GABAB-Receptor–Mediated Currents in Interneurons of the Dentate-Hilus Border

Abstract

GABAB-receptor–mediated inhibition was investigated in anatomically identified inhibitory interneurons located at the border between the dentate gyrus granule cell layer and hilus. Biocytin staining was used to visualize the morphology of recorded cells. A molecular layer stimulus evoked a pharmacologically isolated slow inhibitory postsynaptic current (IPSC), recorded with whole cell patch-clamp techniques, in 55 of 63 interneurons. Application of the GABAB receptor antagonists, CGP 35348 (400 μM) or CGP 55845 (1 μM) 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 GABAB-receptor–mediated. However, in the remaining interneurons, a component of the slow IPSC was resistant to GABAB antagonists. Subtraction of this antagonist resistant current from the slow IPSC isolated the GABAB component (IPSCB). This IPSCB had a similar onset and peak latency to that recorded from granule cells but a significantly shorter duration. The GABAB agonist, baclofen (10 μM), produced a CGP 55845-sensitive outward current in 19 of 27 interneurons. In the eight cells that lacked a baclofen current, strong or repetitive ML stimulation also failed to evoke an IPSCB, indicating that these cells lacked functional GABABreceptor-activated potassium currents. In cells that expressed a baclofen current, the amplitude of this current was ∼50% smaller in interneurons with axons that projected 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 cell body layer (46.1 ± 10.0 pA). Similarly, the IPSCBamplitude was smaller in interneurons projecting to dendritic (9.4 ± 2.7 pA) than perisomatic regions (34.3 ± 5.1 pA). These findings suggest that GABAB inhibition more strongly regulates interneurons with axons that project into perisomatic than dendritic regions. To determine the functional role of GABAB inhibition, we examined the effect of IPSPB on action potential firing and synaptic excitation of these interneurons. IPSPB and IPSPA both suppressed depolarization-induced neuronal firing. However, unlike IPSPA, suppression of firing by IPSPB could be easily overcome with strong depolarization. IPSPB markedly suppressed N-methyl-d-aspartate but not AMPA EPSPs, suggesting that GABAB inhibition may play a role in regulating slow synaptic excitation of these interneurons. Heterogeneous expression of GABAB currents in hilar border interneurons therefore may provide a mechanism for the differential regulation of excitation of these cells and thereby exert an important role in shaping neuronal activity in the dentate gyrus.