Distinct Medial Orbitofrontal–Striatal Circuits Support Dissociable Component Processes of Risk/Reward Decision-Making

Abstract

The medial orbitofrontal cortex (mOFC) regulates a variety of cognitive functions, including refining action selection involving reward uncertainty. This region sends projections to numerous subcortical targets, including the ventral and dorsal striatum, yet how these corticostriatal circuits differentially regulate risk/reward decision-making is unknown. The present study examined the contribution of mOFC circuits linking the nucleus accumbens (NAc) and dorsomedial striatum (DMS) to risk/ reward decision-making using pharmacological disconnections. Male rats were well trained on a probabilistic discounting task involving choice between small/certain or large/risky rewards, with the probability of obtaining the larger reward decreasing or increasing over a session. Disconnection of mOFC-striatal pathways was achieved using infusions of GABA agonists inactivating the mOFC in one hemisphere, combined with NAc or DMS inactivation in the contralateral or ipsilateral hemisphere. Perturbing mOFC fi NAc circuits induced suboptimal, near-random patterns of choice that manifested as a flattening of the discounting curve. Animals were equally likely to stay or shift following rewarded/nonrewarded choices, suggesting this pathway mediates use of information about reward history to stabilize decision biases. In contrast, mOFC fi DMS disconnection impaired adjustments in decision biases, causing opposing changes in risky choice depending on how probabilities varied over time. This was driven by alterations in lose-shift behavior, suggesting mOFC fi DMS circuits track volatility in nonrewarded actions to adjust choice in accordance with changes in profitability. Thus, separate mOFC-striatal projection pathways regulate dissociable processes underlying decision-making, with mOFC fi NAc circuits aiding in establishing and stabilizing tasks states and mOFC fi DMS circuits facilitating transitions across states to promote flexible reward seeking.

Role of Orbitofrontal Cortex and Differential Effects of Acute and Chronic Stress on Motor Impulsivity Measured With 1-Choice Serial Reaction Time Test in Male Rats

“…Indeed, other evidence suggests that VO is required for response inhibition but specifically in value learning when outcomes are not easily predicted or in situations of delay uncertainty ( Meyer and Bucci, 2016 ; Hardung et al, 2017 ; Stolyarova and Izquierdo, 2017 ). Less activation in the MO is consistent with a more substantial role of this subregion and its target areas (ventral striatum and nucleus accumbens) in choice impulsivity (delay and probabilistic discounting) and with the fact that MO is required for maintaining a memory of reward value to guide actions in situations of uncertain outcomes ( Bradfield et al, 2015 ; Dalton et al, 2016 ; Wang et al, 2019 ; Jenni et al, 2022 ), conditions not explicitly tested in our experiments. Integrating anatomical and functional observations, it has been suggested that more medial subregions of rat OFC provide affective and motivational contributions to decision-making, whereas lateral subregions support sensory integration (i.e., associations of stimuli/cues and sensory events to outcomes) ( Izquierdo, 2017 ).…”

“…Although we have focused on OFC in this study, it is important to acknowledge that other brain regions also play an important role in the control of motor impulsivity. For example, basolateral amygdala, which has bidirectional connections with OFC, dorsal and ventral striatum, which are important OFC efferent targets, ventromedial prefrontal cortex, and subthalamic nucleus have all been implicated in the control of motor impulsivity ( Muir et al, 1996 ; Dalley et al, 2002 ; Eagle and Baunez, 2010 ; Donnelly et al, 2015 ; Jenni et al, 2022 ). Recently, a claustrum-mPFC pathway has been shown to regulate impulsive responding in the 5-CSRTT ( Liu et al, 2019 ), Thus, future experiments targeting subpopulations of neurons in the OFC and/or projection-specific input and output pathways, as well as other non-OFC areas, will provide a more refined understanding of the circuits and systems underlying the regulation of motor impulsivity.…”

Medial orbitofrontal neurotrophin systems integrate hippocampal input into outcome-specific value representations

“…A recent study by Jenni and colleagues ( Jenni et al, 2022 ) reported that MO-to-nucleus accumbens projections are necessary to establish and crystalize choice strategy during tasks that assess risky decision-making. Meanwhile, MO-to-dorsomedial striatum projections are necessary for shifting strategies, such that inactivation caused rats to persist in familiar response sequences even when not profitable, reminiscent of response patterns reported here.…”

“…MO function has become clearer in recent years, owing to experiments using inducible and projection-specific manipulations ( Jenni et al, 2022 ; Lichtenberg et al, 2021 ; Loh et al, 2022 ; Malvaez et al, 2019 ). Other investigators have unveiled local neurotransmitter systems necessary for motivated responding ( Jenni et al, 2021 ; Münster et al, 2020 ).…”

The circadian neurobiology of reward

“…These projections regulate the risk-reward decision-making where the disruption of the OFC → NAc circuit leads to impaired patters of choice and OFC → DST adjust choice to changes in profitability. 44 In the basolateral amygdala (BLA), genetically and spatially distinct neuronal populations are activated by rewarding and aversive stimuli respectively, with the latter projecting to the NAc. 45 It is also a part of a positive feedback loop comprising VTA-BLA-NAc, which is activated by sex reward and inhibited by VTA's GABAergic neurons.…”