BackgroundSleep is characterized by extended periods of quiescence and reduced responsiveness to sensory stimuli. Animals ranging from insects to mammals adapt to environments with limited food by suppressing sleep and enhancing their response to food cues, yet little is known about the genetic and evolutionary relationship between these processes. The blind Mexican cavefish, Astyanax mexicanus is a powerful model for elucidating the genetic mechanisms underlying behavioral evolution. A. mexicanus comprises an extant ancestral-type surface dwelling morph and at least five independently evolved cave populations. Evolutionary convergence on sleep loss and vibration attraction behavior, which is involved in prey seeking, have been documented in cavefish raising the possibility that enhanced sensory responsiveness underlies changes in sleep.ResultsWe established a system to study sleep and vibration attraction behavior in adult A. mexicanus and used high coverage quantitative trait loci (QTL) mapping to investigate the functional and evolutionary relationship between these traits. Analysis of surface-cave F2 hybrid fish and an outbred cave population indicates that independent genetic factors underlie changes in sleep/locomotor activity and vibration attraction behavior. High-coverage QTL mapping with genotyping-by-sequencing technology identify two novel QTL intervals that associate with locomotor activity and include the narcolepsy-associated tp53 regulating kinase. These QTLs represent the first genomic localization of locomotor activity in cavefish and are distinct from two QTLs previously identified as associating with vibration attraction behavior.ConclusionsTaken together, these results localize genomic regions underlying sleep/locomotor and sensory changes in cavefish populations and provide evidence that sleep loss evolved independently from enhanced sensory responsiveness.Electronic supplementary materialThe online version of this article (doi:10.1186/s12915-015-0119-3) contains supplementary material, which is available to authorized users.

Summary Sleep is thought to be controlled by two main processes: a circadian clock that primarily regulates sleep timing and a homeostatic mechanism that detects and responds to sleep need. While abundant experimental evidence suggests that sleep need increases with time spent awake, the contributions of different brain arousal systems have not been assessed independently of each other to determine if certain neural circuits, rather than waking per se, selectively contribute to sleep homeostasis. Using the fruit fly, Drosophila melanogaster, we found that sustained thermogenetic activation of three independent neurotransmitter systems promoted nighttime wakefulness. However, only sleep deprivation resulting from activation of cholinergic neurons was sufficient to elicit subsequent homeostatic recovery sleep, as assessed by multiple behavioral criteria. In contrast, sleep deprivation resulting from activation of octopaminergic neurons suppressed homeostatic recovery sleep, indicating that wakefulness can be dissociated from accrual of sleep need. Neurons that promote sleep homeostasis were found to innervate the central brain and motor control regions of the thoracic ganglion. Blocking activity of these neurons suppressed recovery sleep but did not alter baseline sleep, further differentiating between neural control of sleep homeostasis and daily fluctuations in the sleep/wake cycle. Importantly, selective activation of wake-promoting neurons without engaging the sleep homeostat impaired subsequent short-term memory, thus providing evidence that neural circuits that regulate sleep homeostasis are important for behavioral plasticity. Together, our data suggest a neural circuit model involving distinct populations of wake-promoting neurons, some of which are involved in homeostatic control of sleep and cognition.

Summary Taste memories allow animals to modulate feeding behavior in accordance with past experience and avoid the consumption of potentially harmful food [1]. We have developed a single-fly taste memory assay to functionally interrogate the neural circuitry encoding taste memories [2]. Here, we screen a collection of Split-GAL4 lines that label small populations of neurons associated with the fly memory center - the mushroom bodies (MB) [3]. Genetic silencing of PPL1 dopamine neurons disrupts conditioned, but not naïve feeding behavior, suggesting these neurons are selectively involved in the conditioned taste response. We identify two PPL1 subpopulations that innervate the MB α lobe and are essential for aversive taste memory. Thermogenetic activation of these dopamine neurons during training induces memory, indicating these neurons are sufficient for the reinforcing properties of bitter tastant to the MBs. Silencing of either the intrinsic MB neurons, or the output neurons from the α lobe, disrupts taste conditioning. Thermogenetic manipulation of these output neurons alters naïve feeding response, suggesting that dopamine neurons modulate the threshold of response to appetitive tastants. Taken together, these findings detail a neural mechanism underlying the formation of taste memory and provide a functional model for dopamine-dependent plasticity in Drosophila.

