PMID- 20016104 OWN - NLM STAT- MEDLINE DCOM- 20100126 LR - 20211020 IS - 1529-2401 (Electronic) IS - 0270-6474 (Print) IS - 0270-6474 (Linking) VI - 29 IP - 50 DP - 2009 Dec 16 TI - Activity-dependent vesicular monoamine transporter-mediated depletion of the nucleus supports somatic release by serotonin neurons. PG - 15878-87 LID - 10.1523/JNEUROSCI.4210-09.2009 [doi] AB - Packaging by the vesicular monoamine transporter (VMAT) is essential for mood-controlling serotonin transmission but has not been assayed during activity. Here, two-photon imaging of the fluorescent serotonin analog 5,7-dihydroxytryptamine and three-photon imaging of endogenous serotonin were used to study vesicular packaging as it supports release from the soma of serotonin neurons. Glutamate receptor activation in dorsal raphe brain slice evoked somatic release that was mediated solely by vesicle exocytosis. This release was accompanied by VMAT-mediated serotonin depletion from the nucleus, a large compartment free of monoaminergic degradation pathways that has not been implicated in neurotransmission previously. Finally, while some monoamine packaged at rest was held in reserve, monoamine packaged during stimulation was released completely. Hence, somatic vesicles loaded by VMAT during activity rapidly undergo exocytosis. In the absence of active zones and with limited neurotransmitter reuptake, somatic release by serotonin neurons is supported by recruitment from a large pool of extravesicular serotonin in the nucleus and cytoplasm, and preferential release of the newly packaged transmitter. FAU - Colgan, Lesley A AU - Colgan LA AD - Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA. FAU - Putzier, Ilva AU - Putzier I FAU - Levitan, Edwin S AU - Levitan ES LA - eng GR - R21DA25739/DA/NIDA NIH HHS/United States GR - R01 NS053050/NS/NINDS NIH HHS/United States GR - R01NS53050/NS/NINDS NIH HHS/United States GR - R01 NS053050-04/NS/NINDS NIH HHS/United States GR - R21 DA025739/DA/NIDA NIH HHS/United States GR - R21 DA025739-02/DA/NIDA NIH HHS/United States PT - Comparative Study PT - Journal Article PT - Research Support, N.I.H., Extramural PL - United States TA - J Neurosci JT - The Journal of neuroscience : the official journal of the Society for Neuroscience JID - 8102140 RN - 0 (Vesicular Monoamine Transport Proteins) RN - 31363-74-3 (5,7-Dihydroxytryptamine) RN - 333DO1RDJY (Serotonin) SB - IM MH - 5,7-Dihydroxytryptamine/pharmacology MH - Animals MH - Cell Nucleus/drug effects/*metabolism MH - Cells, Cultured MH - Exocytosis/drug effects/physiology MH - Male MH - Neurons/cytology/drug effects/*metabolism MH - PC12 Cells MH - Raphe Nuclei/cytology/drug effects/metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Serotonin/*metabolism MH - Vesicular Monoamine Transport Proteins/*physiology PMC - PMC2796554 MID - NIHMS158627 OTO - NOTNLM OT - SERT OT - VMAT2 OT - fluorescent false neurotransmitter OT - multiphoton microscopy OT - somatodendritic release OT - vesicular transport EDAT- 2009/12/18 06:00 MHDA- 2010/01/27 06:00 PMCR- 2010/06/16 CRDT- 2009/12/18 06:00 PHST- 2009/12/18 06:00 [entrez] PHST- 2009/12/18 06:00 [pubmed] PHST- 2010/01/27 06:00 [medline] PHST- 2010/06/16 00:00 [pmc-release] AID - 29/50/15878 [pii] AID - 3554640 [pii] AID - 10.1523/JNEUROSCI.4210-09.2009 [doi] PST - ppublish SO - J Neurosci. 2009 Dec 16;29(50):15878-87. doi: 10.1523/JNEUROSCI.4210-09.2009.