Circuits that encode and guide alcohol-associated preference

Scaplen, Kristin M.; Talay, Mustafa; Nunez, Kavin; Salamon, Sarah; Waterman, Amanda G; Gang, Sydney; Song, Sophia; Barnea, Gilad; Kaun, Karla R.

doi:10.7554/elife.48730

Cited by 33 publications

(47 citation statements)

References 101 publications

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“…mine induce dopamine release in the fly brain 21,38,[45][46][47] . Therefore, we tested the role of dopamine receptors in the preference for ethanol and methamphetamine by using mutants of the four dopamine receptors: Dop1R1, Dop1R2, Dop2R and DopEcR.…”

Section: Dop1r1 Signaling In the Mushroom Body Regulates Drug Preferementioning

confidence: 99%

“…4a,d), suggesting its role in the drug aversion. Because sugar and ethanol reward is conveyed to the mushroom body (MB) in the context of associative learning 33,38,48,49 , we next tested the role of Dop1R1 in the MB. Genetic knock-down of Dop1R1 in the MB showed a consistent phenotype to the mutant, highlighting the importance of the MB in this behavior ( Fig.…”

Section: Dop1r1 Signaling In the Mushroom Body Regulates Drug Preferementioning

confidence: 99%

“…Natural reward, such as sugar or water, is conveyed by a cluster of dopamine neurons called protocerebral anterior medial (PAM) to the mushroom body (MB) [33][34][35][36][37] . Prolonged exposure of ethanol vapor activates PAM cluster neurons 38 , and blocking PAM neurons or the MB intrinsic or output neurons impairs the ethanol-rewarded olfactory memory 14,[38][39][40] . PAM and the MB intrinsic neurons also influences ethanol preference for oviposition 13 .…”

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confidence: 99%

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Voluntary intake of psychoactive substances is regulated by the dopamine receptor Dop1R1 in Drosophila

Kanno

Hiramatsu

Kondo

et al. 2021

Sci Rep

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Dysregulated motivation to consume psychoactive substances leads to addictive behaviors that often result in serious health consequences. Understanding the neuronal mechanisms that drive drug consumption is crucial for developing new therapeutic strategies. The fruit fly Drosophila melanogaster offers a unique opportunity to approach this problem with a battery of sophisticated neurogenetic tools available, but how they consume these drugs remains largely unknown. Here, we examined drug self-administration behavior of Drosophila and the underlying neuronal mechanisms. We measured the preference of flies for five different psychoactive substances using a two-choice feeding assay and monitored its long-term changes. We found that flies show acute preference for ethanol and methamphetamine, but not for cocaine, caffeine or morphine. Repeated intake of ethanol, but not methamphetamine, increased over time. Preference for methamphetamine and the long-term escalation of ethanol preference required the dopamine receptor Dop1R1 in the mushroom body. The protein level of Dop1R1 increased after repeated intake of ethanol, but not methamphetamine, which correlates with the acquired preference. Genetic overexpression of Dop1R1 enhanced ethanol preference. These results reveal a striking diversity of response to individual drugs in the fly and the role of dopamine signaling and its plastic changes in controlling voluntary intake of drugs.

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Section: Dop1r1 Signaling In the Mushroom Body Regulates Drug Preferementioning

confidence: 99%

Section: Dop1r1 Signaling In the Mushroom Body Regulates Drug Preferementioning

confidence: 99%

mentioning

confidence: 99%

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Voluntary intake of psychoactive substances is regulated by the dopamine receptor Dop1R1 in Drosophila

Kanno

Hiramatsu

Kondo

et al. 2021

Sci Rep

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“…The insect central complex is an evolutionarily conserved central brain region whose ellipsoid body and protocerebral bridge sub-regions have been implicated in navigation [25][26][27][28][29][30][31][32] and sleep [33][34][35] . The central complex fan-shaped body, a laminar neural sub-region, has been implicated in sleep [36][37][38][39] and ethanol preference 40,41 . The fanshaped body was particularly interesting to us because several neuromodulators 42 , their receptors 37,43,44 , as well as dopaminergic inputs 45,46 co-localize in its layers.…”

