Such a synergistic function by the TARP family is also indicated from a study using stg/γ-3-DKO mice (Menuz et al., 2008). γ-3 is highly expressed in cerebellar Golgi cells (Fukaya et al., 2005), and its sole gene ablation did not affect cerebellar contents of AMPA receptors or AMPA receptor-mediated responses in Golgi cells. In stg/γ-3-DKO mice, learn more however, all four AMPA receptor subunits, particularly GluA2 and GluA3, were severely reduced in the cerebellum, and AMPA receptor-mediated responses were reduced to nearly
10% in Golgi cells (Menuz et al., 2008). Multiple TARP members, being expressed with differential combination and stoichiometry in given neuronal populations, may regulate AMPA receptor expression in a cooperative manner. In quantitative Western blot analysis, we found severe reductions in GluA2 and GluA3 and mild reductions in GluA4 in γ-2-KO cerebellum. GluA2–GluA4 were further reduced in γ-2/γ-7-DKO cerebellum. Light-microscopic immunohistochemistry gave a
closely similar result, which was also consistent with their severe reductions at almost all cerebellar find more synapses examined by postembedding immunogold. In γ-7-KO mice, reductions in AMPA receptor subunits were more modest, i.e., mild reductions in GluA3 at the parallel fiber–Purkinje cell and parallel fiber–interneuron synapses and moderate reduction in GluA4 at the mossy fiber–granule cell synapse. As to GluA1, we found mild reductions at the parallel fiber–Purkinje cell and climbing fiber–Purkinje cell synapses
in γ-2-KO mice, and found no reduction at any synapses examined in γ-7-KO mice. Nevertheless, following the ablation of both TARPs, GluA1 was reduced severely at climbing fiber–Purkinje cell synapse and moderately so at the parallel fiber–Purkinje cell and parallel fiber–interneuron synapses. These results suggest that γ-2 or γ-7 per se preferentially promotes synaptic expression of GluA2–GluA4, and that they come to promote GluA1 expression too, when expressed together. AMPA Bay 11-7085 receptors containing an edited GluA2 exhibit either linear or outwardly rectifying current–voltage (I-V) relationships and have low permeability to Ca2+, whereas those lacking GluA2 show strong inward rectification and high Ca2+ permeability (Hollmann et al., 1991; Hume et al., 1991; Verdoorn et al., 1991; Mosbacher et al., 1994; Tsuzuki et al., 2000). In Purkinje cells, AMPA receptors exhibit a linear I-V relationship and thereby little Ca2+ permeability (Tempia et al., 1996; Momiyama et al., 2003), indicating that GluA2-containing receptors are the major form in this neuron. Consistent with this notion, high levels of GluA2 mRNA are expressed together with GluA1 and GluA3 mRNAs in Purkinje cells (Keinänen et al., 1990; Pellegrini-Giampietro et al., 1991; Lambolez et al., 1992).