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The magnitude of long-term potentiation of field potentials induced monosynaptically in region CA3 of guinea pig hippocampus
Neuroscience Research, 3 (1986)660-665 Elsevier Scientific Publishers Ireland I.td
660
NSR 00131
Short Communications
The magnitude of long-term potentiation of field potentials induced monosynaptically in region CA3 of guinea pig hippocampus Masato Higashima and Chosaburo Yamamoto Department of Physiology, Faculty of Medicine, Kanazawa University, Kanazawa 920 (Japan) (Received January 31st, 1986; Accepted March 6th, 1986)
Key words: long-term potentiation - - short-term potentiation - - non-synaptic activation - - hippocampus -
-
guinea pig
SUMMARY The magnitude of long-term potentiation (LTP) was re-examined for monosynaptic transmission between mossy fibers and CA3 neurons in thin sections of the hippocampus of the guinea pig. Although an initial negative deflection in the field potential showed apparent short-term potentiation, this deflection was concluded to reflect non-synaptic activation of CA3 neurons. Accordingly, the magnitude of LTP of monosynaptic transmission was re-calculated at 3.4 +_ 0.9.
Previously, we studied configuration changes of field potentials elicited in region CA3 of the hippocampus during the development of long-term potentiation (LTP) 5. We observed that a single stimulus to the granular layer induced, in the pyramidal cell layer of the region CA3, a negative wave which was augmented only homosynaptically after the development of LTP. We also observed that the negative wave was usually followed by a positive slower wave which was potentiated after a short tetanus to homo- as well as heterosynaptic inputs. From these results, we suggested that the LTP of the negative wave reflected enhanced monosynaptic transmission through synapses between activated mossy fibers (axons of granular cells) and CA3 neurons, and the LTP of the positive response reflected modified interaction among postsynaptic neurons. The negative wave is sometimes complex in configuration, however. For the reason mentioned below, we considered that a negativity induced with short latencies reflected monosynaptic activation and a succeeding one reflected polysynaptic events caused by interaction Correspondence: M. Higashima, Department of Physiology, Faculty of Medicine, Kanazawa University, Kanazawa 920, Japan.
661 among postsynaptic neurons. According to this interpretation, we obtained a very low value for the magnitude of the LTP of the monosynaptic transmission. In the present study, we re-examined this interpretation and re-calculated the magnitude of the LTP in region CA3. Transverse sections (about 0.4 mm thick) of the hippocampal formation of the guinea pig were prepared as described before6, and were incubated in a standard solution for more than 40 min at 36 °C. Electrical activities of the tissue were examined in an observation chamber, in which the tissue was continuously superfused with the standard, or one of the modified solutions. The composition of the standard solution was (mM): NaCI 124, KC1 5, KHEPO 4 1.24, MgSO4 1.3, CaC12 2.4, NaHCO 3 26; and glucose 10. In a low Ca z+ solution, Ca z+ concentration was 1.6mM and Mg 2+ concentration was 6.3 mM. The solutions were saturated with 95~ O z and 5~o CO2. Stimulus pulses of 0.1 ms in duration and less than 20 V in intensity were delivered to the granular layer through a monopolar stainless-steel electrode. Field potentials were recorded from the pyramidal cell layer in the region CA3 with a glass pipette of about 10 # m tip diameter Idled with 150 mM NaCI. During the pre-tetanic period, test stimuli were delivered at 0.1 Hz and the stability of control responses was monitored for 10-15 min. Then, a tetanus was applied at 100 Hz for 1 s. Thereafter, the test stimuli were again repeated at 0.1 Hz and the test responses were observed for more than 15 min. LTP was arbitrarily