2-deoxyglucose-induced long-term potentiation of monosynaptic IPSPs in CA1hippocampal neurons

In previous experiments on excitatory synaptic transmission in CA1, tempora ry (10-20 min) replacement of glucose with 10 mM 2-deoxyglucose (2-DG) cons istently caused a marked and very sustained potentiation (2-DG LTP). To fin d out whether 2-DG has a similar effect on inhibitory synapses, we recorded pharmacologically isolated mononosynaptic inhibitory postsynaptic potentia ls (IPSPs; under current clamp) and inhibitory postsynaptic currents (IPSCs ; under voltage clamp); 2-DG was applied both in the presence and the absen ce of antagonists of N-methyl-D-aspartate (NMDA). In spite of sharply varie d results (some neurons showing large potentiation, lasting for >1 h, and m any little or none), overall there was a significant and similar potentiati on of IPSP conductance, both for the early (at approximate to 30 ms) and la ter (at approximate to 140 ms) components of IPSPs or IPSCs: by 35.1 +/- 10 .25% (mean +/- SE;for n = 24, P = 0.0023) and 36.5 +/- 16.3% (for n = 19, P = 0.038), respectively. The similar potentiation of the early and late IPS P points to a presynaptic mechanism of LTP. Overall, the LTP was statistica lly significant only when 2-DG was applied in the absence of glutamate anta gonists. Tetanic stimulations (in presence or absence of glutamate antagoni sts) only depressed IPSPs (by half). In conclusion, although smaller and mo re variable, 2-DG-induced LTP of inhibitory synapses appears to be broadly similar to the 2-DG-induced LTP of excitatory postsynaptic potentials previ ously observed in CA1.