Hierarchical architecture of dopaminergic circuits enables second-order conditioning in Drosophila
- University of North Carolina at Chapel Hill, United States
- Janelia Research Campus, United States
- Columbia University, United States
Abstract
Dopaminergic neurons with distinct projection patterns and physiological properties compose memory subsystems in a brain. However, it is poorly understood whether or how they interact during complex learning. Here, we identify a feedforward circuit formed between dopamine subsystems and show that it is essential for second-order conditioning, an ethologically important form of higher-order associative learning. The Drosophila mushroom body comprises a series of dopaminergic compartments, each of which exhibits distinct memory dynamics. We find that a slow and stable memory compartment can serve as an effective 'teacher' by instructing other faster and transient memory compartments via a single key interneuron, which we identify by connectome analysis and neurotransmitter prediction. This excitatory interneuron acquires enhanced response to reward-predicting odor after first-order conditioning and, upon activation, evokes dopamine release in the 'student' compartments. These hierarchical connections between dopamine subsystems explain distinct properties of first- and second-order memory long known by behavioral psychologists.
Data availability
The confocal images of expression patterns are available online (http://www.janelia.org/split-gal4). The source data for each figure are included in the manuscript.
Article and author information
Author details
Ashok Litwin-Kumar
Funding
NIH (R01DC018874)
- Toshihide Hige
NSF (DBI-1707398)
- Ashok Litwin-Kumar
Toyobo Biotechnology Foundation Postdoctoral Fellowship
- Daichi Yamada
Japan Society for the Promotion of Science Overseas Research Fellowship
- Daichi Yamada
HHMI
- Daniel Bushey
- Feng Li
- Karen L Hibbard
- Megan Sammons
- Jan Funke
- Yoshinori Aso
NSF (2034783)
- Toshihide Hige
BSF (2019026)
- Toshihide Hige
UNC Junior Faculty Development Award
- Toshihide Hige
Burroughs Wellcome Foundation
- Ashok Litwin-Kumar
Gatsby Charitable Foundation
- Ashok Litwin-Kumar
McKnight Endowment Fund
- Ashok Litwin-Kumar
Simons Collaboration on the Global Brain
- Ashok Litwin-Kumar
- Yoshinori Aso
NIH (R01EB029858)
- 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
- Ilona C Grunwald Kadow, University of Bonn, Germany
Publication history
- Received: March 28, 2022
- Accepted: January 23, 2023
- Accepted Manuscript published: January 24, 2023 (version 1)
Copyright
© 2023, Yamada 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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Hierarchical architecture of dopaminergic circuits enables second-order conditioning in Drosophila
eLife 12:e79042.
https://doi.org/10.7554/eLife.79042
