Nitric oxide acts as a cotransmitter in a subset of dopaminergic neurons to diversify memory dynamics
- Janelia Research Campus, Howard Hughes Medical Institute, United States
- University of Virginia, United States
- Columbia University, United States
Abstract
Animals employ diverse learning rules and synaptic plasticity dynamics to record temporal and statistical information about the world. However, the molecular mechanisms underlying this diversity are poorly understood. The anatomically defined compartments of the insect mushroom body function as parallel units of associative learning, with different learning rates, memory decay dynamics and flexibility (Aso & Rubin 2016). Here we show that nitric oxide (NO) acts as a neurotransmitter in a subset of dopaminergic neurons in Drosophila. NO's effects develop more slowly than those of dopamine and depend on soluble guanylate cyclase in postsynaptic Kenyon cells. NO acts antagonistically to dopamine; it shortens memory retention and facilitates the rapid updating of memories. The interplay of NO and dopamine enables memories stored in local domains along Kenyon cell axons to be specialized for predicting the value of odors based only on recent events. Our results provide key mechanistic insights into how diverse memory dynamics are established in parallel memory systems.
Data availability
Complete transcript data were deposited to NCBI Gene Expression Omnibus (accession number GSE139889).
Article and author information
Author details
Ashok Litwin-Kumar
Funding
Howard Hughes Medical Institute
- Yoshinori Aso
- Robert P Ray
- Xi Long
- Daniel Bushey
- Teri-TB Ngo
- Brandi Sharp
- Christina Christoforou
- Amy Hu
- Andrew L Lemire
- Paul Tillberg
- Gerald M Rubin
National Institutes of Health (R01 GM84128)
- Karol Cichewicz
- Jay Hirsh
Simons Foundation (Global Brain)
- Yoshinori Aso
- Ashok Litwin-Kumar
- Gerald M Rubin
Burroughs Wellcome Foundation
- Ashok Litwin-Kumar
Gatsby Charitable Foundation
- Ashok Litwin-Kumar
National Science Foundation (DBI-1707398)
- Ashok Litwin-Kumar
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Mani Ramaswami, Trinity College Dublin, Ireland
Version history
- Received: June 12, 2019
- Accepted: November 13, 2019
- Accepted Manuscript published: November 14, 2019 (version 1)
- Version of Record published: January 8, 2020 (version 2)
- Version of Record updated: October 22, 2020 (version 3)
Copyright
© 2019, Aso 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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Nitric oxide acts as a cotransmitter in a subset of dopaminergic neurons to diversify memory dynamics
eLife 8:e49257.
https://doi.org/10.7554/eLife.49257
Further reading
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- Neuroscience
The joint storage and reciprocal retrieval of learnt associated signals are presumably encoded by associative memory cells. In the accumulation and enrichment of memory contents in lifespan, a signal often becomes a core signal associatively shared for other signals. One specific group of associative memory neurons that encode this core signal likely interconnects multiple groups of associative memory neurons that encode these other signals for their joint storage and reciprocal retrieval. We have examined this hypothesis in a mouse model of associative learning by pairing the whisker tactile signal sequentially with the olfactory signal, the gustatory signal, and the tail-heating signal. Mice experienced this associative learning show the whisker fluctuation induced by olfactory, gustatory, and tail-heating signals, or the other way around, that is, memories to multi-modal associated signals featured by their reciprocal retrievals. Barrel cortical neurons in these mice become able to encode olfactory, gustatory, and tail-heating signals alongside the whisker signal. Barrel cortical neurons interconnect piriform, S1-Tr, and gustatory cortical neurons. With the barrel cortex as the hub, the indirect activation occurs among piriform, gustatory, and S1-Tr cortices for the second-order associative memory. These associative memory neurons recruited to encode multi-modal signals in the barrel cortex for associative memory are downregulated by neuroligin-3 knockdown. Thus, associative memory neurons can be recruited as the core cellular substrate to memorize multiple associated signals for the first-order and the second-order of associative memories by neuroligin-3-mediated synapse formation, which constitutes neuronal substrates of cognitive activities in the field of memoriology.
