α-Bungarotoxin Blocks Excitatory Synaptic Transmission Between Cercal Sensory Neurones and Giant Interneurone 2 of the Cockroach,<i>Periplaneta Americana</i>

Neonicotinoid insecticides target insect nicotinic acetylcholine receptors (nAChRs) and their adverse effects on non-target insects are of serious concern. We recently found that cofactor TMX3 enables robust functional expression of insect nAChRs in Xenopus laevis oocytes and showed that neonicotinoids (imidacloprid, thiacloprid, and clothianidin) exhibited agonist actions on some nAChRs of the fruit fly (Drosophila melanogaster), honeybee (Apis mellifera) and bumblebee (Bombus terrestris) with more potent actions on the pollinator nAChRs. However, other subunits from the nAChR family remain to be explored. We show that the Dα3 subunit co-exists with Dα1, Dα2, Dβ1, and Dβ2 subunits in the same neurons of adult D. melanogaster, thereby expanding the possible nAChR subtypes in these cells alone from 4 to 12. The presence of Dα1 and Dα2 subunits reduced the affinity of imidacloprid, thiacloprid, and clothianidin for nAChRs expressed in Xenopus laevis oocytes, whereas the Dα3 subunit enhanced it. RNAi targeting Dα1, Dα2 or Dα3 in adults reduced expression of targeted subunits but commonly enhanced Dβ3 expression. Also, Dα1 RNAi enhanced Dα7 expression, Dα2 RNAi reduced Dα1, Dα6, and Dα7 expression and Dα3 RNAi reduced Dα1 expression while enhancing Dα2 expression, respectively. In most cases, RNAi treatment of either Dα1 or Dα2 reduced neonicotinoid toxicity in larvae, but Dα2 RNAi enhanced neonicotinoid sensitivity in adults reflecting the affinity-reducing effect of Dα2. Substituting each of Dα1, Dα2, and Dα3 subunits by Dα4 or Dβ3 subunit mostly increased neonicotinoid affinity and reduced efficacy. These results are important because they indicate that neonicotinoid actions involve the integrated activity of multiple nAChR subunit combinations and counsel caution in interpreting neonicotinoid actions simply in terms of toxicity.

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“…α-Bungarotoxin (α-BTX), a peptide toxin known to block certain insect nAChRs [ 32 ], was tested on D . melanogaster nAChRs expressed in X .…”

Section: Resultsmentioning

confidence: 99%

Functional impact of subunit composition and compensation on Drosophila melanogaster nicotinic receptors–targets of neonicotinoids

et al. 2023

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Distribution of input and output synapses on the central branches of bushcricket and cricket auditory afferent neurones: Immunocytochemical evidence for GABA and glutamate in different populations of presynaptic boutons

Hardt¹,

Watson²

1999

J. Comp. Neurol.

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Modulation of transmitter release from the locust forewing stretch receptor neuron by GABAergic interneurons activated via muscarinic receptors

Judge

Leitch

1999

J. Neurobiol.

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The role of muscarinic receptors in the down‐regulation of acetylcholine (ACh) release from the locust forewing stretch receptor neuron (fSR) terminals has been investigated. Electrical stimulation of the fSR evokes monosynaptic excitatory postsynaptic potentials (EPSPs) in the first basalar motoneuron (BA1), produced mainly by the activation of postsynaptic nicotinic cholinergic receptors. The general muscarinic antagonists scopolamine (10−6 M) and atropine (10−8 to 10−6 M) caused a reversible increase in the amplitude of electrically evoked EPSPs. However, scopolamine (10−6 M) caused a slight depression in the amplitude of responses to ACh pressure‐applied to the soma of BA1. These observations indicate that the EPSP amplitude enhancement is due to the blockade of muscarinic receptors on neurons presynaptic to BA1. The muscarinic receptors may be located on the fSR itself and act as autoreceptors, and/or they may be located on GABAergic interneurons which inhibit ACh release from the fSR. Electron microscopical immunocytochemistry has revealed that GABA‐immunoreactive neurons make presynaptic inputs to the fSR. The GABA antagonist picrotoxin (10−6 M) caused a reversible increase in the EPSP amplitude, which does not appear to be due to an increase in sensitivity of BA1 to ACh, as picrotoxin (10−6 M) slightly decreased ACh responses recorded from BA1. Application of scopolamine (10−6 M) to a preparation preincubated with picrotoxin did not cause the EPSP amplitude enhancement normally seen in control experiments; in fact, it caused a slight depression. This indicates that at least some of the presynaptic muscarinic receptors are located on GABAergic interneurons that modulate transmission at the fSR/BA1 synapse. © 1999 John Wiley & Sons, Inc. J Neurobiol 40: 420–431, 1999

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α-Bungarotoxin Blocks Excitatory Synaptic Transmission Between Cercal Sensory Neurones and Giant Interneurone 2 of the Cockroach,Periplaneta Americana

Cited by 109 publications

References 47 publications

Functional impact of subunit composition and compensation on Drosophila melanogaster nicotinic receptors–targets of neonicotinoids

Functional impact of subunit composition and compensation on Drosophila melanogaster nicotinic receptors–targets of neonicotinoids

Distribution of input and output synapses on the central branches of bushcricket and cricket auditory afferent neurones: Immunocytochemical evidence for GABA and glutamate in different populations of presynaptic boutons

Modulation of transmitter release from the locust forewing stretch receptor neuron by GABAergic interneurons activated via muscarinic receptors

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