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Long-term potentiation in slices from subcortically deafferented hippocampi
Brain Research, 518 (1990) 279-282 Elsevier
279
BRES 24099
Long-term potentiation in slices from subcortically deafferented hippocampi Gfibor Cz6h, Zsolt Horv~th and J~inos Czopf Institute of Physiology, University Medical School of P~cs, P~cs (Hungary)
(Accepted 6 February 1990) Key words." Hippocampus; Long-term potentiation; Subcortical deafferentation; Rat
Long-term potentiation (LTP) can be initiated in CA1, but not in the dentate, region of slices from rats with bilateral subcortical deafferentation at 8 week survival time. At about one week survival time, LTP is present in the CA1 region of all and also in the dentate of about 50% of slices. The results suggest that subcortical cholinergic and catecholaminergic inputs are not required for the LTP in the CA1 area of the rat hippocampus.
Long-term potentiation (LTP) is a stable, relatively long-lasting increase in the magnitude of a post-synaptic response to a constant afferent volley following brief tetanic stimulation of the same afferents. Many papers deal with the relationship of LTP to the neuronal mechanisms underlying learning and memory 22'23. There are also reports on blocking or eliminating the LTP 7' 13,16,20,21,24
Buzs~iki and Gage has recently 3 reported on the absence of LTP in the subcortically deafferented dentate gyrus. They stimulated the angular bundle with high frequency and found the well-known 2 sustained increase of the evoked population spike in the dentate gyrus in normal but not in rats which suffered removal of fibers running in the fimbria-fornix and supracallosal path. There are other reports too on the behavioral deficit in learning task of rats after fimbria-fornix lesion 6"11. The question remains open if a similar deafferentation affects LTP in other parts of the hippocampal formation. We report here on finding LTP in the CA1 pyramidal cells, when tested with stimulation of the Schaffer collaterals in slices cut from rats which had bilateral removal of the subcortical afferents. The experiments were performed on Sprague-Dawley rats of 120-200 g b. wt. Slices were cut from 10 normal rats, and from 17 animals in which the fimbria and fornix had been aspirated bilaterally 1-8 weeks before the electrophysiological tests. Surgery was made under 100 mg/kg ketamine anesthesia and the cingulate bundle, the supracallosal stria, the corpus callosum, the dorsal fornix, the fimbria and the ventral hippocampal commissure
were removed through a hole aspired near the midline from the cingulate and parietal cortex. Completeness of the aspirative lesion of the fimbriafornix fibers was evident when dissecting the hippocampi: the septal (anterior) pole of the hippocampus slipped backward since it lost its anchorage by the fornix. In addition, two further criteria were also used to verify the deafferentation of the hippocampus: one was the absence of acetylcholinesterase reaction in histological slices from the same animals, and the other was the regular occurrence of epileptiform activity in the slice preparations in accord with recent observations in vivo 4. Electrophysiological tests were made on slices maintained in an interface chamber perfused with a fluid containing (in mM): NaCI 124, KCI 3.5, KH2PO 4 1.25, N a H C O 3 24, CaCI 2 1.8, MgSO 4 1.2, D-glucose 10; temperature 36 °C. Field potentials were recorded with glass microelectrodes of 3-10 M~2 filled with 150 mM NaCI. Stimulations were carried out monopolarly (1-10 V pulses of 0.1 ms duration) with a 2 M~2 stainless steel microelectrode. All slices came from the dorsal half of the hippocampus. At least 120 min incubation time was allowed between cutting and testing the slices. Responses in the CA1 region were tested with stimulation of stratum radiatum and recording from the stratum pyramidale, and those in the dentate gyrus with stimulation of the stratum moleculare and recording from the granulare. Responses were initiated with pulses delivered at 0.1 Hz rate and 4 evoked potentials were averaged using an IBM AT compatible computer and Aitken's program 1. Three averages of responses from a 15 min period served
Correspondence: G. Cz6h, Institute of Physiology, University Medical School of PEcs, H-7643 P6cs, Szigetiut 12, Hungary.
