Synapse-Specific Trapping of SNARE Machinery Proteins in the Anesthetized Drosophila Brain

General anesthetics disrupt brain network dynamics through multiple pathways, in part through postsynaptic potentiation of inhibitory ion channels as well as presynaptic inhibition of neuroexocytosis. Common clinical general anesthetic drugs, such as propofol and isoflurane, have been shown to inter...

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Veröffentlicht in:The Journal of neuroscience 2024-06, Vol.44 (24), p.e0588232024
Hauptverfasser: Hines, Adam D, Kewin, Amber B, Van De Poll, Matthew N, Anggono, Victor, Bademosi, Adekunle T, van Swinderen, Bruno
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container_issue 24
container_start_page e0588232024
container_title The Journal of neuroscience
container_volume 44
creator Hines, Adam D
Kewin, Amber B
Van De Poll, Matthew N
Anggono, Victor
Bademosi, Adekunle T
van Swinderen, Bruno
description General anesthetics disrupt brain network dynamics through multiple pathways, in part through postsynaptic potentiation of inhibitory ion channels as well as presynaptic inhibition of neuroexocytosis. Common clinical general anesthetic drugs, such as propofol and isoflurane, have been shown to interact and interfere with core components of the exocytic release machinery to cause impaired neurotransmitter release. Recent studies however suggest that these drugs do not affect all synapse subtypes equally. We investigated the role of the presynaptic release machinery in multiple neurotransmitter systems under isoflurane general anesthesia in the adult female brain using live-cell super-resolution microscopy and optogenetic readouts of exocytosis and neural excitability. We activated neurotransmitter-specific mushroom body output neurons and imaged presynaptic function under isoflurane anesthesia. We found that isoflurane impaired synaptic release and presynaptic protein dynamics in excitatory cholinergic synapses. In contrast, isoflurane had little to no effect on inhibitory GABAergic or glutamatergic synapses. These results present a distinct inhibitory mechanism for general anesthesia, whereby neuroexocytosis is selectively impaired at excitatory synapses, while inhibitory synapses remain functional. This suggests a presynaptic inhibitory mechanism that complements the other inhibitory effects of these drugs.
doi_str_mv 10.1523/JNEUROSCI.0588-23.2024
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Common clinical general anesthetic drugs, such as propofol and isoflurane, have been shown to interact and interfere with core components of the exocytic release machinery to cause impaired neurotransmitter release. Recent studies however suggest that these drugs do not affect all synapse subtypes equally. We investigated the role of the presynaptic release machinery in multiple neurotransmitter systems under isoflurane general anesthesia in the adult female brain using live-cell super-resolution microscopy and optogenetic readouts of exocytosis and neural excitability. We activated neurotransmitter-specific mushroom body output neurons and imaged presynaptic function under isoflurane anesthesia. We found that isoflurane impaired synaptic release and presynaptic protein dynamics in excitatory cholinergic synapses. In contrast, isoflurane had little to no effect on inhibitory GABAergic or glutamatergic synapses. 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subjects Anesthesia
Anesthetics
Anesthetics, Inhalation - pharmacology
Animals
Brain
Brain - drug effects
Brain - metabolism
Cholinergics
Drosophila
Drosophila Proteins - genetics
Drosophila Proteins - metabolism
Excitability
Exocytosis
Female
Fruit flies
General anesthesia
Glutamatergic transmission
Inhibition
Insects
Ion channels
Isoflurane
Isoflurane - pharmacology
Mushroom bodies
Mushroom Bodies - drug effects
Mushroom Bodies - metabolism
Mushroom Bodies - physiology
Neurotransmitter release
Neurotransmitters
Potentiation
Presynapse
Propofol
Proteins
SNAP receptors
SNARE Proteins - metabolism
Synapses
Synapses - drug effects
Synapses - metabolism
Synapses - physiology
Synaptic Transmission - drug effects
Synaptic Transmission - physiology
γ-Aminobutyric acid
title Synapse-Specific Trapping of SNARE Machinery Proteins in the Anesthetized Drosophila Brain
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