Discover millions of ebooks, audiobooks, and so much more with a free trial

Only $11.99/month after trial. Cancel anytime.

Learning and Memory: Mechanisms of Information Storage in the Nervous System
Learning and Memory: Mechanisms of Information Storage in the Nervous System
Learning and Memory: Mechanisms of Information Storage in the Nervous System
Ebook930 pages

Learning and Memory: Mechanisms of Information Storage in the Nervous System

Rating: 0 out of 5 stars

()

Read preview

About this ebook

Learning and Memory: Mechanisms of Information Storage in the Nervous System contains the proceedings of the Seventh International Neurobiological Symposium held at Magdeburg on October 28 to November 2, 1985. Organized into four sections, this book first elucidates the synaptic long-term potentiation. Section II explores hippocampal functions, and Section III describes the biochemistry of memory formation. The last section addresses the principles and modification of learning behavior.
LanguageEnglish
Release dateOct 22, 2013
ISBN9781483161310
Learning and Memory: Mechanisms of Information Storage in the Nervous System

Related to Learning and Memory

Psychology For You

View More

Reviews for Learning and Memory

Rating: 0 out of 5 stars
0 ratings

0 ratings0 reviews

What did you think?

Tap to rate

Review must be at least 10 words

    Book preview

    Learning and Memory - Hansjurgen Matthies

    Exeter

    Participants

    BRAZIL

    I. Izquierdo, Porto Alegre

    BULGARIA

    D. Yonkov, Sofia

    P.R. CHINA

    Su Donghai, Hangzhou

    CUBA

    L. Acosta, Matanzas

    P. Amezaga Acosta, Matanzas

    J. Bergado, Matanzas

    D.M. Leon, Matanzas

    R. Rodriguez, Matanzas

    CZECHOSLOVAKIA

    J. Bureš, Praha

    O. Burešová, Praha

    ek, Praha

    V. Nováková, Praha

    J. Šterc, Praha

    FED. REP. GERMANY and BERLIN (WEST)

    L. Frölich, Heidelberg

    J.P. Huston, Düsseldorf

    R. Menzel, Berlin-West

    T. Messerschmidt, München

    H. Rahmann, Stuttgart

    M. Sarter, Berlin-West

    R. Schmidt, Frankfurt/M.

    W. Seifert, Göttingen

    FRANCE

    M. Amassari-Teule, Gif-sur-Yvette

    G. Chapouthier, Gif-sur-Yvette

    C. Destrade, Talence

    S. Sara, Gif-sur-Yvette

    GERMAN DEM. REP.

    D. Balschun, Halle

    H.-G. Bernstein, Magdeburg

    D. Biesold, Leipzig

    H. Brandl, Berlin

    R. Brödemann, Magdeburg

    A. Dorn, Magdeburg

    A. Ermisch, Leipzig

    U. Frey, Magdeburg

    G. Grecksch, Magdeburg

    J. Gündel, Jena

    B. Günther, Jena

    GERMAN DEM. REP.

