Long-Term Potentiation in the Dentate Gyrus in Vivo is Associated with a Sustained Increase in Extracellular Glutamate

Abstract

There is general agreement concerning the NMDA receptor-mediated events underlying the induction of long-term potentiation (LTP) in two prominent hippocampal projections, the Schaffer-commissural input to CA1 pyramidal cells, and the perforant path input to granule cells of the dentate gyrus (Collingridge and Bliss, 1987; Gustafsson and Wigström, 1988). In contrast, the mechanisms by which the enhanced response is expressed and maintained¹ are not well understood, and there is disagreement as to whether the effect is (i) at least partly presynaptic (Bliss and Lynch, 1988; Routtenberg et al, 1985), (ii) wholly postsynaptic (Kauer et al, 1988; Muller and Lynch, 1988), (iii) not postsynaptic (Malinow et al, 1989), (iv) presynaptic initially, and at least partly postsynaptic after about the first 45 min (Davies et al, 1989) or (v) on the basis of morphological evidence, presynaptic (Applegate et al, 1987), postsynaptic (Greenough et al, 1986), or both (Lee et al. 1980; Chang and Greenough, 1984). We shall not attempt to produce a synthesis of these conflicting views in this chapter, and it is doubtful whether the time is ripe for such an attempt. Our less ambitious purpose is to present a summary of the results we have obtained in the last few years with one technique in one pathway: push-pull perfusion of the dentate gyrus in the rat. Contrary to the experience of Aniksztejn et al, 1989 (see Roisin et al, this volume), we have consistently observed an increase in the concentration of glutamate in the perfusate during LTP in this pathway. We argue that the most economical interpretation of these results is that LTP is at least in part expressed as an increase in glutamate release from potentiated terminals.