G(o) activation is required for both appetitive and aversive memory acquisition in <i>Drosophila</i>

Madalan, Adrian; Yang, Xiao Cui; Ferris, Jacob; Zhang, Shixing; Roman, Gregg

doi:10.1101/lm.024802.111

Cited by 13 publications

(16 citation statements)

References 74 publications

(94 reference statements)

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“…For example in the fly model, the tet-on [38], tet-off [39], GAL4-ER [25], and GeneSwitch [26] techniques are mainly promoter-driven lines that do not display tissue specificity of transgene expression. Some researchers have successfully combined the tet-off (or tet-on) gene expression systems with the Gal4/ UAS system for regulating gene expression [39], [40], [41]. However, the tet-off system uses a GAL4 driver to facilitate downstream tTA gene expression of UAS in specific tissues or cells and further controls target gene expression by the tet operator ( tetO ) upon exposure to doxycycline (Dox).…”

Section: Discussionmentioning

confidence: 99%

A Hormone Receptor-Based Transactivator Bridges Different Binary Systems to Precisely Control Spatial-Temporal Gene Expression in Drosophila

Kuo

Hsu

et al. 2012

PLoS ONE

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The GAL4/UAS gene expression system is a precise means of targeted gene expression employed to study biological phenomena in Drosophila. A modified GAL4/UAS system can be conditionally regulated using a temporal and regional gene expression targeting (TARGET) system that responds to heat shock induction. However heat shock-related temperature shifts sometimes cause unexpected physiological responses that confound behavioral analyses. We describe here the construction of a drug-inducible version of this system that takes advantage of tissue-specific GAL4 driver lines to yield either RU486-activated LexA-progesterone receptor chimeras (LexPR) or β-estradiol-activated LexA-estrogen receptor chimeras (XVE). Upon induction, these chimeras bind to a LexA operator (LexAop) and activate transgene expression. Using GFP expression as a marker for induction in fly brain cells, both approaches are capable of tightly and precisely modulating transgene expression in a temporal and dosage-dependent manner. Additionally, tissue-specific GAL4 drivers resulted in target gene expression that was restricted to those specific tissues. Constitutive expression of the active PKA catalytic subunit using these systems altered the sleep pattern of flies, demonstrating that both systems can regulate transgene expression that precisely mimics regulation that was previously engineered using the GeneSwitch/UAS system. Unlike the limited number of GeneSwitch drivers, this approach allows for the usage of the multitudinous, tissue-specific GAL4 lines for studying temporal gene regulation and tissue-specific gene expression. Together, these new inducible systems provide additional, highly valuable tools available to study gene function in Drosophila.

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Section: Discussionmentioning

confidence: 99%

A Hormone Receptor-Based Transactivator Bridges Different Binary Systems to Precisely Control Spatial-Temporal Gene Expression in Drosophila

Kuo

Hsu

et al. 2012

PLoS ONE

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“…This model is consistent with the findings that the mushroom body RUT-adenylyl cyclase and protein kinase A are important for both appetitive and aversive conditioning (Gervasi et al, 2010; Trannoy et al, 2011). G(o) activation is also required for both appetitive and aversive learning (Madalan et al, 2012), and possibly works downstream of dDA1. The effectors critical only for appetitive learning are unknown at present.…”

Section: Discussionmentioning

confidence: 99%

Appetitive Learning Requires the Alpha1-Like Octopamine Receptor OAMB in theDrosophilaMushroom Body Neurons