def'med as potentiation lasting for more than 15 min after tetanust DL-2-Amino-4-phosphonobutyric acid (APB), a selective blocker of transmission through synapses between mossy fibers and CA3 neurons 7, was added to the perfusing solution at 50 or 100 #M. Fig. 1 shows an example of a negative wave of simply monophasic configuration. When preceded by a conditioning stimulus at an interval of 30 ms, the response was enhanced by about 300~o with a decrease in peak latency (record lb). After the development of LTP, the amplitude of the response was increased by about 200~ (record 2). When perfusion was started with a solution containing 50 #m APB, the peak of the negative wave was gradually decreased in amplitude and split into two successive negative deflections (record 3a). The fn'st deflection (dotted arrow) seems to reflect mainly non-synaptic activation of CA3 neurons, because it was potentiated only marginally in the second response to a paired stimulation (record 3b) and was elicited in the low Ca 2 + solution (record 4b). The second deflection (record 3a, open arrow) seems to reflect the synaptic activation of CA3 neurons, because it was markedly potentiated by a conditioning stimulation (record 3b, arrows) and was suppressed almost completely in the low Ca 2 + solution (record 4b). These results suggest that although the control negative wave in Fig. 1 was simply monophasic it includes deflections reflecting synaptic as well as non-synaptic activation of CA3 neurons. Fig. 2 shows the data of an experiment in which two deflections were discernible in the negative wave of the control response (record la, dotted and open arrows). These two deflections are called, according to the order of generation, early-N and late-N in this communication. When a pair of stimuli were delivered at a 30 ms interval, the
662 1. B e f o r e t e t a n u s
2. A f t e r t e t a n u s
3. A P B
4. a. s t a n d , sol.
b. l o w C a z+
-+I,,nV
"
6ms
c. r e c o v e r y
Fig. 1. Dissociation of non-synaptic and synaptic components in monophasic negative wave. Record la shows control field potcntiais. Record lb shows, in superimposition, a pair of potentials elicited at 30 ms intervals. Record 2a shows field potentials 17 min atter a tetanus. Record 3a shows responses 6 rain after perfusion with 50 #M APB. Record 3b shows a pair of potentiais elicited at 30 ms intervals in 50/~M APB in superimposition. Records 4a, 41) and 4c show responses elicited in the standard solution, 6 rain after perfusion with the low Ca 2 + solution and recovery of the responses after 12 min in the standard solution, respectively. Dotted and open arrows indicate non-synaptic and synaptic components, respectively. Except for records lb and 3b, two responses elicited at 0.1 Hz are superimposed. In this and in the following illustrations, single arrows indicate the second responses to paired stimuli.
1. B e f o r e t e t a n u s
i b -j
~
2. After t e t a n u s
3. APB
4.
~ ' "
~ "l
b. low Ca 2÷ ~'~
,~__~
~
a. stond, sot.
c. r e c o v e r y "1"I 1mY
6ms
Fig. 2. Potentiation and depression oflate-N. Record la shows control responses. Records lb and lc show, in superimposition, a pair of potontiais elicited at intervals of 30 ms and 100 ms, respectively. A double arrow indicates a notch corresponding to the peak of the early-N in the second response. Record 2a shows potentials 17 min atter a tetanus. Record 21) shows a pair of potentials elicited at 30 ms intervals in superimposition. Record 3a shows potentiais 6 rain aiter 50/~M APB. Record 3b shows a pair of potentials elicited at 30 ms intervals in 50/IM APB. Records 4a, 4b and 4c show potentials elicited in the standard solution, 13 rain after low Ca 2+ solution and 15 rain aiter perfusion with the standard solution. In this and in the next illustrations, dotted and open arrows indicate the early-N and late-N, respectively. In records la-4a, 4b and 4c, two field potentials evoked at 0.1 Hz are superimposed.
