Enhanced Inhibitory Synaptic Transmission in the Cerebellar Molecular Layer of the GluRδ2 Knock-Out Mouse

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Abstract
A novel ionotropic glutamate receptor subunit δ2 (GluRδ2), which is specifically expressed in cerebellar Purkinje neurons (PNs), is implicated in the induction of long-term depression. Mutant mice deficient in GluRδ2 (δ2-/-) have abnormal cerebellar synaptic organization and impaired motor coordination and learning. Previous in vivo extracellular recordings inδ2-/- revealed that PN activity distinct from that in wild-type (WT) mice is attributable to enhanced climbing fiber activity. Here, we report that GABAergic synaptic transmission was enhanced in the molecular layer of the cerebellar cortex in δ2-/-. Optical recordings in cerebellar slice preparations indicated that application of bicuculline, a GABAA receptor antagonist, increased the amplitude and area of excitation propagation more in δ2-/- than in WT. Whole-cell patch-clamp recordings from PNs demonstrated that miniature IPSC (mIPSC) amplitude were larger in δ2-/- than in WT. Also, rebound potentiation (RP), a type of long-lasting inhibitory synaptic potentiation inducible by postsynaptic depolarization of PNs in WT, was not induced in slices prepared from δ2-/-. In contrast, RP was induced in cultured PNs prepared from δ2-/-. Pharmacologic activation of climbing fibers in WT in vivo increased mIPSC amplitudes in PNs and prevented RP induction. These results suggest that enhanced climbing fiber activity in δ2-/- potentiates IPSC amplitudes in PNs through RP in vivo, resulting in the prevention of additional RP induction.