Prolonged Intracellular Na+ Dynamics Govern Electrical Activity in Accessory Olfactory Bulb Mitral Cells

PLoS Biol. 2015 Dec 16;13(12):e1002319. doi: 10.1371/journal.pbio.1002319. eCollection 2015 Dec.


Persistent activity has been reported in many brain areas and is hypothesized to mediate working memory and emotional brain states and to rely upon network or biophysical feedback. Here, we demonstrate a novel mechanism by which persistent neuronal activity can be generated without feedback, relying instead on the slow removal of Na+ from neurons following bursts of activity. We show that mitral cells in the accessory olfactory bulb (AOB), which plays a major role in mammalian social behavior, may respond to a brief sensory stimulation with persistent firing. By combining electrical recordings, Ca2+ and Na+ imaging, and realistic computational modeling, we explored the mechanisms underlying the persistent activity in AOB mitral cells. We found that the exceptionally slow inward current that underlies this activity is governed by prolonged dynamics of intracellular Na+ ([Na+]i), which affects neuronal electrical activity via several pathways. Specifically, elevated dendritic [Na+]i reverses the Na+-Ca2+ exchanger activity, thus modifying the [Ca2+]i set-point. This process, which relies on ubiquitous membrane mechanisms, is likely to play a role in other neuronal types in various brain regions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Computational Biology / methods
  • Dendrites / metabolism*
  • Electrophysiological Phenomena
  • Female
  • Ion Channel Gating
  • Kinetics
  • Male
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Microscopy, Fluorescence
  • Microscopy, Video
  • Models, Neurological*
  • Nerve Tissue Proteins / metabolism*
  • Neural Conduction*
  • Neurons / cytology
  • Neurons / metabolism*
  • Olfactory Bulb / cytology
  • Olfactory Bulb / metabolism*
  • Single-Cell Analysis
  • Sodium-Calcium Exchanger / metabolism*
  • Specific Pathogen-Free Organisms


  • Nerve Tissue Proteins
  • Sodium-Calcium Exchanger

Grant support

This work was supported by the Israel Science Foundation ( grant #1350/12, received by Shlomo Wagner and the Gatsby Charitable Foundation ( The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.