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1.
PLoS Genet ; 18(11): e1010289, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36409783

RESUMO

The Serotonin Transporter (SERT) regulates extracellular serotonin levels and is the target of most current drugs used to treat depression. The mechanisms by which inhibition of SERT activity influences behavior are poorly understood. To address this question in the model organism Drosophila melanogaster, we developed new loss of function mutations in Drosophila SERT (dSERT). Previous studies in both flies and mammals have implicated serotonin as an important neuromodulator of sleep, and our newly generated dSERT mutants show an increase in total sleep and altered sleep architecture that is mimicked by feeding the SSRI citalopram. Differences in daytime versus nighttime sleep architecture as well as genetic rescue experiments unexpectedly suggest that distinct serotonergic circuits may modulate daytime versus nighttime sleep. dSERT mutants also show defects in copulation and food intake, akin to the clinical side effects of SSRIs and consistent with the pleomorphic influence of serotonin on the behavior of D. melanogaster. Starvation did not overcome the sleep drive in the mutants and in male dSERT mutants, the drive to mate also failed to overcome sleep drive. dSERT may be used to further explore the mechanisms by which serotonin regulates sleep and its interplay with other complex behaviors.


Assuntos
Proteínas de Drosophila , Drosophila melanogaster , Animais , Masculino , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Proteínas da Membrana Plasmática de Transporte de Serotonina/genética , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Serotonina , Corte , Drosophila/metabolismo , Sono/genética , Mutação , Comportamento Alimentar , Mamíferos/metabolismo
2.
PLoS Genet ; 16(8): e1009003, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32866139

RESUMO

Sensory systems rely on neuromodulators, such as serotonin, to provide flexibility for information processing as stimuli vary, such as light intensity throughout the day. Serotonergic neurons broadly innervate the optic ganglia of Drosophila melanogaster, a widely used model for studying vision. It remains unclear whether serotonin modulates the physiology of interneurons in the optic ganglia. To address this question, we first mapped the expression patterns of serotonin receptors in the visual system, focusing on a subset of cells with processes in the first optic ganglion, the lamina. Serotonin receptor expression was found in several types of columnar cells in the lamina including 5-HT2B in lamina monopolar cell L2, required for spatiotemporal luminance contrast, and both 5-HT1A and 5-HT1B in T1 cells, whose function is unknown. Subcellular mapping with GFP-tagged 5-HT2B and 5-HT1A constructs indicated that these receptors localize to layer M2 of the medulla, proximal to serotonergic boutons, suggesting that the medulla neuropil is the primary site of serotonergic regulation for these neurons. Exogenous serotonin increased basal intracellular calcium in L2 terminals in layer M2 and modestly decreased the duration of visually induced calcium transients in L2 neurons following repeated dark flashes, but otherwise did not alter the calcium transients. Flies without functional 5-HT2B failed to show an increase in basal calcium in response to serotonin. 5-HT2B mutants also failed to show a change in amplitude in their response to repeated light flashes but other calcium transient parameters were relatively unaffected. While we did not detect serotonin receptor expression in L1 neurons, they, like L2, underwent serotonin-induced changes in basal calcium, presumably via interactions with other cells. These data demonstrate that serotonin modulates the physiology of interneurons involved in early visual processing in Drosophila.


Assuntos
Receptor 5-HT1B de Serotonina/genética , Receptores 5-HT1 de Serotonina/genética , Receptores 5-HT2 de Serotonina/genética , Neurônios Serotoninérgicos/metabolismo , Serotonina/metabolismo , Animais , Ritmo Circadiano/genética , Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Regulação da Expressão Gênica/genética , Interneurônios/metabolismo , Proteínas de Membrana/genética , Proteínas do Tecido Nervoso/genética , Neurotransmissores/genética , Receptores de Serotonina/genética , Serotonina/genética , Percepção Visual/genética
3.
Sci Rep ; 12(1): 9728, 2022 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-35710569

RESUMO

Dashboard-mounted touchscreen tablets are now common in vehicles. Screen/phone use in cars likely shifts drivers' attention away from the road and contributes to risk of accidents. Nevertheless, vision is subject to multisensory influences from other senses. Haptics may help maintain or even increase visual attention to the road, while still allowing for reliable dashboard control. Here, we provide a proof-of-concept for the effectiveness of digital haptic technologies (hereafter digital haptics), which use ultrasonic vibrations on a tablet screen to render haptic perceptions. Healthy human participants (N = 25) completed a divided-attention paradigm. The primary task was a centrally-presented visual conjunction search task, and the secondary task entailed control of laterally-presented sliders on the tablet. Sliders were presented visually, haptically, or visuo-haptically and were vertical, horizontal or circular. We reasoned that the primary task would be performed best when the secondary task was haptic-only. Reaction times (RTs) on the visual search task were fastest when the tablet task was haptic-only. This was not due to a speed-accuracy trade-off; there was no evidence for modulation of VST accuracy according to modality of the tablet task. These results provide the first quantitative support for introducing digital haptics into vehicle and similar contexts.


Assuntos
Tecnologia Háptica , Percepção Visual , Humanos , Visão Ocular
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