Synergism of type 1 metabotropic and ionotropic glutamate receptors in cerebellar molecular layer interneurons in vivo

Elife. 2020 May 13:9:e56839. doi: 10.7554/eLife.56839.


Type 1 metabotropic glutamate receptors (mGluR1s) are key elements in neuronal signaling. While their function is well documented in slices, requirements for their activation in vivo are poorly understood. We examine this question in adult mice in vivo using 2-photon imaging of cerebellar molecular layer interneurons (MLIs) expressing GCaMP. In anesthetized mice, parallel fiber activation evokes beam-like Cai rises in postsynaptic MLIs which depend on co-activation of mGluR1s and ionotropic glutamate receptors (iGluRs). In awake mice, blocking mGluR1 decreases Cai rises associated with locomotion. In vitro studies and freeze-fracture electron microscopy show that the iGluR-mGluR1 interaction is synergistic and favored by close association of the two classes of receptors. Altogether our results suggest that mGluR1s, acting in synergy with iGluRs, potently contribute to processing cerebellar neuronal signaling under physiological conditions.

Keywords: calcium imaging; cerebellum; glutamate receptors; in vivo; mglurs; mouse; neuroscience; parallel fiber.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biosensing Techniques
  • Calcium Signaling
  • Calcium-Binding Proteins / genetics
  • Calcium-Binding Proteins / metabolism
  • Cerebellum / metabolism*
  • Cerebellum / ultrastructure
  • Female
  • Interneurons / metabolism*
  • Interneurons / ultrastructure
  • Luminescent Proteins / genetics
  • Luminescent Proteins / metabolism
  • Mice
  • Microscopy, Fluorescence, Multiphoton
  • Motor Activity
  • Receptors, Ionotropic Glutamate / metabolism*
  • Receptors, Metabotropic Glutamate / metabolism*
  • Synaptic Transmission*
  • Walking


  • Calcium-Binding Proteins
  • Luminescent Proteins
  • Receptors, Ionotropic Glutamate
  • Receptors, Metabotropic Glutamate
  • metabotropic glutamate receptor type 1