663 early-N as well as the late-N was apparently potentiated (record lb). The time-course of the initial portion of the descending phase of the potentiated response was identical to that of the early-N in the control, however, and a notch corresponding to the peak of the early-N is noticeable (double arrow). These observations suggest that the conditioning stimulus potentiated mainly the late-N. Actually, a substantial increase was observed only in the amplitude of the late-N at a stimulus interval of 100 ms (record lc). Seventeen minutes after a tetanus, a marked increase was observed in the amplitude of the late-N (record 2a, open arrow), whereas the potentiation of the early-N was marginal. The late-N disappeared in a solution containing APB (record 3a) but was elicited by the second of a paired stimuli (record 3b). In the low Ca 2 ÷ solution, the late-N was almost completely suppressed (record 4b), whereas the early-N was only partly suppressed. Therefore, the early-N and late-N in record la in Fig. 2 mainly reflect the non-synaptic and synaptic activation of CA3 neurons, respectively. The potentials in Fig. 3 are more misleading. The second stimulus of a pair of stimuli elicited an apparently potentiated early-N at a 30 ms stimulus interval (record A2). An apparent potentiation of the early-N is also noted immediately after a tetanus (record A 4 and B). Seventeen minutes after the tetanus, the peak latency of the enhanced response decreased by 2-3 ms (record 5, open arrow), and a step reflecting the peak of the early-N appeared on the descending slope of the response (double arrow). The amplitude of the early-N after the development of LTP was larger than that in the pre-tetanic period over wide intensities of test stimulation (Fig. 3C).
A
8
mV
I.
~' ~g
o/
E
~f
b a.
~'
/
~
4"11mY
.-5-
~t
o
"i 5. • r~
," /
6ms
o
1o 15 20 v stimulus intensity
Fig. 3. Apparent potentiation of early-N. Record A1 shows control potentials. Records A2 and A3 show, in superimposition, a pair of potentials elicited at 30 ms and 100 ms intervals, respectively. Record A4 and A5 show potentials elicited 20 s and 17 min after a tetanus. Record A6 shows potentials 7 min after perfusion with 50 #M APB. Record A7 shows a pair of potentials elicited at 30 ms intervals in 50 #M APB. In panel B, a trace of record A1 (solid line) and record 4 (broken line) are enlarged and redrawn in superimposition. Graph C shows the relation between stimulus strength and potential amplitude. Closed circles and open circles indicate the amplitudes of early-N and late-N, respectively. The data before and 20 min after a tetanus are shown with solid and broken lines, respectively.
664 The data described in the preceding paragraph give us an impression that the early-N can be potentiated by conditioning stimuli, and therefore reflects a synaptic event. In the second response to a paired stimuli at a 100 ms interval, however, the early-N was not substantially potentiated (record A 3). Moreover, when the non-synaptic component was dissociated from the synaptic component under the action of APB (records A 6 and AT) , it was found that the amplitude of the non-synaptic component was almost identical with that of the early-N in the control records (record A 1). This suggests that the early-N observed before the tetanus reflects mainly non-synaptic events. Although Fig. 3 record A 5 and Fig. 3C show that LTP occurred in the early-N, this resulted probably from a superimposition of unpotentiated early-N's on potentiated late-N's generated with a shorter latency. Field potentials elicited in the region CA3 by granular layer stimulation were previously reported to contain a component reflecting the non-synaptic activation of CA3 neurons 6. Two possible mechanisms were proposed for the non-synaptic activation: ephaptic interaction between mossy fibers and CA3 neurons, and invasion of impulses conducting antidromically via axon collaterals of CA3 neurons to the dentate gyms. Although the non-synaptic component was sometimes relatively small in size and was obscured by the synaptic component in the pre-tetanic period, the non-synaptic component was often as large as or larger than the succeeding synaptic component. The latency of the deflection reflecting synaptic activation was longer than that of the non-synaptic component at a low frequency of test stimulation. In paired stimulation enhancement or in post-tetanic potentiation, however, its latency shortened to such an extent that the deflections reflecting synaptic and non-synaptic activation occurred almost simultaneously in the standard solution. This property of the short-term potentiation of the synaptic component lead us to a wrong conclusion in our previous study, in which the presence of short-term potentiation was used as a main criterion in judging a given deflection to reflect a synaptic events. We judged most of the early-N's as deflections reflecting synaptic events because of their apparent short-term potentiation and calculated the magnitude of the LTP of monosynaptic transmission at only 1.3 + 0.4 as expressed by a ratio of potential amplitude measured before and 15 min after a tetanus. In the present study, we selected potentials in which synaptic and non-synaptic components were clearly distinguished and recalculated the magnitude of LTP of monosynaptic transmission at 3.4 + 0.9 (mean + S.D., n = 7). This value is almost comparable to the magnitude of the LTP in region CA1 and in the dentate gyrus 2-4.