0006-8993/90/$03.50 ~ 1990 Elsevier Science Publishers B.V. (Biomedical Division)
280 We considered the e n h a n c e m e n t of the population spike responses as representing LTP if the increase of their amplitude exceeded 20% during the 10-30 rain post-tetanization period. O v e r 90% of the slices from normal rats met this criterion in their C A 1 subfield. F r o m the group of lesioned rats, a total of 5 slices were rejected from further analysis because potentiation r e m a i n e d less then 20% in the CA1 region of them. Stability of the responsiveness was tested in keeping several slices stimulated only with low rate and averaging 4 responses at every 5 min during a 40 rain period. Both some slow increase or decrease of e v o k e d responses were noted as well as some fluctuation of the e v o k e d responses, but these changes r e m a i n e d within 10-15% of the initial size. LTP was tested in 9 slices cut from 4 rats at 8 weeks after subcortical deafferentation. Unlike in normal slices, the CA1 pyramidal cells of lesioned rats r e s p o n d e d with 2 or 3 subsequent p o p u l a t i o n spikes to a single stratum radiatum pulse. We m e a s u r e d changes of each spike separately. The mean amplitude of the first population spike during the pre-tetanization p e r i o d was 2.96 mV (S.D. 0.75). As illustrated in Fig. 2, this amplitude increased by 5 0 - 6 0 % (mean from 7 slices) during the 10-30 rain post-tetanization period. U p to 200% enh a n c e m e n t was observed in individual slices. The second population spike indicated a larger effect of tetanic stimulation: the mean size b e c o m e d o u b l e d from the 1.63 mV mean pre-tetanization value. No sign of LTP was found in the gyrus dentatus area
A
P~
B
Fig. 1. Waveforms of averaged responses and techniques of amplitude measurements. Slice made from a rat after 7 days of subcortical deafferentation. A: response evoked in the stratum pyramidale by stimulation of stratum radiatum of CA1 area during the pre-tetanization period. B: enhancement of the same response at 30 min after tetanization. Peaks measured for calculating sizes of population spikes are indicated. 2 mV (negative) and 1 ms calibrating pulses are shown at the beginning of the traces.
as control to test the viability of the slices. Next, 12 trains of 400 ms, at 80-100 Hz, were delivered in a period of 1 min. Responses e v o k e d again with 0.1 Hz rate were then tested during a p e r i o d of 30 min after the tetanic stimulation. A m p l i t u d e s of the population spikes were m e a s u r e d in the averaged responses as shown in Fig. 1, and n o r m a l i z e d for the mean size of the population spike r e c o r d e d during the 15 rain control period.
in this group.
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Fig. 2. Time course of effects of tetanic stimulation of the CA1 and the dentate area. Mean amplitudes of the first population spike components normalized for the pre-tetanization period are shown from group of slices described in the text. Left: long-lasting potentiation of pyramidal cell firing in slices from normal rats (Control) and in those from rats with short (Young) and long (Old) survival period after subcortical deafferentation. Right: potentiation of the granule cell firing in 12 slices from normal rats (Control) and in 6 slices (LTP) from operated animals with short survival period. Data from 5 other slices from rats with the same survival period indicate no LTP.
