title: Relative contribution of TARPs γ-2 and γ-7 to cerebellar excitatory synaptic transmission and motor behavior.
abstract: 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 γ-2), absent in the ataxic stargazer mouse. Little is known about the function of atypical type II TARPs, such as TARP γ-7, which exhibits variable effects on AMPAR function. Because γ-2 and γ-7 are both strongly expressed in multiple cell types in the cerebellum, we examined the relative contribution of γ-2 and γ-7 to both synaptic transmission in the cerebellum and motor behavior by using both the stargazer mouse and a γ-7 knockout (KO) mouse. We found that the loss of γ-7 alone had little effect on climbing fiber (cf) responses in Purkinje neurons (PCs), yet the additional loss of γ-2 all but abolished cf responses. In contrast, γ-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 γ-2, with and without γ-7 KO background, to examine the relative contribution of γ-2 and γ-7 to PC-dependent motor behavior. Selective deletion of γ-2 in PCs had little effect on motor behavior, yet the additional loss of γ-7 resulted in a severe disruption in motor behavior. Thus, γ-7 is capable of supporting a component of excitatory transmission in PCs, sufficient to maintain essentially normal motor behavior, in the absence of γ-2.
authors.affiliation: Department of Cellular and Molecular Pharmacology, Department of Cellular Neurobiology, Brain Research Institute, Niigata University, Niigata, 951-8585, Japan; and.
authors.forename: Maya
authors.initials: M
authors.lastname: Yamazaki
authors.affiliation: Department of Neuroscience, Genentech, South San Francisco, CA 94080.
authors.forename: Claire E
authors.initials: CE
authors.lastname: Le Pichon
authors.affiliation: Department of Cellular and Molecular Pharmacology, nicoll@cmp.ucsf.edu alexander.jackson@uconn.edu.
authors.forename: Alexander C
authors.initials: AC
authors.lastname: Jackson
authors.affiliation: Department of Cellular and Molecular Pharmacology.
authors.forename: Manuel
authors.initials: M
authors.lastname: Cerpas
authors.affiliation: Department of Cellular Neurobiology, Brain Research Institute, Niigata University, Niigata, 951-8585, Japan; and.
authors.forename: Kenji
authors.initials: K
authors.lastname: Sakimura
authors.affiliation: Department of Neuroscience, Genentech, South San Francisco, CA 94080.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Scearce-Levie
authors.affiliation: Department of Cellular and Molecular Pharmacology, Department of Physiology, University of California, San Francisco, CA 94143; nicoll@cmp.ucsf.edu alexander.jackson@uconn.edu.
authors.forename: Roger A
authors.initials: RA
authors.lastname: Nicoll
mesh_terms: D000818:Animals; D001259:Ataxia / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D001522:Behavior, Animal; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity; D011689:Purkinje Cells / Q000378:metabolism* / Q000473:pathology; D018091:Receptors, AMPA / Q000235:genetics / Q000378:metabolism; D009435:Synaptic Transmission
chemical_list: C113940:Cacng2 protein, mouse; D015220:Calcium Channels; D008565:Membrane Proteins; D018091:Receptors, AMPA; C519955:TARP gamma-7 protein, mouse
keywords: AMPA receptors; TARPs; cerebellum; motor behavior; stargazer