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1.
Cell Death Dis ; 15(6): 388, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38830901

RESUMO

Vitamin B6 is a water-soluble vitamin which possesses antioxidant properties. Its catalytically active form, pyridoxal 5'-phosphate (PLP), is a crucial cofactor for DNA and amino acid metabolism. The inverse correlation between vitamin B6 and cancer risk has been observed in several studies, although dietary vitamin B6 intake sometimes failed to confirm this association. However, the molecular link between vitamin B6 and cancer remains elusive. Previous work has shown that vitamin B6 deficiency causes chromosome aberrations (CABs) in Drosophila and human cells, suggesting that genome instability may correlate the lack of this vitamin to cancer. Here we provide evidence in support of this hypothesis. Firstly, we show that PLP deficiency, induced by the PLP antagonists 4-deoxypyridoxine (4DP) or ginkgotoxin (GT), promoted tumorigenesis in eye larval discs transforming benign RasV12 tumors into aggressive forms. In contrast, PLP supplementation reduced the development of tumors. We also show that low PLP levels, induced by 4DP or by silencing the sgllPNPO gene involved in PLP biosynthesis, worsened the tumor phenotype in another Drosophila cancer model generated by concomitantly activating RasV12 and downregulating Discs-large (Dlg) gene. Moreover, we found that RasV12 eye discs from larvae reared on 4DP displayed CABs, reactive oxygen species (ROS) and low catalytic activity of serine hydroxymethyltransferase (SHMT), a PLP-dependent enzyme involved in thymidylate (dTMP) biosynthesis, in turn required for DNA replication and repair. Feeding RasV12 4DP-fed larvae with PLP or ascorbic acid (AA) plus dTMP, rescued both CABs and tumors. The same effect was produced by overexpressing catalase in RasV12 DlgRNAi 4DP-fed larvae, thus allowing to establish a relationship between PLP deficiency, CABs, and cancer. Overall, our data provide the first in vivo demonstration that PLP deficiency can impact on cancer by increasing genome instability, which is in turn mediated by ROS and reduced dTMP levels.


Assuntos
Deficiência de Vitamina B 6 , Animais , Deficiência de Vitamina B 6/metabolismo , Deficiência de Vitamina B 6/complicações , Proteínas de Drosophila/metabolismo , Proteínas de Drosophila/genética , Vitamina B 6/metabolismo , Vitamina B 6/farmacologia , Drosophila melanogaster/metabolismo , Drosophila melanogaster/genética , Drosophila/metabolismo , Fosfato de Piridoxal/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Carcinogênese/genética , Carcinogênese/patologia , Carcinogênese/metabolismo , Carcinogênese/efeitos dos fármacos , Proteínas ras/metabolismo , Neoplasias/patologia , Neoplasias/metabolismo , Neoplasias/genética , Larva/metabolismo , Humanos
3.
Development ; 151(11)2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38832825

RESUMO

Germ stem cells in Drosophila reside within a specialized stem cell niche, but the effects of stress on these stem cell populations have been elusive. In a new study, Roach and Lenhart show that repeated mating stress induces reversible changes in the germ stem cell niche. To know more about their work, we spoke to first author, Tiffany Roach, and corresponding author, Kari Lenhart, Principal Investigator at Drexel University in Philadelphia, USA.


Assuntos
Células Germinativas , Animais , História do Século XXI , Células Germinativas/citologia , História do Século XX , Nicho de Células-Tronco/fisiologia , Drosophila , Humanos , Biologia do Desenvolvimento/história , Células-Tronco/citologia
4.
Nat Commun ; 15(1): 4696, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38824133

