Serotonin distinctly controls behavioral states in restrained and freely moving Drosophila

Gowda, Swetha B. M.; Banu, Ayesha; Salim, Safa; Peker, Kadir A.; Mohammad, Farhan

doi:10.1016/j.isci.2022.105886

Cited by 4 publications

(5 citation statements)

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“…We used the optogenetic activator, CsChrimson [ 90 ], and the optogenetic inhibitor, GtACR1 [ 91 ], to activate or inhibit Ssdp-expressing neurons respectively, using the GAL4/UAS system. These tools have been extensively used to investigate various kinds of behaviors in Drosophila such as locomotion [ 92 ], sleep [ 93 ], courtship [ 94 ], learning and memory [ 95 ], and stress-related behaviors [ 96 ]. We assessed locomotion, wall-following, habituation learning, and social interaction in 3- to 4-day-old Chrimson-Ssdp [2082-G4] flies upon red illumination and in GtACR1-Ssdp [2082-G4] flies upon green illumination and compared the behaviors to their respective genotypic controls.…”

Section: Resultsmentioning

confidence: 99%

The ortholog of human ssDNA-binding protein SSBP3 influences neurodevelopment and autism-like behaviors in Drosophila melanogaster

et al. 2023

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1p32.3 microdeletion/duplication is implicated in many neurodevelopmental disorders-like phenotypes such as developmental delay, intellectual disability, autism, macro/microcephaly, and dysmorphic features. The 1p32.3 chromosomal region harbors several genes critical for development; however, their validation and characterization remain inadequate. One such gene is the single-stranded DNA-binding protein 3 (SSBP3) and its Drosophila melanogaster ortholog is called sequence-specific single-stranded DNA-binding protein (Ssdp). Here, we investigated consequences of Ssdp manipulations on neurodevelopment, gene expression, physiological function, and autism-associated behaviors using Drosophila models. We found that SSBP3 and Ssdp are expressed in excitatory neurons in the brain. Ssdp overexpression caused morphological alterations in Drosophila wing, mechanosensory bristles, and head. Ssdp manipulations also affected the neuropil brain volume and glial cell number in larvae and adult flies. Moreover, Ssdp overexpression led to differential changes in synaptic density in specific brain regions. We observed decreased levels of armadillo in the heads of Ssdp overexpressing flies, as well as a decrease in armadillo and wingless expression in the larval wing discs, implicating the involvement of the canonical Wnt signaling pathway in Ssdp functionality. RNA sequencing revealed perturbation of oxidative stress-related pathways in heads of Ssdp overexpressing flies. Furthermore, Ssdp overexpressing brains showed enhanced reactive oxygen species (ROS), altered neuronal mitochondrial morphology, and up-regulated fission and fusion genes. Flies with elevated levels of Ssdp exhibited heightened anxiety-like behavior, altered decisiveness, defective sensory perception and habituation, abnormal social interaction, and feeding defects, which were phenocopied in the pan-neuronal Ssdp knockdown flies, suggesting that Ssdp is dosage sensitive. Partial rescue of behavioral defects was observed upon normalization of Ssdp levels. Notably, Ssdp knockdown exclusively in adult flies did not produce behavioral and functional defects. Finally, we show that optogenetic manipulation of Ssdp-expressing neurons altered autism-associated behaviors. Collectively, our findings provide evidence that Ssdp, a dosage-sensitive gene in the 1p32.3 chromosomal region, is associated with various anatomical, physiological, and behavioral defects, which may be relevant to neurodevelopmental disorders like autism. Our study proposes SSBP3 as a critical gene in the 1p32.3 microdeletion/duplication genomic region and sheds light on the functional role of Ssdp in neurodevelopmental processes in Drosophila.

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Section: Resultsmentioning

confidence: 99%

The ortholog of human ssDNA-binding protein SSBP3 influences neurodevelopment and autism-like behaviors in Drosophila melanogaster

et al. 2023

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“…Interestingly, the flies show an impaired PER response at lower sucrose concentrations of 5 mM and even with water, which may be either related to the motor deficits induced by serotonin; or is a startling effect of the first light exposure (flies were kept in the dark for retinal treatment). Alternatively, these differences between PER and OptoPAD response could also be because of differences in brain states of freely moving flies compared to tethered flies ( Gowda et al, 2022 ). Serotonin, a psychoactive neurotransmitter, may coordinate the interplay between feeding and stress differently in an immobilized fly.…”

Section: Discussionmentioning

confidence: 99%

“…Distinct from the sated state, starvation induces motivation to both eat and move ( Knoppein et al, 2000 ). Given that VNC serotonin has been shown to slow down locomotion ( Howard et al, 2019 ) and lead to suppression of arousability ( Pooryasin and Fiala, 2015 ) or enhancement of immobility ( Gowda et al, 2022 ), activating the locomotor serotonergic circuit in the food-deprived state may have an indirect effect on feeding by inhibiting the locomotor drive mediated by starvation and at the same time promoting feeding by activity in SEL neurons. However, more conclusive experiments, especially imaging VNC in feeding flies and specific serotonergic drivers, are required, which could highlight how VNC affects feeding and how the brain state is involved in this circuit.…”

Section: Discussionmentioning

confidence: 99%

Serotonergic control of feeding microstructure in Drosophila

Banu

Gowda

Salim

et al. 2023

Front. Behav. Neurosci.

