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

doi:10.1523/jneurosci.1692-11.2011

Cited by 69 publications

(93 citation statements)

References 58 publications

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“…The members of the other pair are noted as, ADFR and ADFL (right and left amphid chemosensory neurons) and are defi ned as having two amphid sensory dendrites each. The serotonin produced by these two cell pairs has been shown to diffuse into extracellular spaces (Jafari et al, 2011). On the other hand the authors reported three adjacent ring inter neurons, RIH (unpaired), AIMR and AIML (right and left), instead, to transport serotonin (noted as serotonin reuptake transporters, SERT) controlling in this way a behavioral response to food deprivation.…”

Section: Discussionmentioning

confidence: 99%

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Serotonin in Trichinella pseudospiralis: An immunocytochemical study

et al. 2016

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SummaryThis is the fi rst report on the presence and localization of the neurotransmitter serotonin (5-HT) in the nervous system of the nematode Trichinella pseudospiralis, the causative agent of trichinellosis. The orientation of the 5-HT-immunoreactive (5-HT-IR) nerve cells in the adult worm is described. In the anterior region of the worm 5-HT-IR occurs in 7 neurons. Longitudinal nerve cords extend posteriorly from the anterior end. They are connected by transverse commissures. The vulval area is intensively supplied with 5-HT-IR nerve cells and fi bres forming a plexus. Two rows of small 5HT-IR structures, hypodermal glands, are visible along the whole nematode body. Because of the conserved structural features among nematodes the 5-HT-IR neurons observed are likely to have counterparts in the model worm, Caenorhabditis elegans. Some basic differences are evident and demand further study.

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Section: Discussionmentioning

confidence: 99%

“…However, it is tempting to look for homologies between the two worms. In the anterior region of C. elegans, two pairs of 5-HT-IR neurons have been described in detail by Jafari et al (2011). In C. elegans, the fi rst pair is formed by the right and left pharyngeal neurosecretory motor neurons (NSMR and NSML).…”

Section: Discussionmentioning

confidence: 99%

Serotonin in Trichinella pseudospiralis: An immunocytochemical study

et al. 2016

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“…We examined the expression of bas-1, which codes for the aromatic amino acid decarboxylase that converts the TPH-1 product 5-hydroxytryptophan to serotonin (Hare and Loer 2004), the cat-4 gene, which is required to generate a co-factor for TPH-1, and the vesicular monoamine transporter encoded by cat-1 (Duerr et al 1999) (note that the serotonin reuptake transporter mod-5 is not expressed in HSN) (Jafari et al 2011). We found that expression of the entire serotonin pathway is strongly affected in the HSNs of ham-3(n1654) mutants (Figure 1, B and D).…”

Section: Phenotypic Analysis Of Ham-3 Mutants Reveals Neuronal Defectsmentioning

confidence: 99%

The SWI/SNF Chromatin Remodeling Complex Selectively Affects Multiple Aspects of Serotonergic Neuron Differentiation

et al. 2013

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Regulatory programs that control the specification of serotonergic neurons have been investigated by genetic mutant screens in the nematode Caenorhabditis elegans. Loss of a previously uncloned gene, ham-3, affects migration and serotonin antibody staining of the hermaphrodite-specific neuron (HSN) pair. We characterize these defects here in more detail, showing that the defects in serotonin antibody staining are paralleled by a loss of the transcription of all genes involved in serotonin synthesis and transport. This loss is specific to the HSN class as other serotonergic neurons appear to differentiate normally in ham-3 null mutants. Besides failing to migrate appropriately, the HSNs also display axon pathfinding defects in ham-3 mutants. However, the HSNs are still generated and express a subset of their terminal differentiation features in ham-3 null mutants, demonstrating that ham-3 is a specific regulator of select features of the HSNs. We show that ham-3 codes for the C. elegans ortholog of human BAF60, Drosophila Bap60, and yeast Swp73/Rsc6, which are subunits of the yeast SWI/SNF and vertebrate BAF chromatin remodeling complex. We show that the effect of ham-3 on serotonergic fate can be explained by ham-3 regulating the expression of the Spalt/SALL-type Zn finger transcription factor sem-4, a previously identified regulator of serotonin expression in HSNs and of the ham-2 Zn transcription factor, a previously identified regulator of HSN migration and axon outgrowth. Our findings provide the first evidence for the involvement of the BAF complex in the acquisition of terminal neuronal identity and constitute genetic proof by germline knockout that a BAF complex component can have cell-type-specific roles during development. N EURONS that express the neurotransmitter serotonin fulfill a number of critical functions in all nervous systems examined to date. In vertebrates, serotonergic neurons modulate anxiety, cognitive processes, mood, body temperature, sleep, sexual behavior, appetite, and metabolism, and their dysfunction has been connected to a variety of human disorders (Muller and Jacobs 2010). In the hermaphroditic Caenorhabditis elegans nervous system, serotonin also controls a number of distinct behaviors (Schafer 2005;Chase and Koelle 2007). Serotonin is utilized as a neurotransmitter under normal conditions by seven neuron types, the sensory neuron ADF; the interneurons AIM and RIH; the motor neurons hermaphroditespecific neurons (HSNs), the ventral cord motor neurons VC4 and VC5; and the neurosecretory NSM cells (Schafer 2005;Chase and Koelle 2007). Under stress conditions, serotonin is used by an additional neuron type, ASG (Pocock and Hobert 2010). One of the serotonergic neurons, the hermaphrodite-specific motor neuron, HSN, utilizes serotonin to signal to vulval muscles to control egg-laying behavior (Schafer 2005). Unlike most other neurons in the C. elegans nervous system, the two bilaterally symmetric HSNs undergo long-range migration. After terminating migration, they extend th...