281 In 12 slices obtained from 4 rats with 6 - 8 days postoperative survival, tetanic stimulation of the stratum radiatum of CA1 produced also a large increase of the population spike in the stratum pyramidale. The mean enhancement of normalized size of the first population spike component varied between 54 and 68% during the 10-30 min post-tetanization period (Fig. 2). The differences between corresponding points plotting the data from the control and the two operated groups were statistically not significant (Student's t-test, at 0.1 level). The second and the third population spike increased by more than 200%. The mean amplitude of these first 3 population spikes was 2.69, 1.87, and 1.44 mV, respectively, during the pre-tetanization period. Tetanic stimulation of the stratum moleculare in the dentate area of the same 12 slices also potentiated the granule cell population spike response in 6 but not in 5 slices. E n h a n c e m e n t of the population spike in the ones which potentiation was remarkably similar to the LTP seen in the control slices (Fig. 2). In the other slices, marked as 'no LTP', the population spike increased only for a few minutes after the high frequency stimulation. Mean increase of the first population spike component was over 50% from an initial 4.74 (S.D. 1.59) mV, and that of the second spike over 400% from an initial 1.49 (S.D. 0.84) m V amplitude. Twelve slices were selected from experiments made in slices from intact rats for obtaining control data on the LTP in our hands. The mean amplitude of the CA1 population spike response was 4.99 (S.D. 2,64) mV and the mean enhancement was beyond 80% during the 10-30 min post-tetanization period. In 8 slices, the granule cell population spike response showed over 38% potentiation from an initial 3.18 mV mean amplitude (S.D. 1.26). Our results can be summarized as follows: in the CA1 region, high frequency stimulation of the stratum radiatum fibers regularly produces LTP in hippocampi ob1 Aitken, P.G., Kainic acid and penicillin: differential effects on excitatory and inhibitory interactions in the CA1 region of the hippocampal slice, Brain Research, 325 (1985) 261-269. 2 Bliss, T.V.P. and Lomo, T., Long-lasting potentiation of synaptic transmission in the dentate area of the anesthetized rabbit following stimulation of the perforant path, J. Physiol. (Lond.), 232 (1973) 331-356. 3 Buzs~lki, G. and Gage, F.H., Absence of long-term potentiation in the subcortically deafferented dentate gyrus, Brain Research, 484 (1989) 94-101. 4 Buzs~lki, G., Ponomareff, G.L., Bayardo, E, Ruiz, R. and Gage, EH., Neuronal activity in the subcortically denervated hippocampus: a chronic model for epilepsy, Neuroscience, 28 (1989) 527-538. 5 Dravid, A.R. and Van Deusen, E.B., Recovery of choline acetyltransferase and acetylcholinesterase activities in the ipsilateral hippocampus following unilateral, partial transection of the fimbria in rats, Brain Research, 277 (1983) 169-174.
tained from both intact rats and in animals with previous subcortical deafferentation. After one week of subcortical deafferentation, LTP can also be observed in the dentate gyrus. Part of our in vitro data confirm a recent report 3 obtained in vivo from rats which survived subcortical deafferentation as showing no significant LTP in the dentate gyrus. Time course of the effects produced by subcortical deafferentation is being explored to see if the LTP will eventually disappear also in the CA1 region as in the dentate. We also try to find the minimum time needed for diminution of the LTP in the dentate area. At 8 weeks after transection of fibers in the fimbria and fornix, density of afferent synapses is decreased markedly 5'17, but correlation of the anatomical losses with diminution of the LTP is not known. If the LTP would disappear also in the CA1 region a similar effect of subcortical deafferentation with some simple time course difference could explain the apparent discrepancy between the results from Buzs~iki and Gage 3 and our observations. There seem to be other possibilities, however. Mechanism of LTP may not be quite the same in the dentate and the CA1 areas 8'19'23. Involvement of catecholaminergic pathways seems particularly different in the mechanism of LTP in CA1 and dentate 12' 14,15,19. The amount of presynaptic input lost by deafferentation may also be critical (subcortical afferents innervate the gyrus dentatus more densely than the CA1 region9,10,18). Nevertheless, the fact that LTP can be observed in the CA1 area as long as 2 months after subcortical deafferentation argues against the essential role of either monoaminergic or cholinergic subcortical fibers in the mechanisms of LTP in CA1 region. We are grateful to Dr. Gy6rgy Buzs~iki for reading the manuscript and to Zita Cz6h for expert secretarial and technical assistence. Supported by Grants OTKA MTA 2-86-1-513 and 3/566/86 OTKASzEM, Hungary. 