Enhanced inhibitory synaptic transmission in the cerebellar molecular layer of the GluRdelta2 knock-out mouse.
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.
Ohtsuki
Gen
G
Department of Biophysics, Graduate School of Science, Kyoto University, Kyoto 606-8502, Japan.
Kawaguchi
Shin-ya
SY
Mishina
Masayoshi
M
Hirano
Tomoo
T
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D002478:Cells, Cultured / Q000187:drug effects / Q000502:physiology; D058787:GABA-A Receptor Antagonists; D006246:Harmaline / Q000494:pharmacology; D006706:Homeostasis; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D018408:Patch-Clamp Techniques; D011689:Purkinje Cells / Q000187:drug effects / Q000502:physiology*; D017470:Receptors, Glutamate / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D058787:GABA-A Receptor Antagonists; D017470:Receptors, Glutamate; C107913:glutamate receptor delta 2; D005680:gamma-Aminobutyric Acid; D006246:Harmaline; D001640:Bicuculline