2-Deoxyglucose-induced long-term potentiation in CA1 is not prevented by intraneuronal chelator.

In hippocampal slices, temporary (10-20 min) replacement of glucose with 10 mM 2-deoxyglucose is followed by marked and very sustained potentiation of EPSPs (2-DG LTP). To investigate its mechanism, we examined 2-DG's effect in CA1 neurons recorded with sharp 3 M KCl electrodes containing a strong chelator, 50 or 100 mM ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA). In most cases, field EPSPs were simultaneously recorded and conventional LTP was also elicited in some cells by tetanic stimulation of stratum radiatum. 2-DG potentiated intracellular EPSP slopes by 48 +/- 5.1% (SE) in nine cells recorded with plain KCl electrodes and by 52 +/- 6.2% in seven cells recorded with EGTA-containing electrodes. In four of the latter cells, tetanic stimulation (twice 100 Hz for 1 s) failed to evoke LTP (2 +/- 1.1%), although field EPSPs were clearly potentiated (by 28 +/- 6.9%). Thus unlike tetanic LTP, 2-DG LTP is not readily prevented by postsynaptic intraneuronal injection of EGTA. These findings agree with other evidence that the rise in postsynaptic (somatic) [Ca(2+)](i) caused by 2-DG is not the principal trigger for the subsequent 2-DG LTP and that it may be a purely presynaptic phenomenon.