Two Components of Aversive Memory in<i>Drosophila</i>, Anesthesia-Sensitive and Anesthesia-Resistant Memory, Require Distinct Domains Within the Rgk1 Small GTPase

Murakami, Satoshi; Minami-Ohtsubo, Maki; Nakato, Ryuichiro; Shirahige, Katsuhiko; Tabata, Tetsuya

doi:10.1523/jneurosci.3648-16.2017

Cited by 7 publications

(3 citation statements)

References 114 publications

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“…We previously showed that genes tagged with GFSTF faithfully reproduce the expression and subcellular distribution pattern of all tagged proteins tested ( Nagarkar-Jaiswal et al, 2015b ). We confirmed this observation as the similarities between GFSTF localization ( Figure 1—figure supplement 1 ) and published antibody staining for Cactus ( Zhou et al, 2015 ), Rgk1 ( Murakami et al, 2017 ), Discs large 1, and Bruchpilot ( Nagarkar-Jaiswal et al, 2015b ) in the brain are obvious. However, GAL4 strongly amplifies the expression of UAS-mCD8::GFP when compared to the endogenous GFP tagged proteins but the subcellular protein distribution is lost.…”

Section: Resultssupporting

confidence: 80%

A gene-specific T2A-GAL4 library for Drosophila

Lee

Zirin

Kanca

et al. 2018

eLife

253

285

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We generated a library of ~1000 Drosophila stocks in which we inserted a construct in the intron of genes allowing expression of GAL4 under control of endogenous promoters while arresting transcription with a polyadenylation signal 3’ of the GAL4. This allows numerous applications. First, ~90% of insertions in essential genes cause a severe loss-of-function phenotype, an effective way to mutagenize genes. Interestingly, 12/14 chromosomes engineered through CRISPR do not carry second-site lethal mutations. Second, 26/36 (70%) of lethal insertions tested are rescued with a single UAS-cDNA construct. Third, loss-of-function phenotypes associated with many GAL4 insertions can be reverted by excision with UAS-flippase. Fourth, GAL4 driven UAS-GFP/RFP reports tissue and cell-type specificity of gene expression with high sensitivity. We report the expression of hundreds of genes not previously reported. Finally, inserted cassettes can be replaced with GFP or any DNA. These stocks comprise a powerful resource for assessing gene function.

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Section: Resultssupporting

confidence: 80%

A gene-specific T2A-GAL4 library for Drosophila

Lee

Zirin

Kanca

et al. 2018

eLife

253

285

View full text Add to dashboard Cite

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“…Kenyon cells receive dopaminergic input, and acute exposure to cocaine results in altered expression of Ddc, which encodes Dopa decarboxylase, and down-regulation of Dop2R, which encodes a dopamine receptor in C11 in females (Supplemental Table S8). slo, which regulates neurotransmitter release at synapses (Jepson et al 2014), is up-regulated in response to cocaine, as is Rgk1, which plays a role in negative regulation of calcium channel activity (Murakami et al 2017). Down-regulation of jdp can lead to dopamine blockade through its activity as a cochaperone in synaptic vesicle release (Ye et al 2004).…”

Section: Cocaine-modulated Gene Expression In the Mushroom Bodiesmentioning

confidence: 99%

The Drosophila brain on cocaine at single-cell resolution

et al. 2021

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Whereas the neurological effects of cocaine have been well documented, effects of acute cocaine consumption on genome-wide gene expression across the brain remain largely unexplored. This question cannot be readily addressed in humans but can be approached using the Drosophila melanogaster model, where gene expression in the entire brain can be surveyed at once. Flies exposed to cocaine show impaired locomotor activity, including climbing behavior and startle response (a measure of sensorimotor integration), and increased incidence of seizures and compulsive grooming. To identify specific cell populations that respond to acute cocaine exposure, we analyzed single-cell transcriptional responses in duplicate samples of flies that consumed fixed amounts of sucrose or sucrose supplemented with cocaine, in both sexes. Unsupervised clustering of the transcriptional profiles of a total of 86,224 cells yielded 36 distinct clusters. Annotation of clusters based on gene markers revealed that all major cell types (neuronal and glial) as well as neurotransmitter types from most brain regions were represented. The brain transcriptional responses to cocaine showed profound sexual dimorphism and were considerably more pronounced in males than females. Differential expression analysis within individual clusters indicated cluster-specific responses to cocaine. Clusters corresponding to Kenyon cells of the mushroom bodies and glia showed especially large transcriptional responses following cocaine exposure. Cluster specific coexpression networks and global interaction networks revealed a diverse array of cellular processes affected by acute cocaine exposure. These results provide an atlas of sexually dimorphic cocaine-modulated gene expression in a model brain.

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“…as distinct molecular and cellular mechanisms (Comas et al, 2004;Blum et al, 2009;Pagani et al, 2009;Aso et al, 2012;Bouzaiane et al, 2015;Murakami et al, 2017). rut mutants are impaired in specific memory phases (Tully and Quinn, 1985;Han et al, 1992;Blum et al, 2009;Scheunemann et al, 2013), including short-term memory (STM), encoded in γ KC, and MTM encoded in α/β KC (Scheunemann et al, 2013, Bouzaiane et al, 2015.…”

Section: Discussionmentioning

confidence: 99%

DrosophilaMiddle-Term Memory: Amnesiac is Required for PKA Activation in the Mushroom Bodies, a Function Modulated by Neprilysin 1

et al. 2020

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In Drosophila, the mushroom bodies (MB) constitute the central brain structure for olfactory associative memory. As in mammals, the cAMP/PKA pathway plays a key role in memory formation. In the MB, Rutabaga adenylate cyclase acts as a coincidence detector during associative conditioning to integrate calcium influx resulting from acetylcholine stimulation and G protein activation resulting from dopaminergic stimulation. Amnesiac encodes a secreted neuropeptide required in the MB for two phases of aversive olfactory memory. Previous sequence analysis has revealed strong homology with the mammalian pituitary adenylate cyclase-activating peptide (PACAP). Here, we examined whether amnesiac is involved in cAMP/PKA dynamics in response to dopamine and acetylcholine co-stimulation in living flies. Experiments were carried out with both sexes, or with either sex. Our data show that amnesiac is necessary for the PKA activation process that results from coincidence detection in the MB. Since PACAP peptide is cleaved by the human membrane neprilysin hNEP, we searched for an interaction between Amnesiac and Neprilysin 1 (Nep1), a fly neprilysin involved in memory. We show that when Nep1 expression is acutely knocked down in adult MB, memory deficits displayed by amn hypomorphic mutants are rescued. Consistently, Nep1 inhibition also restores normal PKA activation in amn mutant flies. Taken together the results suggest that Nep1 targets Amnesiac degradation in order to terminate its signaling function. Our work thus highlights a key role for Amnesiac in establishing within the MB the PKA dynamics that sustain middleterm memory formation, a function modulated by Nep1.

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Two Components of Aversive Memory inDrosophila, Anesthesia-Sensitive and Anesthesia-Resistant Memory, Require Distinct Domains Within the Rgk1 Small GTPase

Cited by 7 publications

References 114 publications

A gene-specific T2A-GAL4 library for Drosophila

A gene-specific T2A-GAL4 library for Drosophila

The Drosophila brain on cocaine at single-cell resolution

DrosophilaMiddle-Term Memory: Amnesiac is Required for PKA Activation in the Mushroom Bodies, a Function Modulated by Neprilysin 1

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