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To survive, animals maintain energy homeostasis by seeking out food. Compared to freely feeding animals, food-deprived animals may choose different strategies to balance both energy and nutrition demands, per the metabolic state of the animal. Serotonin mediates internal states, modifies existing neural circuits, and regulates animal feeding behavior, including in humans and fruit flies. However, an in-depth study on the neuromodulatory effects of serotonin on feeding microstructure has been held back for several technical reasons. Firstly, most feeding assays lack the precision of manipulating neuronal activity only when animals start feeding, which does not separate neuronal effects on feeding from foraging and locomotion. Secondly, despite the availability of optogenetic tools, feeding in adult fruit flies has primarily been studied using thermogenetic systems, which are confounded with heat. Thirdly, most feeding assays have used food intake as a measurement, which has a low temporal resolution to dissect feeding at the microstructure level. To circumvent these problems, we utilized OptoPAD assay, which provides the precision of optogenetics to control neural activity contingent on the ongoing feeding behavior. We show that manipulating the serotonin circuit optogenetically affects multiple feeding parameters state-dependently. Food-deprived flies with optogenetically activated and suppressed serotonin systems feed with shorter and longer sip durations and longer and shorter inter-sip intervals, respectively. We further show that serotonin suppresses and enhances feeding via 5-HT1B and 5-HT7 receptors, respectively.

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“…To uncover the role of underlying serotonergic circuits that control these alternating locomotor outputs, we employed optogenetics and intersectional genetics to show that broader optogenetic activation of serotonergic neurons promotes immobility with arrested motor behavior, and conversely, inactivation of serotonergic neurons promotes mobility states with increased leg flailing. We report that serotonergic VNC neurons through 5‐HT7 receptors mediate these behavioral states in restrained adult Drosophila (Gowda et al., 2023). We also revealed that these biphasic behavioral states were modulated by several external factors such as hunger state (fed vs. starved), gender, age, past negative experiences, and genetic background.…”

Section: Role Of Neuromodulation In Walkingmentioning

confidence: 99%

“…To better understand how fruit flies respond in a restrained situation, we recently established a novel assay called STRIF (STruggle Response in Immobilized flies) to measure the escape behaviors in restrained Drosophila (Gowda et al., 2023). In the restrained state, flies alternate between phases of flailing with high bursts of motor activity and quiescence phase with ceased leg movements.…”

Section: Role Of Neuromodulation In Walkingmentioning

confidence: 99%

Neuronal mechanisms regulating locomotion in adult Drosophila

Gowda,

Banu,

Hussain

et al. 2024

J of Neuroscience Research

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The coordinated action of multiple leg joints and muscles is required even for the simplest movements. Understanding the neuronal circuits and mechanisms that generate precise movements is essential for comprehending the neuronal basis of the locomotion and to infer the neuronal mechanisms underlying several locomotor‐related diseases. Drosophila melanogaster provides an excellent model system for investigating the neuronal circuits underlying motor behaviors due to its simple nervous system and genetic accessibility. This review discusses current genetic methods for studying locomotor circuits and their function in adult Drosophila. We highlight recently identified neuronal pathways that modulate distinct forward and backward locomotion and describe the underlying neuronal control of leg swing and stance phases in freely moving flies. We also report various automated leg tracking methods to measure leg motion parameters and define inter‐leg coordination, gait and locomotor speed of freely moving adult flies. Finally, we emphasize the role of leg proprioceptive signals to central motor circuits in leg coordination. Together, this review highlights the utility of adult Drosophila as a model to uncover underlying motor circuitry and the functional organization of the leg motor system that governs correct movement.

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Serotonin distinctly controls behavioral states in restrained and freely moving Drosophila

Cited by 4 publications

References 71 publications

The ortholog of human ssDNA-binding protein SSBP3 influences neurodevelopment and autism-like behaviors in Drosophila melanogaster

The ortholog of human ssDNA-binding protein SSBP3 influences neurodevelopment and autism-like behaviors in Drosophila melanogaster

Serotonergic control of feeding microstructure in Drosophila

Neuronal mechanisms regulating locomotion in adult Drosophila

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