RESUMO

Age-related microangiopathy, also known as small vessel disease (SVD), causes damage to the brain, retina, liver, and kidney. Based on the DNA damage theory of aging, we reasoned that genomic instability may underlie an SVD caused by dominant C-terminal variants in TREX1, the most abundant 3'-5' DNA exonuclease in mammals. C-terminal TREX1 variants cause an adult-onset SVD known as retinal vasculopathy with cerebral leukoencephalopathy (RVCL or RVCL-S). In RVCL, an aberrant, C-terminally truncated TREX1 mislocalizes to the nucleus due to deletion of its ER-anchoring domain. Since RVCL pathology mimics that of radiation injury, we reasoned that nuclear TREX1 would cause DNA damage. Here, we show that RVCL-associated TREX1 variants trigger DNA damage in humans, mice, and Drosophila, and that cells expressing RVCL mutant TREX1 are more vulnerable to DNA damage induced by chemotherapy and cytokines that up-regulate TREX1, leading to depletion of TREX1-high cells in RVCL mice. RVCL-associated TREX1 mutants inhibit homology-directed repair (HDR), causing DNA deletions and vulnerablility to PARP inhibitors. In women with RVCL, we observe early-onset breast cancer, similar to patients with BRCA1/2 variants. Our results provide a mechanistic basis linking aberrant TREX1 activity to the DNA damage theory of aging, premature senescence, and microvascular disease.


Assuntos
Dano ao DNA , Exodesoxirribonucleases , Fosfoproteínas , Animais , Exodesoxirribonucleases/genética , Exodesoxirribonucleases/metabolismo , Humanos , Fosfoproteínas/genética , Fosfoproteínas/metabolismo , Camundongos , Reparo de DNA por Recombinação , Fenótipo , Mutação , Drosophila/genética , Envelhecimento/genética , Envelhecimento/metabolismo , Feminino , Drosophila melanogaster/genética , Masculino , Doenças Retinianas , Doenças Vasculares , Doenças Desmielinizantes Hereditárias do Sistema Nervoso Central
5.
Learn Mem ; 31(5)2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38862165

RESUMO

In this review, we aggregated the different types of learning and memory paradigms developed in adult Drosophila and attempted to assess the similarities and differences in the neural mechanisms supporting diverse types of memory. The simplest association memory assays are conditioning paradigms (olfactory, visual, and gustatory). A great deal of work has been done on these memories, revealing hundreds of genes and neural circuits supporting this memory. Variations of conditioning assays (reversal learning, trace conditioning, latent inhibition, and extinction) also reveal interesting memory mechanisms, whereas mechanisms supporting spatial memory (thermal maze, orientation memory, and heat box) and the conditioned suppression of innate behaviors (phototaxis, negative geotaxis, anemotaxis, and locomotion) remain largely unexplored. In recent years, there has been an increased interest in multisensory and multicomponent memories (context-dependent and cross-modal memory) and higher-order memory (sensory preconditioning and second-order conditioning). Some of this work has revealed how the intricate mushroom body (MB) neural circuitry can support more complex memories. Finally, the most complex memories are arguably those involving social memory: courtship conditioning and social learning (mate-copying and egg-laying behaviors). Currently, very little is known about the mechanisms supporting social memories. Overall, the MBs are important for association memories of multiple sensory modalities and multisensory integration, whereas the central complex is important for place, orientation, and navigation memories. Interestingly, several different types of memory appear to use similar or variants of the olfactory conditioning neural circuitry, which are repurposed in different ways.


Assuntos
Memória , Animais , Memória/fisiologia , Drosophila/fisiologia , Corpos Pedunculados/fisiologia , Comportamento Animal/fisiologia
6.
Learn Mem ; 31(5)2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38862166

RESUMO

Drug addiction and the circuitry for learning and memory are intimately intertwined. Drugs of abuse create strong, inappropriate, and lasting memories that contribute to many of their destructive properties, such as continued use despite negative consequences and exceptionally high rates of relapse. Studies in Drosophila melanogaster are helping us understand how drugs of abuse, especially alcohol, create memories at the level of individual neurons and in the circuits where they function. Drosophila is a premier organism for identifying the mechanisms of learning and memory. Drosophila also respond to drugs of abuse in ways that remarkably parallel humans and rodent models. An emerging consensus is that, for alcohol, the mushroom bodies participate in the circuits that control acute drug sensitivity, not explicitly associative forms of plasticity such as tolerance, and classical associative memories of their rewarding and aversive properties. Moreover, it is becoming clear that drugs of abuse use the mushroom body circuitry differently from other behaviors, potentially providing a basis for their addictive properties.


