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

Asaph Zylbertal,Anat Kahan,Yosef Yarom,Shlomo Wagner,Yoram Ben-Shaul,Naoshige Uchida

doi:10.1371/journal.pbio.1002319

Asaph Zylbertal, Anat Kahan + Show 4 more

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https://doi.org/10.1371/journal.pbio.1002319

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Journal: PLoS Biology	Publication Date: Dec 16, 2015
Citations: 83	License type: CC BY 4.0

Affiliation: Hebrew University of Jerusalem, University of Haifa

Abstract

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.

Highlights

The accessory olfactory system, known as the vomeronasal system, mediates chemical communication between conspecifics of most mammalian and reptilian species during social interactions [1]
The principle cells of the accessory olfactory bulb (AOB) may respond to transient stimulation with prolonged activity, sometimes lasting for minutes—a property known as persistent activity
We show how persistent activity can emerge without feedback, relying on slow changes in internal ionic concentrations, which keep a record of past neuronal activity for long periods of time

Summary

Introduction

The accessory olfactory system, known as the vomeronasal system, mediates chemical communication between conspecifics of most mammalian and reptilian species during social interactions [1]. Inputs to this chemosensory system originate from the sensory neurons of the vomeronasal organ (VNO) that synapse on the mitral cells of the accessory olfactory bulb (AOB), which provide the output of the bulb [2]. Persistent activity, defined as the ability of neurons to remain active in the absence of external inputs, was documented in many brain areas. It has been suggested that persistent activity is a neuronal correlate of working memory [4], and that it can mediate neuronal integration over long time scales [5]

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