POSTTETANIC POTENTIATION OF PRIMARY RESPONSE AND LATE NEGATIVE WAVE IN THE SOMATOSENSORY REGION OF THE CORTEX OF THE CAT
I. V. Ocherashvili and R. P. Kashakashvili
UDC 612.825+612.822.3
The experiments were carried out on cats under nembutal anesthesia. Stimulation of the ventroposterolateral nucleus of the thalamus or the white matter by a single stimulus elicited a primary response in the middle layers of the somatosensory cortex, and after it, a late negative wave, the duration of which reaches 40-70 msec. This potential does not have dipole reflection on the surface of the cortex and is apparently generated primarily by stellate cells. As a result of the tetanization of the ventroposterolateral nucleus or the white matter, a sharp increase in the amplitude of the late negative wave is observed, i. e., its posttetanic potentiation, while the primary response changes to a significantly lesser degree. P osttetanic potentiation is observed for 2-2.5 h. Posttetanic potentiation of the late negative wave is probably governed by processes occurring at the level of the middle layers of the cerbral cortex.
When a single stimulus is applied to the ventroposterolateral nucleus of the thalamus [5, 14], or with a single peripheral stimulation [12], an additional negative potential lasting 40-70 msec, which has been called the late negative wave [12], arises following the primary response in the middle layers of the cortex of the corresponding projection area of the cerebral cortex. It has been shown that this wave does not have dipole reflection on the surface, and it has been hypothesized that it mainly indicates activity of the steUate cells [5--7]. Posttetanic potentiation is one of the characteristic properties of synapses involving chemical transmission. This phenomenon has been described in the new cortex of the brain in a number of studies [2--4, 10]. The purpose of the present investigation was a study of the posttetanic potentiation of the primary response and the late negative wave.
METHODS The experiments were set up in cats under nembutal anesthesia (60-70 mg/kg, subcutaneously). Two glass-insulated steel wires were used for the stimulation of the ventroposterolateral nucleus; the distance between the tips was 0.5 mm along the vertical. The stimulation of the white matter was carried out by means of two steel wires with tips thinned out up to 40 tun, and covered with insulation. The distance between the tips was 1.5 mm along the horizontal. The electrode was sunk 3-5 mm relative to the surface of the cortex. Electrolytic destruction of the ventroposterolateral nucleus was carried out in several experiments in which the white matter was stimulated. A bipolar electrode with an interpole distance of 200 lain was used for the direct stimulation of the cortex. The electrical potentials were recorded simultaneously from the surface of the cortex by means of a macroelectrodc (a silver wire with a diameter of 1 mm), and from within - a glass microelectrode filled with 0.1 NaC1, with a tip diameter of 4-5 lain. The distance between the surface maeroelectrode and the microelectrode along the horizontal did not exceed 1 ram. The recording prior to tetanization in response to the stimulation of the ventroposterolateral nucleus, the white matter, or the surface of the cortex, was carried out for 15-30 min, with an interval between runs of 15-20 see. Then, depending upon the goal of the experiment, the application of a series of stimuli (for 20 see, at a frequency of 50 Hz) was carried out through one of the stimulating electrodes, following which the observation of the changes in the electrical reactions was made,
Laboratory of the General Physiology of the Cerebral Cortex, I. S. Beritashvili Institute of Physiology of the Academy of Sciences of the GSSR [AN GSSR], Tbilisi. Translated from Fiziologicheskii Zhurnal SSSR imeni I. M. Sechenova, Vol. 75, No. 10, pp. 1328-1334, October, 1989. Original article submitted February 24, 1989. 484
0097-0549/90/2006-0484512.50 9
Plenum Publishing Corporation
A
Fig. 1. The primary response and the late negative wave arising in the somatosensory area of the cerebral cortex with the application of a single stimulus to the ventroposterolateral nucleus of the thalamus. The duration of the stimulus changes without change in voltage (50 V). In this and the other figures, the upper tracings represent pickup from the surface, and the lower tracings, pickup from the depths of the cortex (in this case, 0.85 mm relative to the pial surface). A) Duration of the stimulus 0.05; B) 0.2; C) 0.5; D) 1 msec; 1-3) the method of measuring the amplitude of the negative phase of the primary response, the positive phase of the primary response, and the late negative wave, respectively.