Assuntos
Memória , Corpos Pedunculados , Animais , Memória/efeitos dos fármacos , Memória/fisiologia , Corpos Pedunculados/fisiologia , Corpos Pedunculados/efeitos dos fármacos , Aprendizagem/fisiologia , Aprendizagem/efeitos dos fármacos , Transtornos Relacionados ao Uso de Substâncias , Drosophila melanogaster/fisiologia , Humanos , Drosophila/fisiologia , Drogas Ilícitas/farmacologia
7.
Learn Mem ; 31(5)2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38862167

RESUMO

Providing metabolic support to neurons is now recognized as a major function of glial cells that is conserved from invertebrates to vertebrates. However, research in this field has focused for more than two decades on the relevance of lactate and glial glycolysis for neuronal energy metabolism, while overlooking many other facets of glial metabolism and their impact on neuronal physiology, circuit activity, and behavior. Here, we review recent work that has unveiled new features of glial metabolism, especially in Drosophila, in the modulation of behavioral traits involving the mushroom bodies (MBs). These recent findings reveal that spatially and biochemically distinct modes of glucose-derived neuronal fueling are implemented within the MB in a memory type-specific manner. In addition, cortex glia are endowed with several antioxidant functions, whereas astrocytes can serve as pro-oxidant agents that are beneficial to redox signaling underlying long-term memory. Finally, glial fatty acid oxidation seems to play a dual fail-safe role: first, as a mode of energy production upon glucose shortage, and, second, as a factor underlying the clearance of excessive oxidative load during sleep. Altogether, these integrated studies performed in Drosophila indicate that glial metabolism has a deterministic role on behavior.


Assuntos
Comportamento Animal , Corpos Pedunculados , Neuroglia , Animais , Corpos Pedunculados/metabolismo , Corpos Pedunculados/fisiologia , Neuroglia/metabolismo , Neuroglia/fisiologia , Comportamento Animal/fisiologia , Drosophila , Metabolismo Energético/fisiologia
8.
Learn Mem ; 31(5)2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38862170

RESUMO

Drosophila larvae are an established model system for studying the mechanisms of innate and simple forms of learned behavior. They have about 10 times fewer neurons than adult flies, and it was the low total number of their neurons that allowed for an electron microscopic reconstruction of their brain at synaptic resolution. Regarding the mushroom body, a central brain structure for many forms of associative learning in insects, it turned out that more than half of the classes of synaptic connection had previously escaped attention. Understanding the function of these circuit motifs, subsequently confirmed in adult flies, is an important current research topic. In this context, we test larval Drosophila for their cognitive abilities in three tasks that are characteristically more complex than those previously studied. Our data provide evidence for (i) conditioned inhibition, as has previously been reported for adult flies and honeybees. Unlike what is described for adult flies and honeybees, however, our data do not provide evidence for (ii) sensory preconditioning or (iii) second-order conditioning in Drosophila larvae. We discuss the methodological features of our experiments as well as four specific aspects of the organization of the larval brain that may explain why these two forms of learning are observed in adult flies and honeybees, but not in larval Drosophila.


Assuntos
Drosophila , Larva , Animais , Drosophila/fisiologia , Cognição/fisiologia , Corpos Pedunculados/fisiologia , Inibição Psicológica , Condicionamento Clássico/fisiologia , Encéfalo/fisiologia , Aprendizagem por Associação/fisiologia , Drosophila melanogaster/fisiologia
9.
Learn Mem ; 31(5)2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38862171

RESUMO

Across animal species, dopamine-operated memory systems comprise anatomically segregated, functionally diverse subsystems. Although individual subsystems could operate independently to support distinct types of memory, the logical interplay between subsystems is expected to enable more complex memory processing by allowing existing memory to influence future learning. Recent comprehensive ultrastructural analysis of the Drosophila mushroom body revealed intricate networks interconnecting the dopamine subsystems-the mushroom body compartments. Here, we review the functions of some of these connections that are beginning to be understood. Memory consolidation is mediated by two different forms of network: A recurrent feedback loop within a compartment maintains sustained dopamine activity required for consolidation, whereas feed-forward connections across compartments allow short-term memory formation in one compartment to open the gate for long-term memory formation in another compartment. Extinction and reversal of aversive memory rely on a similar feed-forward circuit motif that signals omission of punishment as a reward, which triggers plasticity that counteracts the original aversive memory trace. Finally, indirect feed-forward connections from a long-term memory compartment to short-term memory compartments mediate higher-order conditioning. Collectively, these emerging studies indicate that feedback control and hierarchical connectivity allow the dopamine subsystems to work cooperatively to support diverse and complex forms of learning.


