Relative contribution of TARPs γ-2 and γ-7 to cerebellar excitatory synaptic transmission and motor behavior

Transmembrane AMPA receptor regulatory proteins (TARPs) play an essential role in excitatory synaptic transmission throughout the central nervous system (CNS) and exhibit subtype-specific effects on AMPA receptor (AMPAR) trafficking, gating, and pharmacology. The function of TARPs has largely been determined through work on canonical type I TARPs such as stargazin (TARP gamma-2), absent in the ataxic stargazer mouse. Little is known about the function of atypical type II TARPs, such as TARP gamma-7, which exhibits variable effects on AMPAR function. Because gamma-2 and gamma-7 are both strongly expressed in multiple cell types in the cerebellum, we examined the relative contribution of gamma-2 and gamma-7 to both synaptic transmission in the cerebellum and motor behavior by using both the stargazer mouse and a gamma-7 knockout (KO) mouse. We found that the loss of gamma-7 alone had little effect on climbing fiber (cf) responses in Purkinje neurons (PCs), yet the additional loss of gamma-2 all but abolished cf responses. In contrast, gamma-7 failed to make a significant contribution to excitatory transmission in stellate cells and granule cells. In addition, we generated a PC-specific deletion of gamma-2, with and without gamma-7 KO background, to examine the relative contribution of gamma-2 and gamma-7 to PC-dependent motor behavior. Selective deletion of gamma-2 in PCs had little effect on motor behavior, yet the additional loss of gamma-7 resulted in a severe disruption in motor behavior. Thus,gamma-7 is capable of supporting a component of excitatory transmission in PCs, sufficient to maintain essentially normal motor behavior, in the absence of gamma-2.