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Dissel, S.

Publications and source records attributed to Dissel, S..

5 recordsLinked to original sources

An optimized appetitive visual short-term memory paradigm in Drosophila

The ability to generate and recall memory is a behavior that is evolutionarily conserved across the animal kingdom from humans to jellyfish. Memory not only allows previous experiences to inform future decision making, but it also amasses information essential to life, such as memory of quality food sources, shelter, and predator-related associations. Associative memory forms a relationship between two or more distinct and initially unrelated stimuli and can be defined by its temporal characteristics, such as short- and long-term duration, as well as the memory being appetitive or aversive, generating approach or avoidance behavior, respectively. Since its introduction as a memory model in the 1970s, the fruit fly, Drosophila melanogaster, has emerged as a powerful tool for the investigation of memory-related processes. While a variety of memory paradigms have been used extensively in Drosophila, such as appetitive and aversive olfactory memory, the use of appetitive visual memory remains infrequent. A previous study introduced a visual short-term memory (STM) paradigm that could be used for the study of both appetitive and aversive visual memory in Drosophila. However, this protocol required 50+ flies per condition, with three conditions per experiment, and 15 or more replications were frequently used to assess memory. As a result, this paradigm requires substantial numbers of flies, time, and is impractical for large genetic screens. Here, building upon this previous work, we describe an optimized appetite visual STM paradigm in freely moving Drosophila. Using recently published data on sexual dimorphism, innate color preferences, and borrowing practices from related appetitive assays, we have established an approach that minimizes confounding factors, such as sexually dimorphic starvation survival and sucrose preference, as well as pre-training color preference variation between groups. In doing so, we present an appetitive visual STM paradigm requiring substantially fewer replicates and numbers of flies to produce significant learning.

animal behavior and cognition↗

The dorsal fan-shaped body is a neurochemically heterogeneous sleep-regulating center in Drosophila

Sleep is a behavior that is conserved throughout the animal kingdom. Yet, despite extensive studies in humans and animal models, the exact function or functions of sleep remain(s) unknown. A complicating factor in trying to elucidate the function of sleep is the complexity and multiplicity of neuronal circuits that are involved in sleep regulation. It is conceivable that distinct sleep-regulating circuits are only involved in specific aspects of sleep and may underlie different sleep functions. Thus, it would be beneficial to assess the contribution of individual circuits in sleeps putative functions. The intricacy of the mammalian brain makes this task extremely difficult. However, the fruit fly Drosophila melanogaster, with its simpler brain organization, available connectomics, and unparalleled genetics offers the opportunity to interrogate individual sleep-regulating centers. In Drosophila, neurons projecting to the dorsal Fan-Shaped Body (dFB) have been proposed to be key regulators of sleep, particularly sleep homeostasis. We recently demonstrated that the most widely used genetic tool to manipulate dFB neurons, the 23E10-GAL4 driver, expresses in two sleep-regulating neurons (VNC-SP neurons) located in the Ventral Nerve Cord (VNC), the fly analog of the vertebrate spinal cord. Since most data supporting a role for the dFB in sleep regulation have been obtained using 23E10-GAL4, it is unclear whether the sleep phenotypes reported in these studies are caused by dFB neurons or VNC-SP cells. A recent publication replicated our finding that 23E10-GAL4 contains sleep-promoting neurons in the VNC. However, it also proposed that the dFB is not involved in sleep regulation at all, but this suggestion was made using genetic tools that are not dFB-specific and a very mild sleep deprivation protocol. In this study, using a newly created dFB-specific genetic driver line, we demonstrate that the majority of 23E10-GAL4 dFB neurons can promote sleep when activated and that these neurons are involved in sleep homeostasis. We also show that dFB neurons require stronger stimulation than VNC-SP cells to promote sleep. In addition, we demonstrate that dFB-induced sleep can consolidate Short-Term Memory (STM) into Long-Term Memory (LTM), suggesting that the benefit of sleep on memory is not circuit-specific. Finally, we show that dFB neurons are neurochemically heterogeneous and can be divided in 3 populations. Most dFB neurons express both glutamate and acetylcholine, while a minority of cells express only one of these two neurotransmitters. Importantly, dFB neurons do not express GABA, as previously suggested. Using neurotransmitter-specific dFB tools, our data also points at cholinergic dFB neurons as particularly potent at regulating sleep and sleep homeostasis.

neuroscience↗

Breaking free from the clocks tyranny restores memory to brain damaged flies

The relationship between sleep and memory is an active topic of investigation. In this context, we demonstrate that enhancing sleep restores memory to flies with ablated Mushroom Bodies (MB), a key memory center; this is consistent across several memory assays. Mapping the underlying circuitry reveals circadian modulation of a subset of Dopaminergic neurons (DANs) that modulate aversive learning. Using imaging, we show that MB-ablation disrupts, and sleep restores the time of day these neurons are most responsive. Knocking down the receptor for the clock output signal, Pigment-dispersing factor (Pdfr), in this subset of DANs restores memory to MB-ablated flies. Crucially, MB-ablation does not result in memory impairments in the absence of a functioning clock. Our results reveal neuromodulations key role in cognitive restoration, where sleep aids memory in damaged brains, but a functioning clock unexpectedly hinders this process.

neuroscience↗

A Split-GAL4 screen identifies novel sleep-promoting neurons in the Ventral Nerve Cord of Drosophila

As in the mammalian system, sleep in Drosophila is regulated by multiple brain regions. Among them, neurons projecting to the dorsal Fan-Shaped Body (dFB) have been intensively studied and the data suggest they play a critical role in sleep regulation. The 23E10-GAL4 driver is the most widely used tool to label and manipulate dFB neurons. Multiple studies have reported that activation of 23E10-GAL4 neurons promotes sleep. However, anatomical analyses revealed that 23E10-GAL4 labels 23-30 dFB neurons in the Drosophila brain and many non-dFB neurons in the brain and in the Ventral Nerve Cord (VNC), the fly equivalent of the spinal cord. To better understand the role of individual dFB neurons in sleep regulation, we undertook a Split-GAL4 screen to gain access to subsets of 23E10-GAL4 expressing cells. In this study, we report the discovery of two VNC cholinergic sleep-promoting neurons labeled by the 23E10-GAL4 driver.

neuroscience↗

Sleep promoting neurons remodel their response properties to calibrate sleep drive with environmental demands.

Falling asleep at the wrong time can place an individual at risk of immediate physical harm. However, not sleeping degrades cognition and adaptive behavior. To understand how animals match sleep need with environmental demands, we used live-brain imaging to examine the physiological response properties of the Drosophila sleep homeostat (dFB) following interventions that modify sleep (sleep deprivation, starvation, time-restricted feeding, memory consolidation). We report that dFB neurons can distinguish between different types of waking and can change their physiological response-properties accordingly. That is, dFB neurons are not simply passive components of a hard-wired circuit. Rather, the dFB neurons themselves can determine their response to the activity from upstream circuits. Finally, we show that the dFB appears to contain a memory trace of prior exposure to metabolic challenges induced by starvation or time-restricted feeding. Together these data highlight that the sleep homeostat is plastic and suggests an underlying mechanism.

neuroscience↗