Pharmacological identification of cholinergic receptor subtypes: modulation of locomotion and neural circuit excitability in Drosophila larvae

Cole A. Malloy, Eashwar Somasundaram, Aya Omar, Umair Bhutto, Meagan Medley, Nicole Dzubuk, Robin L. Cooper

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


Acetylcholine (ACh) is an abundant neurotransmitter and neuromodulator in many species. In Drosophila melanogaster ACh is the neurotransmitter used in peripheral sensory neurons and is a primary excitatory neurotransmitter and neuromodulator within the central nervous system (CNS). The receptors that facilitate cholinergic transmission are divided into two broad subtypes: the ionotropic nicotinic acetylcholine receptors (nAChRs) and the metabotropic muscarinic acetylcholine receptors (mAChRs). This receptor classification is shared in both mammals and insects; however, both the pharmacological and functional characterization of these receptors within the Drosophila nervous system has lagged behind its mammalian model counterparts. In order to identify the impact of ACh receptor subtypes in regulating the performance of neural circuits within the larval CNS, we used a behavioral and electrophysiological approach to assess cholinergic modulation of locomotion and sensory-CNS-motor circuit excitability. We exposed intact and semi-intact 3rd instar larvae to ACh receptor agonists and antagonists to observe their roles in behavior and regulation of neural circuit excitability and to investigate AChR pharmacological properties in vivo. We combined this with targeted AChR RNAi-mediated knockdown to identify specific receptor subtypes facilitating ACh modulation of circuit efficacy. We identify a contribution by both mAChRs and nAChRs in regulation of locomotor behavior and reveal they play a role in modulation of the excitability of a sensory-CNS-motor circuit. We further reveal a conspicuous role for mAChR-A and mAChR-C in motor neurons in modulation of their input-output efficacy.

Original languageEnglish
Pages (from-to)47-64
Number of pages18
StatePublished - Jul 15 2019

Bibliographical note

Funding Information:
This work was funded by G. Ribble fellowship from Dept. of Biology, Univ. of KY (ES, AO, CM) and by the Kentucky Science and Engineering Foundation ( KSEF-3712-RDE-019 ) at the Kentucky Science and Technology Corporation (RLC, CM).

Publisher Copyright:
© 2019 Elsevier Ltd


  • Drosophila melanogaster
  • acetylcholine
  • behavior
  • electrophysiology
  • pharmacology

ASJC Scopus subject areas

  • Neuroscience (all)


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