RRC ID 59135
Author Roussou IG, Papanikolopoulou K, Savakis C, Skoulakis EMC.
Title Drosophila Bruton's Tyrosine Kinase Regulates Habituation Latency and Facilitation in Distinct Mushroom Body Neurons.
Journal J Neurosci
Abstract Habituation is the adaptive behavioral outcome of processes engaged in timely devaluation of non-reinforced repetitive stimuli, but the neuronal circuits and molecular mechanisms that underlie them are not well understood. To gain insights into these processes we developed and characterized a habituation assay to repetitive footshocks in mixed sex Drosophila groups and demonstrated that acute neurotransmission from adult α/β mushroom body (MB) neurons prevents premature stimulus devaluation. Herein we demonstrate that activity of the non-receptor tyrosine kinase dBtk protein is required within these neurons to prevent premature habituation. Significantly, we also demonstrate that the complementary process of timely habituation to the repetitive stimulation is facilitated by α'/β' MB neurons and also requires dBtk activity. Hence our results provide initial insights into molecular mechanisms engaged in footshock habituation within distinct MB neurons. Importantly, dBtk attenuation specifically within α'/β' neurons leads to defective habituation, which is readily reversible by administration of the antipsychotics clozapine and risperidone suggesting that the loss of the kinase may dysregulate monoamine receptors within these neurons, whose activity underlies the failure to habituate.SIGNIFICANCE STATEMENT Habituation refers to processes underlying decisions to attend or ignore stimuli, which are pivotal to brain function as they underlie selective attention and learning, but the circuits involved and the molecular mechanisms engaged by the process therein are poorly understood. We demonstrate that habituation to repetitive footshock involves two phases mediated by distinct neurons of the Drosophila mushroom bodies and require the function of the dBtk non-receptor tyrosine kinase. Moreover, habituation failure upon dBtk abrogation in neurons where it is required to facilitate the process is readily reversible by antipsychotics, providing conceptual links to particular symptoms of schizophrenia in humans, also characterized by habituation defects and ameliorated by these pharmaceuticals.
Volume 39(44)
Pages 8730-8743
Published 2019-10-30
DOI 10.1523/JNEUROSCI.0633-19.2019
PII JNEUROSCI.0633-19.2019
PMID 31530645
PMC PMC6820202
MeSH Agammaglobulinaemia Tyrosine Kinase / genetics Agammaglobulinaemia Tyrosine Kinase / physiology* Animals Animals, Genetically Modified Drosophila Proteins / genetics Drosophila Proteins / physiology* Drosophila melanogaster / physiology* Electroshock Female Habituation, Psychophysiologic / physiology* Male Mushroom Bodies / physiology* Mutation Protein-Tyrosine Kinases / metabolism* Synaptic Transmission
IF 6.074
Times Cited 0
Drosophila DGRC#109093 DGRC#109095