Rem2 stabilizes intrinsic excitability and spontaneous firing in visual circuits

Elife. 2018 May 29;7:e33092. doi: 10.7554/eLife.33092.


Sensory experience plays an important role in shaping neural circuitry by affecting the synaptic connectivity and intrinsic properties of individual neurons. Identifying the molecular players responsible for converting external stimuli into altered neuronal output remains a crucial step in understanding experience-dependent plasticity and circuit function. Here, we investigate the role of the activity-regulated, non-canonical Ras-like GTPase Rem2 in visual circuit plasticity. We demonstrate that Rem2-/- mice fail to exhibit normal ocular dominance plasticity during the critical period. At the cellular level, our data establish a cell-autonomous role for Rem2 in regulating intrinsic excitability of layer 2/3 pyramidal neurons, prior to changes in synaptic function. Consistent with these findings, both in vitro and in vivo recordings reveal increased spontaneous firing rates in the absence of Rem2. Taken together, our data demonstrate that Rem2 is a key molecule that regulates neuronal excitability and circuit function in the context of changing sensory experience.

Keywords: Rem2; activity-dependent; homeostasis; intrinsic excitability; mouse; neuroscience; plasticity.

Publication types

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

MeSH terms

  • Action Potentials / physiology
  • Animals
  • Female
  • Gene Expression Regulation
  • Male
  • Mice
  • Mice, Knockout
  • Monomeric GTP-Binding Proteins / deficiency
  • Monomeric GTP-Binding Proteins / genetics*
  • Nerve Net / cytology
  • Nerve Net / metabolism*
  • Neuronal Plasticity / genetics*
  • Primary Cell Culture
  • Pyramidal Cells / cytology
  • Pyramidal Cells / metabolism*
  • Rats
  • Sensory Receptor Cells / cytology
  • Sensory Receptor Cells / metabolism*
  • Synapses / genetics
  • Synapses / metabolism
  • Visual Cortex / cytology
  • Visual Cortex / metabolism*


  • Monomeric GTP-Binding Proteins
  • Rem2 protein, mouse
  • Rem2 protein, rat