TY - JOUR
T1 - Regulation of extrasynaptic 5-HT by serotonin reuptake transporter function in 5-HT-absorbing neurons underscores adaptation behavior in Caenorhabditis elegans
AU - Jafari, Gholamali
AU - Xie, Yusu
AU - Kullyev, Andrey
AU - Liang, Bin
AU - Sze, Ji Ying
PY - 2011/6/15
Y1 - 2011/6/15
N2 - 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.
AB - 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.
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U2 - 10.1523/JNEUROSCI.1692-11.2011
DO - 10.1523/JNEUROSCI.1692-11.2011
M3 - Article
C2 - 21677178
AN - SCOPUS:79959289555
SN - 0270-6474
VL - 31
SP - 8948
EP - 8957
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 24
ER -