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“…First, C. elegans allows the use of forward genetic screens to identify the proteins beyond serotonin receptors that mediate serotonin response. Second, the known synaptic wiring of the C. elegans nervous system (White et al 1986) provides the opportunity to directly test whether serotonin acts at synapses or extrasynaptically.Previous studies of C. elegans have shown that, of the precisely 302 neurons found in an adult hermaphrodite, the NSM, HSN, ADF, VC4/5, AIM, and RIH neurons contain serotonin, although the AIM, RIH, and possibly also the VC4/5 neurons do not synthesize serotonin themselves but rather take up serotonin made by the other neurons (Horvitz et al 1982;Sawin et al 2000;Jafari et al 2011). Animals with mutations in the enzymes that synthesize serotonin or in which the NSMs have been ablated are defective for the strong reduction in locomotion behavior, known as enhanced slowing, that occurs when food-deprived animals encounter food (Sawin et al 2000).…”

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confidence: 99%

Receptors and Other Signaling Proteins Required for Serotonin Control of Locomotion inCaenorhabditis elegans

et al. 2012

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A better understanding of the molecular mechanisms of signaling by the neurotransmitter serotonin is required to assess the hypothesis that defects in serotonin signaling underlie depression in humans. Caenorhabditis elegans uses serotonin as a neurotransmitter to regulate locomotion, providing a genetic system to analyze serotonin signaling. From large-scale genetic screens we identified 36 mutants of C. elegans in which serotonin fails to have its normal effect of slowing locomotion, and we molecularly identified eight genes affected by 19 of the mutations. Two of the genes encode the serotonin-gated ion channel MOD-1 and the G-protein-coupled serotonin receptor SER-4. mod-1 is expressed in the neurons and muscles that directly control locomotion, while ser-4 is expressed in an almost entirely non-overlapping set of sensory and interneurons. The cells expressing the two receptors are largely not direct postsynaptic targets of serotonergic neurons. We analyzed animals lacking or overexpressing the receptors in various combinations using several assays for serotonin response. We found that the two receptors act in parallel to affect locomotion. Our results show that serotonin functions as an extrasynaptic signal that independently activates multiple receptors at a distance from its release sites and identify at least six additional proteins that appear to act with serotonin receptors to mediate serotonin response. DEPRESSION is hypothesized to involve dysfunction of the neurotransmitter serotonin (Cowen 2008). Understanding the molecular mechanism of serotonin signaling is complicated by the fact that the human brain expresses 14 types of serotonin receptors, one of which is a serotonin-gated ion channel, and the rest of which are G-protein-coupled receptors (Millan et al. 2008). An additional challenge to understanding serotonin signaling is the fact that serotonin can act locally at synapses where it is released or diffuse away and act at distant receptors. While classical neurotransmitters such as GABA and glutamate appear to function mainly locally at synapses, serotonin can diffuse several microns from its release sites at concentrations sufficient to activate its receptors (Bunin and Wightman 1998). Furthermore, serotonin receptors are often localized at nonsynaptic sites (Kia et al. 1996). These observations suggest that serotonin might act predominantly as an extrasynaptic signal to activate several receptor types on cells distant from its release sites and that the combined action of these several receptors somehow coordinates appropriate responses to serotonin. The details of how such action might occur remain unclear.Caenorhabditis elegans uses serotonin as a neurotransmitter (Horvitz et al. 1982;Chase and Koelle 2007) and provides a model system with the potential to make important contributions to the study of serotonin signaling. First, C. elegans allows the use of forward genetic screens to identify the proteins beyond serotonin receptors that mediate serotonin response. Second, the known...

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Regulation of Extrasynaptic 5-HT by Serotonin Reuptake Transporter Function in 5-HT-Absorbing Neurons Underscores Adaptation Behavior in Caenorhabditis elegans

Cited by 69 publications

References 58 publications

Serotonin in Trichinella pseudospiralis: An immunocytochemical study

Serotonin in Trichinella pseudospiralis: An immunocytochemical study

The SWI/SNF Chromatin Remodeling Complex Selectively Affects Multiple Aspects of Serotonergic Neuron Differentiation

Receptors and Other Signaling Proteins Required for Serotonin Control of Locomotion inCaenorhabditis elegans

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