Associative learning drives longitudinally-graded presynaptic plasticity of neurotransmitter release along axonal compartments
- Scripps Research Institute, United States
- Peking University, China
- Peiking University, China
Abstract
Anatomical and physiological compartmentalization of neurons is a mechanism to increase the computational capacity of a circuit, and a major question is what role axonal compartmentalization plays. Axonal compartmentalization may enable localized, presynaptic plasticity to alter neuronal output in a flexible, experience-dependent manner. Here we show that olfactory learning generates compartmentalized, bidirectional plasticity of acetylcholine release that varies across the longitudinal compartments of Drosophila mushroom body (MB) axons. The directionality of the learning-induced plasticity depends on the valence of the learning event (aversive vs. appetitive), varies linearly across proximal to distal compartments following appetitive conditioning, and correlates with learning-induced changes in downstream mushroom body output neurons (MBONs) that modulate behavioral action selection. Potentiation of acetylcholine release was dependent on the CaV2.1 calcium channel subunit cacophony. In addition, contrast between the positive conditioned stimulus and other odors required the inositol triphosphate receptor (IP3R), which maintained responsivity to odors upon repeated presentations, preventing adaptation. Downstream from the mushroom body, a set of MBONs that receive their input from the g3 MB compartment were required for normal appetitive learning, suggesting that they represent a key node through which reward learning influences decision-making. These data demonstrate that learning drives valence-correlated, compartmentalized, bidirectional potentiation and depression of synaptic neurotransmitter release, which rely on distinct mechanisms and are distributed across axonal compartments in a learning circuit.
Data availability
Raw data have been deposited to Dryad under doi: 10.5061/dryad.dfn2z353h
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Data fgrom: Associative learning drives longitudinally-graded presynaptic plasticity of neurotransmitter release along axonal compartmentsDryad Digital Repository, doi:10.5061/dryad.dfn2z353h.
Article and author information
Author details
Funding
National Institutes of Health (R01NS097237)
- Seth M Tomchik
National Institutes of Health (NS103558)
- Yulong Li
National Institutes of Health (R01NS114403)
- Seth M Tomchik
National Institutes of Health (R00MH092294)
- Seth M Tomchik
Whitehall Foundation (2014-12-31)
- Seth M Tomchik
National Institutes of Health (R35NS097224)
- Ronald L Davis
Beijing Municipal Science & Technology Commission (Z181100001318002)
- Yulong Li
Beijing Brain Initiative of Beijing Municipal Science & Technology Commission (Z181100001518004)
- Yulong Li
Guangdong Grant Key Technologies for Treatment of Brain Disorders"" (2018B030332001)
- Yulong Li
General Program of National Natural Science Foundation of China Projects (31671118,31871087,31925017)
- Yulong Li
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Ilona C Grunwald Kadow, University of Bonn, Germany
Version history
- Preprint posted: June 10, 2021 (view preprint)
- Received: December 30, 2021
- Accepted: March 11, 2022
- Accepted Manuscript published: March 14, 2022 (version 1)
- Version of Record published: March 25, 2022 (version 2)
Copyright
© 2022, Stahl et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Associative learning drives longitudinally-graded presynaptic plasticity of neurotransmitter release along axonal compartments
eLife 11:e76712.
https://doi.org/10.7554/eLife.76712
Further reading
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Acetylcholine is released in visual cortex by axonal projections from the basal forebrain. The signals conveyed by these projections and their computational significance are still unclear. Using two-photon calcium imaging in behaving mice, we show that basal forebrain cholinergic axons in the mouse visual cortex provide a binary locomotion state signal. In these axons, we found no evidence of responses to visual stimuli or visuomotor prediction errors. While optogenetic activation of cholinergic axons in visual cortex in isolation did not drive local neuronal activity, when paired with visuomotor stimuli, it resulted in layer-specific increases of neuronal activity. Responses in layer 5 neurons to both top-down and bottom-up inputs were increased in amplitude and decreased in latency, whereas those in layer 2/3 neurons remained unchanged. Using opto- and chemogenetic manipulations of cholinergic activity, we found acetylcholine to underlie the locomotion-associated decorrelation of activity between neurons in both layer 2/3 and layer 5. Our results suggest that acetylcholine augments the responsiveness of layer 5 neurons to inputs from outside of the local network, possibly enabling faster switching between internal representations during locomotion.
