Basolateral amygdala and orbitofrontal cortex, but not dorsal hippocampus, are necessary for the control of reward-seeking by occasion setters

Fraser, Kurt M.; Janak, Patricia H.

doi:10.1007/s00213-022-06227-0

Cited by 14 publications

(13 citation statements)

References 78 publications

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“…Together, these results strongly implicate the OFC in the sex-biased expression of contextual modulation of reward-seeking. This is consistent with recent studies demonstrating a critical role of the OFC in hierarchical control over cue-evoked behaviors [28][29][30]. More generally, the OFC is proposed to encode task structure including context-dependent contingencies [74][75][76].…”

Section: Discussionsupporting

confidence: 90%

“…Compared to simple forms of associative learning, the neural bases of context-gated associative predictions (or occasion-setting) remain severely understudied. Although recent studies have implicated the orbitofrontal cortex (OFC) in occasion-setting [28–30], most of the behavioral and neurobiological occasion- setting studies have exclusively used male subjects and/or did not explicitly address sex as a biological variable.…”

Section: Introductionmentioning

confidence: 99%

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Sex Differences in Discrimination Behavior and Orbitofrontal Engagement During Context-Gated Reward Prediction

Peterson,

Maheras,

Chavira

et al. 2023

Preprint

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Animals, including humans, rely on contextual information to interpret ambiguous stimuli. Impaired context processing is a hallmark of several neuropsychiatric disorders, including schizophrenia, autism, PTSD, and addiction. While sex differences in the prevalence and manifestations of these disorders are well established, potential sex differences in context processing remain uncertain. Here we examined sex differences in the contextual control over cue-evoked reward seeking and its neural correlates, in rats. Male and female rats were trained in a bidirectional occasion-setting preparation in which the validity of two reward-predictive cues was informed by the presence, or absence, of a background contextual feature (A:X+ / X− / A:Y− / Y+). Females were significantly slower to acquire contextual control over cue-evoked reward seeking. However, once established, the contextual control over behavior was more robust in female rats; it showed less within-session variability (less influence of prior reward) and greater resistance to acute stress. This superior contextual control achieved by females was accompanied by an increased activation of the orbitofrontal cortex compared to males. Critically, these behavioral and neural sex differences were specific to the contextual modulation process and not observed in simple, context-independent, reward prediction tasks. These results indicate a sex-biased trade-off between speed and robustness in the acquisition of contextual modulation. The different distribution of sexes along the Fast↔Steady continuum might reflect different levels of engagement of the orbitofrontal cortex, and might have implications for our understanding of sex differences in psychiatric disorders.

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Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Sex Differences in Discrimination Behavior and Orbitofrontal Engagement During Context-Gated Reward Prediction

Peterson,

Maheras,

Chavira

et al. 2023

Preprint

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“…We have previously demonstrated that frontal cortical and basolateral amygdala activity is necessary for occasion setting, both of which project into the nucleus accumbens, and the activity of glutamatergic amygdala inputs to the nucleus accumbens shapes behavioral responses to discriminative cues (Ambroggi et al, 2008; Fraser and Janak, 2023). Thus, we assessed whether functional glutamate signaling in the nucleus accumbens was essential for occasion setting via infusion of the AMPA and NMDA receptor antagonists CNQX and MK801.…”

Section: Resultsmentioning

confidence: 99%

Contexts facilitate dynamic value encoding in the mesolimbic dopamine system

Fraser,

Collins,

Wolff

et al. 2023

Preprint

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Adaptive behavior in a dynamic environment often requires rapid revaluation of stimuli that deviates from well-learned associations. The divergence between stable value-encoding and appropriate behavioral output remains a critical test to theories of dopamine’s function in learning, motivation, and motor control. Yet how dopamine neurons are involved in the revaluation of cues when the world changes to alter our behavior remains unclear. Here we make use of pharmacology, in vivo electrophysiology, fiber photometry, and optogenetics to resolve the contributions of the mesolimbic dopamine system to the dynamic reorganization of reward-seeking. Male and female rats were trained to discriminate when a conditioned stimulus would be followed by sucrose reward by exploiting the prior, non-overlapping presentation of a separate discrete cue - an occasion setter. Only when the occasion setter’s presentation preceded the conditioned stimulus did the conditioned stimulus predict sucrose delivery. As a result, in this task we were able to dissociate the average value of the conditioned stimulus from its immediate expected value on a trial-to-trial basis. Both the activity of ventral tegmental area dopamine neurons and dopamine signaling in the nucleus accumbens were essential for rats to successfully update behavioral responding in response to the occasion setter. Moreover, dopamine release in the nucleus accumbens following the conditioned stimulus only occurred when the occasion setter indicated it would predict reward. Downstream of dopamine release, we found that single neurons in the nucleus accumbens dynamically tracked the value of the conditioned stimulus. Together these results reveal a novel mechanism within the mesolimbic dopamine system for the rapid revaluation of motivation.

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“…We found that the OFC is critical for the persistent population activity we observed in BLA during reward seeking and, specifically, that OFC input to the BLA contributes to conditioned behavior in this task. Interestingly, multiple previous reports find that simple Pavlovian behavior, such as port entry in response to a reward-predictive cue, is generally unimpaired by either OFC or BLA manipulation; rather, the OFC and BLA roles are restricted to occasions in which a cue-evoked representation of the reward, including its specific features and expected value, is required for appropriate behavior (Hatfield et al, 1996;Gallagher et al, 1999;Pickens et al, 2003Pickens et al, , 2005Ostlund and Balleine, 2007;Burke et al, 2009;Takahashi et al, 2009;Fraser and Janak, 2023). Similarly, electrophysiological and pharmacological studies have suggested that interactions between the OFC and the BLA are required for cue-dependent behavior when information about the expected value is needed (Baxter et al, 2000;Schoenbaum et al, 2003;Izquierdo and Murray, 2004;Saddoris et al, 2005;Churchwell et al, 2009;Lucantonio et al, 2015;Sias et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

Basolateral amygdala population coding of a cued reward seeking state depends on orbitofrontal cortex

Ottenheimer,

Vitale,

Ambroggi

et al. 2024

Preprint

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Basolateral amygdala (BLA) neuronal responses to conditioned stimuli are closely linked to the expression of conditioned behavior. An area of increasing interest is how the dynamics of BLA neurons relate to evolving behavior. Here, we recorded the activity of individual BLA neurons across the acquisition and extinction of conditioned reward seeking and employed population-level analyses to assess ongoing neural dynamics. We found that, with training, sustained cue-evoked activity emerged that discriminated between the CS+ and CS- and correlated with conditioned responding. This sustained population activity continued until reward receipt and rapidly extinguished along with conditioned behavior during extinction. To assess the contribution of orbitofrontal cortex (OFC), a major reciprocal partner to BLA, to this component of BLA neural activity, we inactivated OFC while recording in BLA and found blunted 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 suggest that sustained cue-driven activity in BLA, which in part depends on OFC input, underlies a conditioned reward-seeking state.

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Basolateral amygdala and orbitofrontal cortex, but not dorsal hippocampus, are necessary for the control of reward-seeking by occasion setters

Cited by 14 publications

References 78 publications

Sex Differences in Discrimination Behavior and Orbitofrontal Engagement During Context-Gated Reward Prediction

Sex Differences in Discrimination Behavior and Orbitofrontal Engagement During Context-Gated Reward Prediction

Contexts facilitate dynamic value encoding in the mesolimbic dopamine system

Basolateral amygdala population coding of a cued reward seeking state depends on orbitofrontal cortex

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