Abstract
Reward-seeking in the world is driven by cues that can have ambiguous predictive and motivational value. To produce adaptive, flexible reward-seeking, it is necessary to exploit occasion setters, other distinct features in the environment, to resolve the ambiguity of Pavlovian reward-paired cues. Despite this, very little research has investigated the neurobiological underpinnings of occasion setting, and as a result little is known about which brain regions are critical for occasion setting. To address this, we exploited a recently developed task that was amenable to neurobiological inquiry where a conditioned stimulus is only predictive of reward delivery if preceded in time by the non-overlapping presentation of a separate cue—an occasion setter. This task required male rats to maintain and link cue-triggered expectations across time to produce adaptive reward-seeking. We interrogated the contributions of the basolateral amygdala and orbitofrontal cortex to occasion setting as these regions are thought to be critical for the computation and exploitation of state value, respectively. Reversible inactivation of either structure prior to the occasion-setting task resulted in a profound inability of rats to use the occasion setter to guide reward-seeking. In contrast, inactivation of the dorsal hippocampus, a region fundamental for context-specific responding was without effect nor did inactivation of the basolateral amygdala or orbitofrontal cortex in a standard Pavlovian conditioning preparation affect conditioned responding. We conclude that neural activity within the orbitofrontal cortex and basolateral amygdala circuit is necessary to update and resolve ambiguity in the environment to promote cue-driven reward-seeking.
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Acknowledgements
We thank Alex Haimbaugh and Erin Kong for excellent technical assistance. We would also like to thank Dr. Peter Holland and members of the Janak Lab for their comments, input, and support. We would like to acknowledge the immense impact Dr. Nadia Chaudhri had as an inspiration for this line of research.
Funding
This work was supported by NIH Grants DA035943 to PHJ and DA046136 to KMF.
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Fraser, K.M., Janak, P.H. Basolateral amygdala and orbitofrontal cortex, but not dorsal hippocampus, are necessary for the control of reward-seeking by occasion setters. Psychopharmacology 240, 623–635 (2023). https://doi.org/10.1007/s00213-022-06227-0
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DOI: https://doi.org/10.1007/s00213-022-06227-0