DECREASED MONOSYNAPTIC GABA(B)-MEDIATED INHIBITORY POSTSYNAPTIC POTENTIALS IN HIPPOCAMPAL CA1 PYRAMIDAL CELLS IN THE AGED RAT - PHARMACOLOGICAL CHARACTERIZATION AND POSSIBLE MECHANISMS

1. gamma-Aminobutyric acid (GABA)-mediated inhibitory post synaptic potentials (IPSPs) were compared in young and aged rats in CA1 area of the rat hippocampus, with the use of the in vitro intracellular recording technique. D-2-Amino-5-phosphonovaleric acid (APV) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) were used to suppress synaptic potentials mediated by the excitatory amino acids. 2. Under these conditions, stimulation of the stratum radiatum elicited a monosynaptic fast GABA(A) (fIPSP) and a slow GABA(B) (fIPSP) -mediated IPSP. The fIPSP and the sIPSP were further isolated in the presence of the GABA(B) antagonist CGP 35348 or the GABA(A) antagonists bicuculline or picrotoxin. No age-related changes were observed in the amplitude and the duration of the fIPSP. In contrast, the amplitude (but not the duration) of the sIPSP was significantly reduced in the aged rat. 3. The postsynaptic hyperpolarization and increase in membrane conductance induced in pyramidal cells by bath application of the GABA(B) agonist baclofen were comparable in both groups of animals, indicating that the postsynaptic GABA(B) receptors are not altered in the aged rats. 4. Paired-pulse depression of IPSPs was used in young and aged rats to study possible alterations in GABA release or in presynaptic GABA(B) receptors that control GABA release. When fIPSPs were isolated by bath application of tetrahydro-9-aminoacridine (THA), no significant difference in the magnitude of the paired-pulse depression was observed between young and aged rats. A similar result was found with the paired-pulse depression of isolated sIPSPs in the presence of bicuculline or picrotoxin. These results indicate that the release of GABA and the presynaptic GABA(B) receptors are not altered in the aged animals. 5. Taken together, these results suggest that the decrease of the sIPSPs in the aged rats is not due to an alteration of pre- and postsynaptic GABA(B) receptors but rather to a selective impairment of interneurons responsible for the postsynaptic GABA(B)-mediated IPSPs.