Maturation of a central brain flight circuit in Drosophila requires Fz2/Ca2+ signaling

Agrawal, Tarjani; Hasan, Gaiti

doi:10.7554/elife.07046

Cited by 28 publications

(31 citation statements)

References 68 publications

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“…Roles for specific subsets of DA neurons and their respective MB innervation regions in learning and memory (reviewed in (Aso, Sitaraman, et al 2014; Waddell 2013; Waddell 2016)) and locomotion control (Agrawal & Hasan 2015; Kong et al 2010; Riemensperger et al 2013) have been determined using conditionally regulated silencing and activating genes, and by utilizing live Ca 2+ imaging. In particular, these studies show that subsets of PAM neurons and their innervation to the MB horizontal lobes mediate either aversive or appetitive learning, and that subsets of PPL1 neurons can convey an aversive signal.…”

Section: Discussionmentioning

confidence: 99%

A new brain dopamine‐deficient Drosophila and its pharmacological and genetic rescue

Cichewicz

Garren

Adiele

et al. 2016

Genes Brain and Behavior

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Dopamine (DA) is a neurotransmitter with conserved behavioral roles between invertebrate and vertebrate animals. In addition to its neural functions, in insects DA is a critical substrate for cuticle pigmentation and hardening. Drosophila tyrosine hydroxylase (DTH) is the rate limiting enzyme for DA biosynthesis. Viable brain DA deficient flies were previously generated using tissue selective GAL4-UAS binary expression rescue of a DTH null mutation and these flies show specific behavioral impairments. To circumvent the limitations of rescue via binary expression, here we achieve rescue utilizing genomically integrated mutant DTH. As expected, our DA deficient flies have no detectable DTH or DA in the brain, and show reduced locomotor activity. This deficit can be rescued by L-DOPA/carbidopa feeding, similar to human Parkinson’s disease treatment. Genetic rescue via GAL4/UAS-DTH was also successful, although this required the generation of a new UAS-DTH1 transgene devoid of most untranslated regions, since existing UAS-DTH transgenes express in the brain without a Gal4 driver via endogenous regulatory elements. A surprising finding of our newly constructed UAS-DTH1m is that it expresses DTH at an undetectable level when regulated by dopaminergic GAL4 drivers even when fully rescuing DA, indicating that DTH immunostaining is not necessarily a valid marker for DA expression. This finding necessitated optimizing DA immunohistochemistry, revealing details of DA innervation to the mushroom body and the central complex. When DA rescue is limited to specific DA neurons, DA does not diffuse beyond the DTH-expressing terminals, such that DA signaling can be limited to very specific brain regions.

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Section: Discussionmentioning

confidence: 99%

A new brain dopamine‐deficient Drosophila and its pharmacological and genetic rescue

Cichewicz

Garren

Adiele

et al. 2016

Genes Brain and Behavior

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“…Transient activation of OA/TA neurons may lead to a subtle alteration of flight performance and reduce photopreference in these flies. Similarly, it has been shown that altering the development of specific DA neurons results in flight deficits (reduction of flight time or loss of flight, depending on the treatment [78,79]). Our manipulations lasted for approximately 30 min during adulthood, ruling out such developmental defects.…”

Section: Discussionmentioning

confidence: 99%

A decision underlies phototaxis in an insect

2016

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Like a moth into the flame—phototaxis is an iconic example for innate preferences. Such preferences probably reflect evolutionary adaptations to predictable situations and have traditionally been conceptualized as hard-wired stimulus–response links. Perhaps for that reason, the century-old discovery of flexibility in Drosophila phototaxis has received little attention. Here, we report that across several different behavioural tests, light/dark preference tested in walking is dependent on various aspects of flight. If we temporarily compromise flying ability, walking photopreference reverses concomitantly. Neuronal activity in circuits expressing dopamine and octopamine, respectively, plays a differential role in photopreference, suggesting a potential involvement of these biogenic amines in this case of behavioural flexibility. We conclude that flies monitor their ability to fly, and that flying ability exerts a fundamental effect on action selection in Drosophila. This work suggests that even behaviours which appear simple and hard-wired comprise a value-driven decision-making stage, negotiating the external situation with the animal's internal state, before an action is selected.

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“…Alexa Fluor 488 (A11034, ThermoFisher). Flight assay was performed as previously 444 described (Agrawal and Hasan, 2015). Briefly, flies were anaesthetised on ice for 5 445 min; the flat of a 30G 1" needle (Sigma) was attached to the anterior notum of a fly 446 just posterior to the neck using clear nail varnish, leaving flight muscles unimpeded.…”

Section: Determination Of Nmn and Nad Levels 420mentioning

confidence: 99%

Mitochondrial impairment activates the Wallerian pathway through depletion of NMNAT2 leading to SARM1-dependent axon degeneration

Loreto

Hill

Hewitt

et al. 2019

Preprint

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26Wallerian degeneration of physically injured axons involves a well-defined molecular 27 pathway linking loss of axonal survival factor NMNAT2 to activation of pro-28 degenerative protein SARM1. Manipulating the pathway through these proteins led to 29 the identification of non-axotomy insults causing axon degeneration by a Wallerian-30 like mechanism, including several involving mitochondrial impairment. Mitochondrial 31 dysfunction is heavily implicated in Parkinson's disease, Charcot-Marie-Tooth 32 disease, hereditary spastic paraplegia and other axonal disorders. However, whether 33 and how mitochondrial impairment activates Wallerian degeneration has remained 34 unclear. Here, we show that disruption of mitochondrial membrane potential leads to 35 axonal NMNAT2 depletion in mouse sympathetic neurons, increasing the substrate-36to-product ratio (NMN/NAD) of this NAD-synthesising enzyme, a metabolic fingerprint 37 of Wallerian degeneration. The mechanism appears to involve both impaired NMNAT2 38 synthesis and reduced axonal transport. Expression of WLD S and Sarm1 deletion both 39 protect axons after mitochondrial uncoupling. Blocking the pathway also confers 40 neuroprotection and increases the lifespan of flies with Pink1 loss-of-function 41 mutation, which causes severe mitochondrial defects. These data indicate that 42 mitochondrial impairment replicates all the major steps of Wallerian degeneration, 43 placing it upstream of NMNAT2 loss, with the potential to contribute to axon pathology 44 in mitochondrial disorders. 45 RESULTS 101

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Maturation of a central brain flight circuit in Drosophila requires Fz2/Ca2+ signaling

Cited by 28 publications

References 68 publications

A new brain dopamine‐deficient Drosophila and its pharmacological and genetic rescue

A new brain dopamine‐deficient Drosophila and its pharmacological and genetic rescue

A decision underlies phototaxis in an insect

Mitochondrial impairment activates the Wallerian pathway through depletion of NMNAT2 leading to SARM1-dependent axon degeneration

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