GABAERGIC AND DEVELOPMENTAL INFLUENCES ON HOMOSYNAPTIC LTD AND DEPOTENTIATION IN RAT HIPPOCAMPUS

Low-frequency(1 Hz) stimulation (LFS) was used to elicit long-term dep ression (LTD) or depotentiation of excitatory transmission of the Scha ffer collateral pathway in the CA1 region of the rat hippocampus. Both LTD and depotentiation were found to be homosynaptic and NMDA recepto r (NMDAR) dependent. As NMDAR activation can be modulated by the inhib itory GABAergic system, we tested the hypothesis that GABA plays a rol e in regulating these phenomena. The GABA(B) antagonist CGP 35348 sign ificantly inhibited LTD, but not depotentiation, in slices from young animals (indicating that the GABA(B)-mediated contribution was altered following HFS). The ability to express LTD was found to be developmen tally dependent, as young animals (16-22 d) consistently expressed LTD , whereas LTD was not expressed in naive slices taken from mature (5-1 0 weeks) animals. The GABA(A) antagonist bicuculline did not affect LT D in the young animals, but did enhance LTD expression in slices from mature animals. LFS was also effective in decreasing, or depotentiatin g, responses that had undergone long-term potentiation (LTP) by high-f requency stimulation (HFS). In contrast to LTD, depotentiation was con sistently expressed in slices from both the young and mature groups. M oreover, following an HFS train, LTD (compared to initial baseline res ponse) could be induced in mature slices previously unable to express LTD in the naive state. Thus, the role of GABA in modulating the effec ts of LFS varied with the prior synaptic activity in the slice as well as with the maturity of the animal. Our results suggest that the infl uence of both age and prior synaptic activity (i.e., HFS) on LTD induc tion can be explained by changes in GABAergic systems in young versus mature, and naive Versus tetanized slices.