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Amygdala-cortical circuits in associative reward memory retrieval
No full textAdaptive decision making requires the accurate anticipation or expectation of rewarding events. To survive in our environment, we must retrieve and use detailed associative memories of reward-predictive cues and actions taken to reach a goal to inform and guide our decisions. Often times, this cognitive process and underlying neural mechanisms can go awry, leading to maladaptive reward representation and improper choice behavior. Here, we elucidate the basic brain mechanisms of reward-expectation guided behaviors by employing neuroanatomical tracing alongside targeted pharmacological and chemogenetic manipulations of neural circuitry. The data presented here reveal novel contributions of a basolateral amygdala (BLA) opioid receptor system and of specific amygdala-cortical projection pathways to cue-guided behavior.First, we reveal that the endogenous activation of mu-, but not delta-opioid receptors in the BLA are needed for a reward-predictive cue to guide action selection. BLA mu-opioid receptor antagonism did not disrupt the ability of a reward itself to influence actions, suggesting a selective role for this receptor in mediating cue-outcome memory retrieval. Next, we sought to understand the role of the BLA within a larger neural network, so we first used anterograde and retrograde tract tracers to anatomically map populations of BLA projection neurons to the medial (mOFC) and lateral (lOFC) orbitofrontal cortices, and also identified reciprocal overlap in BLA-OFC (orbitofrontal) circuitry within the frontal cortex. We found spatially distinct populations of BLA→mOFC and BLA→lOFC neurons and dense overlap between OFC cell bodies and BLA terminals in the mOFC and lOFC. Thereafter, we causally manipulated pathways within the BLA-OFC network using a novel projection-specific chemogenetic approach during a series of behavioral tasks designed to assess the retrieval and use of cue- and action-outcome memories. BLA→lOFC projections were required for cue-guided action selection and responding according to a reward’s current value, while BLA→mOFC projections were only required for the latter. Much like the BLA→lOFC pathway, mOFC→BLA projections were needed for reward-predictive cues to guide action selection, and for such cues to influence responding according to a reward’s current value. lOFC inputs to the BLA were not needed for cue-guided action selection, and no projection was found to be necessary for action selection based on a reward’s current value. Taken together, these data provide evidence that distinct projection pathways in the BLA-OFC network coordinate unique and overlapping aspects of reward expectation-guided behaviors, particularly when these behaviors are informed by reward-predictive environmental cues. Often times, mental illness is characterized by improper reward expectation or foresight because patients are deficient in mentally representing anticipated rewards and in reward valuation. Therefore, the findings presented in this work may contribute to our understanding and treatment of psychiatric disease, such as addiction, and suggest that they may arise due to dysfunctional amygdala-OFC circuits
Amygdala-cortical collaboration in reward learning and decision making
No full textAdaptive reward-related decision making requires accurate prospective consideration of the specific outcome of each option and its current desirability. These mental simulations are informed by stored memories of the associative relationships that exist within an environment. In this review, I discuss recent investigations of the function of circuitry between the basolateral amygdala (BLA) and lateral (lOFC) and medial (mOFC) orbitofrontal cortex in the learning and use of associative reward memories. I draw conclusions from data collected using sophisticated behavioral approaches to diagnose the content of appetitive memory in combination with modern circuit dissection tools. I propose that, via their direct bidirectional connections, the BLA and OFC collaborate to help us encode detailed, outcome-specific, state-dependent reward memories and to use those memories to enable the predictions and inferences that support adaptive decision making. Whereas lOFC→BLA projections mediate the encoding of outcome-specific reward memories, mOFC→BLA projections regulate the ability to use these memories to inform reward pursuit decisions. BLA projections to lOFC and mOFC both contribute to using reward memories to guide decision making. The BLA→lOFC pathway mediates the ability to represent the identity of a specific predicted reward and the BLA→mOFC pathway facilitates understanding of the value of predicted events. Thus, I outline a neuronal circuit architecture for reward learning and decision making and provide new testable hypotheses as well as implications for both adaptive and maladaptive decision making
The basolateral amygdala in reward learning and addiction.
No full textSophisticated behavioral paradigms partnered with the emergence of increasingly selective techniques to target the basolateral amygdala (BLA) have resulted in an enhanced understanding of the role of this nucleus in learning and using reward information. Due to the wide variety of behavioral approaches many questions remain on the circumscribed role of BLA in appetitive behavior. In this review, we integrate conclusions of BLA function in reward-related behavior using traditional interference techniques (lesion, pharmacological inactivation) with those using newer methodological approaches in experimental animals that allow in vivo manipulation of cell type-specific populations and neural recordings. Secondly, from a review of appetitive behavioral tasks in rodents and monkeys and recent computational models of reward procurement, we derive evidence for BLA as a neural integrator of reward value, history, and cost parameters. Taken together, BLA codes specific and temporally dynamic outcome representations in a distributed network to orchestrate adaptive responses. We provide evidence that experiences with opiates and psychostimulants alter these outcome representations in BLA, resulting in long-term modified action
Regulation of habit formation in the dorsal striatum
No full textHabits are an essential and pervasive component of our daily lives that allow us to efficiently perform routine tasks. But their disruption contributes to the symptoms that underlie many psychiatric diseases. Emerging data are revealing the cellular and molecular mechanisms of habit formation in the dorsal striatum. New data suggest that in both the dorsolateral and dorsomedial striatum histone deacetylase (HDAC) activity acts as a critical negative regulator of the transcriptional processes underlying habit formation. In this review, we discuss this recent work and draw conclusions relevant to the treatment of diseases marked by maladaptive habits
Dorsomedial prefrontal cortex activation disrupts Pavlovian incentive motivation
No full textThe dorsomedial prefrontal cortex (dmPFC) is known to make important contributions to flexible, reward-motivated behavior. However, it remains unclear if the dmPFC is involved in regulating the expression of Pavlovian incentive motivation, the process through which reward-paired cues promote instrumental reward-seeking behavior, which is modeled in rats using the Pavlovian-instrumental transfer (PIT) task. The current study examined this question using a bidirectional chemogenetic strategy in which inhibitory (hM4Di) or excitatory (hM3Dq) designer G-protein coupled receptors were virally expressed in dmPFC neurons, allowing us to later stimulate or inhibit this region by administering CNO prior to PIT testing. We found that dmPFC inhibition did not alter the tendency for a reward-paired cue to instigate instrumental reward-seeking behavior, whereas dmPFC stimulation disrupted the expression of this motivational influence. Neither treatment altered cue-elicited anticipatory activity at the reward-delivery port, indicating that dmPFC stimulation did not lead to more widespread motor suppression. A reporter-only control experiment indicated that our CNO treatment did not have non-specific behavioral effects. Thus, the dmPFC does not mediate the expression of Pavlovian incentive motivation but instead has the capacity to exert pronounced inhibitory control over this process, suggesting that it is involved in adaptively regulating cue-motivated behavior
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