Correlation between long‐term potentiation and release of endogenous amino acids from dentate gyrus of anaesthetized rats.

Abstract

SUMMARY1. The relationship between long-term potentiation (l.t.p.) and the release of endogenous amino acid transmitters has been investigated in the dentate gyrus of rats anaesthetized with urethane.2. The molecular layer was perfused with artificial cerebrospinal fluid using a push-pull cannula. The perfusate was collected and analysed for glutamate, aspartate, glycine, glutamine and y-aminobutyric acid (GABA) using high-performance liquid chromatography (h.p.l.c.) with fluorometric detection.3. Recording electrodes were attached to the cannula to enable responses evoked by test stimuli to the perforant path to be monitored in the molecular and cell body layers.4. Perfusion was continued for 3 h while test stimuli were delivered to the perforant path at 30 s intervals. In the control group (n = 8), no further stimulation was given. In a second group (n = 8), a single high-frequency train (250 Hz for 200 ms) was delivered at the end of the first hour to induce l.t.p. The average potentiation of the slope of the excitatory post-synaptic potential (e.p.s.p.) 2 h later was 150. In a third group (n = 8), the train to the perforant path was paired with a train to the commissural input to the dentate gyrus, a procedure which blocks the induction of l.t.p.5. In the potentiated group, there was an increase in the concentrations of glutamate and aspartate following the induction of l.t.p., relative to the decline seen in corresponding periods of the control group. This increase remained statistically significant for 1-5 h in the case of glutamate and for 45 min in the case of aspartate.6. There were no l.t.p.-associated changes in the release of glutamine or glycine; there was an indication that l.t.p. may be associated with a decrease in the release of GABA.7. Increasing the frequency and intensity of perforant path activation resulted in enhanced concentrations of glutamate and aspartate in the perfusate; no such changes occurred when granule cells were activated antidromically.8. We discuss the origin of the relative increases in the concentration of glutamate and aspartate which are found in the perfusate following the induction of l.t.p. and

Presynaptic plasticity: The regulation of Ca2+-dependent transmitter release

“…Furthermore the experiments of Bliss and co-workers indicate that LTP is maintained, at least in part, by a sustained increase in transmitter (e.g. glutamate) release (Bliss et al, 1988(Bliss et al, , 1986Errington et al, 1987;Lynch et al, 1989a). These findings were challenged by Ben-Ari and co-workers (Anikszteijn et al, 1989(Anikszteijn et al, , 1991, but confirmed by recent observations in our group (Ghijsen and Lopes da Ghijsen et al, 1992).…”

Bidirectional Regulation of Protein Kinase Mζ in the Maintenance of Long-Term Potentiation and Long-Term Depression

“…Thus, there is evidence to support modifications presynaptically (Bliss et al, 1986;Malgaroli and Tsien, 1992;Bolshakov and Seigelbaum, 1994;Stevens and Wang, 1994), postsynaptically (Davies et al, 1989;Zalutsky and Nicoll, 1990;Manabe et al, 1992;Isaac et al, 1995;Liao et al, 1995;Oliet et al, 1996), and even on different postsynaptic receptors (Muller and Lynch, 1988;Kullman, 1994;Selig et al, 1995). Our experiments suggest that these modifications are maintained by autonomous PKC phosphorylation that is increased or decreased by the pattern of ongoing afferent activity.…”

Long‐term potentiation and the mechanisms of memory

“…The mechanism could involve presynaptic changes (increased glutamate release), postsynaptic changes (increased number of AMPA receptors or changes of the binding properties of AMPA receptors), or glial changes (reduced uptake of glutamate by glial cells) [Bindman et al, 19911. Indeed, the issue is complex because there is evidence in favor of all these changes, some of it contradictory [Bliss et al, 1986;Foster and McNaughton, 1991;Tsumoto, 1992;Voronin, 19891. At this time, perhaps the most favored hypothesis is that LTP is maintained through a combination of pre-and postsynaptic mechanisms, a combination which may be different in different synapses and that might, in some, include morphological or extrasynaptic changes [Bindman et al, 1991;Bliss and Collingridge, 1993;Colley and Routtenberg, 1993;Hawkins et al, 19931. There is now little doubt that protein phosphorylation, perhaps of glutamatergic receptors, and perhaps mainly through the intervention of PKC, is crucial for the first 3 or so hours of the maintenance phase [Colley and Routtenberg, 1993;Reymann et al, 19881, and that later other mechanisms enter into play, like protein synthesis and gene expression [see Colley and Routtenberg, 1993;Sheu et al, 19931. After 3 h, LTP can be blocked by protein synthesis inhibitors, the best studied of which is anisomycin applied to CA1 slices [Frey et al, 19881 or to the dentate gyrus in freely moving rats [Matthies, 19891.…”