ACKNOWLEDGEMENTS
This work was supported by a grant from the Ministry of Education of Japan (60570495).
665 REFERENCES 1 Andersen, P., Sundberg, S.H., Sveen, O., Swarm, J.W. and Wigstrom, H., Possible mechanisms for long-lasting potentiation of synaptic transmission in hippocampal slices from guinea-pigs,J. Physiol. (London), 302 (1980) 463-482. 2 Duffy, C.J. and Teyler, T.J., Development of potentiation in the dentate gyrus of rat: physiology and anatomy, Brain Res. Bull., 3 (1978) 425-430. 3 Dunwiddie, T. and Lynch, G., Long-term potentiation and depression of synaptic responses in the rat hippocampus: localization and frequency dependency, J. Physiol. (London), 276 (1978) 353-367. 4 Haas, H.L. and Greene, R.W., Long-term potentiation and 4-amino-pyddine, Cell. MoL Neurobiol., 5 (1985) 297-301. 5 Higashima, M. and Yamamoto, C., Two components of long-term potentiation in mossy fiber-induced excitation in hippocampus, Exp. Neurol., 90 (1985) 529-539. 6 Yamamoto, C., Activation of hippocampal neurons by mossy fiber stimulation in thin brain sections in vitro, Exp. Brain Res., 14 (1972) 423-435. 7 Yamamoto, C., Sawada, S. and Takada, S., Suppressing action of 2-amino-4-phosphonobutyricacid on mossy fiber-induced excitation in the guinea pig hippocampus, Exp. Brain Res., 51 (1983) 128-134.
660
NSR 00131
Short Communications
The magnitude of long-term potentiation of field potentials induced monosynaptically in region CA3 of guinea pig hippocampus Masato Higashima and Chosaburo Yamamoto Department of Physiology, Faculty of Medicine, Kanazawa University, Kanazawa 920 (Japan) (Received January 31st, 1986; Accepted March 6th, 1986)
Key words: long-term potentiation - - short-term potentiation - - non-synaptic activation - - hippocampus -
-
guinea pig
SUMMARY The magnitude of long-term potentiation (LTP) was re-examined for monosynaptic transmission between mossy fibers and CA3 neurons in thin sections of the hippocampus of the guinea pig. Although an initial negative deflection in the field potential showed apparent short-term potentiation, this deflection was concluded to reflect non-synaptic activation of CA3 neurons. Accordingly, the magnitude of LTP of monosynaptic transmission was re-calculated at 3.4 +_ 0.9.
Previously, we studied configuration changes of field potentials elicited in region CA3 of the hippocampus during the development of long-term potentiation (LTP) 5. We observed that a single stimulus to the granular layer induced, in the pyramidal cell layer of the region CA3, a negative wave which was augmented only homosynaptically after the development of LTP. We also observed that the negative wave was usually followed by a positive slower wave which was potentiated after a short tetanus to homo- as well as heterosynaptic inputs. From these results, we suggested that the LTP of the negative wave reflected enhanced monosynaptic transmission through synapses between activated mossy fibers (axons of granular cells) and CA3 neurons, and the LTP of the positive response reflected modified interaction among postsynaptic neurons. The negative wave is sometimes complex in configuration, however. For the reason mentioned below, we considered that a negativity induced with short latencies reflected monosynaptic activation and a succeeding one reflected polysynaptic events caused by interaction Correspondence: M. Higashima, Department of Physiology, Faculty of Medicine, Kanazawa University, Kanazawa 920, Japan.
