A Comparative approach in Drosophila larvae to identify the neuronal circuits signaling punishment and reward in associative olfactory learning
Zusammenfassung der Projektergebnisse
The aim of my Emmy-Noether application was to establish the Drosophila larvae as a model organism to analyse the behavioural, neuronal and molecular basis of learning and memory. Learning and memory is not only found in higher vertebrates. Also simple animals - as the larvae of Drosophila - can be used to study how associations are formed in the brain and persist over time. In the last decade work of several labs showed that Drosophila larvae are able to evaluate odors based on prior experience. Drosophila larvae are able to avoid an odor that was paired with a punishing stimulus (e.g. electric shock or high salt concentration). In addition, they are also able to prefer odors that were beforehand with a rewarding stimulus (sugar, moderate heat, low salt concentrations). But why is it advantageous to analyze learning and memory in Drosophila larvae? First, the simple brain of the larvae consists of only about 10000 functional neurons, which offers a realistic possibility to identify single neurons that are triggering specific aspects of different behaviors. Second, in the last decade simple behavioral experiments were designed and introduced that allow for testing the preference of the animals towards odors, tastants, light, temperature and mechanosensory stimuli. Meanwhile, this also includes the formation of associations of most of these stimuli. Third, based on the recent emphasis on genetic tool making in the last years for Drosophila several thousand Gal4 lines and related variations were created that in principle already nowadays allow for the genetic manipulation of every single neuron in the larval brain at a specific time point in nearly every possible way. Fourth, there is a significant effort made by the larval research community to reconstruct the every single synapse of every single neurons of the larval brain. These advantages might bring a full-brain, single-cell, and single-synapse understanding for different types of behavior into reach for the larva. The aim of this Emmy-Noether application was to establish three technical milestones: 1. Establishment of a database that lists and organizes the expression patterns of different Gal4 driver lines. 2. Introducing Calcium imaging to the larval field to record physiological responses of different types of larval neurons. 3. Automating larval learning experiments to allow screening experiments of several hundred transgenic animal. In addition five different questions were postulated that can be addressed with the new set of technical achievements: Aim1: Do larvae associate odors with "good" and "bad" stimuli on the behavioral level? Aim2: How are the neuronal networks organized that signal "good" and "bad" in the larval brain to establish different types of appetitive and aversive memories? Aim3: Where are the memory centers located in the larval brain that are able to form associations between different sensory stimuli? Aim4: Do larval memories persist over metamorphosis? Aim5: How is lithium chloride able to increase the memory of Drosophila larvae?
Projektbezogene Publikationen (Auswahl)
- Consolidated and labile odor memory are separately encoded within the Drosophila brain. Journal of Neurosci, 2012 Nov 28;32(48):17163-71
Scheunemann L, Jost E, Richlitzki A, Day J, Sujith S, Thum AS, Efetova M, Davies SA, Schwaerzel M
(Siehe online unter https://doi.org/10.1523/JNEUROSCI.3286-12.2012) - Nutritional Value-Dependent and Nutritional Value-Independent Effects on Drosophila melanogaster Larval Behavior. Chem Senses. 2012 Oct;37(8):711-21
Rohwedder A, Pfitzenmaier JE, Ramsperger N, Apostolopoulou AA, Widmann A, Thum AS
(Siehe online unter https://doi.org/10.1093/chemse/bjs055) - The Role of octopamine and tyramine in Drosophila larval locomotion. J Comp Neurol. 2012 Nov 1;520(16):3764-85
Selcho M, Pauls D, El Jundi B, Stocker RF, Thum AS
(Siehe online unter https://doi.org/10.1002/cne.23152) - The Serotonergic Central Nervous System of the Drosophila Larva: Anatomy and Behavioral Function. PLoS ONE, 2012;7(10):e47518
Huser A, Rohwedder A, Maiolo EM, Selcho M, Pauls D, von Essen A, Gupta T, Sprecher SG, Birman S, Riemensperger T, Stocker RF, Thum AS
(Siehe online unter https://doi.org/10.1371/journal.pone.0047518) - Appetitive associative olfactory learning in Drosophila larvae. J Vis Exp. 2013 Feb 18;(72)
Apostolopoulou AA, Widmann A, Rohwedder A, Pfitzenmaier JE, Thum AS
(Siehe online unter https://doi.org/10.3791/4334) - Mushroom body miscellanea: transgenic Drosophila strains expressing anatomical and physiological sensor proteins in Kenyon cells. Front Neural Circuits. 2013 Sep 23;7:147
Pech U, Dipt S, Barth J, Singh P, Jauch M, Thum AS, Fiala A, Riemensperger T
(Siehe online unter https://doi.org/10.3389/fncir.2013.00147) - Characterization of the octopaminergic and tyraminergic neurons in the central brain of Drosophila larvae. J Comp Neurol. 2014 Apr 20
Selcho M, Pauls D, Huser A, Stocker RF, Thum AS
(Siehe online unter https://doi.org/10.1002/cne.23616) - Composition of agarose substrate affects behavioral output of Drosophila larvae. Front Behav Neurosci. 2014 Jan 28;8:11
Apostolopoulou AA, Hersperger F, Mazija L, Widmann A, Wüst A, Thum AS
(Siehe online unter https://doi.org/10.3389/fnbeh.2014.00011) - Neuropeptide F neurons modulate sugar reward during associative olfactory learning of Drosophila larvae. J Comp Neurol. 2015 Dec 15;523(18):2637-64
Rohwedder A, Selcho M, Chassot B, Thum AS
(Siehe online unter https://doi.org/10.1002/cne.23873) - Four Individually Identified Paired Dopamine Neurons Signal Reward in Larval Drosophila. Curr Biol. 2016 Mar 7;26(5):661-9
Rohwedder A, Wenz NL, Stehle B, Huser A, Yamagata N, Zlatic M, Truman JW, Tanimoto H, Saumweber T, Gerber B, Thum AS
(Siehe online unter https://doi.org/10.1016/j.cub.2016.01.012) - Genetic Dissection of Aversive Associative Olfactory Learning and Memory in Drosophila Larvae. PLoS Genet. 2016 Oct 21;12(10):e1006378
Widmann A, Artinger M, Biesinger L, Boepple K, Peters C, Schlechter J, Selcho M, Thum AS
(Siehe online unter https://doi.org/10.1371/journal.pgen.1006378) - The complete connectome of a learning and memory centre in an insect brain. Nature. 2017 Aug 9;548(7666):175-182
Eichler K, Li F, Litwin-Kumar A, Park Y, Andrade I, Schneider-Mizell CM, Saumweber T, Huser A, Eschbach C, Gerber B, Fetter RD, Truman JW, Priebe CE, Abbott LF, Thum AS, Zlatic M, Cardona A.
(Siehe online unter https://doi.org/10.1038/nature23455)