    W. Haschke, Jena

    U. Haselhorst, Magdeburg

    H.-R. Heise, Magdeburg

    L. Hetey, Berlin

    H. Hoffmann, Magdeburg

    W. Hoffmann, Radebeul

    B. Homfeld, Leipzig

    R. Honza, Magdeburg

    R. Jork, Magdeburg

    E. Kammerer, Magdeburg

    G. Keller, Dresden

    S. Kirchoff, Magdeburg

    F. Klingberg, Leipzig

    M. Krug, Magdeburg

    M. Künnemann, Magdeburg

    L. Lindenau, Magdeburg

    B. Lößner, Magdeburg

    W. Löw, Magdeburg

    H. Matthies, Magdeburg

    H.K. Matthies, Magdeburg

    R. Morgenstern, Berlin

    M. Müller, Magdeburg

    P. Müller-Welde, Magdeburg

    J. Oehler, Dresden

    J. Ott, Magdeburg

    T. Ott, Berlin

    L. Pickenhain, Leipzig

    W. Pohle, Magdeburg

    N. Popov, Magdeburg

    C. Rauca, Magdeburg

    M. Reiser, Magdeburg

    K.G. Reymann, Magdeburg

    N. Roth, Magdeburg

    F. Rothe, Magdeburg

    W. Rüdiger, Berlin

    H. Rüthrich, Magdeburg

    H.-L. Rüthrich, Magdeburg

    H. Schenk, Magdeburg

    R. Schlichthaar, Jena

    I. Schmidt, Magdeburg

    J. Schmidt, Dresden

    S. Schmidt, Magdeburg

    S. Schulzeck, Magdeburg

    H. Schröder, Magdeburg

    T. Schuster, Berlin

    M. Schütte, Magdeburg

    H. Schwarzberg, Magdeburg

    C. Schweigert, Magdeburg

    B. Seidel, Leipzig

    K.-H. Smalla, Magdeburg

    S. Staak, Magdeburg

    C. Steinhäuser, Jena

    W. Thiemann, Magdeburg

    W. Tischmeyer, Magdeburg

    J. Wenzel, Berlin

    GERMAN DEM. REP.

    W. Wetzel, Magdeburg

    E. Winkelmann, Leipzig

    G. Wolf, Magdeburg

    HUNGARY

    G. Buzsáki, Pécs

    M. Fekete, Szeget

    IRELAND

    B. Leonard, Galway

    ITALY

    A. Giuditta, Naples

    A.G. Sadile, Naples

    NETHERLANDS

    W.H. Gispen, Utrecht

    P. De Graan, Utrecht

    B.P.C. Melchers, Amsterdam

    NORWAY

    Ø. Hvalby, Oslo

    POLAND

    J. Vetulani, Krakow

    I. Lukaszewska-Bulat, Warszawa

    SWITZERLAND

    H.L. Haas, Zürich

    B. Siegfried, Zürich

    U. K.

    T.V.P. Bliss, London

    G. Horn, Cambridge

    S.P.R. Rose, Milton Keynes

    U. S. A.

    R.J. Carey, Syracuse, NY

    A. Dunn, Gainesville, FL

    P.E. Gold, Charlottesville, VI

    J.L. Martinez, Berkeley, CA

    J.L. McGaugh, Irvine, CA

    R.B. Messing, Minneapolis, MI

    M. Rosenzweig, Berkeley, CA

    U. S. S. R.

    R.A. Danilova, Moscow

    E.A. Gromova, Puschino

    M. Koridze, Tbilisi

    O.K. Koshtoyants, Moscow

    T.N. Oniani, Tbilisi

    A.S. Pivovarov, Moscow

    V. Skrebitzky, Moscow

    O.S. Vinogradova, Puschino

    L.L. Voronin, Moscow

    Participants of the symposium in front of Haus des Lehrers, Magdeburg (G.D.R.)

    Section I

    SYNAPTIC LONG-TERM POTENTIATION

    Opening Remarks

    H. Matthies,     

    Institute of Neurobiology and Brain Research, Academy of Science of GDR and Institute of Pharmacology and Toxicology, Medical Academy, DDR - 3090 Magdeburg, Leipziger Str. 44, GDR

    Publisher Summary

    This chapter presents remarks on the Neurobiological Symposium. The investigations of learning behavior are progressing well because of the advances in cell physiology and molecular biology. The role of brain structures and neuronal cells as the substrate of behavior can hardly be understood by electrical events only; the elucidation of chemical processes is necessary as well. The biochemistry of memory formation is gaining importance in this way directing attention not only to long-term changes but also to the early stages of information storage when transmitter signals have to be transferred into the metabolic changes of the neuron. Because of its physiological importance in learning and memory formation as well as its methodical advantages resulting from morphological and physiological properties, memory research will have to deal in depth with the hippocampal structures. Both neurohumoral relations and the peripheral portions of the body involved in learning and memory should be taken into consideration without neglecting the pharmacology of learning and memory as it provides sufficient theoretical background for the practical realization of efforts and results in basic research.

