RESUMEN
Animal behavior is reflected by locomotor patterns. To decipher the underlying neural circuitry locomotion has to be monitored over often longer time periods. Here a simple adaptation is described to constrain movement of third instar Drosophila larvae to a defined area and use Frustrated total internal reflection based imaging method (FIM) imaging to monitor larval movements up to 1 h. It is demonstrated that the combination of FIM imaging and long analysis periods facilitates the conduction of food choice assays and provides the means to easily quantify food preferences.
Asunto(s)
Drosophila , Preferencias Alimentarias , Animales , Estudios de Factibilidad , Larva , LocomociónRESUMEN
Animals are able to move and react in manifold ways to external stimuli. Thus, environmental stimuli need to be detected, information must be processed, and, finally, an output decision must be transmitted to the musculature to get the animal moving. All these processes depend on the nervous system which comprises an intricate neuronal network and many glial cells. Glial cells have an equally important contribution in nervous system function as their neuronal counterpart. Manifold roles are attributed to glia ranging from controlling neuronal cell number and axonal pathfinding to regulation of synapse formation, function, and plasticity. Glial cells metabolically support neurons and contribute to the blood-brain barrier. All of the aforementioned aspects require extensive cell-cell interactions between neurons and glial cells. Not surprisingly, many of these processes are found in all phyla executed by evolutionarily conserved molecules. Here, we review the recent advance in understanding neuron-glia interaction in Drosophila melanogaster to suggest that work in simple model organisms will shed light on the function of mammalian glial cells, too.
Asunto(s)
Proteínas de Drosophila , Drosophila , Animales , Drosophila melanogaster , Mamíferos , Neuroglía/fisiología , Neuronas/fisiologíaRESUMEN
The functionality of the nervous system requires transmission of information along axons with high speed and precision. Conductance velocity depends on axonal diameter whereas signaling precision requires a block of electrical crosstalk between axons, known as ephaptic coupling. Here, we use the peripheral nervous system of Drosophila larvae to determine how glia regulates axonal properties. We show that wrapping glial differentiation depends on gap junctions and FGF-signaling. Abnormal glial differentiation affects axonal diameter and conductance velocity and causes mild behavioral phenotypes that can be rescued by a sphingosine-rich diet. Ablation of wrapping glia does not further impair axonal diameter and conductance velocity but causes a prominent locomotion phenotype that cannot be rescued by sphingosine. Moreover, optogenetically evoked locomotor patterns do not depend on conductance speed but require the presence of wrapping glial processes. In conclusion, our data indicate that wrapping glia modulates both speed and precision of neuronal signaling.
Asunto(s)
Drosophila melanogaster/fisiología , Animales , Animales Modificados Genéticamente , Axones/fisiología , Diferenciación Celular , Proteínas de Drosophila/genética , Proteínas de Drosophila/fisiología , Drosophila melanogaster/citología , Drosophila melanogaster/genética , Larva/citología , Larva/fisiología , Locomoción/fisiología , Modelos Neurológicos , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/fisiología , Neuroglía/citología , Neuroglía/fisiología , Optogenética , Sistema Nervioso Periférico/citología , Sistema Nervioso Periférico/fisiología , Fenotipo , Receptores de Factores de Crecimiento de Fibroblastos/fisiología , Transducción de SeñalRESUMEN
Cabeza (caz) is the single Drosophila melanogaster orthologue of the human FET proteins FUS, TAF15, and EWSR1, which have been implicated in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. In this study, we identified Xrp1, a nuclear chromatin-binding protein, as a key modifier of caz mutant phenotypes. Xrp1 expression was strongly up-regulated in caz mutants, and Xrp1 heterozygosity rescued their motor defects and life span. Interestingly, selective neuronal Xrp1 knockdown was sufficient to rescue, and neuronal Xrp1 overexpression phenocopied caz mutant phenotypes. The caz/Xrp1 genetic interaction depended on the functionality of the AT-hook DNA-binding domain in Xrp1, and the majority of Xrp1-interacting proteins are involved in gene expression regulation. Consistently, caz mutants displayed gene expression dysregulation, which was mitigated by Xrp1 heterozygosity. Finally, Xrp1 knockdown substantially rescued the motor deficits and life span of flies expressing ALS mutant FUS in motor neurons, implicating gene expression dysregulation in ALS-FUS pathogenesis.
Asunto(s)
Proteínas de Unión al ADN/metabolismo , Proteínas de Drosophila/metabolismo , Neuronas Motoras/metabolismo , Mutación , Proteínas de Unión al ARN/metabolismo , Factor de Transcripción TFIID/metabolismo , Animales , Proteínas de Unión al ADN/genética , Proteínas de Drosophila/genética , Drosophila melanogaster , Técnicas de Silenciamiento del Gen , Humanos , Dominios Proteicos , Proteínas de Unión al ARN/genética , Factor de Transcripción TFIID/genéticaRESUMEN
Specialized glial subtypes provide support to developing and functioning neural networks. Astrocytes modulate information processing by neurotransmitter recycling and release of neuromodulatory substances, whereas ensheathing glial cells have not been associated with neuromodulatory functions yet. To decipher a possible role of ensheathing glia in neuronal information processing, we screened for glial genes required in the Drosophila central nervous system for normal locomotor behavior. Shopper encodes a mitochondrial sulfite oxidase that is specifically required in ensheathing glia to regulate head bending and peristalsis. shopper mutants show elevated sulfite levels affecting the glutamate homeostasis which then act on neuronal network function. Interestingly, human patients lacking the Shopper homolog SUOX develop neurological symptoms, including seizures. Given an enhanced expression of SUOX by oligodendrocytes, our findings might indicate that in both invertebrates and vertebrates more than one glial cell type may be involved in modulating neuronal activity.
Asunto(s)
Proteínas de Drosophila/metabolismo , Neuroglía/metabolismo , Sulfito-Oxidasa/metabolismo , Animales , Astrocitos/metabolismo , Drosophila , Proteínas de Drosophila/genética , Glutamatos/metabolismo , Sulfito-Oxidasa/genética , Sulfitos/metabolismoRESUMEN
In populations of Drosophila larvae, both, an aggregation and a dispersal behavior can be observed. However, the mechanisms coordinating larval locomotion in respect to other animals, especially in close proximity and during/after physical contacts are currently only little understood. Here we test whether relevant information is perceived before or during larva-larva contacts, analyze its influence on behavior and ask whether larvae avoid or pursue collisions. Employing frustrated total internal reflection-based imaging (FIM) we first found that larvae visually detect other moving larvae in a narrow perceptive field and respond with characteristic escape reactions. To decipher larval locomotion not only before but also during the collision we utilized a two color FIM approach (FIM(2c)), which allowed to faithfully extract the posture and motion of colliding animals. We show that during collision, larval locomotion freezes and sensory information is sampled during a KISS phase (german: Kollisions Induziertes Stopp Syndrom or english: collision induced stop syndrome). Interestingly, larvae react differently to living, dead or artificial larvae, discriminate other Drosophila species and have an increased bending probability for a short period after the collision terminates. Thus, Drosophila larvae evolved means to specify behaviors in response to other larvae.