GABA(B)-receptor-mediated currents in interneurons of the dentate-hilus border

GABA(B)-receptor-mediated inhibition was investigated in anatomically ident ified inhibitory interneurons located at the border between the dentate gyr us granule cell layer and hilus. Biocytin staining was used to visualize th e morphology of recorded cells. A molecular layer stimulus evoked a pharmac ologically isolated slow inhibitory postsynaptic current (IPSC), recorded w ith whole cell patch-clamp techniques, in 55 of 63 interneurons. Applicatio n of the GABA(B) receptor antagonists, CGP 35348 (400 mu M) or CGP 55845 (1 mu M) to a subset of 25 interneurons suppressed the slow IPSC by an amount ranging from 10 to 100%. In 56% of these cells, the slow IPSC was entirely GABA(B)-receptor-mediated. However, in the remaining interneurons, a compo nent of the slow IPSC was resistant to GABA(B) antagonists. Subtraction of this antagonist resistant current from the slow IPSC isolated the GABA(B) c omponent (IPSCB). This IPSCB had a similar onset and peak latency to that r ecorded from granule cells but a significantly shorter duration, The GABA(B ) agonist, baclofen (10 mu M), produced a CGP 55845-sensitive outward curre nt in 19 of 27 interneurons. In the eight cells that lacked a baclofen curr ent, strong or repetitive ML stimulation also failed to evoke an IPSCB, ind icating that these cells lacked functional GABA(B) receptor-activated potas sium currents. In cells that expressed a baclofen current, the amplitude of this current was similar to 50% smaller in interneurons with axons that pr ojected into the granule cell dendritic layer (22.2 +/- 5.3 pA; mean +/- SE ) than in interneurons with axons that projected into or near the granule c ell body layer (46.1 +/- 10.0 pA). Similarly, the IPSCB amplitude was small er in interneurons projecting to dendritic (9.4 +/- 2.7 pA) than perisomati c regions (34.3 +/- 5.1 pA). These findings suggest that GABA(B) inhibition more strongly regulates interneurons with axons that project into perisoma tic than dendritic regions. To determine the functional role of GABA(B) inh ibition, we examined the effect of IPSPA on action potential firing and syn aptic excitation of these interneurons. IPSPB and IPSPA both suppressed dep olarization-induced neuronal firing. However, unlike IPSPA, suppression of firing by IPSPB could be easily overcome with strong depolarization IPSPB m arkedly suppressed N-methyl-D-aspartate but not AMPA EPSPs, suggesting that GABA(B) inhibition may play a role in regulating slow synaptic excitation of these interneurons. Heterogeneous expression of GABA(B) currents in hila r border interneurons therefore may provide a mechanism for the differentia l regulation of excitation of these cells and thereby exert an important ro le in shaping neuronal activity in the dentate gyrus.