INVESTIGATION
RESULTS
It is shown in Fig. 1A that when a single stimulus, duration 0.05 msec, is applied to the ventroposterolateral nucleus, the initial phase of the primary response appeared in the depths of the cortex (in this case, at 1 mm), and its dipole reflection appeared on the surface. An increase in the duration of the stimulus led to the appearance of the negative phase of the primary response on the surface of the cortex, while the late negative wave appeared in its depths (denoted by the broken line), which increased up to a certain limit as the duration of the stimulus increased (Fig. 1B-D). Comparison of the electrical reactions shown in this figure demonstrates that the late negative wave, by contrast with the primary response, has no dipole reflection on the surface of the cortex, which is in agreement with previously published data [5-7]. The method of measuring the amplitude of these potentials is shown in Fig. 1D. The late negative wave, as a rule, had its greatest magnitude in the middle layers of the cortex, 0.6-1.6 mm. As will be shown below (Fig. 4B, and Fig. 5B), similar potentials can be evoked by stimulation of the white matter. It should be noted that the effects described in this study did not change their character depending on whether the ventroposterolateral nucleus or the white matter were stimulated. The primary response and the late negative wave, recorded prior to tetanization of the ventroposterolateral nucleus, are shown in Fig. 2A. These electrical reactions can be evoked for several hours, and are characterized by a high degree of stability. A posttetanic potentiation of the late negative wave was observed following tetanization of the ventroposterolateral nucleus (Fig. 2B-D). It can be seen from the graph in Fig. 2E, that this effect developed gradually and was maximally expressed at the 50th to 80th rain. For example, at the 75th min, the amplitude of the late negative wave was increased by 150%. It should be noted that the posttetanic potentiation is preceded by a brief (up to 2-3 min) depression of the late negative wave. Attenuation of the posttetanic potentiation took place at the 110th to 125th min; however, complete recovery of this potential was not observed. It can also be seen from Fig. 2 that the primary response (picked up from the surface of the cortex), by contrast with the late negative wave, did not experience sharp changes, but some increase (by 30--40%) of the negative phase was observed over the course of the first 20 min, while the positive phase remained unchanged. It should be noted that the initial phase of the primary response, picked up from the depths of the cortex, also underwent posttetanic potentia485
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Fig. 2. Posttetanic potentiation of the primary response and the late negative wave evoked by stimulation of the ventroposterolateral nucleus. A) Primary response and the late negative wave (pickup from the depths of the cortex at 0.9 ram) arising in response to the application of a single stimulus (50 V, 0.5 reset) to the ventroposterolateral nucleus prior to tetanization; B-D) Changes in the evoked responses following tetanization of the ventroposterolateral nucleus (20 sec, 50 Hz, 50 V, 0.5 rnsec); B) At the 12th rain after completion of tetanization; C) At the 75th rain; D) The 120th rain; D) Graph of the values of the amplitudes of the positive and negative phases of the primary response and of the late negative wave following tetanization of the ventrolateral nucleus. Along the abscissa: time following tetanization, min; along the ordinate: amplitude of the aboveenumerated potentials in percent relative to their background values (100%). Small circles: white represent the negative, black and white, the positive phases of the primary response; black, the late negative wave.
tion, but to a significantly lesser degree than the late negative wave, (This effect is more clearly shown in Fig. 3). However, as already noted, the amplitude of the surface positive phase of the primary response did not change. The initial phase of the primary response arising in the depths of the cortex (0.95 ram) upon stimulation of the white matter by a single stimulus is shown in Fig. 3A. In this ease the late negative wave did not appear when the voltage of the stimulus was increased up to 100 V and the duration up to 2 msec. It should be noted that only the primary response appeared in several preparations, independent of the intensity of the stimulus. However, as can be seen from Fig. 3B-F, the late negative wave was clearly expressed for 30 rain following tetanization of the white matter. The amplitude of this potential was 0.2 mV at the 3rd rain following the completion of the tetanization and 0.4 mV at the 15th rain (Fig. 3B, D); it attenuated at the 30th rain to 0,2 mV (Fig. 3F), and did not change through the following 30 rain. It can also be seen from this figure that an increase in amplitude (approximately by 20-25%) took place at the initial phase of the primary response, in addition to the appearance of the late negative wave. Thus, it follows from the data presented that tetanic stimulation of the ventroposterolateral nucleus of the white matter elicits a sharp intensification (Fig. 2) or even the appearance (Fig. 3) of the late negative wave, while posttetanic potentiation of the primary response is expressed to a significantly lesser degree. 486
]1
40 msec
Fig. 3. The appearance of the late negative wave as a result of the tetanization of the white matter. The recording was made only from the depths of the cortex (1.2 ram). A) The response arising upon stimulation of the white matter by a single stimulus (80 V, 0.5 msec) prior to tetanization; B-F) The electrical reactions following tetanization of the white matter (20 sec, 50 Hz, 80 V, 0.5 msec); B) At the 3rd; C) At the 6th; D) At the 15th; E) At the 20th; F) At the 30th min following the completion of tetanization.
