by the Schaffer collaterals occurred. This potential inhibited the spike of the apical dendrite evoked by stimulation of the Schaffer collaterals (FIG. 2A, FIG. 3F). The degree of the inhibition was strongest approximately at the peak of the slow potential, though sometimes dis- crepancy of slight degree occurred. Considering from the fact that the slow potential was of a long duration and showed summation on double shocks, it is apparent that the inhibitory potential is of postsynaptic nature. A B FiG. 2. Slow potential of the apical dendrite evoked by intrahip- pocampal stimulation. A: two stimuli were delivered at various time intervals. Note inhibition of the spike by slow potential. B: a spike evoked by stimulation of the Schaffer collaterals (Right) and slow potential evoked by intrahippocampal stimulation (Left). 360 Y. FUJITA AND Y. NAKAMURA A B FIG. 3. Laminar analysis of slow potential evoked by intrahippocampal stimulation. Zero point is arbitrary. The pyramidal cell layer is considered to be located at 200 micra. A: spike of the apical dendrite evoked by stimulation of CA4. B: slow potential of the apical dendrite evoked by intrahippocampal stimulation. C: a spike evoked by stronger stimulation of the same point as in the case of B. Note that the spike is larger in the apical dendrite layer than in the cell layer and that the spike in the cell layer is diphasic i.e. initially positive and later negative. Also note that slow negative deflection of the cell layer in C is much smaller than that in B. D: a typical spike of the apical dendrite recorded at 500 micra. Note a notch on the rising phase and after-positivity. E: slow potential evoked by intrahippocampal stimulation. F: inhibition of the spike by the slow potential. As described above, stimulation of the neural structure which was situated within 300 micra from the alveus, evoked a slow positive potential in the apical dendrite layer, together with a negative deflection of the same duration in the cell layer. The latter was explained as a sink of the inhibitory postsynaptic potential of the apical dendrite. Therefore, no matter how the intensity of the stimulus may be increased, no spike should be generated from the slow negative wave seen in the cell layer. However, if stronger stimulus was delivered to the FORNICAL STIMULATION AND HIPPOCAMPUS 361 same point, there arose spike potentials from the cell layer down to the deeper part of the apical dendrite (FIG. 3C). In the apical dendrite layer the spike was seen superimposed on slow positive potential, while the spike potential above the phase-reversal point was observed superimposed on the slow negative potential. The amplitude of the spike was larger in the apical dendrite layer as compared with that above the phase-reversal point. The most remarkable facts were that the amplitude of the slow negative potential in the cell layer was decreased as the intensity of the stimulus was increased, and the spike potential seen in the cell layer was usually diphasic; that is, initially positive and later negative. From these observations, it was quite apparent that the spike potentials seen on these occasions were similar to those evoked by stimulation of the Schaffer collaterals. Therefore, it was concluded that by increasing the intensity of the stimulus, the Schaffer collaterals or some other fibres afferent to the apical dendrite were stimulated owing to the current spread. It was noteworthy that the increase in the intensity of the stimulus brought a reduction in the amplitude of the slow negative wave, and that the diphasic spike potential in the cell layer was initially positive and later negative. This definitely points to a conclusion that the negative wave in the cell layer is not the precursor to the spike potential. More- AB C FIG. 4. EPSP and spike of the apical dendrite. Zero point is arbitrary. The pyramidal cell layer is considered to be located at zero. Stimulus was delivered to the super- ficial layer of CA2 and it was considered that synapses near the soma were activated. A: spike of the apical dendrite evoked by stimula- tion of CA3. B: EPSP arised near the soma. C: spike evoked by stimulation of the super- ficial layer. 362 Y. FUJITA AND Y. NAKAMURA over, the slow wave inhibits the spike of the apical dendrite. The diphasic spike potential seen in the cell layer was considered as the spike of the soma which was propagated from the deeper part of the apical dendrite. Sometimes, by increasing the intensity of the stimulus, a monophasic spike was seen in the cell layer, together with spike potentials along the apical dendrite (FIG.
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