Dataset Information

Quantitative evaluation of serotonin release and clearance in Drosophila.

ABSTRACT: Serotonin signaling plays a key role in the regulation of development, mood and behavior. Drosophila is well suited for the study of the basic mechanisms of serotonergic signaling, but the small size of its nervous system has previously precluded the direct measurements of neurotransmitters. This study demonstrates the first real-time measurements of changes in extracellular monoamine concentrations in a single larval Drosophila ventral nerve cord. Channelrhodopsin-2-mediated, neuronal type-specific stimulation is used to elicit endogenous serotonin release, which is detected using fast-scan cyclic voltammetry at an implanted microelectrode. Release is decreased when serotonin synthesis or packaging are pharmacologically inhibited, confirming that the detected substance is serotonin. Similar to tetanus-evoked serotonin release in mammals, evoked serotonin concentrations are 280-640nM in the fly, depending on the stimulation length. Extracellular serotonin signaling is prolonged after administering cocaine or fluoxetine, showing that transport regulates the clearance of serotonin from the extracellular space. When ChR2 is targeted to dopaminergic neurons, dopamine release is measured demonstrating that this method is broadly applicable to other neurotransmitter systems. This study shows that the dynamics of serotonin release and reuptake in Drosophila are analogous to those in mammals, making this simple organism more useful for the study of the basic physiological mechanisms of serotonergic signaling.

SUBMITTER: Borue X

PROVIDER: S-EPMC2691387 | biostudies-literature | 2009 May

REPOSITORIES: biostudies-literature

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Quantitative evaluation of serotonin release and clearance in Drosophila.

Borue Xenia X Cooper Stephanie S Hirsh Jay J Condron Barry B Venton B Jill BJ

Journal of neuroscience methods 20090304 2

Serotonin signaling plays a key role in the regulation of development, mood and behavior. Drosophila is well suited for the study of the basic mechanisms of serotonergic signaling, but the small size of its nervous system has previously precluded the direct measurements of neurotransmitters. This study demonstrates the first real-time measurements of changes in extracellular monoamine concentrations in a single larval Drosophila ventral nerve cord. Channelrhodopsin-2-mediated, neuronal type-spec ...[more]

PMID: 19428541

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Project description:Selective serotonin reuptake inhibitors (SSRIs) were designed to treat depression by increasing serotonin levels throughout the brain via inhibition of clearance from the extracellular space. Although increases in serotonin levels are observed after acute SSRI exposure, 3-6 weeks of continuous use is required for relief from the symptoms of depression. Thus, it is now believed that plasticity in multiple brain systems that are downstream of serotonergic inputs contributes to the therapeutic efficacy of SSRIs. The onset of antidepressant effects also coincides with desensitization of somatodendritic serotonin autoreceptors in the dorsal raphe nucleus (DRN), suggesting that disrupting inhibitory feedback within the serotonin system may contribute to the therapeutic effects of SSRIs. Previously, we showed that chronic SSRI treatment caused a frequency-dependent facilitation of serotonin signaling that persisted in the absence of uptake inhibition. In this work, we use in vivo fast-scan cyclic voltammetry in mice to investigate a similar facilitation after a single treatment of the SSRI citalopram hydrobromide. Acute citalopram hydrobromide treatment resulted in frequency-dependent increases of evoked serotonin release in the substantia nigra pars reticulata. These increases were independent of changes in uptake velocity, but required SERT expression. Using microinjections, we show that the frequency-dependent enhancement in release is because of SERT inhibition in the DRN, demonstrating that SSRIs can enhance serotonin release by inhibiting uptake in a location distal to the terminal release site. The novel finding that SERT inhibition can disrupt modulatory mechanisms at the level of the DRN to facilitate serotonin release will help future studies investigate serotonin's role in depression and motivated behavior. In this work, stimulations of the dorsal raphe nucleus (DRN) evoke serotonin release that is recorded in the substantia nigra pars reticulata (SNpr) using in vivo fast-scan cyclic voltammetry. Systemic administration of a selective serotonin reuptake inhibitor (SSRI) causes both an increase in t1/2 and an increase in [5-HT]max in the SNpr. Local application of SSRI to the DRN recapitulates the increase in [5-HT]max observed in the SNpr without affecting uptake. Thus, SSRIs increase serotonin signaling via two distinct SERT-mediated mechanisms.

Dataset Information

Quantitative evaluation of serotonin release and clearance in Drosophila.

Publications

Quantitative evaluation of serotonin release and clearance in Drosophila.

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