Assuntos
Dopamina , Corpos Pedunculados , Animais , Dopamina/metabolismo , Dopamina/fisiologia , Corpos Pedunculados/fisiologia , Corpos Pedunculados/metabolismo , Drosophila/fisiologia , Retroalimentação Fisiológica/fisiologia , Consolidação da Memória/fisiologia , Rede Nervosa/fisiologia , Rede Nervosa/metabolismo , Neurônios Dopaminérgicos/fisiologia , Neurônios Dopaminérgicos/metabolismo , Vias Neurais/fisiologia
10.
Learn Mem ; 31(5)2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38862174

RESUMO

To survive in changing environments, animals need to learn to associate specific sensory stimuli with positive or negative valence. How do they form stimulus-specific memories to distinguish between positively/negatively associated stimuli and other irrelevant stimuli? Solving this task is one of the functions of the mushroom body, the associative memory center in insect brains. Here we summarize recent work on sensory encoding and memory in the Drosophila mushroom body, highlighting general principles such as pattern separation, sparse coding, noise and variability, coincidence detection, and spatially localized neuromodulation, and placing the mushroom body in comparative perspective with mammalian memory systems.


Assuntos
Memória , Corpos Pedunculados , Corpos Pedunculados/fisiologia , Animais , Memória/fisiologia , Drosophila/fisiologia
11.
Learn Mem ; 31(5)2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38862172

RESUMO

How does the brain translate sensory information into complex behaviors? With relatively small neuronal numbers, readable behavioral outputs, and an unparalleled genetic toolkit, the Drosophila mushroom body (MB) offers an excellent model to address this question in the context of associative learning and memory. Recent technological breakthroughs, such as the freshly completed full-brain connectome, multiomics approaches, CRISPR-mediated gene editing, and machine learning techniques, led to major advancements in our understanding of the MB circuit at the molecular, structural, physiological, and functional levels. Despite significant progress in individual MB areas, the field still faces the fundamental challenge of resolving how these different levels combine and interact to ultimately control the behavior of an individual fly. In this review, we discuss various aspects of MB research, with a focus on the current knowledge gaps, and an outlook on the future methodological developments required to reach an overall view of the neurobiological basis of learning and memory.


Assuntos
Drosophila , Corpos Pedunculados , Corpos Pedunculados/fisiologia , Animais , Drosophila/fisiologia , Memória/fisiologia , Aprendizagem por Associação/fisiologia
12.
Learn Mem ; 31(5)2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38862173

RESUMO

The intricate molecular and structural sequences guiding the formation and consolidation of memories within neuronal circuits remain largely elusive. In this study, we investigate the roles of two pivotal presynaptic regulators, the small GTPase Rab3, enriched at synaptic vesicles, and the cell adhesion protein Neurexin-1, in the formation of distinct memory phases within the Drosophila mushroom body Kenyon cells. Our findings suggest that both proteins play crucial roles in memory-supporting processes within the presynaptic terminal, operating within distinct plasticity modules. These modules likely encompass remodeling and maturation of existing active zones (AZs), as well as the formation of new AZs.


Assuntos
Proteínas de Drosophila , Memória , Corpos Pedunculados , Terminações Pré-Sinápticas , Proteínas rab3 de Ligação ao GTP , Animais , Corpos Pedunculados/fisiologia , Corpos Pedunculados/metabolismo , Terminações Pré-Sinápticas/fisiologia , Terminações Pré-Sinápticas/metabolismo , Proteínas de Drosophila/metabolismo , Memória/fisiologia , Proteínas rab3 de Ligação ao GTP/metabolismo , Proteínas rab3 de Ligação ao GTP/genética , Proteínas do Tecido Nervoso/metabolismo , Drosophila , Vesículas Sinápticas/metabolismo , Vesículas Sinápticas/fisiologia
13.
Nat Commun ; 15(1): 5091, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38876988

