Basolateral Amygdala to Orbitofrontal Cortex Projections Enable Cue-Triggered Reward Expectations

Abstract

To make an appropriate decision, one must anticipate potential future rewarding events, even when they are not readily observable. These expectations are generated by using observable information (e.g., stimuli or available actions) to retrieve often quite detailed memories of available rewards. The basolateral amygdala (BLA) and orbitofrontal cortex (OFC) are two reciprocally connected key nodes in the circuitry supporting such outcome-guided behaviors. But there is much unknown about the contribution of this circuit to decision making, and almost nothing known about the whether any contribution is via direct, monosynaptic projections, or the direction of information transfer. Therefore, here we used designer receptor-mediated inactivation of OFC¡BLA or BLA¡OFC projections to evaluate their respective contributions to outcome-guided behaviors in rats. Inactivation of BLA terminals in the OFC, but not OFC terminals in the BLA, disrupted the selective motivating influence of cue-triggered reward representations over reward-seeking decisions as assayed by Pavlovian-to-instrumental transfer. BLA¡OFC projections were also required when a cued reward representation was used to modify Pavlovian conditional goal-approach responses according to the reward's current value. These projections were not necessary when actions were guided by reward expectations generated based on learned action-reward contingencies, or when rewards themselves, rather than stored memories, directed action. These data demonstrate that BLA¡OFC projections enable the cue-triggered reward expectations that can motivate the execution of specific action plans and allow adaptive conditional responding.

The use of chemogenetics in behavioural neuroscience: receptor variants, targeting approaches and caveats

“…In addition, intracranial cannulas are implanted above the projection target region. To date, several studies have used local infusions of CNO into the projection target region to cause selective manipulation of only the DREADD‐expressing terminals in the target region (Lichtenberg et al ., ; Mahler et al ., ; McGlinchey and Aston‐Jones, ; Stachniak et al ., ; Venniro et al ., ). For example, Ge et al .…”

“…In addition, intracranial cannulas are implanted above the projection target region. To date, several studies have used local infusions of CNO into the projection target region to cause selective manipulation of only the DREADD-expressing terminals in the target region (Lichtenberg et al, 2017;Mahler et al, 2014;McGlinchey and Aston-Jones, 2017;Stachniak et al, 2014;Venniro et al, 2017). For example, Ge et al (2017) used this approach to show that inactivation of entorhinal cortex terminals in the dorsal dentate gyrus significantly decreased contextinduced reinstatement of heroin seeking.…”

Connectivity characterization of the mouse basolateral amygdalar complex

“…That is, animals with loss of BLA function are unable to accurately predict the rewarding or punishing outcome of a reinforcer that enables the selection of the more advantageous behavior. It is speculated that the connections of the BLA with the lateral part of the orbitofrontal cortex (ORBl) are relevant for the appropriate assessment of expected outcomes and consequently the selection of appropriate action [127][128][129] , a reasonable expectation given that the ORB is speculated to be involved in goal-directed behaviors and its dysfunction renders patients unable to make proper judgments based on anticipated consequences [130][131][132] . Tract tracing studies in rats report strong projections from BLA to ORB, typically the ORBl and ORBvl 133,134 .…”

Distinct cortical-amygdala projections drive reward value encoding and retrieval

“…Clozapine N-oxide (CNO; 1mM/0.5µl) was infused into the BLA to inactivate these terminals ( Fig. S10) 48 during the sucrose re-exposure, incentive learning opportunity and lever pressing was assessed the following day drug-free ( Fig. 3a).…”