Long Term Potentiation is not Associated with a Sustained Enhanced Release of Glutamate in the Rat Hippocampus in Vivo and in Vitro

Abstract

Long term potentiation (LTP) first observed by Bliss and Lomo in 1973 is defined as a long lasting enhancement of synaptic transmission, produced by a high frequency train of electrical stimulation delivered to afferent pathways in the mammalian hippocampus. This LTP has been extensively studied by an experimental model of learning and memory (eg. review Teyler and DisCenna 1987) in particular in the hippocampus, a cortical structure which plays an important role in memory and learning. Different hypothesis have been suggested to explain the mechanism of induction and maintenance of LTP (Bliss and Lynch 1988, Wigstrom and Gustafsson 1988). LTP includes an initiation phase (20 min to 1 hour) and a maintenance phase which persists for several hours in vitro and days in vivo and which includes protein synthesis and post translational modification. It is for instance clear that a rise in Ca++ in the postsynaptic element plays a crucial role in initiating the sequence of events which will trigger the long lasting modification. This can be induced in certain synapses (the CA1 Schaffer collaterals system or perforant path-granules cell synapses) by the activation of the NMDA- channel complex (Bliss and Lynch, 1987). In other systems (Cf. the hippocampal mossy fibers synapse) it can be induced by the activation of voltage dependent Ca++ channels (Griffith et al. 1986). However the subsequent events and in particular the contribution of the presynaptic and postsynaptic elements of the potentiated signal have not been determined.There are several indications that a postsynaptic change underlines the maintenance of LTP. This includes i) the selective increase in the non NMDA component after LTP (Kauer et al., 1988 a) which cannot be readily reconciled with a presynaptic type of mechanism, ii) the delayed increase in quisqualate responses after LTP (Davies et al. 1989), suggesting in increase in the efficacy or density of post synaptic quisqualate receptors in keeping with the theory suggested initially by Baudry et al., in 1980, iii) the induction of LTP by direct post synaptic regulation of protein kinase C system (Hu et al., 1987, Malenka et al., 1989, Malinow et al., 1989) iiii) the increase in number of receptor sites for glutamate (Lynch et al., 1982). Other modifications have been reported including a change in the postsynaptic morphology (Fifkova and Van Harreveld 1977, Chang and Greenough 1984). The involvement of protein synthesis in the latter phases of LTP (Frey et al., 1988, Otani et al. 1989) as well as the release of new proteins (Duffy et al. 1981, Charriaut-Marlangue et al. 1988, Fazeli et al. 1988) may contribute to the persistent effects.