Taste is the primary sensory system for detecting food quality and palatability. Drosophila detects five distinct taste modalities that include sweet, bitter, salt, water, and the taste of carbonation. Of these, sweet-sensing neurons appear to have utility for the detection of nutritionally rich food while bitter-sensing neurons signal toxicity and confer repulsion. Growing evidence in mammals suggests that taste for fatty acids (FAs) signals the presence of dietary lipids and promotes feeding. While flies appear to be attracted to fatty acids, the neural basis for fatty acid detection and attraction are unclear. Here, we demonstrate that a range of FAs are detected by the fly gustatory system and elicit a robust feeding response. Flies lacking olfactory organs respond robustly to FAs, confirming that FA attraction is mediated through the gustatory system. Furthermore, flies detect FAs independent of pH, suggesting the molecular basis for FA taste is not due to acidity. We show that low and medium concentrations of FAs serve as an appetitive signal and they are detected exclusively through the same subset of neurons that sense appetitive sweet substances, including most sugars. In mammals, taste perception of sweet and bitter substances is dependent on phospholipase C (PLC) signaling in specialized taste buds. We find that flies mutant for norpA, a Drosophila ortholog of PLC, fail to respond to FAs. Intriguingly, norpA mutants respond normally to other tastants, including sucrose and yeast. The defect of norpA mutants can be rescued by selectively restoring norpA expression in sweet-sensing neurons, corroborating that FAs signal through sweet-sensing neurons, and suggesting PLC signaling in the gustatory system is specifically involved in FA taste. Taken together, these findings reveal that PLC function in Drosophila sweet-sensing neurons is a conserved molecular signaling pathway that confers attraction to fatty acids.

In the gustatory systems of mammals and flies, different populations of sensory cells recognize different taste modalities, such that there are cells that respond selectively to sugars and others to bitter compounds. This organization readily allows animals to distinguish compounds of different modalities but may limit the ability to distinguish compounds within one taste modality. Here, we developed a behavioral paradigm in Drosophila melanogaster to evaluate directly the tastes that a fly distinguishes. These studies reveal that flies do not discriminate among different sugars, or among different bitter compounds, based on chemical identity. Instead, flies show a limited ability to distinguish compounds within a modality based on intensity or palatability. Taste associative learning, similar to olfactory learning, requires the mushroom bodies, suggesting fundamental similarities in brain mechanisms underlying behavioral plasticity. Overall, these studies provide insight into the discriminative capacity of the Drosophila gustatory system and the modulation of taste behavior.chemosensory | gustatory | neurobiology T he gustatory system allows animals to detect chemical compounds in the environment and determine their value as potential food sources. To make this assessment, animals detect two different features of taste stimuli with the gustatory system: the concentration and the quality of a taste compound. In humans, taste concentration is perceived as intensity and taste quality as a component of flavor. Determining how these two features of taste stimuli are encoded by the nervous system and used to direct behavior is central for the neural basis of taste perception.Mammals are thought to detect five different general taste qualities or modalities: sugars, bitter compounds, salt, acids, and amino acids (1). Each taste modality is detected by a unique taste cell population in the periphery, such that the activation of different taste cells provides a simple mechanism to encode modality. In addition, taste cells show dose-dependent activation, providing the potential to encode different concentrations.Although taste cell activity readily allows for modality and concentration discrimination, does it allow for finer discrimination of individual taste compounds? Animals distinguish sugars from bitter compounds, but do they distinguish compounds within a single modality? In principle, different sugars could activate slightly different taste cell populations or activate the same population with different temporal properties, and these differences could be exploited to allow for the discrimination of individual compounds. Alternatively, different taste compounds could activate the same taste cell population with a different efficacy and lead to a perceived difference in sugar concentration or intensity rather than quality.The Drosophila gustatory system provides an attractive model for studies of taste discrimination because it is an experimentally tractable system that retains similarities to mammalian taste. Like ...