Regulating energy metabolism is critical to maintain homeostasis of cellular and systemic functions. In the brain, specialised centres for energy storage regulation finely communicate with the ...periphery and integrate signals about internal states. As a result, the behavioural responses can be directly adjusted accordingly to the energetic demands. In the fruit fly Drosophila melanogaster, one of these regulatory centres is the mushroom bodies (MBs), a brain region involved in olfactory memory. The integration of metabolic cues by the MBs has a crucial impact on learned behaviour. In this review, we explore recent advances supporting the interplay between energy metabolism and memory establishment, as well as the instructive role of energy during the switch between memory phases.
Memory consolidation is one of the most complex functions in the brain, and it involves energy-demanding processes, such as the synthesis of new proteins.Recent studies in Drosophila have provided functional insights about the link between energy metabolism and long-term memory establishment. At the cellular level, neurons of the mushroom bodies (MBs) (a memory centre) overlap with circuits that regulate energy metabolism.Specific MB neurons are involved in energy storage regulation and food perception. Artificially interfering with the activity of those neurons results in changes in body weight, food-intake behaviour, and metabolic processes.Internal states, such as hunger and satiety, and the integration of metabolic factors by MBs affects learning and memory outcome.In addition to metabolic supply, energy is also implemented as an instructive cue. The level of energy is translated into neural activity, and can act as a gate between different memory phases.
Neurons are the fundamental building blocks of nervous systems. It appears intuitive that the human brain is made up of hundreds, if not thousands different types of neurons. Conversely, the ...seemingly diffuse nerve net of Cnidaria is often assumed to be simple. However, evidence that the Cnidaria nervous system is indeed simple is sparse. Recent technical advances make it possible to assess the diversity and function of neurons with unprecedented resolution. Transgenic animals expressing genetically encoded Calcium sensors allow direct physiological assessments of neural responses within the nerve net and provide insight into the spatial organization of the nervous system. Moreover, response and activity patterns allow the characterization of cell types on a functional level. Molecular and genetic identities on the other hand can be assessed combining single-cell transcriptomic analysis with correlations of gene expression in defined neurons. Here I review recent advances on these two experimental strategies focusing on
,
, and
.
The evolutionary origin of synapses and neurons is an enigmatic subject that inspires much debate. Non‐bilaterian metazoans, both with and without neurons and their closest relatives already contain ...many components of the molecular toolkits for synapse functions. The origin of these components and their assembly into ancient synaptic signaling machineries are particularly important in light of recent findings on the phylogeny of non‐bilaterian metazoans. The evolution of synapses and neurons are often discussed only from a metazoan perspective leaving a considerable gap in our understanding. By taking an integrative approach we highlight the need to consider different, but extremely relevant phyla and to include the closest unicellular relatives of metazoans, the ichthyosporeans, filastereans and choanoflagellates, to fully understand the evolutionary origin of synapses and neurons. This approach allows for a detailed understanding of when and how the first pre‐ and postsynaptic signaling machineries evolved.
The evolutionary origin of synapses and neurons is an enigmatic subject that inspires much debate. Most of our knowledge and recent discussions are biased towards a metazoan perspective, leaving a considerable gap in our understanding. Recent work has now revealed important insights into the emergence and co‐regulation of complex synaptic signaling machineries from studies in the closest unicellular relatives of metazoans (choanoflagellates, filastereans, and ichthyosporeans).
Monoamines like serotonin, dopamine, and adrenaline/noradrenaline (epinephrine/norepinephrine) act as neuromodulators in the nervous system. They play a role in complex behaviours, cognitive ...functions such as learning and memory formation, as well as fundamental homeostatic processes such as sleep and feeding. However, the evolutionary origin of the genes required for monoaminergic modulation is uncertain. Using a phylogenomic approach, in this study, we show that most of the genes involved in monoamine production, modulation, and reception originated in the bilaterian stem group. This suggests that the monoaminergic system is a bilaterian novelty and that its evolution may have contributed to the Cambrian diversification.
The inclusion of cephalopods in the legislation related to the use of animals for experimental purposes has been based on the precautionary principle that these animals have the capacity to ...experience pain, suffering, distress, and lasting harm. Recent studies have expanded this view and supported it. Handling cephalopod mollusks in research is challenging and whenever more invasive procedures are required, sedation and/or anesthesia becomes necessary. Therefore, finding adequate, safe, and effective anesthetics appears mandatory. Several substances have been considered in sedating cephalopods, in some instances applying those utilized for fish. However, species-specific variability requires more detailed studies. Despite long-lasting experience being linked to classic studies on squid giant axons, evidence of action on putative anesthetic substances is scarce for
Loligo vulgaris
and particularly for their embryos. The aim of the current study was to evaluate effects elicited by immersion of squid embryos in anesthetic solutions and examine whether these forms display a similar reaction to anesthetics as adults do. Different concentrations of ethanol (EtOH; 2, 2.5, and 3%) and magnesium chloride (MgCl
2
; 1, 1.5, and 1.8%) were tested by adopting a set of indicators aimed at exploring the physiological responses of squid embryos. Forty-two embryos of the common squid
Loligo vulgaris
(stages 27–28) were assigned to three conditions (EtOH, MgCl
2,
and controls) and video recorded for 15 min (5 min before, 5 min during, and 5 min after immersion in the anesthetic solutions). In each group, the heart rate, respiratory rate, buoyancy, chromatophore activity, and tentacles/arms responses were assessed to evaluate the embryos' vitality and responsiveness to stimulation. Both substances provoked a decrease in heart and respiratory rates and inhibited buoyancy, chromatophores, and tentacles/arms responses; no adverse effects were observed. EtOH had a faster onset of action and faster recovery than MgCl
2
, being potentially more adequate as an anesthetic for shorter procedures. Even though MgCl
2
caused a longer muscle relaxation, the reversibility was not confirmed for the 1.8% concentration; however, lower concentrations triggered similar results as the ones obtained with the highest EtOH concentrations. We have shown that the late developmental stages of
Loligo vulgaris
embryos could represent a good model to evaluate anesthetics for cephalopods since they can display similar reactions to anesthetics as adults animals do.
