Serotonin is necessary for place memory in Drosophila

133

151

Pavlovian olfactory learning in Drosophila produces two genetically distinct forms of intermediate-term memories: anesthesia-sensitive memory, which requires the amnesiac gene, and anesthesiaresistant memory (ARM), which requires the radish gene. Here, we report that ARM is specifically enhanced or inhibited in flies with elevated or reduced serotonin (5HT) levels, respectively. The requirement for 5HT was additive with the memory defect of the amnesiac mutation but was occluded by the radish mutation. This result suggests that 5HT and Radish protein act on the same pathway for ARM formation. Three supporting lines of evidence indicate that ARM formation requires 5HT released from only two dorsal paired medial (DPM) neurons onto the mushroom bodies (MBs), the olfactory learning and memory center in Drosophila: (i) DPM neurons were 5HT-antibody immunopositive; (ii) temporal inhibition of 5HT synthesis or release from DPM neurons, but not from other serotonergic neurons, impaired ARM formation; (iii) knocking down the expression of d5HT1A serotonin receptors in α/β MB neurons, which are innervated by DPM neurons, inhibited ARM formation. Thus, in addition to the Amnesiac peptide required for anesthesia-sensitive memory formation, the two DPM neurons also release 5HT acting on MB neurons for ARM formation.brain | olfaction | aversive conditioning | neurotransmitter P avlovian olfactory learning in Drosophila involves coincidence detection of a conditioned stimulus (CS), an odor, and an unconditioned stimulus (US), an electric shock (1). After one session of aversive olfactory conditioning, flies can form short-and intermediate-term memories but not long-term memory (LTM), which requires repetitive spaced training and is dependent on protein synthesis (2, 3). The intermediate-term memory has been dissected further into an anesthesia-sensitive form (ASM) that requires a gene called "amnesiac" and an anesthesia-resistant form (ARM) that requires the radish gene (4-6). Three hours after one session of training, ARM and ASM contribute equally to performance and can be distinguished by application of a short cold shock-induced anesthesia that impairs ASM but not ARM. Importantly, although ARM is consolidated, in the sense that it is resistant to cold shock, it is not thought to be a protein synthesisdependent memory because it is resistant to cycloheximide (CXM) (2). One day after repetitive spaced training, both ARM and LTM are thought to contribute to memory performance. In contrast, repetitive massed training without rest intervals induces only radish-dependent ARM without detectable cAMP response element binding protein-dependent LTM measured 1 d after training (2, 3) (but see ref.2 for an alternative model). Thus, more than one genetically distinct memory-storage system contributes to performance both at intermediate time points (e.g., 3 h after one training session) and at later time points (e.g., 24 h after repetitive training). Given the complexity of memory consolidation observed at the genetic level, much effor...

Section: Resultsmentioning

confidence: 99%

Serotonin–mushroom body circuit modulating the formation of anesthesia-resistant memory in Drosophila

Lee

Lin

Chang

et al. 2011

133

151

“…In the adult Drosophila brain, a relatively small number of neurons are serotonergic yet they arborize extensively throughout the brain (14,29). Serotonin is detected in all neuropils of the optic lobes (lamina, medulla, lobula, and lobula plate) (29), including wide-field tangential neurons.…”

Section: Discussionmentioning

confidence: 99%

“…4F). Indeed, white mutants have diminished concentrations of the neurotransmitters serotonin, dopamine, and histamine (13,14) and concomitant behavioral phenotypes affecting courtship (15), spatial learning (16), and olfactory learning (17). To further investigate the role of white, we assayed the mutants brown, scarlet, and cinnabar (which encodes an enzyme in the xanthommatin synthesis pathway downstream of Scarlet but not in the serotonin synthesis pathway).…”

Section: All Strains Exhibit More Behavioral Variability Than Expectementioning

confidence: 99%

Phototactic personality in fruit flies and its suppression by serotonin and white