B
A
\, Fig. 4. Posttetanic potentiation of the late negative wave and the dendritic potential of the direct response of the cortex. A) Diagram of the position of the electrodes: 1) stimulating electrode in the white matter; 2) stimulating electrode on the surface of the cortex; 3) macroelectrode on the surface of the cortex; 4) microelectrode placed deep in the cortex. B) Dendritic potentials picked up by means of macroelectrode (3) during stimulation of the surface of the cortex through electrode (2). C) Primary response (picked up by macroelectrode (3)) and the late negative wave (picked up from the depths of the cortex at 1.6 mm by microelectrode (4)) during stimulation of the white matter through electrode (1). In B) and C): Oscillograms: on the left (without numbers) are the responses recorded prior to the tetanization of the white matter. The parameters of the stimuli applied through electrode (1) 50 V, 0.4 msec; through electrode (2) 30 V, 0.02 msec. The numbers in the remaining osciUograms represent the time (min) following tetanization of the white matter (20 sec, 50 Hz, 50 V, 0.4 msec).
The direct cortical response, the dendritic potential, which is known [9] to be the summated manifestation of the excitatory postsynaptic potentials of the apical dendrites of layer 1 of the cortex, was also observed in the next series of experiments, along with the potentials arising with stimulation of the white matter. The schema of the placement of the electrodes in such experiments is presented in Fig. 4A. The dendritic potentials elicited by direct stimulation of the cortex 487
A
B
4L7m s e c
Fig. 5. Posttetanic potentiation of the dendritic potential of the direct response of the cortex and the electrical reactions arising upon stimulation of the white matter. Diagram of the position of the electrodes is the same as in Fig. 4, A. A) Dendritic potentials evoked by stimulation of the surface of the cortex by a single stimulus (20 V, 0.05 msec); B) The primary response and late negative wave (pickup from the depths of the cortex at 1 ram) upon stimulation of the white matter by a single stimulus (50 V, 0.7 msec). Oscillograms on the left (without numbers) represent the responses prior to tetanization of the surface of the cortex. The numbers in the remaining oscillograms indicate the time (min) following completion of tetanization of the surface of the cortex (20 sec, 50 Hz, 20 V, 0.05 msec).
through electrode 1 are shown in Fig. 4B, and the primary response and late negative wave arising with stimulation of the white matter through electrode 2, in Fig. 4C. It can be seen from this figure that tetanic stimulation of the white matter led to the development of posttetanic potentiation of the late negative wave (Fig. 4C), while the dendritic potential evoked in approximately the same time intervals, did not change (Fig. 4B). It should be noted that stimuli of near-threshold intensity were used for direct stimulation of the cortex, permitting elicitation of the dendritic potential in "pure form" [9]. When tetanic stimulation of the surface of the cortex was carried out through electrode 2, the reverse effect was observed, namely, posttetanic potentiation of the dendritic potential (Fig. 5A) and the absence of this effect in the electrical reactions evoked by stimulation of the white matter (Fig. 5B). The posttetanic potentiation of the dendritic potential (increase in its amplitude by almost 100%) lasted 20 min; it then returned to its initial value. DISCUSSION OF RESULTS It can be seen from the results presented that the late negative wave is subjected to posttetanic potentiation to a significantly greater degree than the primary response. This fact again confirms the previously advanced hypothesis that the late negative wave is a more sensitive indicator of the functional state of the projection region of the cortex than is the primary response [6]. As already noted, the late negative wave has no reflection on the surface of the cortex, as a result of which this potential and the changes which take place with it remain outside of the field of vision when only potentials picked up from