Interdependent Conductances Drive Infraslow Intrinsic Rhythmogenesis in a Subset of Accessory Olfactory Bulb Projection Neurons

J Neurosci. 2016 Mar 16;36(11):3127-44. doi: 10.1523/JNEUROSCI.2520-15.2016.


The accessory olfactory system controls social and sexual behavior. However, key aspects of sensory signaling along the accessory olfactory pathway remain largely unknown. Here, we investigate patterns of spontaneous neuronal activity in mouse accessory olfactory bulb mitral cells, the direct neural link between vomeronasal sensory input and limbic output. Both in vitro and in vivo, we identify a subpopulation of mitral cells that exhibit slow stereotypical rhythmic discharge. In intrinsically rhythmogenic neurons, these periodic activity patterns are maintained in absence of fast synaptic drive. The physiological mechanism underlying mitral cell autorhythmicity involves cyclic activation of three interdependent ionic conductances: subthreshold persistent Na(+) current, R-type Ca(2+) current, and Ca(2+)-activated big conductance K(+) current. Together, the interplay of these distinct conductances triggers infraslow intrinsic oscillations with remarkable periodicity, a default output state likely to affect sensory processing in limbic circuits.

Significance statement: We show for the first time that some rodent accessory olfactory bulb mitral cells-the direct link between vomeronasal sensory input and limbic output-are intrinsically rhythmogenic. Driven by ≥ 3 distinct interdependent ionic conductances, infraslow intrinsic oscillations show remarkable periodicity both in vitro and in vivo. As a novel default state, infraslow autorhythmicity is likely to affect limbic processing of pheromonal information.

Keywords: intrinsic oscillations; mitral cell; olfactory bulb; pacemaker; rhythmogenesis; vomeronasal system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 6-Cyano-7-nitroquinoxaline-2,3-dione / pharmacology
  • Action Potentials / drug effects
  • Action Potentials / physiology*
  • Animals
  • Calcium / metabolism
  • Calcium Channel Blockers / pharmacology
  • Cardiovascular Agents / pharmacology
  • Excitatory Amino Acid Antagonists / pharmacology
  • Group II Phospholipases A2
  • In Vitro Techniques
  • Mice
  • Mice, Inbred C57BL
  • Models, Neurological
  • Neurons / classification
  • Neurons / drug effects
  • Neurons / physiology*
  • Olfactory Bulb / cytology*
  • Olfactory Pathways / physiology*
  • Periodicity*
  • Pyrimidines / pharmacology
  • Spider Venoms / pharmacology
  • Valine / analogs & derivatives
  • Valine / pharmacology
  • omega-Agatoxin IVA / pharmacology


  • Calcium Channel Blockers
  • Cardiovascular Agents
  • Excitatory Amino Acid Antagonists
  • Pyrimidines
  • SNX 482
  • Spider Venoms
  • omega-Agatoxin IVA
  • ICI D2788
  • 6-Cyano-7-nitroquinoxaline-2,3-dione
  • 2-amino-5-phosphopentanoic acid
  • Group II Phospholipases A2
  • Valine
  • Calcium