Depolarization-induced depression of inhibitory transmission in cerebellar Purkinje cells.

Several forms of depolarization-induced plasticity in inhibitory transmission have been reported to occur in cerebellar Purkinje cells (PCs), namely depolarization-induced suppression of inhibition (DSI), depolarization-induced potentiation of inhibition (DPI), and rebound potentiation (RP). Here, we describe another form of synaptic plasticity for gamma-amino butyric acid (GABA)ergic transmission in PCs. Immediately following depolarization trains in a PC, evoked inhibitory postsynaptic currents (eIPSCs) changed their direction from outward to inward currents under a recording condition in which eIPSCs were elicited as an outward current. Subsequently, the eIPSC amplitude remained depressed (depolarization-induced depression of inhibition [DDI]) for more than 20 min under the blockade of cannabinoid and N-methyl-D-aspartic acid (NMDA) receptor-mediated DSI and DPI, respectively. This DDI was completely abolished by intracellular infusion of the fast Ca(2+)-chelating agent BAPTA and by inhibition of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII). Furthermore, DDI was strongly suppressed by calcium-activated chloride channel (CaCC) blockers, while an inhibitor of cation-chloride cotransporters (CCCs) partially blocked DDI during the early phase. Exogenous GABA-induced inhibition of spontaneous spike activity was attenuated in ∼50% of the PCs by climbing fiber stimulation-induced depolarization. These results suggest that activation of both CaCCs and CCCs was necessary for alteration of [Cl(-)]i after activation of CaMKII following elevation of [Ca(2+)]i in PCs. DDI may provide another mechanism for regulation of inhibitory inputs to PCs within the neuronal networks of the cerebellar cortex.