Section: A Decision Making Neuronal Ensemble Converges On the Fan-shamentioning

confidence: 99%

A neural signature of choice under sensory conflict inDrosophila

Sareen

McCurdy

Nitabach

2020

Preprint

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Feeding decisions are fundamental to survival, and decision making is often disrupted in disease, yet the neuronal and molecular mechanisms of adaptive decision making are not well understood. Here we show that the neural activity in a small population of neurons projecting to the fan-shaped body in the central brain of Drosophila represents food choice during sensory conflict. We found that hungry flies made tradeoffs between appetitive and aversive values of food in a decision making task to choose unpalatable bittersweet food with high sucrose concentration over sucrose-only food with less sucrose. Using cell-specific optogenetics and receptor RNAi knockdown during the decision task, we identified an upstream neuropeptidergic and dopaminergic network that likely relays internal state and other decision relevant information, like valence and previous experience, to the fan-shaped body. Importantly, calcium imaging revealed that these fan-shaped body neurons were strongly inhibited by rejected food choice, suggesting that this neural activity is a representation of behavioral choice. FB response to food choice is modulated by taste, previous experience, and hunger state, which the fan-shaped body neurons likely integrate to encode choice before relaying decision information to downstream motor circuits for behavioral implementation. Our results uncover a neural substrate for choice encoding in a genetically tractable model to enable mechanistic dissection of decision making at neuronal, cellular, and molecular levels.

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“…In rodents, Rac1 in the dorsal versus ventral striatum plays opposite roles in cocaine-induced reward and spine maturation [214,215]. Furthermore, Scaplen et al recently showed that population-level dopaminergic activation encodes alcohol rewards, whereas specific microcircuits encode cued activation of alcohol memories [216]. Ideally, mechanistic studies will employ fly genetic tools and increasing insight provided by the completed fly connectome [217] to parse out the specific cell populations or circuits in which genes play a given role.…”

Section: Future Directionsmentioning

confidence: 99%

Flying Together: Drosophila as a Tool to Understand the Genetics of Human Alcoholism

Lathen

Merrill

Rothenfluh

2020

IJMS

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Alcohol use disorder (AUD) exacts an immense toll on individuals, families, and society. Genetic factors determine up to 60% of an individual’s risk of developing problematic alcohol habits. Effective AUD prevention and treatment requires knowledge of the genes that predispose people to alcoholism, play a role in alcohol responses, and/or contribute to the development of addiction. As a highly tractable and translatable genetic and behavioral model organism, Drosophila melanogaster has proven valuable to uncover important genes and mechanistic pathways that have obvious orthologs in humans and that help explain the complexities of addiction. Vinegar flies exhibit remarkably strong face and mechanistic validity as a model for AUDs, permitting many advancements in the quest to understand human genetic involvement in this disease. These advancements occur via approaches that essentially fall into one of two categories: (1) discovering candidate genes via human genome-wide association studies (GWAS), transcriptomics on post-mortem tissue from AUD patients, or relevant physiological connections, then using reverse genetics in flies to validate candidate genes’ roles and investigate their molecular function in the context of alcohol. (2) Utilizing flies to discover candidate genes through unbiased screens, GWAS, quantitative trait locus analyses, transcriptomics, or single-gene studies, then validating their translational role in human genetic surveys. In this review, we highlight the utility of Drosophila as a model for alcoholism by surveying recent advances in our understanding of human AUDs that resulted from these various approaches. We summarize the genes that are conserved in alcohol-related function between humans and flies. We also provide insight into some advantages and limitations of these approaches. Overall, this review demonstrates how Drosophila have and can be used to answer important genetic questions about alcohol addiction.

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Circuits that encode and guide alcohol-associated preference

Cited by 33 publications

References 101 publications

Voluntary intake of psychoactive substances is regulated by the dopamine receptor Dop1R1 in Drosophila

Voluntary intake of psychoactive substances is regulated by the dopamine receptor Dop1R1 in Drosophila

A neural signature of choice under sensory conflict inDrosophila

Flying Together: Drosophila as a Tool to Understand the Genetics of Human Alcoholism

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