Wings of Change: aPKC/FoxP-dependent plasticity in steering motor neurons underlies operant self-learning in .

Background: Motor learning is central to human existence, such as learning to speak or walk, sports moves, or rehabilitation after injury. Evidence suggests that all forms of motor learning share an evolutionarily conserved molecular plasticity pathway. Here, we present novel insights into the neural processes underlying operant self-learning, a form of motor learning in the fruit fly

Methods: We operantly trained wild type and transgenic fruit flies, tethered at the torque meter, in a motor learning task that required them to initiate and maintain turning maneuvers around their vertical body axis (yaw torque).

Biological aging of two innate behaviors of Drosophila melanogaster: Escape climbing versus courtship learning and memory.

Motor and cognitive aging can severely affect life quality of elderly people and burden health care systems. In search for diagnostic behavioral biomarkers, it has been suggested that walking speed can predict forms of cognitive decline, but in humans, it remains challenging to separate the effects of biological aging and lifestyle. We examined a possible association of motor and cognitive decline in Drosophila, a genetic model organism of healthy aging.

Gap junctions desynchronize a neural circuit to stabilize insect flight.

Insect asynchronous flight is one of the most prevalent forms of animal locomotion used by more than 600,000 species. Despite profound insights into the motor patterns, biomechanics and aerodynamics underlying asynchronous flight, the architecture and function of the central-pattern-generating (CPG) neural network remain unclear. Here, on the basis of an experiment-theory approach including electrophysiology, optophysiology, Drosophila genetics and mathematical modelling, we identify a miniaturized circuit solution with unexpected properties.

Dscam1 Has Diverse Neuron Type-Specific Functions in the Developing CNS.

Two key features endow Down syndrome cell adhesion molecule 1 (Dscam1) with the potential to provide a ubiquitous code for neuronal arbor self-avoidance. First, Dscam1 contains three large cassettes of alternative exons, so that stochastic alternative splicing yields 19,008 Dscam1 isoforms with different Ig ectodomains. Second, each neuron expresses a different subset of Dscam1 isoforms, and isoform-specific homophilic binding causes repulsion.

Brain connectivity inversely scales with developmental temperature in Drosophila.

Variability of synapse numbers and partners despite identical genes reveals the limits of genetic determinism. Here, we use developmental temperature as a non-genetic perturbation to study variability of brain wiring and behavior in Drosophila. Unexpectedly, slower development at lower temperatures increases axo-dendritic branching, synapse numbers, and non-canonical synaptic partnerships of various neurons, while maintaining robust ratios of canonical synapses.

Separation of presynaptic Ca2 and Ca1 channel function in synaptic vesicle exo- and endocytosis by the membrane anchored Ca pump PMCA.

Synaptic vesicle (SV) release, recycling, and plastic changes of release probability co-occur side by side within nerve terminals and rely on local Ca signals with different temporal and spatial profiles. The mechanisms that guarantee separate regulation of these vital presynaptic functions during action potential (AP)-triggered presynaptic Ca entry remain unclear. Combining genetics with electrophysiology and imaging reveals the localization of two different voltage-gated calcium channels at the presynaptic terminals of glutamatergic neuromuscular synapses (the Ca2 homolog, Dmca1A or cacophony, and the Ca1 homolog, Dmca1D) but with spatial and functional separation.

A Systematic Nomenclature for the Drosophila Ventral Nerve Cord.

Drosophila melanogaster is an established model for neuroscience research with relevance in biology and medicine. Until recently, research on the Drosophila brain was hindered by the lack of a complete and uniform nomenclature. Recognizing this, Ito et al.

Differential localization of voltage-gated potassium channels during metamorphosis.

Neuronal excitability is determined by the combination of different ion channels and their sub-neuronal localization. This study utilizes protein trap fly strains with endogenously tagged channels to analyze the spatial expression patterns of the four Shaker-related voltage-gated potassium channels, K1-4, in the larval, pupal, and adult ventral nerve cord. We find that all four channels (Shaker, K1; Shab, K2; Shaw, K3; and Shal, K4) each show different spatial expression patterns in the ventral nerve cord and are predominantly targeted to different sub-neuronal compartments.

