| Abstrakt: |
Intrinsic GABAergic interneurons provide inhibitory input to the principal neurons of the hippocampus. The majority of interneurons located in stratum oriens (s.o.) of the CA1 region express the hyperpolarization-activated cation current known as Ih. In an effort to elucidate the role of this current in regulating the baseline excitability of these neurons and its participation in the regulation of the release of GABA onto CA1 pyramidal neurons, we utilized whole cell electrophysiological recordings from both populations of cells. In voltage-clamp experiments, hyperpolarization of the interneuron membrane initiated a large inward current with an estimated activation threshold of 51.6 ± 7.6 mV and a half-maximal voltage of −73.0 ± 7.0 mV. This current was blocked by bath application of the Ihinhibitors ZD 7288 (50 μM) or cesium (2 mM). Current-clamp experiments at the interneuron resting membrane potential (−61.3 ± 1.2 mV) revealed a significant hyperpolarization, a decrease in the rate of spontaneous action potential discharge, an increase in the cellular input resistance, and the elimination of rebound afterdepolarizations during blockade ofIhwith ZD 7288 (50 μM). The hyperpolarizing effect of ZD 7288 was also substantially larger in interneurons clamped near −80 mV using current injection through the pipette. In addition to neurons exhibitingIh, recordings were obtained from a small population of s.o. interneurons that did not exhibit this current. These cells demonstrated resting membrane potentials that were significantly more negative (−73.6 ± 5.5 mV) than those observed in neurons expressing Ih, suggesting that this current contributes to more depolarized membrane potentials in these cells. Recordings from postsynaptic pyramidal neurons demonstrated that blockade of Ihwith ZD 7288 caused a substantial reduction (∼43%) in the frequency of spontaneous action potential-dependent inhibitory postsynaptic currents (IPSCs), without altering their average amplitude. However, miniature action-potential-independent IPSC frequency, amplitude, and decay kinetics were unaltered by ZD 7288. These data suggest thatIhis active at the resting membrane potential in s.o. interneurons and as a result contributes to the spontaneous activity of these cells and to the tonic inhibition of CA1 pyramidal neurons in the hippocampus. |