RESUMO

Living organisms synchronize their biological activities with the earth's rotation through the circadian clock, a molecular mechanism that regulates biology and behavior daily. This synchronization factually maximizes positive activities (e.g., social interactions, feeding) during safe periods, and minimizes exposure to dangers (e.g., predation, darkness) typically at night. Beyond basic circadian regulation, some behaviors like sleep have an additional layer of homeostatic control, ensuring those essential activities are fulfilled. While sleep is predominantly governed by the circadian clock, a secondary homeostatic regulator, though not well-understood, ensures adherence to necessary sleep amounts and hints at a fundamental biological function of sleep beyond simple energy conservation and safety. Here we explore sleep regulation across seven Drosophila species with diverse ecological niches, revealing that while circadian-driven sleep aspects are consistent, homeostatic regulation varies significantly. The findings suggest that in Drosophilids, sleep evolved primarily for circadian purposes. The more complex, homeostatically regulated functions of sleep appear to have evolved independently in a species-specific manner, and are not universally conserved. This laboratory model may reproduce and recapitulate primordial sleep evolution.


Assuntos
Evolução Biológica , Ritmo Circadiano , Drosophila , Sono , Especificidade da Espécie , Animais , Sono/fisiologia , Drosophila/fisiologia , Ritmo Circadiano/fisiologia , Homeostase , Relógios Circadianos/fisiologia , Masculino , Feminino
14.
Elife ; 132024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38869942

RESUMO

Movement is a key feature of animal systems, yet its embryonic origins are not fully understood. Here, we investigate the genetic basis underlying the embryonic onset of movement in Drosophila focusing on the role played by small non-coding RNAs (microRNAs, miRNAs). To this end, we first develop a quantitative behavioural pipeline capable of tracking embryonic movement in large populations of fly embryos, and using this system, discover that the Drosophila miRNA miR-2b-1 plays a role in the emergence of movement. Through the combination of spectral analysis of embryonic motor patterns, cell sorting and RNA in situs, genetic reconstitution tests, and neural optical imaging we define that miR-2b-1 influences the emergence of embryonic movement by exerting actions in the developing nervous system. Furthermore, through the combination of bioinformatics coupled to genetic manipulation of miRNA expression and phenocopy tests we identify a previously uncharacterised (but evolutionarily conserved) chloride channel encoding gene - which we term Movement Modulator (Motor) - as a genetic target that mechanistically links miR-2b-1 to the onset of movement. Cell-specific genetic reconstitution of miR-2b-1 expression in a null miRNA mutant background, followed by behavioural assays and target gene analyses, suggest that miR-2b-1 affects the emergence of movement through effects in sensory elements of the embryonic circuitry, rather than in the motor domain. Our work thus reports the first miRNA system capable of regulating embryonic movement, suggesting that other miRNAs are likely to play a role in this key developmental process in Drosophila as well as in other species.


Assuntos
MicroRNAs , Animais , MicroRNAs/metabolismo , MicroRNAs/genética , Drosophila melanogaster/genética , Drosophila melanogaster/embriologia , Regulação da Expressão Gênica no Desenvolvimento , Movimento , Embrião não Mamífero/metabolismo , Drosophila/genética , Drosophila/embriologia , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo
15.
PLoS Biol ; 22(6): e3002662, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38870210

RESUMO

The polygonal shape of cells in proliferating epithelia is a result of the tensile forces of the cytoskeletal cortex and packing geometry set by the cell cycle. In the larval Drosophila epidermis, two cell populations, histoblasts and larval epithelial cells, compete for space as they grow on a limited body surface. They do so in the absence of cell divisions. We report a striking morphological transition of histoblasts during larval development, where they change from a tensed network configuration with straight cell outlines at the level of adherens junctions to a highly folded morphology. The apical surface of histoblasts shrinks while their growing adherens junctions fold, forming deep lobules. Volume increase of growing histoblasts is accommodated basally, compensating for the shrinking apical area. The folded geometry of apical junctions resembles elastic buckling, and we show that the imbalance between the shrinkage of the apical domain of histoblasts and the continuous growth of junctions triggers buckling. Our model is supported by laser dissections and optical tweezer experiments together with computer simulations. Our analysis pinpoints the ability of histoblasts to store mechanical energy to a much greater extent than most other epithelial cell types investigated so far, while retaining the ability to dissipate stress on the hours time scale. Finally, we propose a possible mechanism for size regulation of histoblast apical size through the lateral pressure of the epidermis, driven by the growth of cells on a limited surface. Buckling effectively compacts histoblasts at their apical plane and may serve to avoid physical harm to these adult epidermis precursors during larval life. Our work indicates that in growing nondividing cells, compressive forces, instead of tension, may drive cell morphology.


