We next examined the synaptic levels of AMPA receptor subunits in VTA DA neurons using double-labeling post-embedding immunoelectron microscopy (Fig. 5). Specifically, the relative amounts of the AMPA receptor subunits GluR1 (Fig. 5A-D) and GluR2/3 (Fig. 5E-H) in the postsynaptic density (PSD) in VTA DA neurons (identified by tyrosine hydroxylase labeling) were compared in wild-type, Girk1−/−, and Girk2−/− mice. Synaptic densities of GluR1 and GluR2/3 levels were significantly elevated (~2-fold) in VTA DA neurons from Girk1−/− and Girk2−/− mice, suggesting that the elevated frequency of sEPSCs measured in VTA DA neurons from Girk1−/− and Girk2−/− mice is due to the increased synaptic distribution of AMPA receptors.