6 Dunnett, S.B., Low, W.C., Iversen, S.D., Stenevi, U. and Bj6rklund, A., Septal transplants restore maze learning in rats with fimbria-fornix lesion, Brain Research, 251 (1981) 335-348. 7 Dunwiddie, T., Madison, D. and Lynch, G., Synaptic transmission is required for initiation of long-term potentiation, Brain Research, 150 (1978) 413-417. 8 Dunwiddie, T.V., Roberson, N.L. and Worth, T., Modulation of long-term potentiation: effects of adrenergic and neuroleptic drugs, Pharmacol. Biochem. Behav., 17 (1982) 1257-1264. 9 Fibiger, H.C., The organization and some projections of cholinergic neurons of the mammalian forebrain, Brain Res. Rev., 4 (1982) 327-388. 10 Frotscher, M. and L6r~lnth, C., Cholinergic innervation of the rat hippocampus as revealed by choline acetyltransferase immunocytochemistry: a combined light and electron microscopic study, J. Comp. Neurol., 239 (1985) 237-246. 11 Gage, F.H., Bj6rklund, A., Stenevi, U. and Dunnett, S.B., Functional correlates of compensatory collateral sprouting by
282
12 13 14 15 16
17 18
aminergic and cholinergic afferents in the hippocampal formation, Brain Research, 268 (1983) 39-47. Gold, P.E., Delanoy, R.L. and Merrin, J., Modulation of long-term potentiation by peripherally administered amphetamine and epinephrine, Brain Research, 305 (1984) 103-107. Hopkins, W.E and Johnston, D., fl-Adrenergic receptor regulation of long-term potentiation in the hippocampus, Soc. Neurosci. Abstr., 9 (1983) A248.12. Hopkins, W.E and Johnston, D., Frequency-dependent noradrenergic modulation of long-term potentiation in the hippocampus, Science, 226 (1984) 350-352. Krug, M., Chepkova, A.N., Geyer, C. and Ott, T., Aminergic blockade modulates long-term potentiation in the dentate gyrus of freely moving rats, Brain Res. Bull., 11 (1983) 1-6. Lynch, G., Larson, J., Kelso, S., Barrionuevo, G. and Schottler, E, Intracellular injections of EGTA block induction of hippocampal long-term potentiation, Nature (Lond.), 305 (1983) 719-721. Mellgren, S.L. and Srebro, B., Changes in acetylcholinesterase and distribution of degenerating fibers in the hippocampal region after septal lesions in the rat, Brain Research, 52 (1973) 19-36. Nyakas, C., Luiten, P.G.M., Spencer, D.G. and Traber, J., Detailed projection patterns of septal and diagonal band
19
20
21 22 23 24
efferents to the hippocampus in the rat with emphasis on innervation of CA1 and dentate gyrus, Brain Res. Bull., 18 (1987) 533-545. Stanton, P.K. and Sarvey, J.M., Depletion of norepinephrine, but not serotonin, reduces long-term potentiation in the dentate gyrus of rat hippocampal slices, J. Neurosci., 5 (1985) 21692176. Stringer, J.L., Greenfield, L.J., Hackett, J.T. and Guyenet, P.G., Blockade of long-term potentiation by phencyclidine and sigma opiates in the hippocampus in vivo and in vitro, Brain Research, 280 (1983) 127-138. Stringer, J.L. and Guyenet, P.G., Elimination of long-term potentiation in the hippocampus by phencyclidine and ketamine, Brain Research, 258 (1983) 159-164. Swanson, L.W., Teyler, T.J. and Thompson, R.J., Hippocampal long-term potentiation: mechanisms and implications for memory, Neurosci. Res. Progr. Bull., 20 (1982) 613-769. Teyler, T.J. and DiScenna, P., Long-term potentiation, Annu. Rev. Neurosci., 10 (1987) 131-161. Wigstr6m, H., Swann, J.W. and Andersen, P., Calcium dependency of synaptic long-lasting potentiation in the hippocampal slice, Acta Physiol. Scand.. 105 (1979) 126-128.
279
BRES 24099
Long-term potentiation in slices from subcortically deafferented hippocampi Gfibor Cz6h, Zsolt Horv~th and J~inos Czopf Institute of Physiology, University Medical School of P~cs, P~cs (Hungary)
(Accepted 6 February 1990) Key words." Hippocampus; Long-term potentiation; Subcortical deafferentation; Rat
Long-term potentiation (LTP) can be initiated in CA1, but not in the dentate, region of slices from rats with bilateral subcortical deafferentation at 8 week survival time. At about one week survival time, LTP is present in the CA1 region of all and also in the dentate of about 50% of slices. The results suggest that subcortical cholinergic and catecholaminergic inputs are not required for the LTP in the CA1 area of the rat hippocampus.