Assuntos
Epiderme , Larva , Morfogênese , Animais , Epiderme/metabolismo , Larva/crescimento & desenvolvimento , Drosophila melanogaster/crescimento & desenvolvimento , Células Epidérmicas , Células Epiteliais/citologia , Células Epiteliais/fisiologia , Células Epiteliais/metabolismo , Fenômenos Biomecânicos , Junções Aderentes/metabolismo , Forma Celular , Simulação por Computador , Drosophila/crescimento & desenvolvimento , Modelos Biológicos
16.
Learn Mem ; 31(5)2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38876485

RESUMO

The common fruit fly Drosophila melanogaster provides a powerful platform to investigate the genetic, molecular, cellular, and neural circuit mechanisms of behavior. Research in this model system has shed light on multiple aspects of brain physiology and behavior, from fundamental neuronal function to complex behaviors. A major anatomical region that modulates complex behaviors is the mushroom body (MB). The MB integrates multimodal sensory information and is involved in behaviors ranging from sensory processing/responses to learning and memory. Many genes that underlie brain disorders are conserved, from flies to humans, and studies in Drosophila have contributed significantly to our understanding of the mechanisms of brain disorders. Genetic mutations that mimic human diseases-such as Fragile X syndrome, neurofibromatosis type 1, Parkinson's disease, and Alzheimer's disease-affect MB structure and function, altering behavior. Studies dissecting the effects of disease-causing mutations in the MB have identified key pathological mechanisms, and the development of a complete connectome promises to add a comprehensive anatomical framework for disease modeling. Here, we review Drosophila models of human neurodevelopmental and neurodegenerative disorders via the effects of their underlying mutations on MB structure, function, and the resulting behavioral alterations.


Assuntos
Modelos Animais de Doenças , Corpos Pedunculados , Doenças Neurodegenerativas , Transtornos do Neurodesenvolvimento , Animais , Corpos Pedunculados/fisiologia , Doenças Neurodegenerativas/fisiopatologia , Doenças Neurodegenerativas/genética , Doenças Neurodegenerativas/patologia , Transtornos do Neurodesenvolvimento/genética , Transtornos do Neurodesenvolvimento/fisiopatologia , Drosophila melanogaster , Humanos , Drosophila
17.
Learn Mem ; 31(5)2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38876486

RESUMO

The brain constantly compares past and present experiences to predict the future, thereby enabling instantaneous and future behavioral adjustments. Integration of external information with the animal's current internal needs and behavioral state represents a key challenge of the nervous system. Recent advancements in dissecting the function of the Drosophila mushroom body (MB) at the single-cell level have uncovered its three-layered logic and parallel systems conveying positive and negative values during associative learning. This review explores a lesser-known role of the MB in detecting and integrating body states such as hunger, thirst, and sleep, ultimately modulating motivation and sensory-driven decisions based on the physiological state of the fly. State-dependent signals predominantly affect the activity of modulatory MB input neurons (dopaminergic, serotoninergic, and octopaminergic), but also induce plastic changes directly at the level of the MB intrinsic and output neurons. Thus, the MB emerges as a tightly regulated relay station in the insect brain, orchestrating neuroadaptations due to current internal and behavioral states leading to short- but also long-lasting changes in behavior. While these adaptations are crucial to ensure fitness and survival, recent findings also underscore how circuit motifs in the MB may reflect fundamental design principles that contribute to maladaptive behaviors such as addiction or depression-like symptoms.


Assuntos
Comportamento Animal , Corpos Pedunculados , Animais , Corpos Pedunculados/fisiologia , Comportamento Animal/fisiologia , Sono/fisiologia , Fome/fisiologia , Drosophila/fisiologia , Sede/fisiologia , Neurônios/fisiologia
18.
Learn Mem ; 31(5)2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38876487

RESUMO

Animal brains need to store information to construct a representation of their environment. Knowledge of what happened in the past allows both vertebrates and invertebrates to predict future outcomes by recalling previous experience. Although invertebrate and vertebrate brains share common principles at the molecular, cellular, and circuit-architectural levels, there are also obvious differences as exemplified by the use of acetylcholine versus glutamate as the considered main excitatory neurotransmitters in the respective central nervous systems. Nonetheless, across central nervous systems, synaptic plasticity is thought to be a main substrate for memory storage. Therefore, how brain circuits and synaptic contacts change following learning is of fundamental interest for understanding brain computations tied to behavior in any animal. Recent progress has been made in understanding such plastic changes following olfactory associative learning in the mushroom bodies (MBs) of Drosophila A current framework of memory-guided behavioral selection is based on the MB skew model, in which antagonistic synaptic pathways are selectively changed in strength. Here, we review insights into plasticity at dedicated Drosophila MB output pathways and update what is known about the plasticity of both pre- and postsynaptic compartments of Drosophila MB neurons.


