Orbitofrontal cortex mediates sustained basolateral amygdala encoding of cued reward seeking states

Basolateral amygdala (BLA) neurons are engaged by emotionally salient stimuli. An area of increasing interest is how BLA dynamics relate to evolving reward-seeking behavior, especially under situations of uncertainty or ambiguity. Here, we recorded the activity of individual BLA neurons in male rats across the acquisition and extinction of conditioned reward seeking. We assessed ongoing neural dynamics in a task where long reward cue presentations preceded an unpredictable, variably-time reward delivery. We found that, with training, BLA neurons discriminated the CS+ and CS- cues with sustained cue-evoked activity that correlated with behavior and terminated only after reward receipt. BLA neurons were bidirectionally modulated, with a majority showing prolonged inhibition during cued reward seeking. Strikingly, population-level analyses revealed that neurons showing cue-evoked inhibitions and those showing excitations similarly represented the CS+ and behavioral state. This sustained population code rapidly extinguished in parallel with conditioned behavior. We next assessed the contribution of orbitofrontal cortex (OFC), a major reciprocal partner to BLA. Inactivation of OFC while simultaneously recording in BLA revealed a blunting of sustained cue-evoked activity in BLA that accompanied reduced reward seeking. Optogenetic disruption of BLA activity and OFC terminals in BLA also reduced reward seeking. Our data indicate that the BLA represents reward seeking states via sustained, bidirectional cue-driven neural encoding. This code is regulated by cortical input and is important for the maintenance of vigilant reward seeking behavior. Significance Statement Appropriate representation of the current need for motivated reward seeking, especially under situations of uncertainty or ambiguity, is critical for adaptive behavior. Here, we recorded activity of neurons in the basolateral amygdala (BLA) in rats during conditioned reward seeking, finding a sustained cue-evoked population-level code, which terminated once reward was received. Inactivation of a major BLA input, the orbitofrontal cortex (OFC), blunted sustained cue-evoked activity in BLA and reduced reward seeking. Optogenetic disruption of BLA activity and OFC terminals in BLA also reduced reward seeking. Together, these results show that the BLA represents conditioned motivational states with sustained neural activity - this signal is critical for cue-invigorated reward seeking and depends on functional input from the orbitofrontal cortex.