Long-term potentiation (LTP) is a stable, relatively long-lasting increase in the magnitude of a post-synaptic response to a constant afferent volley following brief tetanic stimulation of the same afferents. Many papers deal with the relationship of LTP to the neuronal mechanisms underlying learning and memory 22'23. There are also reports on blocking or eliminating the LTP 7' 13,16,20,21,24
Buzs~iki and Gage has recently 3 reported on the absence of LTP in the subcortically deafferented dentate gyrus. They stimulated the angular bundle with high frequency and found the well-known 2 sustained increase of the evoked population spike in the dentate gyrus in normal but not in rats which suffered removal of fibers running in the fimbria-fornix and supracallosal path. There are other reports too on the behavioral deficit in learning task of rats after fimbria-fornix lesion 6"11. The question remains open if a similar deafferentation affects LTP in other parts of the hippocampal formation. We report here on finding LTP in the CA1 pyramidal cells, when tested with stimulation of the Schaffer collaterals in slices cut from rats which had bilateral removal of the subcortical afferents. The experiments were performed on Sprague-Dawley rats of 120-200 g b. wt. Slices were cut from 10 normal rats, and from 17 animals in which the fimbria and fornix had been aspirated bilaterally 1-8 weeks before the electrophysiological tests. Surgery was made under 100 mg/kg ketamine anesthesia and the cingulate bundle, the supracallosal stria, the corpus callosum, the dorsal fornix, the fimbria and the ventral hippocampal commissure
were removed through a hole aspired near the midline from the cingulate and parietal cortex. Completeness of the aspirative lesion of the fimbriafornix fibers was evident when dissecting the hippocampi: the septal (anterior) pole of the hippocampus slipped backward since it lost its anchorage by the fornix. In addition, two further criteria were also used to verify the deafferentation of the hippocampus: one was the absence of acetylcholinesterase reaction in histological slices from the same animals, and the other was the regular occurrence of epileptiform activity in the slice preparations in accord with recent observations in vivo 4. Electrophysiological tests were made on slices maintained in an interface chamber perfused with a fluid containing (in mM): NaCI 124, KCI 3.5, KH2PO 4 1.25, N a H C O 3 24, CaCI 2 1.8, MgSO 4 1.2, D-glucose 10; temperature 36 °C. Field potentials were recorded with glass microelectrodes of 3-10 M~2 filled with 150 mM NaCI. Stimulations were carried out monopolarly (1-10 V pulses of 0.1 ms duration) with a 2 M~2 stainless steel microelectrode. All slices came from the dorsal half of the hippocampus. At least 120 min incubation time was allowed between cutting and testing the slices. Responses in the CA1 region were tested with stimulation of stratum radiatum and recording from the stratum pyramidale, and those in the dentate gyrus with stimulation of the stratum moleculare and recording from the granulare. Responses were initiated with pulses delivered at 0.1 Hz rate and 4 evoked potentials were averaged using an IBM AT compatible computer and Aitken's program 1. Three averages of responses from a 15 min period served
Correspondence: G. Cz6h, Institute of Physiology, University Medical School of PEcs, H-7643 P6cs, Szigetiut 12, Hungary.
