Ethanol Sensitivity and Tolerance in Long‐Term Memory Mutants of <i>Drosophila melanogaster</i>

Berger, Karen H.; Kong, Eric C.; Dubnau, Josh; Tully, Tim; Moore, Monica; Heberlein, Ulrike

doi:10.1111/j.1530-0277.2008.00659.x

Cited by 59 publications

(77 citation statements)

References 68 publications

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“…An alternate device to measure the effect of alcohol on motor control in flies is the inebriometer, a vertical column in which ethanol vapor is circulated through rising baffles and the loss of postural control or sensitivity of the fly can be measured by determining the time it takes to fall to the bottom of the column 38,39 . The inebriometer provides an automated readout of loss-of-postural control and has proven valuable for alcohol research in Drosophila 9,22,39,40 , but this behavioral paradigm requires relatively expensive equipment, space for the apparatus, and time to calibrate and optimize conditions. Thus, the inebriometer may not be well suited for many undergraduate teaching laboratories with limited budgets or space, or for researchers performing circadian assays.…”

Section: Discussionmentioning

confidence: 99%

The FlyBar: Administering Alcohol to Flies

Linde

Fumagalli

Roman

et al. 2014

JoVE

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Fruit flies (Drosophila melanogaster) are an established model for both alcohol research and circadian biology. Recently, we showed that the circadian clock modulates alcohol sensitivity, but not the formation of tolerance. Here, we describe our protocol in detail. Alcohol is administered to the flies using the FlyBar. In this setup, saturated alcohol vapor is mixed with humidified air in set proportions, and administered to the flies in four tubes simultaneously. Flies are reared under standardized conditions in order to minimize variation between the replicates. Three-day old flies of different genotypes or treatments are used for the experiments, preferably by matching flies of two different time points (e.g., CT 5 and CT 17) making direct comparisons possible. During the experiment, flies are exposed for 1 hr to the pre-determined percentage of alcohol vapor and the number of flies that exhibit the Loss of Righting reflex (LoRR) or sedation are counted every 5 min. The data can be analyzed using three different statistical approaches. The first is to determine the time at which 50% of the flies have lost their righting reflex and use an Analysis of the Variance (ANOVA) to determine whether significant differences exist between time points. The second is to determine the percentage flies that show LoRR after a specified number of minutes, followed by an ANOVA analysis. The last method is to analyze the whole times series using multivariate statistics. The protocol can also be used for non-circadian experiments or comparisons between genotypes. Video LinkThe video component of this article can be found at

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Section: Discussionmentioning

confidence: 99%

The FlyBar: Administering Alcohol to Flies

Linde

Fumagalli

Roman

et al. 2014

JoVE

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“…Earlier evidence suggested a common mechanism between ethanol responses (i.e., a rapid but short-lived increase in motor activity with ethanol exposure followed by loss of motor control) and learning based on cAMP and Fas2 functions (Moore et al 1998;Cheng et al 2001). Based on two different genetic screens, the relationship between these two behaviors was recently re-examined (Berger et al 2008;Laferriere et al 2008). Although it appears that there is a common set of genes important for ethanol response behavior and learning, there is no overall correlation between the two processes.…”

Section: Different Genetic Requirements For Several Forms Of Learningmentioning

confidence: 99%

Short-term memories in Drosophila are governed by general and specific genetic systems

Zars

2010

Learn. Mem.