    For the first time organized in 1967, the Magdeburg Neurobiological Symposium has become a good tradition in the course of the past 18 years, even if it cannot look back on a centuries-old history like the city of Magdeburg which was first mentioned in 805. Magdeburg’s importance as a main centre of the medieval German Empire grew but the town was almost completely destroyed in the 17th century. However, under its mayor Otto von Guericke - the discoverer of the vacuum who became known beyond the boundaries by the famous historical experiment with the hemispheres -Magdeburg was reconstructed. Grown up again to a big industrial centre in the 19th and 20th century, Magdeburg was reduced to rubble for the second time during World War II, but it rose from the ruins and ranks among the most important industrial cities of the G.D.R. today enjoying a good reputation as a town of science and culture, too.

    To complete the development of neurosciences paid increasing attention to at the Magdeburg Medical Academy during the past two decades, the Institute of Neurobiology and Brain Research of the G.D.R. Academy of Sciences was founded which is to be built here in the coming two years.

    The augmenting role neurosciences play in this city found expression in six neurobiological symposia with an increasing number of participants from abroad. The great attraction these Magdeburg meetings have for the scientists is probably due to the agreeable size, to sufficient time for discussion and the resulting familiar atmosphere.

    The meetings were originally only concerned with neuropharmacology but we are now focusing more and more on neurobiology of learning, memory and neuronal plasticity thus simultaneously emphasizing the interdisciplinary character of these symposia.

    During the VIIth International Neurobiological Symposium this topic will again be discussed in detail and completed with the approach to a phenomenon which is of growing interest to memory research either as a fundamental mechanism of information storage in the central nervous system or at least as a suitable experimental model: the long-term potentiation of synaptic transmission.

    Therefore, it is a particular pleasure for us to welcome Tim Bliss who discovered this remarkable long-lasting change in synaptic function more than ten years ago as well as all the other colleagues having contributed considerably to the elucidation of this kind of synaptic plasticity.

    The investigations of learning behaviour are progressing well now due to the advances in cell physiology and molecular biology. The role of brain structures and neuronal cells as the substrate of behaviour can hardly be understood by electrical events only; the elucidation of chemical processes is necessary as well, even if we are confronted with great methodical problems arising from the dimensions of the individual cell.

    Nevertheless, biochemistry of memory formation is gaining importance in this way directing our attention not only to long-term changes but also more and more to early stages of information storage when transmitter signals have to be transferred into metabolic changes of the neuron.

    Because of its physiological importance in learning and memory formation as well as its methodical advantages resulting from morphological and physiological properties, memory research will have to deal in depth with the hippocampal structures. During our meeting special emphasis will, therefore, be placed upon experimental studies devoted to the hippocampus.

    However, learning and behaviour cannot finally be confined to molecular and cellular components of the brain; we have to take a fresh integrative look at the whole organism and its environmental interactions. Both neurohumoral relations and the peripheral portions of the body involved in learning and memory should be taken into consideration without neglecting pharmacology of learning and memory as it provides sufficient theoretical background for the practical realization of our efforts and results in basic research.

    Finally, I should like to wish all participants a very fruitful, successful and stimulating course of our VIIth Neurobiological Symposium. I hope our meeting will offer you the opportunity to exchange new views, results and ideas, to deepen old friendships and to form new ones.

    Whenever we meet for discussion in a friendly atmosphere we do not only contribute to the progress of science but also to a better understanding of all people in a peaceful world.

    Presynaptic Mechanisms in Hippocampal Long-term Potentiation

    T.V.P. Bliss, M.L. Errington, K.J. Feasey and M.A. Lynch,     Division of Neurophysiology and Neuropharmacology, National Institute for Medical Research, Mill Hill, London NW7 1AA, UK

    Publisher Summary

    Although the long-term potentiation (LTP) of synaptic efficacy in the hippocampus following brief tetanic stimulation was first described in 1973, the mechanism underlying the phenomenon remains obscure. Evidence to date suggests that both pre- and post-synaptic mechanisms are involved in the induction of LTP. This chapter analyzes presynaptic mechanisms in hippocampal LTP. There is evidence that presynaptic mechanisms leading to a sustained increase in transmitter release are involved in the maintenance of LTP. The use of a technique in which electrophysiological recording is combined with push-pull perfusion has allowed to collect perfusate and monitor evoked potentials simultaneously and has, thus, made it possible to correlate changes in transmitter release with changes in electrophysiological responses.

