Input-timing-dependent plasticity at incoming synapses of the mushroom body facilitates olfactory learning in Drosophila

Qiao, Jing‐Da; Yang, Shengxi; Geng, Hua; Yung, Wing‐Ho; Yao, Ke

doi:10.1016/j.cub.2022.09.054

Cited by 8 publications

(9 citation statements)

References 60 publications

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“…We could determine whether the cells are firing action currents and record the firing modes, such as tonic or burst firing. Moreover, the approach of recording evoked EPSP from AL to MB, previously used to reveal input-timing-dependent plasticity in the MB circuit during olfactory learning ( Qiao et al, 2022b ), has the potential to investigate the synaptic and molecular causes of epilepsy. The latency of evoked EPSP can measure the time interval of monosynaptic transmission in target synapses ( Gil and Amitai, 1996 ).…”

Section: Discussionmentioning

confidence: 99%

“…Evoked EPSPs between the antennal lobe (AL) and the mushroom body (MB) were stimulated by current pulses (0.5 ms; 0.1–0.5 mA) from the stimulation electrode on the antennal lobe (presynaptic structure). Then the evoked EPSPs were recorded by whole-cell recording on the MB neurons (postsynaptic structure) ( Qiao et al, 2022b ). Different intensities of current pulses were applied for establishing the input-output relationship.…”

Section: Methodsmentioning

confidence: 99%

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Efficient strategies based on behavioral and electrophysiological methods for epilepsy-related gene screening in the Drosophila model

Liu

et al. 2023

Front. Mol. Neurosci.

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IntroductionWith the advent of trio-based whole-exome sequencing, the identification of epilepsy candidate genes has become easier, resulting in a large number of potential genes that need to be validated in a whole-organism context. However, conducting animal experiments systematically and efficiently remains a challenge due to their laborious and time-consuming nature. This study aims to develop optimized strategies for validating epilepsy candidate genes using the Drosophila model.MethodsThis study incorporate behavior, morphology, and electrophysiology for genetic manipulation and phenotypic examination. We utilized the Gal4/UAS system in combination with RNAi techniques to generate loss-of-function models. We performed a range of behavioral tests, including two previously unreported seizure phenotypes, to evaluate the seizure behavior of mutant and wild-type flies. We used Gal4/UAS-mGFP flies to observe the morphological alterations in the brain under a confocal microscope. We also implemented patch-clamp recordings, including a novel electrophysiological method for studying synapse function and improved methods for recording action potential currents and spontaneous EPSCs on targeted neurons.ResultsWe applied different techniques or methods mentioned above to investigate four epilepsy-associated genes, namely Tango14, Klp3A, Cac, and Sbf, based on their genotype-phenotype correlation. Our findings showcase the feasibility and efficiency of our screening system for confirming epilepsy candidate genes in the Drosophila model.DiscussionThis efficient screening system holds the potential to significantly accelerate and optimize the process of identifying epilepsy candidate genes, particularly in conjunction with trio-based whole-exome sequencing.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Efficient strategies based on behavioral and electrophysiological methods for epilepsy-related gene screening in the Drosophila model

Liu

et al. 2023

Front. Mol. Neurosci.

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“…Clusters of fly dopaminergic neurons that project to the ellipsoid body, the fan-shaped body and the lateral accessory lobes are thought to share homologies with the striatum-projecting dopaminergic neurons of the substantia nigra in mammals. Both the fruit fly central complex and vertebrate basal ganglia mediate a range of functions from motor control and sensorimotor integration to action selection and decision making to motivation (Strauss, 2002; Claridge-Chang et al, 2009; Kong et al, 2010) and learning (McCurdy et al, 2021; Zolin et al, 2021; Fisher et al, 2022; Qiao et al, 2022; Taisz and Jefferis, 2022; Yamada et al, 2023). It has been found that fruit flies lacking the DA-synthetizing tyrosine hydroxylase enzyme in the central nervous system show reduced activity and locomotor deficit that worsen with age, and also exhibit marked impairments in associative learning based on both appetitive and aversive reinforcement (Riemensperger et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Altered reactivity to threatening stimuli inDrosophilamodels of Parkinson’s disease, revealed by a trial-based assay