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In a dynamic environment, there is an adaptive value in the ability of animals to acquire and express memories. That both simple and complex animals can learn is therefore not surprising. How animals have solved this problem genetically and anatomically probably lies somewhere in a range between a single molecular/anatomical mechanism that applies to all situations and a specialized mechanism for each learning situation. With an intermediate level of nervous system complexity, the fruit fly Drosophila has both general and specific resources to support different short-term memories. Some biochemical/cellular mechanisms are common between learning situations, indicating that flies do not have a dedicated system for each learning context. The opposite possible extreme does not apply to Drosophila either. Specialization in some biochemical and anatomical terms suggests that there is not a single learning mechanism that applies to all conditions. The distributed basis of learning in Drosophila implies that these systems were independently selected.In a dynamic environment, there is adaptive value in the ability to learn from experience and use memories to make predictions about future good or bad events. Thus, it is not surprising that the ability to learn evolved early and is found in diverse organisms, from relatively simple animals like C. elegans and Aplysia, to insects, and mammals. Learning mechanisms can in principle lie between two extremes-either a single mechanism that is applied to all situations, or a unique mechanism for each learning context. Learning mechanisms here indicates the molecular and anatomical structures, or the system, that supports formation of a memory. It is now clear that Drosophila, an animal with an intermediate level of nervous system complexity, solves learning problems with an intermediate system. That is, flies have multiple overlapping molecular and anatomical structures that are critical for memory formation in different conditions. Thus, as an example, although the mushroom bodies in the fly brain are important for some forms of learning, other brain structures are important in several different learning contexts. Specificity of memory formation systems in different learning situations is further supported by investigations into the biogenic amines and the isolation of several mutations that alter learning. Although a model for how the Drosophila brain supports learning is far from complete, results from the last decade have rejected the notion of a single learning mechanism in Drosophila.Three types of learning in Drosophila will be discussed with respect to anatomical and genetic organization. These include classical olfactory conditioning, operant place conditioning, and operant and classical visual conditioning. The behavioral tests will be only briefly described here as they have been recently well reviewed elsewhere (Davis 2005;Keene and Waddell 2007;Heisenberg and Gerber 2008).

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“…To investigate the molecular pathways influencing ethanol preference in flies, the same study identified a mutant, krasavietz (kra, also known as exba/elF5C), a translational repressor that also play a role in axon guidance (Lee et al 2007), that had decreased ethanol preference. It is noteworthy that kra was previously shown to exhibit decreased ethanol sensitivity and strong defect in rapid and chronic ethanol tolerance in the study of long-term memory mutants earlier discussed (Berger et al 2008), suggesting that other behavioural responses to ethanol (in this case, ethanol sensitivity and/or tolerance) may influence ethanol preference. This also indicates that candidate genes potentially implicated in ethanol sensitivity and/or tolerance will serve as potential targets not only for more detailed future investigations but also for research on alcohol preference and addiction.…”

Section: Ethanol-induced Behaviour Genetics Studies In Drosophilamentioning

confidence: 95%

“…ethanol sensitivity and development of ethanol tolerance) in Drosophila. One of such pathways potentially implicated in increased ethanol sensitivity in a recent study of ethanol responses in long-term memory mutants of Drosophila is kinase signalling pathway (Berger et al 2008). This pathway is defined by three mutants [ikar, potentially affecting the gene, Lk6, encoding a kinase with sequence homology to mammalian Mnk1 and Mnk2 (Reiling et al 2005); iks, whose potential corresponding gene, rhomboid, encodes a positive regulator of epidermal growth factor receptor-mediated signalling (Urban et al 2002) and rafael, implicating the gene, Dad, encoding a negative regulator of transforming growth factor-ß (TGF-ß) signalling (Tsuneizumi et al 1997)].…”

Section: Ethanol-induced Behaviour Genetics Studies In Drosophilamentioning

confidence: 98%

Genetic approaches to alcohol addiction: gene expression studies and recent candidates from Drosophila

Awofala

2010

Invert Neurosci

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Ethanol intake causes gene expression changes resulting in cellular and molecular adaptations that could be associated with a predisposition to alcohol dependence. Recently, several research groups have used high-throughput gene expression profiling to search for alcohol-responsive genes in Drosophila melanogaster. Comparison of data from these studies highlights the functional similarities in their results despite differences in their experimental approach and selection cases. Notably, alcohol-responsive gene sets associated with stress response, olfaction, metabolism, proteases, transcriptional regulation, regulation of signal transduction, nucleic acid binding and cytoskeletal organisation were markedly common to these studies. These data support the view that changes in gene expression in alcoholics are associated with widespread cellular functions.

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Ethanol Sensitivity and Tolerance in Long‐Term Memory Mutants of Drosophila melanogaster

Abstract: Background-It has become increasingly clear that molecular and neural mechanisms underlying learning and memory and drug addiction are largely shared. To confirm and extend these findings, we analyzed ethanol-responsive behaviors of a collection of Drosophila long-term memory mutants.

Cited by 59 publications

References 68 publications

The FlyBar: Administering Alcohol to Flies

The FlyBar: Administering Alcohol to Flies

Short-term memories in Drosophila are governed by general and specific genetic systems

Genetic approaches to alcohol addiction: gene expression studies and recent candidates from Drosophila

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