et al. 2013

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Associative learning is a fundamental form of behavioral plasticity. Octopamine plays central roles in various learning types in invertebrates, however the target receptors and underlying mechanisms are poorly understood. Drosophila provides a powerful system to uncover the mechanisms for learning and memory. Here, we report that OAMB in the mushroom body neurons mediates the octopamine’s signal for appetitive olfactory learning. The octopamine receptor OAMB has two isoforms (OAMB-K3 and OAMB-AS), differing in the third cytoplasmic loop and downstream sequence. The activation of each OAMB isoform increases intracellular Ca2+ similar to the alpha1 adrenergic receptor, while OAMB-K3 additionally stimulates cAMP production. The oamb null mutants showed severely impaired learning in appetitive olfactory conditioning that tests flies’ capacity to learn and remember the odor associated with sugar reward. This deficit was also seen in the hypomorphic mutant with reduced OAMB expression in the mushroom bodies, the brain structure crucial for olfactory conditioning. Consistently, the oamb mutant’s learning phenotype was fully rescued by conditional expression of either OAMB isoform in the mushroom body αβ and γ neurons. These results indicate that the OAMB receptor is a key molecule mediating the octopamine’s signal for appetitive olfactory learning and its functional site is the mushroom body αβ and γ neurons. This study represents a critical step forward in understanding the cellular mechanism and neural circuit mediating reward learning and memory.

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“…Since GNAO1 encephalopathy is often associated with developmental delay and cognitive 15 impairment 11 , it would be interesting to see whether the movement phenotype we have seen in female Gnao1 +/G184S and male Gnao1 +/G203R mice is due to a neurodevelopmental malfunction or to ongoing active signaling alterations. G o coupled GPCRs play an important role in hippocampal memory formation 56,57 . Additional behavioral tests will be valuble to assess the learning and memory ability of the Gnao1 mutant mice.…”

Section: Discussionmentioning

confidence: 99%

Mouse Models ofGNAO1-Associated Movement Disorder: Allele- and sex-specific differences in phenotypes

Feng

Larrivee

Demireva

et al. 2018

Preprint

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BackgroundInfants and children with dominant de novo mutations in GNAO1 exhibit movement disorders, epilepsy, or both. Children with loss-of-function (LOF) mutations exhibit Epileptiform Encephalopathy 17 (EIEE17). Gain-of-function (GOF) mutations or those with normal function are found in patients with Neurodevelopmental Disorder with Involuntary Movements (NEDIM).There is no animal model with a human mutant GNAO1 allele. ObjectivesHere we develop a mouse model carrying a human GNAO1 mutation and determine whether clinical features of the GNAO1 mutation including movement disorder would be evident in the mouse model. MethodsA mouse Gnao1 knock-in GOF mutation (G203R) was created by CRISPR/Cas9 methods. The resulting offspring and littermate controls were subjected to a battery of behavioral tests. A previously reported GOF mutant mouse knock-in (Gnao1 +/G184S ) was also studied for comparison. ResultsGnao1 +/G203R mutant mice are viable and gain weight comparably to controls. Homozygotes are non-viable. Grip strength was decreased in both males and females. Male Gnao1 +/G203R mice were strongly affected in movement assays (RotaRod and DigiGait) while females were not.Male Gnao1 +/G203R mice also showed enhanced seizure propensity in the pentylenetetrazole kindling test. Mice with a G184S GOF knock-in also showed movement-related behavioral phenotypes but females were more strongly affected than males. ConclusionsGnao1 +/G203R mice phenocopy children with heterozygous GNAO1 G203R mutations, showing both movement disorder and a relatively mild epilepsy pattern. This mouse model should be useful in mechanistic and preclinical studies of GNAO1-related movement disorders.

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G(o) activation is required for both appetitive and aversive memory acquisition in Drosophila

Cited by 13 publications

References 74 publications

A Hormone Receptor-Based Transactivator Bridges Different Binary Systems to Precisely Control Spatial-Temporal Gene Expression in Drosophila

A Hormone Receptor-Based Transactivator Bridges Different Binary Systems to Precisely Control Spatial-Temporal Gene Expression in Drosophila

Appetitive Learning Requires the Alpha1-Like Octopamine Receptor OAMB in theDrosophilaMushroom Body Neurons

Mouse Models ofGNAO1-Associated Movement Disorder: Allele- and sex-specific differences in phenotypes

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