Alzheimer disease (AD) is one of the main causes of age-related dementia and neurodegeneration. However, the onset of the disease and the mechanisms causing cognitive defects are not well understood. ...Aggregation of amyloidogenic peptides is a pathological hallmark of AD and is assumed to be a central component of the molecular disease pathways. Pan-neuronal expression of Aβ42Arctic peptides in Drosophila melanogaster results in learning and memory defects. Surprisingly, targeted expression to the mushroom bodies, a center for olfactory memories in the fly brain, does not interfere with learning but accelerates forgetting. We show here that reducing neuronal excitability either by feeding Levetiracetam or silencing of neurons in the involved circuitry ameliorates the phenotype. Furthermore, inhibition of the Rac-regulated forgetting pathway could rescue the Aβ42Arctic-mediated accelerated forgetting phenotype. Similar effects are achieved by increasing sleep, a critical regulator of neuronal homeostasis. Our results provide a functional framework connecting forgetting signaling and sleep, which are critical for regulating neuronal excitability and homeostasis and are therefore a promising mechanism to modulate forgetting caused by toxic Aβ peptides.
Cell diversity of the brain and how it is affected by starvation, remains largely unknown. Here, we introduce a single cell transcriptome atlas of the entire
first instar larval brain. We first ...assigned cell-type identity based on known marker genes, distinguishing five major groups: neural progenitors, differentiated neurons, glia, undifferentiated neurons and non-neural cells. All major classes were further subdivided into multiple subtypes, revealing biological features of various cell-types. We further assessed transcriptional changes in response to starvation at the single-cell level. While after starvation the composition of the brain remains unaffected, transcriptional profile of several cell clusters changed. Intriguingly, different cell-types show very distinct responses to starvation, suggesting the presence of cell-specific programs for nutrition availability. Establishing a single-cell transcriptome atlas of the larval brain provides a powerful tool to explore cell diversity and assess genetic profiles from developmental, functional and behavioral perspectives.
Through analysis of the Drosophila ionotropic receptors (IRs), a family of variant ionotropic glutamate receptors, we reveal that most IRs are expressed in peripheral neuron populations in diverse ...gustatory organs in larvae and adults. We characterise IR56d, which defines two anatomically-distinct neuron classes in the proboscis: one responds to carbonated solutions and fatty acids while the other represents a subset of sugar- and fatty acid-sensing cells. Mutational analysis indicates that IR56d, together with the broadly-expressed co-receptors IR25a and IR76b, is essential for physiological responses to carbonation and fatty acids, but not sugars. We further demonstrate that carbonation and fatty acids both promote IR56d-dependent attraction of flies, but through different behavioural outputs. Our work provides a toolkit for investigating taste functions of IRs, defines a subset of these receptors required for carbonation sensing, and illustrates how the gustatory system uses combinatorial expression of sensory molecules in distinct neurons to coordinate behaviour.
The ability to learn and form memories allows animals to adapt their behavior based on previous experiences. Associative learning, the process through which organisms learn about the relationship ...between two distinct events, has been extensively studied in various animal taxa. However, the existence of associative learning, prior to the emergence of centralized nervous systems in bilaterian animals, remains unclear. Cnidarians such as sea anemones or jellyfish possess a nerve net, which lacks centralization. As the sister group to bilaterians, they are particularly well suited for studying the evolution of nervous system functions. Here, we probe the capacity of the starlet sea anemone
to form associative memories by using a classical conditioning approach. We developed a protocol combining light as the conditioned stimulus with an electric shock as the aversive unconditioned stimulus. After repetitive training, animals exhibited a conditioned response to light alone-indicating that they learned the association. In contrast, all control conditions did not form associative memories. Besides shedding light on an aspect of cnidarian behavior, these results root associative learning before the emergence of NS centralization in the metazoan lineage and raise fundamental questions about the origin and evolution of cognition in brainless animals.
Animals must sense their surroundings and be able to distinguish between relevant and irrelevant cues. An enticing area of research aims to uncover the mechanisms by which animals respond to chemical ...signals that constitute critical sensory input. In this review, we describe the principles of a model chemosensory system: the Drosophila larva. While distinct in many ways, larval behaviour is reminiscent of the dogmatic goals of life: to reach a stage of reproductive potential. It takes into account a number of distinct and identifiable parameters to ultimately provoke or modulate appropriate behavioural output. In this light, we describe current knowledge of chemosensory anatomy, genetic components, and the processing logic of chemical cues. We outline recent advancements and summarize the hypothesized neural circuits of sensory systems. Furthermore, we note yet-unanswered questions to create a basis for further investigation of molecular and systemic mechanisms of chemosensation in Drosophila and beyond.
PDF