the surface of the cortex are observed. It is conjectured that posttetanic potentiation is related to memory [13]. The late negative wave belongs to the closed type of electrical fields, and is apparently generated mainly by the stellate cells, which, in the opinion of Beritashvili [1], are the principal perceptual sensory elements of the projection regions of the cerebral cortex. Thus, the observed phenomenon of posttetanic potentiation of the late negative wave is of particular interest. Apparently, when specific afferent impulse activity enters the cortex, the stellate cells are capable of preserving the trace of the excitation for a comparatively long period of time, while the large pyramidal cells (to judge their activity on the basis of the primary response) possess this capacity to a lesser degree. Other authors have come to a similar conclusion on the basis of an analysis of the biochemical and structural changes which appear as a result of the formation of a dominant focus in the cortex [8]. In the description of the results of these investigations it was noted that the initial phase of the primary response, which was picked up from the depths of the cortex, was subject (but in a significantly attenuated form) to posttetanic potentiation, while the surface-positive phase of the primary response did not undergo any changes. On the basis of this fact it may be proposed that the in,:ease in the amplitude of the initial phase of the primary response, which arises in the depths of the cortex, is also determined by intensification of the ac488
tivity of the stellate cells, which participate in the formation of this potential [11]. As already noted, the activity of these ceUs is not reflected on the surface of the cortex. It may be inferred that the posttetanic potentiation of the late negative wave with stimulation of the ventroposterolateral nucleus is governed by processes which take place in the cortex, and not in this thalamic nucleus, since similar effects are observed in the experiments involving stimulation of the white matter as well. The experiments with parallel recording of the dendritic potential (Fig. 4) enable us to hypothesize that the process of posttetanic potentiation under these experimental conditions is localized in the region of g~neration of the late negative wave, i. e., in the middle layers of the cortex. It is known that both the dendritic potential of the direct response of the cortex and the negative phase of the primary response as well reflect the excitatory postsynaptic potentials of the apical dendrites. However, it is demonstrated in Fig. 5 that the negative phase of the primary response did not change during the time that the amplitude of the dendritic potential was increased. This fact apparently indicates that when a weak stimulus is applied to the surface of the cortex, and given subcortical stimulation, various systems of axodendritic synapses are activated. We can also hypothesize from the recordings presented in Figs. 4 and 5 that posttetanic potentiation may unfold at different levels of the cortex independently of one another. Analysis of the posttetanic potentiation of the dendritic potential of the direct response of the cortex has permitted the conclusion that this phenomenon is associated with presynaptic changes in the axodendritic synapses [3, 4, 10]. It is possible that the development of the posttetanic potentiation of the late negative wave is associated with analogous changes in the presynaptic terminals of the afferent fibers which form monosynaptic contacts with the stellate cells [15]. However, this question requires special investigation.
L I T E R A T U R E CITED 1. 2. 3. 4. 5.
6. 7.
8. 9. 10. I I. 12. 13. 14. 15.
