High frequency stimulation activates hot spots of spontaneous synaptic transmission

Neuronal transmitters are released at the morphological specializations known as active zones (AZs). Transmitters can be released either in response to a stimulus or spontaneously, and spontaneous transmission is a vital component of neuronal communication. Employing postsynaptically tethered calciu...

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Main Authors: Herson Astacio, Maria Bykhovskaia
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-04-01
Series:Frontiers in Synaptic Neuroscience
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Online Access:https://www.frontiersin.org/articles/10.3389/fnsyn.2025.1539868/full
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author Herson Astacio
Maria Bykhovskaia
author_facet Herson Astacio
Maria Bykhovskaia
author_sort Herson Astacio
collection DOAJ
description Neuronal transmitters are released at the morphological specializations known as active zones (AZs). Transmitters can be released either in response to a stimulus or spontaneously, and spontaneous transmission is a vital component of neuronal communication. Employing postsynaptically tethered calcium sensor GCaMP, we investigated how nerve stimulation affects spontaneous transmission at individual AZs at the Drosophila neuromuscular synapse. Optical monitoring of spontaneous transmission at individual AZs revealed that prolonged high-frequency stimulation (HFS, 30 Hz for 1 min) selectively activates the hot spots of spontaneous transmission, including the individual AZs with elevated activities as well as AZ clusters. In contrast, a brief tetanus (2 s) activated numerous low-activity AZs. We employed Monte-Carlo simulations of spontaneous transmission based on a three-state model of AZ preparedness, which incorporated longer-lasting (minutes) and shorter-lasting (sub-seconds to seconds) high-activity states of AZs. The simulations produced an accurate quantitative description of the variability and time-course of spontaneous transmission at individual AZs before and after the stimulation and suggested that HFS activates both longer-lasting and shorter-lasting states of AZ preparedness.
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spelling doaj-art-b2c602fc06654d56b81ae896f6426e832025-08-20T02:17:10ZengFrontiers Media S.A.Frontiers in Synaptic Neuroscience1663-35632025-04-011710.3389/fnsyn.2025.15398681539868High frequency stimulation activates hot spots of spontaneous synaptic transmissionHerson AstacioMaria BykhovskaiaNeuronal transmitters are released at the morphological specializations known as active zones (AZs). Transmitters can be released either in response to a stimulus or spontaneously, and spontaneous transmission is a vital component of neuronal communication. Employing postsynaptically tethered calcium sensor GCaMP, we investigated how nerve stimulation affects spontaneous transmission at individual AZs at the Drosophila neuromuscular synapse. Optical monitoring of spontaneous transmission at individual AZs revealed that prolonged high-frequency stimulation (HFS, 30 Hz for 1 min) selectively activates the hot spots of spontaneous transmission, including the individual AZs with elevated activities as well as AZ clusters. In contrast, a brief tetanus (2 s) activated numerous low-activity AZs. We employed Monte-Carlo simulations of spontaneous transmission based on a three-state model of AZ preparedness, which incorporated longer-lasting (minutes) and shorter-lasting (sub-seconds to seconds) high-activity states of AZs. The simulations produced an accurate quantitative description of the variability and time-course of spontaneous transmission at individual AZs before and after the stimulation and suggested that HFS activates both longer-lasting and shorter-lasting states of AZ preparedness.https://www.frontiersin.org/articles/10.3389/fnsyn.2025.1539868/fullactive zoneGCaMPhigh frequency stimulationDrosophilaneuromuscular junction
spellingShingle Herson Astacio
Maria Bykhovskaia
High frequency stimulation activates hot spots of spontaneous synaptic transmission
Frontiers in Synaptic Neuroscience
active zone
GCaMP
high frequency stimulation
Drosophila
neuromuscular junction
title High frequency stimulation activates hot spots of spontaneous synaptic transmission
title_full High frequency stimulation activates hot spots of spontaneous synaptic transmission
title_fullStr High frequency stimulation activates hot spots of spontaneous synaptic transmission
title_full_unstemmed High frequency stimulation activates hot spots of spontaneous synaptic transmission
title_short High frequency stimulation activates hot spots of spontaneous synaptic transmission
title_sort high frequency stimulation activates hot spots of spontaneous synaptic transmission
topic active zone
GCaMP
high frequency stimulation
Drosophila
neuromuscular junction
url https://www.frontiersin.org/articles/10.3389/fnsyn.2025.1539868/full
work_keys_str_mv AT hersonastacio highfrequencystimulationactivateshotspotsofspontaneoussynaptictransmission
AT mariabykhovskaia highfrequencystimulationactivateshotspotsofspontaneoussynaptictransmission