Associative learning in larval and adultDrosophilais impaired by the dopamine-synthesis inhibitor 3-Iodo-L-tyrosine

Abstract

Across the animal kingdom, dopamine plays a crucial role in conferring reinforcement signals that teach animals about the causal structure of the world. In the fruit fly Drosophila melanogaster, dopaminergic reinforcement has largely been studied using genetics, whereas pharmacological approaches have received less attention. Here, we apply the dopamine-synthesis inhibitor 3-Iodo-L-tyrosine (3IY), which causes acute systemic inhibition of dopamine signaling, and investigate its effects on Pavlovian conditioning. We find that 3IY feeding impairs sugar reward learning in larvae while leaving task-relevant behavioral faculties intact, and that additional feeding of a precursor of dopamine (L-3,4-dihydroxyphenylalanine, L-DOPA), rescues this impairment. Concerning a different developmental stage and for the aversive valence domain, we furthermore demonstrate that punishment learning by activating the dopaminergic neuron PPL1-γ1pedc in adult flies is also impaired by 3IY feeding and can likewise be rescued by L-DOPA. Our findings exemplify the advantages of using a pharmacological approach in combination with the genetic techniques available in D. melanogaster to manipulate neuronal and behavioral function.

Compromising tyrosine hydroxylase function establishes a delusion-like temporal profile of reinforcement by dopamine neurons inDrosophila

“…Acute feeding of 3IY, an inhibitor of the TH enzyme required for dopamine synthesis, impaired such punishment memory (Figure 1D; ISI - 15s) (for a repetition see Supplementary Figure 4). Of note is that 3IY feeding leaves task-relevant sensory-motor faculties intact (Thoener et al 2021). In a further repetition of the experiment the effect of 3IY feeding on punishment memory could be rescued by an additional feeding of L-DOPA (Figure 1E; ISI - 15s).…”

“…Unless mentioned otherwise, we used 3-iodo-L-tyrosine (3IY), an inhibitor of the TH enzyme which is rate-limiting for the synthesis of dopamine (Figure 1C), in a procedure that followed Thoener et al (2021). Specifically, in different sets of newly hatched flies, either a plain 5% sucrose solution (CAS: 57-50-1, Hartenstein, Würzburg, Germany; in EVIAN water) was offered to the flies as their sole food, or it was offered in mixture with 5mg/ml 3IY (CAS: 70-78-0, Sigma, Steinheim, Germany; stored at −20°C) or in mixture with 5mg/ml 3IY plus 10mg/ml 3,4-dihydroxy-L-phenylalanine (L-DOPA), a precursor of dopamine (CAS: 59-92-7, Sigma, Steinheim, Germany).…”

High-resolution analysis of individual Drosophila melanogaster larvae uncovers individual variability in locomotion and its neurogenetic modulation

“…In the present study, we focused on locomotion and used the IMBA to compare innate and learned behaviour in odour gradients (figures 2 – 4 , electronic supplementary material, figures S4–S7), phenotype a mutant (figures 5 – 7 ) and study the effects of optogenetic neuronal activation (figures 8 – 13 ). Other future applications may include the screening of pharmacological effectors [ 87 ] and libraries for RNAi knockdown, and comparisons across inbred strains of Drosophila or across species.…”

Phenylacetaldehyde induced olfactory conditioning in Drosophila melanogaster (Diptera: Drosophilidae) larvae

“…Traditionally, olfactory learning paradigms using larvae have employed odorants such as ethyl acetate, 1-butanol, isoamyl acetate, 1-octanol, etc. categorized as aliphatic esters and alcohols ( Aceves-Pina and Quinn 1979 , Heisenberg et al 1985 , Honjo and Furukubo-Tokunaga 2005 , Khurana et al 2009 , Brunner et al 2020 , Thoener et al 2021 ). However, studies on dose-dependent olfactory behavior, learning, and cognition of larvae using PAH, an aromatic compound still need to be completed.…”