title: Depolarization-induced depression of inhibitory transmission in cerebellar Purkinje cells.
abstract: 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.
authors.affiliation: Department of Pharmacology, Nippon Medical School Tokyo, 113-8602, Japan.
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Satoh
authors.forename: Lihui
authors.initials: L
authors.lastname: Qu
authors.forename: Hidenori
authors.initials: H
authors.lastname: Suzuki
authors.forename: Fumihito
authors.initials: F
authors.lastname: Saitow
keywords: Ca2+/Calmodulin-dependent protein kinase II; GABAergic synaptic transmission; cerebellum; chloride ion; synaptic plasticity