    INTRODUCTION

    Although long-term potentiation (LTP) of synaptic efficacy in the hippocampus following brief tetanic stimulation was first described in 1973 (Bliss and Lømo, 1973), the mechanism underlying the phenomenon remains obscure. Evidence to date suggests that both pre- and post-synaptic mechanisms are involved in the induction of LTP. The first direct evidence indicating postsynaptic involvement was provided by Lynch and his colleagues, who showed that intracellular injection of EGTA into CA1 pyramidal cells in vitro prevented the induction of LTP in the majority of cells tested (Lynch, Larson, Kelso, Barrionuevo and Schottler, 1983). Since EGTA presumably blocks LTP by chelating cytoplasmic Ca²+ this result also emphasizes the importance of Ca²+ in the induction of LTP. The intracellular injection of caesium chloride, which blocks K+ currents, has also been reported to prevent the induction of LTP in treated cells (Haas and Rose, 1984). More recent in vitro experiments have suggested that intense dendritic depolarization is a necessary, though not sufficient, condition for the induction of LTP. Thus, depolarisation of the postsynaptic cell, whether produced by passing current through an intracellular electrode (Wigström, Gustafsson, Huang and Abrahams, 1986), or by iontophoresis of glutamate onto dendrites (Andersen, Hvalby, Hu and Lacaille, personal communication; see Andersen, 1986), failed to cause LTP; on the other hand, in both cases, the conjunction of depolarization with low-frequency stimulation of afferent fibres did result in LTP. It therefore seems likely that the induction of LTP requires activation of both presynaptic and postsynaptic components.

    The mechanisms involved in the maintenance of LTP have been studied to a lesser extent. A postsynaptic hypothesis was proposed in 1980 by Baudry and Lynch (1980a), who suggested that high-frequency stimulation led to an increase in the number of postsynaptic glutamate receptors. It was suggested that the postulated unmasking of these additional receptors could result from activation of a Ca²+-dependent protease, following Ca²+ influx during high-frequency activation (Baudry and Lynch 1980a; 1980b). These authors later reported that the number of glutamate receptors was increased in membrane fractions obtained from potentiated CA1 slices compared to controls (Lynch, Halpain and Baudry, 1982). However, two subsequent studies, one in CA1 (Sastry and Goh, 1984) and the other in the dentate gyrus (Lynch, Errington and Bliss, 1985a) have failed to confirm an overall increase in glutamate binding in potentiated tissue, though an increase, beyond the resolution of the binding assay, in one or other of the glutamate receptor subtypes remains a possibility. Morphological studies have also provided evidence of postsynaptic involvement. Thus it has been reported that tetanization results in an increase in the diameter of dendritic spines in the perforant path terminal zone (Fifkova and van Harreveld, 1977) and an increase in the number of shaft synapses in CA1 (Lee, Schottler, Oliver and Lynch, 1980; Chang and Greenough, 1984). Morphological changes accompanying LTP in the dentate gyrus have also been observed (Wenzel and Matthies, 1985). Evidence that LTP is accompanied by changes in transmitter release, first suggested by in vitro experiments of Skrede and Malthe-Sørenssen (1981), has come from a series of in vivo and in vitro studies in our laboratory which will be reviewed in this chapter (Dolphin, Errington and Bliss, 1982; Bliss, Douglas, Errington and Lynch, 1985, 1986; Feasey and Lynch, 1984; Feasey, Lynch and Bliss, 1986). We will argue that our results provide strong evidence that the maintenance of LTP is linked to a sustained increase in transmitter release.

    LTP AND TRANSMITTER RELEASE: IN VIVO STUDIES.