661 among postsynaptic neurons. According to this interpretation, we obtained a very low value for the magnitude of the LTP of the monosynaptic transmission. In the present study, we re-examined this interpretation and re-calculated the magnitude of the LTP in region CA3. Transverse sections (about 0.4 mm thick) of the hippocampal formation of the guinea pig were prepared as described before6, and were incubated in a standard solution for more than 40 min at 36 °C. Electrical activities of the tissue were examined in an observation chamber, in which the tissue was continuously superfused with the standard, or one of the modified solutions. The composition of the standard solution was (mM): NaCI 124, KC1 5, KHEPO 4 1.24, MgSO4 1.3, CaC12 2.4, NaHCO 3 26; and glucose 10. In a low Ca z+ solution, Ca z+ concentration was 1.6mM and Mg 2+ concentration was 6.3 mM. The solutions were saturated with 95~ O z and 5~o CO2. Stimulus pulses of 0.1 ms in duration and less than 20 V in intensity were delivered to the granular layer through a monopolar stainless-steel electrode. Field potentials were recorded from the pyramidal cell layer in the region CA3 with a glass pipette of about 10 # m tip diameter Idled with 150 mM NaCI. During the pre-tetanic period, test stimuli were delivered at 0.1 Hz and the stability of control responses was monitored for 10-15 min. Then, a tetanus was applied at 100 Hz for 1 s. Thereafter, the test stimuli were again repeated at 0.1 Hz and the test responses were observed for more than 15 min. LTP was arbitrarily def'med as potentiation lasting for more than 15 min after tetanust DL-2-Amino-4-phosphonobutyric acid (APB), a selective blocker of transmission through synapses between mossy fibers and CA3 neurons 7, was added to the perfusing solution at 50 or 100 #M. Fig. 1 shows an example of a negative wave of simply monophasic configuration. When preceded by a conditioning stimulus at an interval of 30 ms, the response was enhanced by about 300~o with a decrease in peak latency (record lb). After the development of LTP, the amplitude of the response was increased by about 200~ (record 2). When perfusion was started with a solution containing 50 #m APB, the peak of the negative wave was gradually decreased in amplitude and split into two successive negative deflections (record 3a). The fn'st deflection (dotted arrow) seems to reflect mainly non-synaptic activation of CA3 neurons, because it was potentiated only marginally in the second response to a paired stimulation (record 3b) and was elicited in the low Ca 2 + solution (record 4b). The second deflection (record 3a, open arrow) seems to reflect the synaptic activation of CA3 neurons, because it was markedly potentiated by a conditioning stimulation (record 3b, arrows) and was suppressed almost completely in the low Ca 2 + solution (record 4b). These results suggest that although the control negative wave in Fig. 1 was simply monophasic it includes deflections reflecting synaptic as well as non-synaptic activation of CA3 neurons. Fig. 2 shows the data of an experiment in which two deflections were discernible in the negative wave of the control response (record la, dotted and open arrows). These two deflections are called, according to the order of generation, early-N and late-N in this communication. When a pair of stimuli were delivered at a 30 ms interval, the
662 1. B e f o r e t e t a n u s
2. A f t e r t e t a n u s
3. A P B
4. a. s t a n d , sol.
b. l o w C a z+
-+I,,nV
"
6ms
c. r e c o v e r y
Fig. 1. Dissociation of non-synaptic and synaptic components in monophasic negative wave. Record la shows control field potcntiais. Record lb shows, in superimposition, a pair of potentials elicited at 30 ms intervals. Record 2a shows field potentials 17 min atter a tetanus. Record 3a shows responses 6 rain after perfusion with 50 #M APB. Record 3b shows a pair of potentiais elicited at 30 ms intervals in 50/~M APB in superimposition. Records 4a, 41) and 4c show responses elicited in the standard solution, 6 rain after perfusion with the low Ca 2 + solution and recovery of the responses after 12 min in the standard solution, respectively. Dotted and open arrows indicate non-synaptic and synaptic components, respectively. Except for records lb and 3b, two responses elicited at 0.1 Hz are superimposed. In this and in the following illustrations, single arrows indicate the second responses to paired stimuli.