Assuntos
Drosophila , Corpos Pedunculados , Plasticidade Neuronal , Animais , Corpos Pedunculados/fisiologia , Plasticidade Neuronal/fisiologia , Drosophila/fisiologia , Sinapses/fisiologia , Aprendizagem por Associação/fisiologia , Memória/fisiologia
19.
Nat Commun ; 15(1): 4872, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38849331

RESUMO

Brain evolution has primarily been studied at the macroscopic level by comparing the relative size of homologous brain centers between species. How neuronal circuits change at the cellular level over evolutionary time remains largely unanswered. Here, using a phylogenetically informed framework, we compare the olfactory circuits of three closely related Drosophila species that differ in their chemical ecology: the generalists Drosophila melanogaster and Drosophila simulans and Drosophila sechellia that specializes on ripe noni fruit. We examine a central part of the olfactory circuit that, to our knowledge, has not been investigated in these species-the connections between projection neurons and the Kenyon cells of the mushroom body-and identify species-specific connectivity patterns. We found that neurons encoding food odors connect more frequently with Kenyon cells, giving rise to species-specific biases in connectivity. These species-specific connectivity differences reflect two distinct neuronal phenotypes: in the number of projection neurons or in the number of presynaptic boutons formed by individual projection neurons. Finally, behavioral analyses suggest that such increased connectivity enhances learning performance in an associative task. Our study shows how fine-grained aspects of connectivity architecture in an associative brain center can change during evolution to reflect the chemical ecology of a species.


Assuntos
Evolução Biológica , Drosophila , Corpos Pedunculados , Especificidade da Espécie , Animais , Corpos Pedunculados/fisiologia , Corpos Pedunculados/citologia , Corpos Pedunculados/anatomia & histologia , Drosophila/fisiologia , Drosophila/anatomia & histologia , Neurônios/fisiologia , Drosophila melanogaster/fisiologia , Drosophila melanogaster/anatomia & histologia , Filogenia , Olfato/fisiologia , Odorantes , Condutos Olfatórios/fisiologia , Condutos Olfatórios/anatomia & histologia , Masculino , Feminino , Terminações Pré-Sinápticas/fisiologia
20.
Commun Biol ; 7(1): 702, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38849449

RESUMO

The Drosophila model is pivotal in deciphering the pathophysiological underpinnings of various human ailments, notably aging and cardiovascular diseases. Cutting-edge imaging techniques and physiology yield vast high-resolution videos, demanding advanced analysis methods. Our platform leverages deep learning to segment optical microscopy images of Drosophila hearts, enabling the quantification of cardiac parameters in aging and dilated cardiomyopathy (DCM). Validation using experimental datasets confirms the efficacy of our aging model. We employ two innovative approaches deep-learning video classification and machine-learning based on cardiac parameters to predict fly aging, achieving accuracies of 83.3% (AUC 0.90) and 79.1%, (AUC 0.87) respectively. Moreover, we extend our deep-learning methodology to assess cardiac dysfunction associated with the knock-down of oxoglutarate dehydrogenase (OGDH), revealing its potential in studying DCM. This versatile approach promises accelerated cardiac assays for modeling various human diseases in Drosophila and holds promise for application in animal and human cardiac physiology under diverse conditions.


Assuntos
Envelhecimento , Cardiomiopatia Dilatada , Modelos Animais de Doenças , Aprendizado de Máquina , Animais , Cardiomiopatia Dilatada/fisiopatologia , Cardiomiopatia Dilatada/genética , Envelhecimento/fisiologia , Drosophila melanogaster/fisiologia , Aprendizado Profundo , Coração/fisiopatologia , Coração/fisiologia , Humanos , Drosophila/fisiologia
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