I.S. Beritov, The Structure and Functions of the Cerebral Cortex [in Russian], Nattka, Moscow (1969). L.L. Voronin, "Prolonged potentiation of the reactions of the neocortex of the intact brain and surviving sections of cortex," Fiziol. Zh. SSSR 70, No. 8, 1167-1177 (1984). R.P. Kashakashviti, "The influence of calcium ions on the posttetanic potentiation of dendritic potentials of the cerbral cortex," Soobshch. AN GSSR. 112, No. 2, 397-400 (1983). R.P. Kashakashvili, "The influence of tetraethylammonium ions on the posttetanic potentiation of dendritic potentials of the cerebral cortex," Soobshch. AN GSSR. 114, No. 2, 385-388 (1984). I.V. Ocherashvili, "Some characteristics of the late negative wave and of the slow negative potential arising in the somatosensory cortex upon stimulation of the ventroposterolateral nucleus of the thalamus in the cat," Soobshch. AN GSSR. 100, No. 3,657-660 (1980). I.V. Ocherashvili, "The late negative wave arising in the somatosensory cortex of the cat upon stimulation of the ventroposterolateral nucleus of the thalamus," Izv. AN GSSR Ser. Biol. 8, No. 4, 238-243 (1982). I.V. Ocherashvili, "The slow electrical potentials appearing following the primary response in the somatosensory area of the cerebral cortex of the cat upon stimulation of the ventroposterolateral nucleus of the thalamus," Neirofiziologiya 17, No. 4, 435-441(1985). R.A. Pavlygina, A. K. Melikova, and F. A. Brazovskaya, "Trace neuron-glial reorganization occurring with the creation of a dominant focus," in: The Functions of the Neuroglia [in Russian], Metsniereba, Tbilisi (1987), p. 363-366. A.I. Roimbak, "Dendritic potentials and the effect on them of GABA," in: Central and Peripheral Mechanisms of Nervous Activity [in Russian], Izd-vo AN Arm. SSR, Erevan (1966), pp. 365-372. A. L Roimbak, R. P. Kashakashvili, I. K. Gogodze, and K. V. Kutkhashvili, "The posttetanic potentiation of dendritic potentials of the cerebral cortex," Fiziol. Zh. SSSR 70, No. 8, 1108-1115 (1984). F. N. Serkov, The Electrophysiology of the Higher Divisions of the Auditory System [in Russian], Naukova Dumka, Kiev (1977). V, Bonnet, "Analyse osciUographique des potentials 6voqu6s des aires de reception corticales," Arch. Inter. Physiol. Biochim. 69, No. 5, 609-616 (1961). L C. Eccles, "Synaptic plasticity," Naturwissenschaften 66, No. 3, 147-153 (1979). D. Morin and M. Steriade, "Development from primary to augmenting responses in the somatosensory system," Brain Res. 205, No. 1, 49--66 (i981). E. L. White, "Thalamocortical synaptic relations: a review with emphasis on the primary sensory areas of the neocortex," Brain Res. 1, No. 3,275-311 (1979). 489
I. V. Ocherashvili and R. P. Kashakashvili
UDC 612.825+612.822.3
The experiments were carried out on cats under nembutal anesthesia. Stimulation of the ventroposterolateral nucleus of the thalamus or the white matter by a single stimulus elicited a primary response in the middle layers of the somatosensory cortex, and after it, a late negative wave, the duration of which reaches 40-70 msec. This potential does not have dipole reflection on the surface of the cortex and is apparently generated primarily by stellate cells. As a result of the tetanization of the ventroposterolateral nucleus or the white matter, a sharp increase in the amplitude of the late negative wave is observed, i. e., its posttetanic potentiation, while the primary response changes to a significantly lesser degree. P osttetanic potentiation is observed for 2-2.5 h. Posttetanic potentiation of the late negative wave is probably governed by processes occurring at the level of the middle layers of the cerbral cortex.
When a single stimulus is applied to the ventroposterolateral nucleus of the thalamus [5, 14], or with a single peripheral stimulation [12], an additional negative potential lasting 40-70 msec, which has been called the late negative wave [12], arises following the primary response in the middle layers of the cortex of the corresponding projection area of the cerebral cortex. It has been shown that this wave does not have dipole reflection on the surface, and it has been hypothesized that it mainly indicates activity of the steUate cells [5--7]. Posttetanic potentiation is one of the characteristic properties of synapses involving chemical transmission. This phenomenon has been described in the new cortex of the brain in a number of studies [2--4, 10]. The purpose of the present investigation was a study of the posttetanic potentiation of the primary response and the late negative wave.
