PRESYNAPTIC ACTIONS OF GABA AND BACLOFEN IN CA1 REGION OF THE GUINEA-PIG HIPPOCAMPUS IN-VITRO

The presynaptic actions of GABA and (+/-)baclofen on the stratum radiatum in the CA1 region of guinea-pig hippocampal slices were investigated using a modified grease-gap recording technique. D.c. potential shifts were recorded in response to varying concentrations of GABA and (+/-)baclofen. In Ca2+-free media containing tetrodotoxin, bath applications of GABA (2.5 mu M to 20 mM) produced depolarizations which were concentration-dependent. Maximum depolarization was attained with 1O mM GABA. Superfusion of(+/-)baclofen (0.125-500 mu M) produced a concentration-dependent hyperpolarization which peaked at a concentration of 250 mu M. The GABA-induced depolarization but not the (+/-)baclofen-induced hyperpolarization was depressed by the GABA(A) antagonists bicuculline and picrotoxinin. The(+/-)baclofen-induced hyperpolarization but not the GABA-induced depolarization was suppressed by CGP 35 348, a GABA(B) antagonist. In the presence of bicuculline, GABA (0.5-5.0 mM) occasionally caused a hyperpolarization which could be blocked by CGP 35 348. These results indicate that the primary presynaptic action of GABA on the d.c. potential in the CA1 region of the hippocampus is to produce a GABA(A) receptor-mediated depolarization, while (+/-)baclofen induces a GABA(B) receptor-mediated hyperpolarization. The grease-gap d.c. potential recording technique, described in this paper, is expected to be useful in examining changes in the membrane potentials of presynaptic terminals.