Jj. Wagner et Be. Alger, GABAERGIC AND DEVELOPMENTAL INFLUENCES ON HOMOSYNAPTIC LTD AND DEPOTENTIATION IN RAT HIPPOCAMPUS, The Journal of neuroscience, 15(2), 1995, pp. 1577-1586
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.