Kain

Stokes

Bivort

2012

157

205

Drosophila typically move toward light (phototax positively) when startled. The various species of Drosophila exhibit some variation in their respective mean phototactic behaviors; however, it is not clear to what extent genetically identical individuals within each species behave idiosyncratically. Such behavioral individuality has indeed been observed in laboratory arthropods; however, the neurobiological factors underlying individual-to-individual behavioral differences are unknown. We developed "FlyVac," a high-throughput device for automatically assessing phototaxis in single animals in parallel. We observed surprising variability within every species and strain tested, including identically reared, isogenic strains. In an extreme example, a domesticated strain of Drosophila simulans harbored both strongly photopositive and strongly photonegative individuals. The particular behavior of an individual fly is not heritable and, because it persists for its lifetime, constitutes a model system for elucidating the molecular mechanisms of personality. Although all strains assayed had greater than expected variation (assuming binomial sampling), some had more than others, implying a genetic basis. Using genetics and pharmacology, we identified the metabolite transporter White and white-dependent serotonin as suppressors of phototactic personality. Because we observed behavioral idiosyncrasy in all experimental groups, we suspect it is present in most behaviors of most animals.ethology | stochasticity | bet-hedging | Ischnopterapion virens F ew debates in biology have generated broader interest than nature versus nurture. Not surprisingly, both heritable and environmental factors play significant roles in shaping an organism's traits. However, the precise contributions of genetic and environmental factors to complex traits, such as most behaviors, are poorly understood. Behavioral individuality, in the absence of genetic variation, has indeed been observed in the laboratory. Specifically, clonal pea aphids were shown to vary in their predator escape behavior, and these differences were maintained for at least 5 d (1). In another example, the naïve odor preference of fruit flies was highly variable across individuals (2). These experiments suggest that even when deterministic influences from genetics and environment are held constant, there is nevertheless considerable behavioral variability. Drosophila is an ideal model system to test whether individuals, matched both genetically and environmentally, possess unique behavioral personalities, and what genetic and neurobiological factors control the magnitude of this idiosyncrasy.To determine whether individuals are behaving idiosyncratically we need to measure the trial-to-trial variation in an individual's behavior and compare that to the variation between individuals. If we observe greater variability between individuals than within individuals (that cannot be explained by sampling error), this would constitute evidence for behavioral idiosyncrasy. This analysis req...

“…To confirm this, we blocked activity specifically in PAM neurons by combining HL7-GAL4 (expressed in PAM neurons and some TH-GAL4-positive neurons) with the TH-specific GAL4-repressor line TH-GAL80 (36). This led to decreased oviposition preference (Fig.…”

Section: Different Subsets Of Dopamine Neurons Drive Competing Behavimentioning

confidence: 92%

Competing dopamine neurons drive oviposition choice for ethanol in Drosophila

Azanchi

Kaun

Heberlein

2013

101

100

The neural circuits that mediate behavioral choice evaluate and integrate information from the environment with internal demands and then initiate a behavioral response. Even circuits that support simple decisions remain poorly understood. In Drosophila melanogaster, oviposition on a substrate containing ethanol enhances fitness; however, little is known about the neural mechanisms mediating this important choice behavior. Here, we characterize the neural modulation of this simple choice and show that distinct subsets of dopaminergic neurons compete to either enhance or inhibit egg-laying preference for ethanol-containing food. Moreover, activity in α′β′ neurons of the mushroom body and a subset of ellipsoid body ring neurons (R2) is required for this choice. We propose a model where competing dopaminergic systems modulate oviposition preference to adjust to changes in natural oviposition substrates.I n nature, rotting fruit is the social hub for the fruit fly Drosophila melanogaster. Flies use fermenting fruit as a food source (1) and a site for oviposition (2). The choice of a suitable oviposition substrate is an ecologically important decision with a direct impact on species fitness. However, other than having a clear preference for fermenting fruit, how females choose oviposition sites in nature is largely unknown.One of the main metabolites of fermentation is ethanol, which is present in ripe fleshy fruits (3). Although ethanol concentrations in the fruit are rather low [≤5% (vol/vol)] (4), plumes containing ethanol vapor can act as long-distance signals to attract flies to rotting fruit (3, 5). When given the choice, female flies prefer to lay their eggs on media containing low concentrations of ethanol (up to 5%) (6), which leads to enhanced fitness of the developing larva and the adult fly.D. melanogaster's resistance to ethanol toxicity may have evolved to allow inhabitation of ethanol-containing environments (7). For example, adult flies allowed to mate on ethanolcontaining media improve mating success and fecundity (8). Although rearing larvae on food containing relatively high ethanol concentrations delays development and decreases survival (9-11), larvae reared on low concentrations of ethanol develop into heavier adults (7,12). This weight increase may be a result of D. melanogaster larvae metabolizing ethanol and using it as a food source (12). Ingestion of ethanol during the larval stage has additional benefits, such as protection from natural parasites such as endoparasitoid wasps (13).Studies on the neural circuits underlying the oviposition program and choice of oviposition substrates have been initiated only recently in D. melanogaster (14, 15). Ethanol is a particularly intriguing stimulus for oviposition preference, because it has, depending on concentration, both beneficial and detrimental effects on developing larvae. In flies, the function of dopaminergic neurons has been implicated in responses to both rewarding and aversive stimuli (16-19), making it a candidate neuromodulator to signa...