Department of Psychology and Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada.
Department of Psychology and Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada
J Neurosci. 2022 Mar 30;42(13):2743-2755. doi: 10.1523/JNEUROSCI.2097-21.2022. Epub 2022 Feb 8.
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 → 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 → 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 → 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 → NAc circuits aiding in establishing and stabilizing tasks states and mOFC → DMS circuits facilitating transitions across states to promote flexible reward seeking. The medial orbitofrontal cortex regulates a variety of goal-directed behaviors, yet the functional circuits through which it mediates higher order decision-making functions are unclear. The present study revealed that different mOFC projection pathways facilitate diverse aspects of decision-making involving risks and rewards by engaging separate networks of neurons that interface with distinct ventral and dorsal striatal targets. These findings clarify some of the normal functions of these corticostriatal pathways and may have implications for understanding how dysfunction in these circuits relate to certain psychiatric disorders.
内侧眶额皮层（mOFC）调节多种认知功能，包括细化涉及奖励不确定性的行动选择。该区域向众多皮质下靶点发送投射，包括腹侧和背侧纹状体，但这些皮质纹状体回路如何差异调节风险/奖励决策尚不清楚。本研究使用药理学分离法研究了内侧眶额皮层连接伏隔核（NAc）和背侧纹状体（DMS）的回路对风险/奖励决策的贡献。雄性大鼠在涉及从小/确定到大/风险奖励之间选择的概率折扣任务中接受了良好的训练，获得较大奖励的概率在一个会话中减少或增加。使用在一侧半球中使 mOFC 失活的 GABA 激动剂输注来实现 mOFC-纹状体通路的分离，同时在对侧或同侧半球中使 NAc 或 DMS 失活。扰乱 mOFC→NAc 回路导致选择出现次优、近乎随机的模式，表现为折扣曲线变平。动物在奖励/非奖励选择后同样有可能停留或转移，这表明该途径介导了对奖励历史信息的使用，以稳定决策偏差。相比之下，mOFC→DMS 分离会损害决策偏差的调整，导致风险选择的相反变化，具体取决于概率随时间的变化。这是由损失转移行为的改变驱动的，这表明 mOFC→DMS 回路跟踪非奖励动作的波动性，以根据盈利能力的变化调整选择。因此，分离的 mOFC-纹状体投射途径调节决策的不同分离过程，mOFC→NAc 回路有助于建立和稳定任务状态，而 mOFC→DMS 回路则促进状态之间的转换，以促进灵活的奖励寻求。内侧眶额皮层调节多种目标导向行为，但介导其高级决策功能的功能回路尚不清楚。本研究表明，不同的 mOFC 投射途径通过参与与不同腹侧和背侧纹状体靶点接口的分离神经元网络，促进涉及风险和奖励的决策的不同方面。这些发现阐明了这些皮质纹状体通路的一些正常功能，并且可能对理解这些回路的功能障碍如何与某些精神障碍相关具有重要意义。
