Distinct cortical-amygdala projections drive reward value encoding and retrieval

Abstract

The value of an anticipated rewarding event is crucial information in the decision to engage in its pursuit. The networks responsible for encoding and retrieval this value are largely unknown. Using glutamate biosensors and pharmacological manipulations, we found that basolateral amygdala (BLA) glutamatergic activity tracks and mediates both the encoding and retrieval of the hungerstate-dependent value of a palatable food reward. Projection-specific chemogenetic and optogenetic manipulations revealed and it wathe orbitofrontal cortex (OFC) supports the BLA in these processes. Critically, the function of the ventrolateral (lOFC) and medial (mOFC)OFCBLA projections was found to be doubly dissociable. Whereas activity in lOFCBLA projections is necessary for and sufficient to drive encoding of a positive change in the value of a reward, mOFCBLA projections are necessary and sufficient for retrieving this value from memory to guide reward pursuit. These data reveal a new circuit for adaptive reward valuation and pursuit and provide mechanistic insight into the dysfunction in these processes that characterizes myriad psychiatric diseases.. CC-BY-NC-ND 4.0 International license It is made available under a (which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint . http://dx.doi.org/10.1101/299958 doi: bioRxiv preprint first posted online Apr. 11, 2018; Malvaez et al., 3 Prospective consideration of the outcomes of potential action choices is crucial to adaptive decision making. Chief among these considerations is the value of anticipated rewarding events.This incentive information is state-dependent; e.g., a food reward is more valuable when hungry than when sated. It is also learned. The value of a specific reward is encoded during its experience in a relevant state 1 . Retrieval of the previously-encoded value of an anticipated reward allows adaptive reward pursuit decisions. Dysfunction in either the value encoding or retrieval process will lead to the aberrant reward pursuit and ill-informed decision making─ cognitive symptoms that characterize myriad psychiatric diseases. Despite importance to understanding adaptive and maladaptive behavior, little is known of the neural circuits that support reward value encoding and retrieval.The basolateral amygdala (BLA) has long been known to mediate emotional learning [2][3][4] . Accordingly, this structure is necessary for reward value encoding [5][6][7][8][9][10][11][12][13] . But the circuitry supporting the BLA in this function is unknown. Whether the BLA participates in retrieving reward value is less clear and has been disputed 7,10,11 and its contribution, if any, to active decision making is uncertain.Given the BLA is densely innervated by glutamatergic projections from regions themselves implicated in reward learning and decision making 14,15 , we sought to begin to fill these gaps in knowledge by using electroenzymatic biosensors to characterize...

Review of Orbitofrontal Cortex in Alcohol Dependence: A Disrupted Cognitive Map?

“…Recent work suggests OFC is critical for incentive learning processes, both at the point of encoding the updated value (Baltz et al, 2018; Malvaez et al, 2019) and when retrieving the updated value from memory to control responding (Malvaez et al, 2019). However, it is currently unknown whether alcohol‐induced deficits in incentive learning are largely driven by changes to OFC function.…”

Optogenetic silencing of neurotransmitter release with a naturally occurring invertebrate rhodopsin

“…This is consistent with our observation of GIRK channel-independent suppression of spikeevoked Ca 2+ transients after eOPN3 activation. Thus, if locally activated at synaptic terminals, eOPN3 is a robust and broadly applicable optogenetic tool for inhibition of synaptic neurotransmission, similar to the DREADD receptor hM4Di, which has been successfully used for presynaptic silencing in a variety of neuronal cell types and systems (Stachniak, et al, 2014;Evans, et al, 2018;Malvaez, et al, 2019).…”

Alcohol Dependence Differentially Alters Action and Outcome Related Orbitofrontal Cortex Activity

“…A hallmark of OFC function is its contribution to reward evaluation and updating, with increases in OFC activity observed during outcome anticipation and presentation (Rolls et al, 1996; Jones et al, 2012; Wallis, 2012; Stalnaker et al, 2014, 2015, 2018). Recent works have shown that inhibition of OFC activity during periods of outcome presentation prevent outcome evaluation and updating (Baltz et al, 2018; Malvaez et al, 2019). Further, recent work in humans has suggested that OFC encodes reward identity expectations (Howard & Kahnt, 2018), which contribute to the generation of prediction errors even when there is no change in value (Stalnaker et al, 2018).…”

“…Several lines of evidence implicate the OFC as a key contributor to computations that can contribute to value-based decision-making processes (Fellows, 2007; Wallis, 2007; Gremel & Costa, 2013; Stalnaker et al, 2015; Padoa-Schioppa & Conen, 2017) as well as to compulsive control (Milad & Rauch, 2012; Pauls et al, 2014; Robbins et al, 2019; Lüscher et al, 2020). In particular, manipulations of OFC function support a role for OFC in the updating and retrieval of expected outcome value to control behavior (Gremel & Costa, 2013; Rhodes & Murray, 2013; Baltz et al, 2018; Malvaez et al, 2019), as well as in compulsive action control (Ahmari et al, 2013; Burguière et al, 2013; Pascoli et al, 2015, 2018). Animal models of alcohol dependence have revealed long-lasting dependence-induced disruptions to OFC dependent processes including behavioral flexibility and outcome devaluation (Badanich et al, 2011; Kroener et al, 2012; M. F. Lopez et al, 2014; Fernandez et al, 2017; Renteria et al, 2018, 2020).…”