PMID- 26674618 OWN - NLM STAT- MEDLINE DCOM- 20160510 LR - 20220309 IS - 1545-7885 (Electronic) IS - 1544-9173 (Print) IS - 1544-9173 (Linking) VI - 13 IP - 12 DP - 2015 Dec TI - Prolonged Intracellular Na+ Dynamics Govern Electrical Activity in Accessory Olfactory Bulb Mitral Cells. PG - e1002319 LID - 10.1371/journal.pbio.1002319 [doi] LID - e1002319 AB - 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. FAU - Zylbertal, Asaph AU - Zylbertal A AD - Department of Neurobiology, Institute of Life Sciences, Hebrew University and the Edmond and Lily Safra Center for Brain Sciences, Jerusalem, Israel. FAU - Kahan, Anat AU - Kahan A AD - School of Medicine, Department of Medical Neurobiology, Hebrew University, Jerusalem, Israel. FAU - Ben-Shaul, Yoram AU - Ben-Shaul Y AD - School of Medicine, Department of Medical Neurobiology, Hebrew University, Jerusalem, Israel. FAU - Yarom, Yosef AU - Yarom Y AD - Department of Neurobiology, Institute of Life Sciences, Hebrew University and the Edmond and Lily Safra Center for Brain Sciences, Jerusalem, Israel. FAU - Wagner, Shlomo AU - Wagner S AD - Sagol Department of Neurobiology, University of Haifa, Haifa, Israel. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20151216 PL - United States TA - PLoS Biol JT - PLoS biology JID - 101183755 RN - 0 (Nerve Tissue Proteins) RN - 0 (Sodium-Calcium Exchanger) SB - IM CIN - PLoS Biol. 2015 Dec;13(12):e1002320. PMID: 26674750 MH - Animals MH - Computational Biology/methods MH - Dendrites/*metabolism MH - Electrophysiological Phenomena MH - Female MH - Ion Channel Gating MH - Kinetics MH - Male MH - Mice, Inbred BALB C MH - Mice, Inbred C57BL MH - Microscopy, Fluorescence MH - Microscopy, Video MH - *Models, Neurological MH - Nerve Tissue Proteins/*metabolism MH - *Neural Conduction MH - Neurons/cytology/*metabolism MH - Olfactory Bulb/cytology/*metabolism MH - Single-Cell Analysis MH - Sodium-Calcium Exchanger/*metabolism MH - Specific Pathogen-Free Organisms PMC - PMC4684409 COIS- The authors have declared that no competing interests exist. EDAT- 2015/12/18 06:00 MHDA- 2016/05/11 06:00 PMCR- 2015/12/16 CRDT- 2015/12/18 06:00 PHST- 2015/09/07 00:00 [received] PHST- 2015/11/05 00:00 [accepted] PHST- 2015/12/18 06:00 [entrez] PHST- 2015/12/18 06:00 [pubmed] PHST- 2016/05/11 06:00 [medline] PHST- 2015/12/16 00:00 [pmc-release] AID - PBIOLOGY-D-15-02588 [pii] AID - 10.1371/journal.pbio.1002319 [doi] PST - epublish SO - PLoS Biol. 2015 Dec 16;13(12):e1002319. doi: 10.1371/journal.pbio.1002319. eCollection 2015 Dec.