Journal
CELL REPORTS
Volume 39, Issue 7, Pages -Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2022.110756
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Funding
- NIH [R01 DA047869, U19 NS104648, F32 MH112320]
- ARO [W911NF1710554]
- Brain Research Foundation
- Simons Collaboration on the Global Brain
- New York Stem Cell Foundation
- U.S. Department of Defense (DOD) [W911NF1710554] Funding Source: U.S. Department of Defense (DOD)
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This study investigates the role of different input pathways in the nucleus accumbens in guiding choices. It finds that the prelimbic cortical inputs represent actions and choices, while the midline thalamic inputs represent cues. The choice-selective activity in the prelimbic cortical inputs is organized in sequences that persist beyond the outcome.
How are actions linked with subsequent outcomes to guide choices? The nucleus accumbens, which is implicated in this process, receives glutamatergic inputs from the prelimbic cortex and midline regions of the thalamus. However, little is known about whether and how representations differ across these input pathways. By comparing these inputs during a reinforcement learning task in mice, we discovered that prelimbic cortical inputs preferentially represent actions and choices, whereas midline thalamic inputs preferentially represent cues. Choice-selective activity in the prelimbic cortical inputs is organized in sequences that persist beyond the outcome. Through computational modeling, we demonstrate that these sequences can support the neural implementation of reinforcement-learning algorithms, in both a circuit model based on synaptic plasticity and one based on neural dynamics. Finally, we test and confirm a prediction of our circuit models by direct manipulation of nucleus accumbens input neurons.
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