Postnatal Increases in Axonal Conduction Velocity of an Identified Interneuron Require Fast Sodium, L-Type Calcium and Shaker Potassium Channels.

During early postnatal life, speed up of signal propagation through many central and peripheral neurons has been associated with an increase in axon diameter or/and myelination. Especially in unmyelinated axons postnatal adjustments of axonal membrane conductances is potentially a third mechanism but solid evidence is lacking. Here, we show that axonal action potential (AP) conduction velocity in the giant fiber (GF) interneuron, which is required for fast long-distance signal conduction through the escape circuit, is increased by 80% during the first day of adult life.

Longitudinal assessment of health-span and pre-death morbidity in wild type .

The increase in human life expectancy is accompanied by age-related cognitive and motor disability, thus raising the demand for strategies toward healthy aging. This requires understanding the biology of normal aging and late-life functional phenotypes. Genetic model organisms, such as , can help identifying evolutionary conserved mechanisms underlying aging.

Tyramine action on motoneuron excitability and adaptable tyramine/octopamine ratios adjust locomotion to nutritional state.

Adrenergic signaling profoundly modulates animal behavior. For example, the invertebrate counterpart of norepinephrine, octopamine, and its biological precursor and functional antagonist, tyramine, adjust motor behavior to different nutritional states. In larvae, food deprivation increases locomotor speed via octopamine-mediated structural plasticity of neuromuscular synapses, whereas tyramine reduces locomotor speed, but the underlying cellular and molecular mechanisms remain unknown.

Structural and Molecular Properties of Insect Type II Motor Axon Terminals.

A comparison between the axon terminals of octopaminergic efferent dorsal or ventral unpaired median neurons in either desert locusts () or fruit flies () across skeletal muscles reveals many similarities. In both species the octopaminergic axon forms beaded fibers where the boutons or varicosities form type II terminals in contrast to the neuromuscular junction (NMJ) or type I terminals. These type II terminals are immunopositive for both tyramine and octopamine and, in contrast to the type I terminals, which possess clear synaptic vesicles, only contain dense core vesicles.

Tyramine Actions on Flight Behavior Are Affected by a Glial Dehydrogenase/Reductase.

The biogenic amines octopamine (OA) and tyramine (TA) modulate insect motor behavior in an antagonistic manner. OA generally enhances locomotor behaviors such as larval crawling and flight, whereas TA decreases locomotor activity. However, the mechanisms and cellular targets of TA modulation of locomotor activity are incompletely understood.

Intra-neuronal Competition for Synaptic Partners Conserves the Amount of Dendritic Building Material.

Brain development requires correct targeting of multiple thousand synaptic terminals onto staggeringly complex dendritic arbors. The mechanisms by which input synapse numbers are matched to dendrite size, and by which synaptic inputs from different transmitter systems are correctly partitioned onto a postsynaptic arbor, are incompletely understood. By combining quantitative neuroanatomy with targeted genetic manipulation of synaptic input to an identified Drosophila neuron, we show that synaptic inputs of two different transmitter classes locally direct dendrite growth in a competitive manner.

Apoptotic Activity of MeCP2 Is Enhanced by C-Terminal Truncating Mutations.

Methyl-CpG binding protein 2 (MeCP2) is a widely abundant, multifunctional protein most highly expressed in post-mitotic neurons. Mutations causing Rett syndrome and related neurodevelopmental disorders have been identified along the entire MECP2 locus, but symptoms vary depending on mutation type and location. C-terminal mutations are prevalent, but little is known about the function of the MeCP2 C-terminus.

MECP2 impairs neuronal structure by regulating KIBRA.

Using a Drosophila model of MECP2 gain-of-function, we identified memory associated KIBRA as a target of MECP2 in regulating dendritic growth. We found that expression of human MECP2 increased kibra expression in Drosophila, and targeted RNAi knockdown of kibra in identified neurons fully rescued dendritic defects as induced by MECP2 gain-of-function. Validation in mouse confirmed that Kibra is similarly regulated by Mecp2 in a mammalian system.

