mGluR2 acts through inhibitory Galpha subunits to regulate transmission and long-term plasticity at hippocampal mossy fiber-CA3 synapses

Proc Natl Acad Sci U S A. 2006 Apr 18;103(16):6380-5. doi: 10.1073/pnas.0601267103. Epub 2006 Apr 10.


Presynaptic inhibitory G protein-coupled receptors play a critical role in regulating transmission at a number of synapses in the central and peripheral nervous system. We generated transgenic mice that express a constitutively active form of an inhibitory Galpha subunit to examine the molecular mechanisms underlying the actions of one such receptor, metabotropic glutamate receptor (mGluR) 2, at mossy fiber-CA3 synapses in the hippocampus. mGluR2 participates in at least three types of mossy fiber synaptic plasticity, (i) transient suppression of synaptic transmission, (ii) long-term depression (LTD), and (iii) inhibition of long-term potentiation (LTP), and we find that inhibitory Galpha signaling is sufficient to account for the actions of mGluR2 in each. The fact that constitutively active Galphai2 occludes the transient suppression of synaptic transmission by mGluR2, while enhancing LTD, suggests further that these two forms of plasticity are expressed via different mechanisms. In addition, the LTP deficit observed in constitutively active Galphai2-expressing mice suggests that mGluR2 activation may serve as a metaplastic switch to permit the induction of LTD by inhibiting LTP.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenylyl Cyclase Inhibitors
  • Animals
  • GTP-Binding Protein alpha Subunit, Gi2 / genetics
  • GTP-Binding Protein alpha Subunit, Gi2 / metabolism*
  • Hippocampus / chemistry
  • Hippocampus / metabolism
  • Long-Term Synaptic Depression* / genetics
  • Mice
  • Mice, Transgenic
  • Mossy Fibers, Hippocampal / metabolism*
  • RNA, Messenger / analysis
  • RNA, Messenger / metabolism
  • Receptors, Metabotropic Glutamate / agonists
  • Receptors, Metabotropic Glutamate / antagonists & inhibitors
  • Receptors, Metabotropic Glutamate / metabolism*
  • Synapses / metabolism*
  • Synaptic Transmission* / genetics


  • Adenylyl Cyclase Inhibitors
  • RNA, Messenger
  • Receptors, Metabotropic Glutamate
  • metabotropic glutamate receptor 2
  • GTP-Binding Protein alpha Subunit, Gi2