Long-term plasticity in interneurons of the dentate gyrus

Single interneurons influence thousands of postsynaptic principal cells, an d the control of interneuronal excitability is an important regulator of th e computational properties of the hippocampus. However, the mechanisms unde rlying long-term alterations in the input-output functions of interneurons are not fully understood. We report a mechanism of interneuronal plasticity that leads to the functional enhancement of the gain of glutamatergic inpu ts in the absence of long-term potentiation of the excitatory synaptic curr ents. Interneurons in the dentate gyrus exhibit a characteristic, limited ( approximate to8 mV) depolarization of their resting membrane potential afte r high-frequency stimulation of the perforant path. The depolarization can be observed with either whole-cell or perforated patch electrodes, and it l asts in excess of 3 h. The long-term depolarization is specific to interneu rons, because granule cells do not show it. The depolarization requires the activation of Ca2+-permeable alpha -amino-3-hydroxy-5-methyl-4-isoxazolepr opionic acid (AMPA) receptors and the rise of intracellular Ca2+, but not N -methyl-o-aspartate (NMDA) receptor activation. Data on the maintenance of the depolarization point to a major role for a long-term change in the rate of electrogenic Na+/K+-ATPase pump function in interneurons. As a result o f the depolarization, interneurons after the tetanus respond with action po tential discharges to previously subthreshold excitatory postsynaptic poten tials (EPSPs), even though the EPSPs are not potentiated. These results dem onstrate that the plastic nature of the interneuronal resting membrane pote ntial underlies a unique form of long-term regulation of the gain of excita tory inputs to gamma -aminobutyric acid (CABA)ergic neurons.