    Use of a technique in which electrophysiological recording is combined with push-pull perfusion has allowed us to collect perfusate and monitor evoked potentials simultaneously (Errington, Dolphin and Bliss, 1983), and has thus made it possible to correlate changes in transmitter release with changes in electrophysiological responses. Using this method, our first experiments demonstrated that LTP in the perforant path-granule cell synapses of the anaesthetized rat was accompanied by a prolonged increase in release of ³H glutamate newly synthesized from ³H glutamine (Dolphin, Errington and Bliss, 1982). We have recently extended these studies to investigate the release of endogenous amino acids in the dentate gyrus following induction of LTP (Bliss, Douglas, Errington and Lynch, 1985, 1986). The results of these experiments are summarized in Fig. 1. In control animals, release of both glutamate and aspartate decreased with time but following the high-frequency train given to induce LTP, release of glutamate was increased and release of both amino acids was significantly enhanced compared to control. There was no significant change in release of glutamine or glycine. In the case of glutamate the change persisted for at least three hours after the train (third hour not shown), and was more marked than the increase in release of aspartate which persisted for only two hours. The increase in transmitter release is correlated with LTP rather than with the high-frequency train itself, as we have shown in a number of ways. In the first place, in animals in which the high-frequency train failed, for unknown reasons, to produce LTP there was no increase in the release of ³H glutamate (Dolphin et al, 1982). Furthermore, when the induction of LTP was suppressed by delivery of a high-frequency train of stimuli to the commissural input immediately before the high-frequency train was delivered to the perforant path (Douglas, Goddard and Riives, 1982), the associated increase in release of endogenous glutamate and aspartate was also blocked (Bliss et al., 1986). Finally, blocking the induction of LTP by perfusion of the NMDA antagonist APV prevented any increase in endogenous transmitter release (Lynch, Errington and Bliss, 1985). Thus in the dentate gyrus there is a consistent correlation between LTP and a sustained increase in transmitter release, strongly implying the existence of a presynaptic component in the maintenance of LTP.

    Fig. 1 In vivo release of endogenous aspartate (Asp), glutamate (Glu), glutamine (Gln), and glycine (Gly) associated with stimulus-induced LTP in the dentate gyrus of rats anaesthetized with urethane. A push-pull cannula with attached recording electrodes was lowered into the molecular layer of the dentate gyrus, and the area perfused at a rate of 6 µL/min. Test shocks were delivered at 30 second intervals to the perforant path to monitor the amplitude of evoked population responses. Samples of perfusate were collected at 15 minute intervals. After 1 hour (arrows) animals in the experimental group received a single high-frequency train (250 Hz, 200 msec) to induce LTP. Fluorescent derivatives of amino acids were formed by mixing samples of perfusate with ophthalaldehyde/mercaptoethanol. Amino acids were separated by reverse phase HPLC, and quantified fluorometrically. Results are presented above as the mean hourly release (± SEM) of the four amino acids, expressed as a percentage of the mean in the first hour. In control animals (hatched histograms, n=8) release of all amino acids decreased with time. In experimental animals (plain histograms, n=8), release of aspartate and glutamate were greater than corresponding control values following the induction of LTP while Gln and Gly were unchanged. The increase was significant (p ≤ 0.05) for two hours in the case of aspartate and three hours in the case of glutamate (third hour not shown). See Bliss et al (1986) for further details.

    It is important to establish whether this association is a general phenomenon or confined to LTP in the dentate gyrus. In order to investigate this question, LTP was induced in area CA3 of the hippocampus by delivering a high frequency train to the excitatory commissural projection to pyramidal cells. Figure 2b shows that following the induction of LTP, there was a significant increase in the release of aspartate which persisted for the duration of the experiment. There was no significant change in release of glutamate, glutamine or glycine.

    Fig. 2 In vivo release of endogenous amino acids associated with (a) Ca²+-induced and (b) tetanically induced LTP in the commissural input to area CA3. After one hour LTP was induced either by perfusion with 10 mM Ca²+ for 5-8 minutes (a), or by delivery of a high- frequency train (250 Hz for 200 msec, arrows). Other details are as for Fig. 1. In both cases there was a sustained increase in the release of aspartate in the two sub sequent hours (p ≤ 0.05), and no change in the release of glutamate, glutamine or glycine compared to corresponding values in the control groups (n=8 for all experimental and control groups).