0006-8993/90/$03.50 ~ 1990 Elsevier Science Publishers B.V. (Biomedical Division)
280 We considered the e n h a n c e m e n t of the population spike responses as representing LTP if the increase of their amplitude exceeded 20% during the 10-30 rain post-tetanization period. O v e r 90% of the slices from normal rats met this criterion in their C A 1 subfield. F r o m the group of lesioned rats, a total of 5 slices were rejected from further analysis because potentiation r e m a i n e d less then 20% in the CA1 region of them. Stability of the responsiveness was tested in keeping several slices stimulated only with low rate and averaging 4 responses at every 5 min during a 40 rain period. Both some slow increase or decrease of e v o k e d responses were noted as well as some fluctuation of the e v o k e d responses, but these changes r e m a i n e d within 10-15% of the initial size. LTP was tested in 9 slices cut from 4 rats at 8 weeks after subcortical deafferentation. Unlike in normal slices, the CA1 pyramidal cells of lesioned rats r e s p o n d e d with 2 or 3 subsequent p o p u l a t i o n spikes to a single stratum radiatum pulse. We m e a s u r e d changes of each spike separately. The mean amplitude of the first population spike during the pre-tetanization p e r i o d was 2.96 mV (S.D. 0.75). As illustrated in Fig. 2, this amplitude increased by 5 0 - 6 0 % (mean from 7 slices) during the 10-30 rain post-tetanization period. U p to 200% enh a n c e m e n t was observed in individual slices. The second population spike indicated a larger effect of tetanic stimulation: the mean size b e c o m e d o u b l e d from the 1.63 mV mean pre-tetanization value. No sign of LTP was found in the gyrus dentatus area
A
P~
B
Fig. 1. Waveforms of averaged responses and techniques of amplitude measurements. Slice made from a rat after 7 days of subcortical deafferentation. A: response evoked in the stratum pyramidale by stimulation of stratum radiatum of CA1 area during the pre-tetanization period. B: enhancement of the same response at 30 min after tetanization. Peaks measured for calculating sizes of population spikes are indicated. 2 mV (negative) and 1 ms calibrating pulses are shown at the beginning of the traces.
as control to test the viability of the slices. Next, 12 trains of 400 ms, at 80-100 Hz, were delivered in a period of 1 min. Responses e v o k e d again with 0.1 Hz rate were then tested during a p e r i o d of 30 min after the tetanic stimulation. A m p l i t u d e s of the population spikes were m e a s u r e d in the averaged responses as shown in Fig. 1, and n o r m a l i z e d for the mean size of the population spike r e c o r d e d during the 15 rain control period.
in this group.
Dentafe
CA I 1.8-
1,8-
1.6-
1.4-
rol 1.2-
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Fig. 2. Time course of effects of tetanic stimulation of the CA1 and the dentate area. Mean amplitudes of the first population spike components normalized for the pre-tetanization period are shown from group of slices described in the text. Left: long-lasting potentiation of pyramidal cell firing in slices from normal rats (Control) and in those from rats with short (Young) and long (Old) survival period after subcortical deafferentation. Right: potentiation of the granule cell firing in 12 slices from normal rats (Control) and in 6 slices (LTP) from operated animals with short survival period. Data from 5 other slices from rats with the same survival period indicate no LTP.
281 In 12 slices obtained from 4 rats with 6 - 8 days postoperative survival, tetanic stimulation of the stratum radiatum of CA1 produced also a large increase of the population spike in the stratum pyramidale. The mean enhancement of normalized size of the first population spike component varied between 54 and 68% during the 10-30 min post-tetanization period (Fig. 2). The differences between corresponding points plotting the data from the control and the two operated groups were statistically not significant (Student's t-test, at 0.1 level). The second and the third population spike increased by more than 200%. The mean amplitude of these first 3 population spikes was 2.69, 1.87, and 1.44 mV, respectively, during the pre-tetanization period. Tetanic stimulation of the stratum moleculare in the dentate area of the same 12 slices also potentiated the granule cell population spike response in 6 but not in 5 slices. E n h a n c e m e n t of the population spike in the ones which potentiation was remarkably similar to the LTP seen in the control slices (Fig. 2). In the other slices, marked as 'no LTP', the population spike increased only for a few minutes after the high frequency stimulation. Mean increase of the first population spike component was over 50% from an initial 4.74 (S.D. 1.59) mV, and that of the second spike over 400% from an initial 1.49 (S.D. 0.84) m V amplitude. Twelve slices were selected from experiments made in slices from intact rats for obtaining control data on the LTP in our hands. The mean amplitude of the CA1 population spike response was 4.99 (S.D. 2,64) mV and the mean enhancement was beyond 80% during the 10-30 min post-tetanization period. In 8 slices, the granule cell population spike response showed over 38% potentiation from an initial 3.18 mV mean amplitude (S.D. 1.26). Our results can be summarized as follows: in the CA1 region, high frequency stimulation of the stratum radiatum fibers regularly produces LTP in hippocampi ob1 Aitken, P.G., Kainic acid and penicillin: differential effects on excitatory and inhibitory interactions in the CA1 region of the hippocampal slice, Brain Research, 325 (1985) 261-269. 2 Bliss, T.V.P. and Lomo, T., Long-lasting potentiation of synaptic transmission in the dentate area of the anesthetized rabbit following stimulation of the perforant path, J. Physiol. (Lond.), 232 (1973) 331-356. 3 Buzs~lki, G. and Gage, F.H., Absence of long-term potentiation in the subcortically deafferented dentate gyrus, Brain Research, 484 (1989) 94-101. 4 Buzs~lki, G., Ponomareff, G.L., Bayardo, E, Ruiz, R. and Gage, EH., Neuronal activity in the subcortically denervated hippocampus: a chronic model for epilepsy, Neuroscience, 28 (1989) 527-538. 5 Dravid, A.R. and Van Deusen, E.B., Recovery of choline acetyltransferase and acetylcholinesterase activities in the ipsilateral hippocampus following unilateral, partial transection of the fimbria in rats, Brain Research, 277 (1983) 169-174.
