Distinct cortical–amygdala projections drive reward value encoding and retrieval

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The value of an anticipated rewarding event is a crucial component of the decision to engage in its pursuit. But little is known of the networks responsible for encoding and retrieving this value. By using biosensors and pharmacological manipulations, we found that basolateral amygdala (BLA) glutamatergic activity tracks and mediates encoding and retrieval of the state-dependent incentive value of a palatable food reward. Projection-specific, bidirectional chemogenetic and optogenetic manipulations revealed that the orbitofrontal cortex (OFC) supports the BLA in these processes. Critically, the function of ventrolateral and medial OFC→BLA projections is doubly dissociable. Whereas lateral OFC→BLA projections are necessary and sufficient for encoding of the positive value of a reward, medial OFC→BLA projections are necessary and sufficient for retrieving this value from memory. These data reveal a new circuit for adaptive reward valuation and pursuit and provide insight into the dysfunction in these processes that characterizes myriad psychiatric diseases.

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Fig. 1: BLA glutamate release tracks reward value encoding and retrieval.
Fig. 2: BLA glutamate receptor activity is necessary for reward value encoding and retrieval.
Fig. 3: lOFC→BLA and mOFC→BLA projections are necessary for reward value encoding and retrieval, respectively.
Fig. 4: Optical stimulation of lOFC terminals in BLA concurrently with reward experience is sufficient to drive positive value assignment.
Fig. 5: Optical stimulation of mOFC→BLA projections is sufficient to enhance reward value retrieval.

Data availability

All data that support the findings of this study are available from the corresponding author upon reasonable request.

Code availability

Custom-written Python-based code is available from the corresponding author upon request.


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This research was supported by NIH grants DA035443, MH106972, and NS087494 to K.M.W. and NIH grants DA038942 and DA024635 to M.M. We acknowledge helpful feedback from N. Lichtenberg and A. Izquierdo on these data and this manuscript.

Author information

M.M. and K.M.W. designed the research and analyzed and interpreted the data. M.M. conducted the research with assistance from C.S., M.D.M., and V.Y.G. M.M. and K.M.W. wrote the manuscript.

Correspondence to Kate M. Wassum.

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Malvaez, M., Shieh, C., Murphy, M.D. et al. Distinct cortical–amygdala projections drive reward value encoding and retrieval. Nat Neurosci 22, 762–769 (2019) doi:10.1038/s41593-019-0374-7

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