The Journal of Neurophysiology Vol. 82 No. 3 September 1999, pp. 1438-1450
Copyright ©1999 by the American Physiological Society

GABA_B-Receptor-Mediated Currents in Interneurons of the Dentate-Hilus Border

Departments of  ¹Pharmacology,  ²Pediatrics (Neurology),  ³Surgery (Neurosurgery), and  ⁴Neurobiology, Duke University Medical Center, Durham, North Carolina, 27710

Mott, David D., Qiang Li, Maxine M. Okazaki, Dennis A. Turner, and Darrell V. Lewis. GABA_B-Receptor-Mediated Currents in Interneurons of the Dentate-Hilus Border. J. Neurophysiol. 82: 1438-1450, 1999. GABA_B-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 GABA_B 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 GABA_B-receptor-mediated. However, in the remaining interneurons, a component of the slow IPSC was resistant to GABA_B antagonists. Subtraction of this antagonist resistant current from the slow IPSC isolated the GABA_B component (IPSC_B). This IPSC_B had a similar onset and peak latency to that recorded from granule cells but a significantly shorter duration. The GABA_B 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 IPSC_B, indicating that these cells lacked functional GABA_B receptor-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 IPSC_B amplitude was smaller in interneurons projecting to dendritic (9.4 ± 2.7 pA) than perisomatic regions (34.3 ± 5.1 pA). These findings suggest that GABA_B inhibition more strongly regulates interneurons with axons that project into perisomatic than dendritic regions. To determine the functional role of GABA_B inhibition, we examined the effect of IPSP_B on action potential firing and synaptic excitation of these interneurons. IPSP_B and IPSP_A both suppressed depolarization-induced neuronal firing. However, unlike IPSP_A, suppression of firing by IPSP_B could be easily overcome with strong depolarization. IPSP_B markedly 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 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.