tained from both intact rats and in animals with previous subcortical deafferentation. After one week of subcortical deafferentation, LTP can also be observed in the dentate gyrus. Part of our in vitro data confirm a recent report 3 obtained in vivo from rats which survived subcortical deafferentation as showing no significant LTP in the dentate gyrus. Time course of the effects produced by subcortical deafferentation is being explored to see if the LTP will eventually disappear also in the CA1 region as in the dentate. We also try to find the minimum time needed for diminution of the LTP in the dentate area. At 8 weeks after transection of fibers in the fimbria and fornix, density of afferent synapses is decreased markedly 5'17, but correlation of the anatomical losses with diminution of the LTP is not known. If the LTP would disappear also in the CA1 region a similar effect of subcortical deafferentation with some simple time course difference could explain the apparent discrepancy between the results from Buzs~iki and Gage 3 and our observations. There seem to be other possibilities, however. Mechanism of LTP may not be quite the same in the dentate and the CA1 areas 8'19'23. Involvement of catecholaminergic pathways seems particularly different in the mechanism of LTP in CA1 and dentate 12' 14,15,19. The amount of presynaptic input lost by deafferentation may also be critical (subcortical afferents innervate the gyrus dentatus more densely than the CA1 region9,10,18). Nevertheless, the fact that LTP can be observed in the CA1 area as long as 2 months after subcortical deafferentation argues against the essential role of either monoaminergic or cholinergic subcortical fibers in the mechanisms of LTP in CA1 region. We are grateful to Dr. Gy6rgy Buzs~iki for reading the manuscript and to Zita Cz6h for expert secretarial and technical assistence. Supported by Grants OTKA MTA 2-86-1-513 and 3/566/86 OTKASzEM, Hungary. 6 Dunnett, S.B., Low, W.C., Iversen, S.D., Stenevi, U. and Bj6rklund, A., Septal transplants restore maze learning in rats with fimbria-fornix lesion, Brain Research, 251 (1981) 335-348. 7 Dunwiddie, T., Madison, D. and Lynch, G., Synaptic transmission is required for initiation of long-term potentiation, Brain Research, 150 (1978) 413-417. 8 Dunwiddie, T.V., Roberson, N.L. and Worth, T., Modulation of long-term potentiation: effects of adrenergic and neuroleptic drugs, Pharmacol. Biochem. Behav., 17 (1982) 1257-1264. 9 Fibiger, H.C., The organization and some projections of cholinergic neurons of the mammalian forebrain, Brain Res. Rev., 4 (1982) 327-388. 10 Frotscher, M. and L6r~lnth, C., Cholinergic innervation of the rat hippocampus as revealed by choline acetyltransferase immunocytochemistry: a combined light and electron microscopic study, J. Comp. Neurol., 239 (1985) 237-246. 11 Gage, F.H., Bj6rklund, A., Stenevi, U. and Dunnett, S.B., Functional correlates of compensatory collateral sprouting by
282
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