Abstract
Neurons of the subthalamic nucleus (STN) are very sensitive to applied currents, firing at 10-20/s during spontaneous activity, but increasing to peak firing rates of 200/s with applied currents <0.5 nA. They receive a powerful tonic excitatory input from neurons in the cerebral cortex, yet in vivo maintain an irregular firing rate only slightly higher than the autonomous firing rate seen in slices. Spike frequency adaptation acts to normalize background firing rate by removing slow trends in firing due to changes in average input. Subthalamic neurons have been previously described as showing little spike frequency adaptation, but this was based on tests using brief stimuli. We applied long-duration depolarizing current steps to STN neurons in slices and observed a very strong spike frequency adaptation with a time constant of 20 s and that recovered at a similar rate. This adaptation could return firing to near-baseline levels during prolonged current pulses that transiently drove the cells at high rates. The current responsible for adaptation was studied in voltage clamp during and after high-frequency driving of the cell and was determined to be a slowly accumulating K(+) current. This current was independent of calcium or sodium entry and could be induced with long-duration voltage steps after blockade of action potentials. In addition to the adaptation current, driven firing produced slow inactivation of the persistent Na(+) current, which also contributed to the reduced excitability of STN cells during and after driven firing.