Radixin regulates synaptic GABA A receptor density and is essential for reversal learning and short-term memory

Torben J. Hausrat, Mary Muhia, Kimberly Gerrow, Philip Thomas, Wiebke Hirdes, Sachiko Tsukita, Frank F. Heisler, Lena Herich, Sylvain Dubroqua, Petra Breiden, Joram Feldon, Jürgen R. Schwarz, Kay Yan Benjamin Yee, Trevor G. Smart, Antoine Triller, Matthias Kneussel

Research output: Journal article publicationJournal articleAcademic researchpeer-review

64 Citations (Scopus)

Abstract

Neurotransmitter receptor density is a major variable in regulating synaptic strength. Receptors rapidly exchange between synapses and intracellular storage pools through endocytic recycling. In addition, lateral diffusion and confinement exchanges surface membrane receptors between synaptic and extrasynaptic sites. However, the signals that regulate this transition are currently unknown. GABA A receptors containing α 5-subunits (GABA A R-α 5) concentrate extrasynaptically through radixin (Rdx)-mediated anchorage at the actin cytoskeleton. Here we report a novel mechanism that regulates adjustable plasma membrane receptor pools in the control of synaptic receptor density. RhoA/ROCK signalling regulates an activity-dependent Rdx phosphorylation switch that uncouples GABA A R-α 5 from its extrasynaptic anchor, thereby enriching synaptic receptor numbers. Thus, the unphosphorylated form of Rdx alters mIPSCs. Rdx gene knockout impairs reversal learning and short-term memory, and Rdx phosphorylation in wild-type mice exhibits experience-dependent changes when exposed to novel environments. Our data suggest an additional mode of synaptic plasticity, in which extrasynaptic receptor reservoirs supply synaptic GABA A Rs.
Original languageEnglish
Article number6872
JournalNature Communications
Volume6
DOIs
Publication statusPublished - 20 Apr 2015
Externally publishedYes

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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