Regulation of extrasynaptic 5-HT by serotonin reuptake transporter function in 5-HT-absorbing neurons underscores adaptation behavior in Caenorhabditis elegans

Gholamali Jafari, Yusu Xie, Andrey Kullyev, Bin Liang, Ji Ying Sze

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Serotonin [5-hydroxytryptamine (5-HT)]-absorbing neurons use serotonin reuptake transporter (SERT) to uptake 5-HT from extra cellular space but do not synthesize it. While 5-HT-absorbing neurons have been identified in diverse organisms from Caenorhabditis elegans to humans, their function has not been elucidated. Here, we show that SERT in 5-HT-absorbing neurons controls behavioral response to food deprivation in C. elegans. The AIM and RIH inter neurons uptake 5-HT released from chemosensory neurons and secretory neurons. Genetic analyses suggest that 5-HT secreted by both synaptic vesicles and dense core vesicles diffuse readily to the extra synaptic space adjacent to the AIM and RIH neurons. Loss of mod-5/SERT function blocks the 5-HT absorption. mod-5/SERT mutants have been shown to exhibit exaggerated locomotor response to food deprivation. We found that transgenic expression of MOD-5/SERTinthe 5-HT-absorbing neurons fully corrected the exaggerated behavior. Experiments of cell-specific inhibition of synaptic transmission suggest that the synaptic release of 5-HT from the 5-HT-absorbing neurons is not required for this behavioral modulation. Our data point to the role of 5-HT-absorbing neurons as temporal-spatial regulators of extra synaptic 5-HT. Regulation of extra synaptic 5-HT levels by 5-HT-absorbing neurons may represent a fundamental mechanism of 5-HT homeostasis, integrating the activity of 5-HT-producing neurons with distant targets in the neural circuits, and could be relevant to some actions of selective serotonin reuptake inhibitors in humans.

Original languageEnglish (US)
Pages (from-to)8948-8957
Number of pages10
JournalJournal of Neuroscience
Volume31
Issue number24
DOIs
StatePublished - Jun 15 2011

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Serotonin Plasma Membrane Transport Proteins
Caenorhabditis elegans
Serotonin
Neurons
Food Deprivation
Synaptic Vesicles
Secretory Vesicles
Serotonin Uptake Inhibitors

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Regulation of extrasynaptic 5-HT by serotonin reuptake transporter function in 5-HT-absorbing neurons underscores adaptation behavior in Caenorhabditis elegans. / Jafari, Gholamali; Xie, Yusu; Kullyev, Andrey; Liang, Bin; Sze, Ji Ying.

In: Journal of Neuroscience, Vol. 31, No. 24, 15.06.2011, p. 8948-8957.

Research output: Contribution to journalArticle

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