Kajtor,

Billes,

Király

et al. 2023

Preprint

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The fruit fly Drosophila melanogaster emerges as an affordable, genetically tractable model of behavior and brain diseases. However, despite the surprising level of evolutionary conservation from flies to humans, significant genetic and circuit-level differences hinder the interpretability of fruit fly models for human disease. Therefore, to facilitate fly-to-human translation with more direct behavior-level comparison, we surveyed the rarely-exploited, rich behavioral repertoire of fruit flies with genetic alterations relevant to Parkinson's disease (PD). Flies displayed variable behaviors, including freezing, slowing and running, in response to predator-mimicking passing shadows used as threatening stimuli in a single-animal trial-based assay. We found that the expression of human mutant Parkin in flies resulted in reduced walking speed and decreased reactivity to passing shadows. Flies with dopamine receptor mutations showed similar alterations, consistent with the motor and cognitive deficits typical in humans with PD. However, Drosophila overexpressing the human form of α-synuclein manifested in only moderate phenotypical alterations, suggesting that other fruit fly models may be favored in PD research. We also found age-dependent trends in behavioral choice across the fly lifespan, while dopamine receptor mutant flies maintained their decreased general reactivity throughout all age groups. Our data demonstrate that single-trial behavioral analysis can reveal subtle behavioral changes in mutant flies that can be used to further our understanding of disease pathomechanisms and help gauge the validity of genetic Drosophila models of neurodegeneration.

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“…[8] To determine the impact of Zfh2 knockdown on neuronal excitability, the electrophysiological activity of projection neurons was recorded. [29] Spontaneous activity was assessed using a 700B amplifier, 1440B Digital Analog converter, and pClamp 10.5 software (Molecular Devices, San Jose, CA, USA). A cell with an access resistance of <30 MΩ was used for analysis.…”

Section: Drosophila Experimentsmentioning

confidence: 99%

“…32 The standard external and internal solutions and patch pipette were prepared as described previously. 33 Spontaneous activities were acquired using the 700B amplifier, 1440B Digital-Analog converter, and pClamp 10.5 software (Molecular Devices, San Jose, CA, USA). A cell with an access resistance of <30 MΩ sample was used for analysis.…”

Section: Drosophila Experimentsmentioning

confidence: 99%

ZFHX3variants cause childhood partial epilepsy and infantile spasms with favorable outcomes

Luo

Wang

et al. 2023

Preprint

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Background: TheZFHX3gene is highly expressed in the developing brain and plays vital roles in embryonic development, cell proliferation, neuronal differentiation, and neuronal death. The association between theZFHX3gene and human disease was undefined. This study aims to explore the relationship betweenZFHX3variants and epilepsy. Methods: Whole-exome sequencing was performed in patients with partial epilepsy without acquired causes.Drosophilamodel ofZfh2(ortholog ofZFHX3) knockdown was used to validate the association betweenZFHX3and epilepsy. The expression level ofZFHX3in different developmental stages was analyzed by using the data in humans from the Brainspan database and in flies and mice determined by RT-qPCR. Results: Eight pairs of compound heterozygous variants inZFHX3were identified in eight unrelated cases of childhood epilepsies. All patients presented partial epilepsy, including two with early spasms and one with frequent nonconvulsive status epilepticus. The three cases with severe epilepsies also had neurodevelopmental abnormities. However, all patients became seizure-free, including the patients with spasms. These variants had no or low allele frequencies in controls and presented statistically higher frequency in the case cohort than the controls. The number of recessiveZFHX3variants identified in this cohort was significantly more than the expected number of the East Asian population and that of the control of 1942 asymptomatic parents. Variants were predicted to be damaging by protein modeling and/or in silico prediction tools. Genotype-phenotype correlation analysis revealed that the patients with missense variants in C-terminus or C-terminus-truncated variant exhibited mild phenotype (only partial epilepsy). Knockdown ofZfh2in flies led to increased susceptibility to seizures and abnormal firing of excitability neurons. InDrosophila, the expression ofZfh2is high in larvae, decreased in pupae and early adults, and increased in later adults. In mice,Zfhx3is predominantly expressed in fetuses and decreased dramatically after birth. In humans, the data from the Brainspan database showed thatZFHX3is highly expressed in the embryonic period and decreased after birth with a nadir at approximately 10 years old. The dramatical decreasing ofZFHX3in early life correlated with the natural course of the illness. Conclusion:ZFHX3variants were potentially associated with partial epilepsy of childhood and infant spasms. The correlation between the outcome and gene expression stage provided insight into the underlying mechanism of the natural course of illness, potentially being helpful in management of the patients.

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Input-timing-dependent plasticity at incoming synapses of the mushroom body facilitates olfactory learning in Drosophila

Cited by 8 publications

References 60 publications

Efficient strategies based on behavioral and electrophysiological methods for epilepsy-related gene screening in the Drosophila model

Efficient strategies based on behavioral and electrophysiological methods for epilepsy-related gene screening in the Drosophila model

Altered reactivity to threatening stimuli inDrosophilamodels of Parkinson’s disease, revealed by a trial-based assay

ZFHX3variants cause childhood partial epilepsy and infantile spasms with favorable outcomes

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