    Exposure of hippocampal slices to a high concentration of Ca²+ for a few minutes induces a form of LTP which was first demonstrated in the Schaffer-commissural pathway to area CA1 (Turner, Baimbridge and Miller, 1982). A similar Ca²+-induced potentiation can be produced in vivo in the commissural projection to area CA3 (Bliss, Dolphin and Feasey, 1984). We found that Ca²+-induced potentiation, like tetanically induced LTP, was accompanied by a significant increase in aspartate release, with no change in release of glutamate, glutamine or glycine (Fig. 2a). These results suggest, first, that aspartate rather than glutamate may be the transmitter in this pathway; second, that a common mechanism may be involved in the two types of potentiation; and third, that the association between release of transmitter candidates and LTP is not confined to the dentate gyrus but is also found in CA3.

    LTP AND TRANSMITTER RELEASE: IN VITRO STUDIES

    In an another approach to the question of how LTP is related to changes in the release process, we performed a series of ex vivo experiments in which LTP was first induced in vivo, the hippocampus removed 45 min later, divided into three parts, and the following measurements made in vitro: (a) K+-stimulated release of preloaded radiolabelled aspartate and glutamate from tissue slices, (b) high affinity uptake of aspartate and glutamate into homogenates and (c) total binding of glutamate to a crude membrane preparation obtained from control animals and animals in which LTP had been induced. The experiments were carried out in three areas of the hippocampus, the dentate gyrus, area CA1 and area CA3. In the release experiments, tissue slices were prepared from control and potentiated tissue and release of preloaded transmitter was examined by a method previously described (Feasey, Lynch and Bliss, 1986). Results are shown in Fig. 3: in the dentate gyrus (top panel) K+-induced, Ca²+-dependent release of ¹⁴C glutamate was significantly increased in potentiated preparations compared to controls. While release of ³H aspartate was also enhanced, the increase did not reach statistical significance. Accumulation of radiolabel into control and potentiated tissue was similar and both basal release and K+-induced Ca²+-independent release were unaffected by potentiation. In area CA1, release of ³H aspartate was significantly increased in potentiated compared to control tissue, while release of glutamate was similar in both preparations (Fig. 3, middle panel). In area CA3, K+-dependent Ca²+-dependent release of both ³H aspartate and ¹⁴C glutamate was significantly increased in potentiated tissue (Fig. 3, bottom panel). In CA1 and CA3, as in the dentate gyrus, accumulation of radiolabel, basal and K+-induced Ca²+-independent release were similar in control and potentiated tissue.

    Fig. 3 K+-induced, Ca²+-dependent release of ³H asp and ¹⁴C glu from control and potentiated tissue. Slices of control and potentiated tissue were prepared using a McIlwain tissue chopper and incubated in Krebs solution containing radiolabelled aspartate or glutamate. Release was studied in the absence and presence of Ca²+ using the filtration method previously described (Feasey et al., 1986). Results presented are mean release values (±SEM) expressed as a percentage of the total radiolabel present in the tissue at the start of the incubation period. In areas CA1 and CA3 release of ³H asp from potentiated tissue (hatched histograms) was significantly greater than from control tissue (plain histograms; p ≤ 0.05). In the dentate gyrus and area CA3 release of ¹⁴Cglu from potentiated tissue was greater than from control tissue (p ≤ 0.05; n=6-8 for all groups in the experiments illustrated in Figs 3–5).

    The results of our in vitro experiments support those of the in vivo studies in demonstrating an increase in transmitter release in potentiated tissue. The association between enhanced release and LTP is apparently a general phenomenon since it was found in the dentate gyrus, CA1 and CA3. The finding that basal (i.e. resting) release was not changed in potentiated tissue is at variance with the results of Skrede and Malthe-Sørensson (1981) who reported an increase in resting release of ³H D-aspartate in potentiated slices of CA1/CA3. It is possible that this difference arises from the use of different isomers in the two studies. We chose the naturally occurring L-isomer in preference to the D-isomer because a) the main justification for using the D-isomer (that it is metabolically stable) was nullified by the fact that in preliminary studies we found the L-isomers to be minimally metabolized (83% of the ¹⁴C radiolabel was recovered as glutamate and 96% of the ³H radiolabel was recovered as aspartate) and b) the release profile of D-aspartate using the filtration method did not resemble the profile of either L-aspartate or L-glutamate. Another difference in technique which might explain the discrepancy is that in the present study, LTP was induced in vivo, rather than in vitro.

