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 language | English (US) |
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Pages (from-to) | 8948-8957 |
Number of pages | 10 |
Journal | Journal of Neuroscience |
Volume | 31 |
Issue number | 24 |
DOIs | |
State | Published - Jun 15 2011 |
ASJC Scopus subject areas
- Neuroscience(all)