1. B e f o r e t e t a n u s
i b -j
~
2. After t e t a n u s
3. APB
4.
~ ' "
~ "l
b. low Ca 2÷ ~'~
,~__~
~
a. stond, sot.
c. r e c o v e r y "1"I 1mY
6ms
Fig. 2. Potentiation and depression oflate-N. Record la shows control responses. Records lb and lc show, in superimposition, a pair of potontiais elicited at intervals of 30 ms and 100 ms, respectively. A double arrow indicates a notch corresponding to the peak of the early-N in the second response. Record 2a shows potentials 17 min atter a tetanus. Record 21) shows a pair of potentials elicited at 30 ms intervals in superimposition. Record 3a shows potentiais 6 rain aiter 50/~M APB. Record 3b shows a pair of potentials elicited at 30 ms intervals in 50/IM APB. Records 4a, 4b and 4c show potentials elicited in the standard solution, 13 rain after low Ca 2+ solution and 15 rain aiter perfusion with the standard solution. In this and in the next illustrations, dotted and open arrows indicate the early-N and late-N, respectively. In records la-4a, 4b and 4c, two field potentials evoked at 0.1 Hz are superimposed.
663 early-N as well as the late-N was apparently potentiated (record lb). The time-course of the initial portion of the descending phase of the potentiated response was identical to that of the early-N in the control, however, and a notch corresponding to the peak of the early-N is noticeable (double arrow). These observations suggest that the conditioning stimulus potentiated mainly the late-N. Actually, a substantial increase was observed only in the amplitude of the late-N at a stimulus interval of 100 ms (record lc). Seventeen minutes after a tetanus, a marked increase was observed in the amplitude of the late-N (record 2a, open arrow), whereas the potentiation of the early-N was marginal. The late-N disappeared in a solution containing APB (record 3a) but was elicited by the second of a paired stimuli (record 3b). In the low Ca 2 ÷ solution, the late-N was almost completely suppressed (record 4b), whereas the early-N was only partly suppressed. Therefore, the early-N and late-N in record la in Fig. 2 mainly reflect the non-synaptic and synaptic activation of CA3 neurons, respectively. The potentials in Fig. 3 are more misleading. The second stimulus of a pair of stimuli elicited an apparently potentiated early-N at a 30 ms stimulus interval (record A2). An apparent potentiation of the early-N is also noted immediately after a tetanus (record A 4 and B). Seventeen minutes after the tetanus, the peak latency of the enhanced response decreased by 2-3 ms (record 5, open arrow), and a step reflecting the peak of the early-N appeared on the descending slope of the response (double arrow). The amplitude of the early-N after the development of LTP was larger than that in the pre-tetanic period over wide intensities of test stimulation (Fig. 3C).
A
8
mV
I.
~' ~g
o/
E
~f
b a.
~'
/
~
4"11mY
.-5-
~t
o
"i 5. • r~
," /
6ms
o
1o 15 20 v stimulus intensity
Fig. 3. Apparent potentiation of early-N. Record A1 shows control potentials. Records A2 and A3 show, in superimposition, a pair of potentials elicited at 30 ms and 100 ms intervals, respectively. Record A4 and A5 show potentials elicited 20 s and 17 min after a tetanus. Record A6 shows potentials 7 min after perfusion with 50 #M APB. Record A7 shows a pair of potentials elicited at 30 ms intervals in 50 #M APB. In panel B, a trace of record A1 (solid line) and record 4 (broken line) are enlarged and redrawn in superimposition. Graph C shows the relation between stimulus strength and potential amplitude. Closed circles and open circles indicate the amplitudes of early-N and late-N, respectively. The data before and 20 min after a tetanus are shown with solid and broken lines, respectively.