Glial expression of Swiss cheese (SWS), the Drosophila orthologue of neuropathy target esterase (NTE), is required for neuronal ensheathment and function.

Mutations in Drosophila Swiss cheese (SWS) or its vertebrate orthologue neuropathy target esterase (NTE), respectively, cause progressive neuronal degeneration in Drosophila and mice and a complex syndrome in humans that includes mental retardation, spastic paraplegia and blindness. SWS and NTE are widely expressed in neurons but can also be found in glia; however, their function in glia has, until now, remained unknown. We have used a knockdown approach to specifically address SWS function in glia and to probe for resulting neuronal dysfunctions.

Transient BK outward current enhances motoneurone firing rates during Drosophila larval locomotion.

Key Points: We combine in situ electrophysiology with genetic manipulation in Drosophila larvae aiming to investigate the role of fast calcium-activated potassium currents for motoneurone firing patterns during locomotion. We first demonstrate that slowpoke channels underlie fast calcium-activated potassium currents in these motoneurones. By conducting recordings in semi-intact animals that produce crawling-like movements, we show that slowpoke channels are required specifically in motoneurones for maximum firing rates during locomotion.

Dendrites are dispensable for basic motoneuron function but essential for fine tuning of behavior.

Dendrites are highly complex 3D structures that define neuronal morphology and connectivity and are the predominant sites for synaptic input. Defects in dendritic structure are highly consistent correlates of brain diseases. However, the precise consequences of dendritic structure defects for neuronal function and behavioral performance remain unknown.

Sequential acquisition of cacophony calcium currents, sodium channels and voltage-dependent potassium currents affects spike shape and dendrite growth during postembryonic maturation of an identified Drosophila motoneuron.

During metamorphosis the CNS undergoes profound changes to accommodate the switch from larval to adult behaviors. In Drosophila and other holometabolous insects, adult neurons differentiate either from respecified larval neurons, newly born neurons, or are born embryonically but remain developmentally arrested until differentiation during pupal life. This study addresses the latter in the identified Drosophila flight motoneuron 5.

Dscam1 is required for normal dendrite growth and branching but not for dendritic spacing in Drosophila motoneurons.

Down syndrome cell adhesion molecule, Dscam, serves diverse neurodevelopmental functions, including axon guidance and synaptic adhesion, as well as self-recognition and self-avoidance, depending on the neuron type, brain region, or species under investigation. In Drosophila, the extensive molecular diversity that results from alternative splicing of Dscam1 into >38,000 isoforms provides neurons with a unique molecular code for self-recognition in the nervous system. Each neuron produces only a small subset of Dscam1 isoforms, and distinct Dscam1 isoforms mediate homophilic interactions, which in turn, result in repulsion and even spacing of self-processes, while allowing contact with neighboring cells.

Temporal coherency between receptor expression, neural activity and AP-1-dependent transcription regulates Drosophila motoneuron dendrite development.

Neural activity has profound effects on the development of dendritic structure. Mechanisms that link neural activity to nuclear gene expression include activity-regulated factors, such as CREB, Crest or Mef2, as well as activity-regulated immediate-early genes, such as fos and jun. This study investigates the role of the transcriptional regulator AP-1, a Fos-Jun heterodimer, in activity-dependent dendritic structure development.

Putative excitatory and putative inhibitory inputs are localised in different dendritic domains in a Drosophila flight motoneuron.

Input-output computations of individual neurons may be affected by the three-dimensional structure of their dendrites and by the location of input synapses on specific parts of their dendrites. However, only a few examples exist of dendritic architecture which can be related to behaviorally relevant computations of a neuron. By combining genetic, immunohistochemical and confocal laser scanning methods this study estimates the location of the spike-initiating zone and the dendritic distribution patterns of putative synaptic inputs on an individually identified Drosophila flight motorneuron, MN5.

Preparation of Drosophila central neurons for in situ patch clamping.

Short generation times and facile genetic techniques make the fruit fly Drosophila melanogaster an excellent genetic model in fundamental neuroscience research. Ion channels are the basis of all behavior since they mediate neuronal excitability. The first voltage gated ion channel cloned was the Drosophila voltage gated potassium channel Shaker(1,2).