Ana C Sias,1 Ashleigh K Morse,1 Sherry Wang,1 Venuz Y Greenfield,1 Caitlin M Goodpaster,1 Tyler M Wrenn,1 Andrew M Wikenheiser,1,2,3 Sandra M Holley,4 Carlos Cepeda,4 Michael S Levine,2,4 and Kate M Wassum1,2,3,5


1Department of Psychology, University of California, Los Angeles, Los Angeles, United States
2Brain Research Institute, University of California, Los Angeles, Los Angeles, United States
3Integrative Center for Learning and Memory, University of California, Los Angeles, Los Angeles, United States
4Intellectual and Developmental Disabilities Research Center, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United States
5Integrative Center for Addictive Disorders, University of California, Los Angeles, Los Angeles, United States




Adaptive reward-related decision making often requires accurate and detailed representation of potential available rewards. Environmental reward-predictive stimuli can facilitate these representations, allowing one to infer which specific rewards might be available and choose accordingly. This process relies on encoded relationships between the cues and the sensory-specific details of the rewards they predict. Here, we interrogated the function of the basolateral amygdala (BLA) and its interaction with the lateral orbitofrontal cortex (lOFC) in the ability to learn such stimulus-outcome associations and use these memories to guide decision making. Using optical recording and inhibition approaches, Pavlovian cue-reward conditioning, and the outcome-selective Pavlovian-to-instrumental transfer (PIT) test in male rats, we found that the BLA is robustly activated at the time of stimulus-outcome learning and that this activity is necessary for sensory-specific stimulus-outcome memories to be encoded, so they can subsequently influence reward choices. Direct input from the lOFC was found to support the BLA in this function. Based on prior work, activity in BLA projections back to the lOFC was known to support the use of stimulus-outcome memories to influence decision making. By multiplexing optogenetic and chemogenetic inhibition we performed a serial circuit disconnection and found that the lOFC→BLA and BLA→lOFC pathways form a functional circuit regulating the encoding (lOFC→BLA) and subsequent use (BLA→lOFC) of the stimulus-dependent, sensory-specific reward memories that are critical for adaptive, appetitive decision making.



Electrode access resistances were maintained at <30 MΩ. Green light (535 nm, 1 s pulse, 0.25–1 mW; CoolLED Ltd, Andover, UK) was delivered through the epifluorescence illumination pathway using Chroma Technologies filter cubes to activate ArchT and inhibit BLA cell bodies.

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The pE-100 series is a family of single-wavelength fluorescence LED Illumination Systems, and in this case provides narrow-band illumination at 535 nm which can be precisely controlled.

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