METHODS The experiments were set up in cats under nembutal anesthesia (60-70 mg/kg, subcutaneously). Two glass-insulated steel wires were used for the stimulation of the ventroposterolateral nucleus; the distance between the tips was 0.5 mm along the vertical. The stimulation of the white matter was carried out by means of two steel wires with tips thinned out up to 40 tun, and covered with insulation. The distance between the tips was 1.5 mm along the horizontal. The electrode was sunk 3-5 mm relative to the surface of the cortex. Electrolytic destruction of the ventroposterolateral nucleus was carried out in several experiments in which the white matter was stimulated. A bipolar electrode with an interpole distance of 200 lain was used for the direct stimulation of the cortex. The electrical potentials were recorded simultaneously from the surface of the cortex by means of a macroelectrodc (a silver wire with a diameter of 1 mm), and from within - a glass microelectrode filled with 0.1 NaC1, with a tip diameter of 4-5 lain. The distance between the surface maeroelectrode and the microelectrode along the horizontal did not exceed 1 ram. The recording prior to tetanization in response to the stimulation of the ventroposterolateral nucleus, the white matter, or the surface of the cortex, was carried out for 15-30 min, with an interval between runs of 15-20 see. Then, depending upon the goal of the experiment, the application of a series of stimuli (for 20 see, at a frequency of 50 Hz) was carried out through one of the stimulating electrodes, following which the observation of the changes in the electrical reactions was made,
Laboratory of the General Physiology of the Cerebral Cortex, I. S. Beritashvili Institute of Physiology of the Academy of Sciences of the GSSR [AN GSSR], Tbilisi. Translated from Fiziologicheskii Zhurnal SSSR imeni I. M. Sechenova, Vol. 75, No. 10, pp. 1328-1334, October, 1989. Original article submitted February 24, 1989. 484
0097-0549/90/2006-0484512.50 9
Plenum Publishing Corporation
A
Fig. 1. The primary response and the late negative wave arising in the somatosensory area of the cerebral cortex with the application of a single stimulus to the ventroposterolateral nucleus of the thalamus. The duration of the stimulus changes without change in voltage (50 V). In this and the other figures, the upper tracings represent pickup from the surface, and the lower tracings, pickup from the depths of the cortex (in this case, 0.85 mm relative to the pial surface). A) Duration of the stimulus 0.05; B) 0.2; C) 0.5; D) 1 msec; 1-3) the method of measuring the amplitude of the negative phase of the primary response, the positive phase of the primary response, and the late negative wave, respectively.
INVESTIGATION
RESULTS
It is shown in Fig. 1A that when a single stimulus, duration 0.05 msec, is applied to the ventroposterolateral nucleus, the initial phase of the primary response appeared in the depths of the cortex (in this case, at 1 mm), and its dipole reflection appeared on the surface. An increase in the duration of the stimulus led to the appearance of the negative phase of the primary response on the surface of the cortex, while the late negative wave appeared in its depths (denoted by the broken line), which increased up to a certain limit as the duration of the stimulus increased (Fig. 1B-D). Comparison of the electrical reactions shown in this figure demonstrates that the late negative wave, by contrast with the primary response, has no dipole reflection on the surface of the cortex, which is in agreement with previously published data [5-7]. The method of measuring the amplitude of these potentials is shown in Fig. 1D. The late negative wave, as a rule, had its greatest magnitude in the middle layers of the cortex, 0.6-1.6 mm. As will be shown below (Fig. 4B, and Fig. 5B), similar potentials can be evoked by stimulation of the white matter. It should be noted that the effects described in this study did not change their character depending on whether the ventroposterolateral nucleus or the white matter were stimulated. The primary response and the late negative wave, recorded prior to tetanization of the ventroposterolateral nucleus, are shown in Fig. 2A. These electrical reactions can be evoked for several hours, and are characterized by a high degree of stability. A posttetanic potentiation of the late negative wave was observed following tetanization of the ventroposterolateral nucleus (Fig. 2B-D). It can be seen from the graph in Fig. 2E, that this effect developed gradually and was maximally expressed at the 50th to 80th rain. For example, at the 75th min, the amplitude of the late negative wave was increased by 150%. It should be noted that the posttetanic potentiation is preceded by a brief (up to 2-3 min) depression of the late negative wave. Attenuation of the posttetanic potentiation took place at the 110th to 125th min; however, complete recovery of this potential was not observed. It can also be seen from Fig. 2 that the primary response (picked up from the surface of the cortex), by contrast with the late negative wave, did not experience sharp changes, but some increase (by 30--40%) of the negative phase was observed over the course of the first 20 min, while the positive phase remained unchanged. It should be noted that the initial phase of the primary response, picked up from the depths of the cortex, also underwent posttetanic potentia485
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Fig. 2. Posttetanic potentiation of the primary response and the late negative wave evoked by stimulation of the ventroposterolateral nucleus. A) Primary response and the late negative wave (pickup from the depths of the cortex at 0.9 ram) arising in response to the application of a single stimulus (50 V, 0.5 reset) to the ventroposterolateral nucleus prior to tetanization; B-D) Changes in the evoked responses following tetanization of the ventroposterolateral nucleus (20 sec, 50 Hz, 50 V, 0.5 rnsec); B) At the 12th rain after completion of tetanization; C) At the 75th rain; D) The 120th rain; D) Graph of the values of the amplitudes of the positive and negative phases of the primary response and of the late negative wave following tetanization of the ventrolateral nucleus. Along the abscissa: time following tetanization, min; along the ordinate: amplitude of the aboveenumerated potentials in percent relative to their background values (100%). Small circles: white represent the negative, black and white, the positive phases of the primary response; black, the late negative wave.
