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Publication : Enhanced inhibitory synaptic transmission in the cerebellar molecular layer of the GluRdelta2 knock-out mouse.

First Author  Ohtsuki G Year  2004
Journal  J Neurosci Volume  24
Issue  48 Pages  10900-7
PubMed ID  15574740 Mgi Jnum  J:109764
Mgi Id  MGI:3629809 Doi  10.1523/JNEUROSCI.2240-04.2004
Citation  Ohtsuki G, et al. (2004) Enhanced inhibitory synaptic transmission in the cerebellar molecular layer of the GluRdelta2 knock-out mouse. J Neurosci 24(48):10900-7
abstractText  A novel ionotropic glutamate receptor subunit delta2 (GluRdelta2), which is specifically expressed in cerebellar Purkinje neurons (PNs), is implicated in the induction of long-term depression. Mutant mice deficient in GluRdelta2 (delta2-/-) have abnormal cerebellar synaptic organization and impaired motor coordination and learning. Previous in vivo extracellular recordings indelta2-/- 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 delta2-/-. Optical recordings in cerebellar slice preparations indicated that application of bicuculline, a GABA(A) receptor antagonist, increased the amplitude and area of excitation propagation more in delta2-/- than in WT. Whole-cell patch-clamp recordings from PNs demonstrated that miniature IPSC (mIPSC) amplitude were larger in delta2-/- 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 delta2-/-. In contrast, RP was induced in cultured PNs prepared from delta2-/-. 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 delta2-/- potentiates IPSC amplitudes in PNs through RP in vivo, resulting in the prevention of additional RP induction.
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