664 The data described in the preceding paragraph give us an impression that the early-N can be potentiated by conditioning stimuli, and therefore reflects a synaptic event. In the second response to a paired stimuli at a 100 ms interval, however, the early-N was not substantially potentiated (record A 3). Moreover, when the non-synaptic component was dissociated from the synaptic component under the action of APB (records A 6 and AT) , it was found that the amplitude of the non-synaptic component was almost identical with that of the early-N in the control records (record A 1). This suggests that the early-N observed before the tetanus reflects mainly non-synaptic events. Although Fig. 3 record A 5 and Fig. 3C show that LTP occurred in the early-N, this resulted probably from a superimposition of unpotentiated early-N's on potentiated late-N's generated with a shorter latency. Field potentials elicited in the region CA3 by granular layer stimulation were previously reported to contain a component reflecting the non-synaptic activation of CA3 neurons 6. Two possible mechanisms were proposed for the non-synaptic activation: ephaptic interaction between mossy fibers and CA3 neurons, and invasion of impulses conducting antidromically via axon collaterals of CA3 neurons to the dentate gyms. Although the non-synaptic component was sometimes relatively small in size and was obscured by the synaptic component in the pre-tetanic period, the non-synaptic component was often as large as or larger than the succeeding synaptic component. The latency of the deflection reflecting synaptic activation was longer than that of the non-synaptic component at a low frequency of test stimulation. In paired stimulation enhancement or in post-tetanic potentiation, however, its latency shortened to such an extent that the deflections reflecting synaptic and non-synaptic activation occurred almost simultaneously in the standard solution. This property of the short-term potentiation of the synaptic component lead us to a wrong conclusion in our previous study, in which the presence of short-term potentiation was used as a main criterion in judging a given deflection to reflect a synaptic events. We judged most of the early-N's as deflections reflecting synaptic events because of their apparent short-term potentiation and calculated the magnitude of the LTP of monosynaptic transmission at only 1.3 + 0.4 as expressed by a ratio of potential amplitude measured before and 15 min after a tetanus. In the present study, we selected potentials in which synaptic and non-synaptic components were clearly distinguished and recalculated the magnitude of LTP of monosynaptic transmission at 3.4 + 0.9 (mean + S.D., n = 7). This value is almost comparable to the magnitude of the LTP in region CA1 and in the dentate gyrus 2-4.
ACKNOWLEDGEMENTS
This work was supported by a grant from the Ministry of Education of Japan (60570495).
665 REFERENCES 1 Andersen, P., Sundberg, S.H., Sveen, O., Swarm, J.W. and Wigstrom, H., Possible mechanisms for long-lasting potentiation of synaptic transmission in hippocampal slices from guinea-pigs,J. Physiol. (London), 302 (1980) 463-482. 2 Duffy, C.J. and Teyler, T.J., Development of potentiation in the dentate gyrus of rat: physiology and anatomy, Brain Res. Bull., 3 (1978) 425-430. 3 Dunwiddie, T. and Lynch, G., Long-term potentiation and depression of synaptic responses in the rat hippocampus: localization and frequency dependency, J. Physiol. (London), 276 (1978) 353-367. 4 Haas, H.L. and Greene, R.W., Long-term potentiation and 4-amino-pyddine, Cell. MoL Neurobiol., 5 (1985) 297-301. 5 Higashima, M. and Yamamoto, C., Two components of long-term potentiation in mossy fiber-induced excitation in hippocampus, Exp. Neurol., 90 (1985) 529-539. 6 Yamamoto, C., Activation of hippocampal neurons by mossy fiber stimulation in thin brain sections in vitro, Exp. Brain Res., 14 (1972) 423-435. 7 Yamamoto, C., Sawada, S. and Takada, S., Suppressing action of 2-amino-4-phosphonobutyricacid on mossy fiber-induced excitation in the guinea pig hippocampus, Exp. Brain Res., 51 (1983) 128-134.