HIPPOCAMPAL CA1 LACUNOSUM-MOLECULARE INTERNEURONS - MODULATION OF MONOSYNAPTIC GABAERGIC IPSCS BY PRESYNAPTIC GABA(B) RECEPTORS

1. Whole cell patch-clamp recordings were employed to characterize mon osynaptic inhibitory postsynaptic currents (IPSCs) in morphologically and electrophysiologically identified interneurons located in the stra tum lacunosum moleculare, or near the border of the stratum radiatum ( LM interneurons), in the CA1 region of hippocampal slices taken from 3 - to 4-wk-old rats. Monosynaptic IPSCs, evoked in the presence of glut amate receptor antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 20 mu M) and D-2-amino-5-phosphopentanoate (APV; 50 mu M) were biphas ic. The gamma-aminobutyric acid-A (GABA(A)) receptor antagonist, bicuc ulline (20 mu M), blocked the fast IPSC, and the slow IPSC was blocked by the GABA(B) receptor antagonist CGP35348 (500 mu M). 2. Monosynapt ic IPSCs were evoked by electrical stimulation in several distant regi ons including the stratum radiatum, the stratum oriens, the stratum la cunosum-moleculare, and the molecular layer of dentate gyrus, suggesti ng an extensive network of inhibitory interneurons in the hippocampus. In paired recordings of CA1 interneurons and pyramidal cells, IPSCs w ere evoked by electrical stimulation of most of these distal regions w ith the exception of the molecular layer of dentate gyrus, which evoke d an IPSC only in LM interneurons. 3. Frequent(>0.1 Hz) stimulation de pressed the evoked IPSCs. With a paired-pulse protocol, the second IPS C was depressed and the maximal depression (40-50%) was observed with an interstimulus interval of 100-200 ms. 4. The GABA(B) receptor agoni st baclofen (1 mu M) reduced the amplitude of evoked IPSCs and the pai red-pulse depression of the second IPSC. The GABA(B) receptor antagoni st CGP35348 (0.5-1 mM) had no significant effect on the amplitude of i solated IPSCs. However, CGP35348 reduced but did not fully block paire d-pulse depression, suggesting that this depression is partly due to t he activation of presynaptic GABA(B) receptors. 5. The paired-pulse de pression depended on the level of transmitter release. Potentiation of synaptic release of GABA, by increasing the extracellular Ca2+ concen tration to 4 mM and reducing the extracellular Mg2+ concentration to 0 .1 mM, enhanced the depression. Reduction of transmitter release by in creasing extracellular Mg2+ concentration to 7 mM diminished the paire d-pulse depression of IPSCs. After potentiation of transmitter release , CGP35348 was less efficient in reducing the paired-pulse depression, suggesting that enhancement of depression by high-calcium/low-magnesi um medium was preferentially due to the potentiation of a GABA(B)-inde pendent component. 6. In summary, monosynaptic IPSCs recorded in LM in terneurons show similar features to those recorded in pyramidal cells. The strong correlation between the level of transmitter release and t he degree of paired-pulse depression may have important physiological consequences, because in synapses with a high level of activity and a high level of GABA release, inhibition is powerful, but depression can develop more readily.