tion, but to a significantly lesser degree than the late negative wave, (This effect is more clearly shown in Fig. 3). However, as already noted, the amplitude of the surface positive phase of the primary response did not change. The initial phase of the primary response arising in the depths of the cortex (0.95 ram) upon stimulation of the white matter by a single stimulus is shown in Fig. 3A. In this ease the late negative wave did not appear when the voltage of the stimulus was increased up to 100 V and the duration up to 2 msec. It should be noted that only the primary response appeared in several preparations, independent of the intensity of the stimulus. However, as can be seen from Fig. 3B-F, the late negative wave was clearly expressed for 30 rain following tetanization of the white matter. The amplitude of this potential was 0.2 mV at the 3rd rain following the completion of the tetanization and 0.4 mV at the 15th rain (Fig. 3B, D); it attenuated at the 30th rain to 0,2 mV (Fig. 3F), and did not change through the following 30 rain. It can also be seen from this figure that an increase in amplitude (approximately by 20-25%) took place at the initial phase of the primary response, in addition to the appearance of the late negative wave. Thus, it follows from the data presented that tetanic stimulation of the ventroposterolateral nucleus of the white matter elicits a sharp intensification (Fig. 2) or even the appearance (Fig. 3) of the late negative wave, while posttetanic potentiation of the primary response is expressed to a significantly lesser degree. 486
]1
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Fig. 3. The appearance of the late negative wave as a result of the tetanization of the white matter. The recording was made only from the depths of the cortex (1.2 ram). A) The response arising upon stimulation of the white matter by a single stimulus (80 V, 0.5 msec) prior to tetanization; B-F) The electrical reactions following tetanization of the white matter (20 sec, 50 Hz, 80 V, 0.5 msec); B) At the 3rd; C) At the 6th; D) At the 15th; E) At the 20th; F) At the 30th min following the completion of tetanization.
B
A
\, Fig. 4. Posttetanic potentiation of the late negative wave and the dendritic potential of the direct response of the cortex. A) Diagram of the position of the electrodes: 1) stimulating electrode in the white matter; 2) stimulating electrode on the surface of the cortex; 3) macroelectrode on the surface of the cortex; 4) microelectrode placed deep in the cortex. B) Dendritic potentials picked up by means of macroelectrode (3) during stimulation of the surface of the cortex through electrode (2). C) Primary response (picked up by macroelectrode (3)) and the late negative wave (picked up from the depths of the cortex at 1.6 mm by microelectrode (4)) during stimulation of the white matter through electrode (1). In B) and C): Oscillograms: on the left (without numbers) are the responses recorded prior to the tetanization of the white matter. The parameters of the stimuli applied through electrode (1) 50 V, 0.4 msec; through electrode (2) 30 V, 0.02 msec. The numbers in the remaining osciUograms represent the time (min) following tetanization of the white matter (20 sec, 50 Hz, 50 V, 0.4 msec).
The direct cortical response, the dendritic potential, which is known [9] to be the summated manifestation of the excitatory postsynaptic potentials of the apical dendrites of layer 1 of the cortex, was also observed in the next series of experiments, along with the potentials arising with stimulation of the white matter. The schema of the placement of the electrodes in such experiments is presented in Fig. 4A. The dendritic potentials elicited by direct stimulation of the cortex 487
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B
4L7m s e c
Fig. 5. Posttetanic potentiation of the dendritic potential of the direct response of the cortex and the electrical reactions arising upon stimulation of the white matter. Diagram of the position of the electrodes is the same as in Fig. 4, A. A) Dendritic potentials evoked by stimulation of the surface of the cortex by a single stimulus (20 V, 0.05 msec); B) The primary response and late negative wave (pickup from the depths of the cortex at 1 ram) upon stimulation of the white matter by a single stimulus (50 V, 0.7 msec). Oscillograms on the left (without numbers) represent the responses prior to tetanization of the surface of the cortex. The numbers in the remaining oscillograms indicate the time (min) following completion of tetanization of the surface of the cortex (20 sec, 50 Hz, 20 V, 0.05 msec).
