Adaptive regulation of neuronal excitability by a voltage-independent potassium conductance

Many neurons receive a continuous, or 'tonic', synaptic input, which increa ses their membrane conductance, and so modifies the spatial and temporal in tegration of excitatory signals(1-3). In cerebellar granule cells, although the frequency of inhibitory synaptic currents is relatively low, the spill over of synaptically released GABA (gamma -aminobutyric acid)(4) gives rise to a persistent conductance mediated by the GABA(A) receptor(5-7) that als o modifies the excitability of granule cells(8). Here we show that this ton ic conductance is absent in granule cells that lack the alpha6 and delta -s ubunits of the GABAA receptor. The response of these granule cells to excit atory synaptic input remains unaltered, owing to an increase in a 'leak' co nductance, which is present at rest, with properties characteristic of the two-pore-domain K+ channel TASK-1 (refs 9- 12). Our results highlight the i mportance of tonic inhibition mediated by GABAA receptors, loss of which tr iggers a form of homeostatic plasticity leading to a change in the magnitud e of a voltage-independent K+ conductance that maintains normal neuronal be haviour.