    In order to establish that the primary effect of LTP was on release and that our results could not be explained by some effect secondary to a change in high-affinity uptake, homogenate was prepared from control or potentiated tissue and the uptake of ³H aspartate and ¹⁴C glutamate examined according to the method of Storm-Mathisen (1977). The findings are summarized in Figure 4 for the dentate gyrus (top panel), area CA1 (middle panel) and area CA3 (bottom panel) and indicate that in the three areas examined high-affinity uptake of both transmitters was unchanged following LTP. Thus LTP is accompanied by an increase in release of transmitter which cannot be accounted for by a change in uptake.

    Fig. 4 High affinity uptake of ³H asp and ¹⁴C glu in homogenate prepared from control and potentiated tissue. Results presented are the mean values (± SEM) expressed as µmol/g protein/min. The method of Storm-Mathisen (1977) was used to examine high affinity uptake. There was no significant difference in uptake of either ³H asp or ¹⁴C glu into potentiated tissue (hatched histograms) compared to control tissue (plain histograms) in the dentate gyrus, area CA1 or area CA3.

    To examine possible concomitant postsynaptic effects, the method of Lynch, G. et al. (1982) was used to investigate the effect of potentiation on specific binding of ³H glutamate to a crude membrane preparation. Figure 5 shows the results obtained in these experiments. In the dentate gyrus (top panel), area CA1 (middle panel) and area CA3 (bottom panel), the presence of Ca²+ enhanced specific binding of glutamate as previously reported by Lynch, G. et al. (1982) but unlike these workers we found no evidence of an increase in binding associated with LTP either in the absence (left) or presence (right) of Ca²+ in any of the three areas studied. Again, it should be noted that in the present experiments, LTP was induced in vivo in the anaesthetised rat whereas in the earlier study, LTP was induced In vitro (Lynch, G. et al., 1982). However, since Sastry and Goh (1984) also failed to detect increased binding in CA1 tissue which had been potentiated in vitro, it is unlikely that differences in the type of preparation can account for the disparity in results. It is also worth emphasizing that both in our experiments and in those of Lynch, G. et al. (1982), only total glutamate receptor binding was investigated and this might have masked any change in binding to receptor subtypes.

    Fig. 5 Specific binding of ³H glutamate to a membrane fraction prepared from control or potentiated tissue. A crude membrane fraction was prepared from control and potentiated tissue according to the method of Lynch et al. (1982). Binding was investigated in the presence or absence of Ca²+, and in the presence or absence of excess cold glutamate to assess non-specific binding. Results presented are values for specific binding of ³H glu in control (plain histograms) and potentiated (hatched histograms) tissue, expressed as pmol/mg protein. Results indicate that specific binding was increased in the presence of Ca²+ but that there was no significant difference between binding to control or potentiated tissue.

    CONCLUSION

    In this chapter, we have presented evidence that presynaptic mechanisms leading to a sustained increase in transmitter release are involved in the maintenance of LTP. Some recent experiments have given a clue to the nature of the cellular mechanisms involved. At several different concentrations of Ca²+, release of ¹⁴C glutamate was significantly greater in slices prepared from potentiated tissue than from control tissue. This suggests that there is an increase in the sensitivity of the release process to Ca²+ associated with LTP (Lynch and Bliss, 1986). We have found no evidence to support the view that the number of receptors is increased in LTP. On the other hand, the changes in number and morphology of dendritic spines which have been reported by several laboratories suggest that postsynaptic mechanisms also play a role. Thus, as with the induction of LTP, the maintenance of the effect appears to depend on both presynaptic and postsynaptic factors.

    REFERENCES

    Andersen, P.Changeux J.P., et al, eds. Neural and molecular bases of learning. Heidelberg & New York: Springer-Verlag,

    Enjoying the preview?
    Page 1 of 1