TRANSIENT EXPRESSION OF A NOVEL TYPE OF GABA RESPONSE IN RAT CA3 HIPPOCAMPAL-NEURONS DURING DEVELOPMENT

1. Intracellular recordings were used to study the effects of gamma-aminobutyric acid (GABA) on rat CA3 hippocampal neurones during the first two weeks of postnatal life. 2. In the presence of tetrodotoxin (TTX, 1 mu M), from postnatal day 0 (P0) to P12 both GABA (0.1-1 mM) and isoguvacine (10 mu M) induced a membrane depolarization associated with an increase in input conductance whereas baclofen (30-100 mu M) produced a membrane hyperpolarization. 3. Bicuculline (50 mu M) reduced the effects of GABA and abolished the response to isoguvacine without affecting the response to baclofen. 4. This novel bicuculline-insensitive GABA response was chloride dependent and was blocked by picrotoxin (10-100 mu M) in an uncompetitive way. In bicuculline and picrotoxin, a GABA(B)-mediated hyperpolarization appeared. 5. Towards the end of the second postnatal week, bicuculline blocked the GABA-induced depolarization and revealed a small hyperpolarizing response which was blocked by the GABA(B) antagonist CGP 35348 (0.5-1. mM). 6. It is suggested that, during development, the GABA response was mediated through the conventional GABA(A) and GABA(B) receptors as well as a new bicuculline-baclofen insensitive type of receptor.