Improved spatial learning is associated with increased hippocampal but not prefrontal long-term potentiation in mGluR4 knockout mice

Genes Brain Behav. 2013 Aug;12(6):615-25. doi: 10.1111/gbb.12052. Epub 2013 Jun 20.


Although much information about metabotropic glutamate receptors (mGluRs) and their role in normal and pathologic brain function has been accumulated during the last decades, the role of group III mGluRs is still scarcely documented. Here, we examined mGluR4 knockout mice for types of behavior and synaptic plasticity that depend on either the hippocampus or the prefrontal cortex (PFC). We found improved spatial short- and long-term memory in the radial arm maze, which was accompanied by enhanced long-term potentiation (LTP) in hippocampal CA1 region. In contrast, LTP in the PFC was unchanged when compared with wild-type controls. Changes in paired-pulse facilitation that became overt in the presence of the GABAA antagonist picrotoxin indicated a function of mGluR4 in maintaining the excitation/inhibition balance, which is of crucial importance for information processing in the brain and the deterioration of these processes in neuropsychological disorders such as autism, epilepsy and schizophrenia.

Keywords: CA1 region; GABAA receptors; dentate gyrus; hippocampus; long-term potentiation; metabotropic glutamate receptors; metaplasticity; prefrontal cortex; spatial learning; synaptic plasticity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CA1 Region, Hippocampal / drug effects
  • CA1 Region, Hippocampal / metabolism*
  • CA1 Region, Hippocampal / physiology
  • GABA-A Receptor Antagonists / pharmacology
  • Long-Term Potentiation*
  • Maze Learning*
  • Memory, Long-Term
  • Memory, Short-Term
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Picrotoxin / pharmacology
  • Prefrontal Cortex / drug effects
  • Prefrontal Cortex / metabolism*
  • Prefrontal Cortex / physiology
  • Receptors, Metabotropic Glutamate / genetics*
  • Receptors, Metabotropic Glutamate / metabolism


  • GABA-A Receptor Antagonists
  • Receptors, Metabotropic Glutamate
  • Picrotoxin
  • metabotropic glutamate receptor 4