through electrode 1 are shown in Fig. 4B, and the primary response and late negative wave arising with stimulation of the white matter through electrode 2, in Fig. 4C. It can be seen from this figure that tetanic stimulation of the white matter led to the development of posttetanic potentiation of the late negative wave (Fig. 4C), while the dendritic potential evoked in approximately the same time intervals, did not change (Fig. 4B). It should be noted that stimuli of near-threshold intensity were used for direct stimulation of the cortex, permitting elicitation of the dendritic potential in "pure form" [9]. When tetanic stimulation of the surface of the cortex was carried out through electrode 2, the reverse effect was observed, namely, posttetanic potentiation of the dendritic potential (Fig. 5A) and the absence of this effect in the electrical reactions evoked by stimulation of the white matter (Fig. 5B). The posttetanic potentiation of the dendritic potential (increase in its amplitude by almost 100%) lasted 20 min; it then returned to its initial value. DISCUSSION OF RESULTS It can be seen from the results presented that the late negative wave is subjected to posttetanic potentiation to a significantly greater degree than the primary response. This fact again confirms the previously advanced hypothesis that the late negative wave is a more sensitive indicator of the functional state of the projection region of the cortex than is the primary response [6]. As already noted, the late negative wave has no reflection on the surface of the cortex, as a result of which this potential and the changes which take place with it remain outside of the field of vision when only potentials picked up from the surface of the cortex are observed. It is conjectured that posttetanic potentiation is related to memory [13]. The late negative wave belongs to the closed type of electrical fields, and is apparently generated mainly by the stellate cells, which, in the opinion of Beritashvili [1], are the principal perceptual sensory elements of the projection regions of the cerebral cortex. Thus, the observed phenomenon of posttetanic potentiation of the late negative wave is of particular interest. Apparently, when specific afferent impulse activity enters the cortex, the stellate cells are capable of preserving the trace of the excitation for a comparatively long period of time, while the large pyramidal cells (to judge their activity on the basis of the primary response) possess this capacity to a lesser degree. Other authors have come to a similar conclusion on the basis of an analysis of the biochemical and structural changes which appear as a result of the formation of a dominant focus in the cortex [8]. In the description of the results of these investigations it was noted that the initial phase of the primary response, which was picked up from the depths of the cortex, was subject (but in a significantly attenuated form) to posttetanic potentiation, while the surface-positive phase of the primary response did not undergo any changes. On the basis of this fact it may be proposed that the in,:ease in the amplitude of the initial phase of the primary response, which arises in the depths of the cortex, is also determined by intensification of the ac488
tivity of the stellate cells, which participate in the formation of this potential [11]. As already noted, the activity of these ceUs is not reflected on the surface of the cortex. It may be inferred that the posttetanic potentiation of the late negative wave with stimulation of the ventroposterolateral nucleus is governed by processes which take place in the cortex, and not in this thalamic nucleus, since similar effects are observed in the experiments involving stimulation of the white matter as well. The experiments with parallel recording of the dendritic potential (Fig. 4) enable us to hypothesize that the process of posttetanic potentiation under these experimental conditions is localized in the region of g~neration of the late negative wave, i. e., in the middle layers of the cortex. It is known that both the dendritic potential of the direct response of the cortex and the negative phase of the primary response as well reflect the excitatory postsynaptic potentials of the apical dendrites. However, it is demonstrated in Fig. 5 that the negative phase of the primary response did not change during the time that the amplitude of the dendritic potential was increased. This fact apparently indicates that when a weak stimulus is applied to the surface of the cortex, and given subcortical stimulation, various systems of axodendritic synapses are activated. We can also hypothesize from the recordings presented in Figs. 4 and 5 that posttetanic potentiation may unfold at different levels of the cortex independently of one another. Analysis of the posttetanic potentiation of the dendritic potential of the direct response of the cortex has permitted the conclusion that this phenomenon is associated with presynaptic changes in the axodendritic synapses [3, 4, 10]. It is possible that the development of the posttetanic potentiation of the late negative wave is associated with analogous changes in the presynaptic terminals of the afferent fibers which form monosynaptic contacts with the stellate cells [15]. However, this question requires special investigation.
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