Hierarchical architecture of dopaminergic circuits enables second-order conditioning in Drosophila
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
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.
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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Further reading
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- Neuroscience
When navigating environments with changing rules, human brain circuits flexibly adapt how and where we retain information to help us achieve our immediate goals.
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- Neuroscience
When holding visual information temporarily in working memory (WM), the neural representation of the memorandum is distributed across various cortical regions, including visual and frontal cortices. However, the role of stimulus representation in visual and frontal cortices during WM has been controversial. Here, we tested the hypothesis that stimulus representation persists in the frontal cortex to facilitate flexible control demands in WM. During functional MRI, participants flexibly switched between simple WM maintenance of visual stimulus or more complex rule-based categorization of maintained stimulus on a trial-by-trial basis. Our results demonstrated enhanced stimulus representation in the frontal cortex that tracked demands for active WM control and enhanced stimulus representation in the visual cortex that tracked demands for precise WM maintenance. This differential frontal stimulus representation traded off with the newly-generated category representation with varying control demands. Simulation using multi-module recurrent neural networks replicated human neural patterns when stimulus information was preserved for network readout. Altogether, these findings help reconcile the long-standing debate in WM research, and provide empirical and computational evidence that flexible stimulus representation in the frontal cortex during WM serves as a potential neural coding scheme to accommodate the ever-changing environment.