Howard Hughes Medical Institute, Department of Neurobiology, Harvard Medical School, Boston, MA, USA.
Nature. 2021 Nov;599(7886):645-649. doi: 10.1038/s41586-021-04055-4. Epub 2021 Nov 3.
The ability to suppress actions that lead to a negative outcome and explore alternative actions is necessary for optimal decision making. Although the basal ganglia have been implicated in these processes, the circuit mechanisms underlying action selection and exploration remain unclear. Here, using a simple lateralized licking task, we show that indirect striatal projection neurons (iSPN) in the basal ganglia contribute to these processes through modulation of the superior colliculus (SC). Optogenetic activation of iSPNs suppresses contraversive licking and promotes ipsiversive licking. Activity in lateral superior colliculus (lSC), a region downstream of the basal ganglia, is necessary for task performance and predicts lick direction. Furthermore, iSPN activation suppresses ipsilateral lSC, but surprisingly excites contralateral lSC, explaining the emergence of ipsiversive licking. Optogenetic inactivation reveals inter-collicular competition whereby each hemisphere of the superior colliculus inhibits the other, thus allowing the indirect pathway to disinhibit the contralateral lSC and trigger licking. Finally, inactivating iSPNs impairs suppression of devalued but previously rewarded licking and reduces exploratory licking. Our results reveal that iSPNs engage the competitive interaction between lSC hemispheres to trigger a motor action and suggest a general circuit mechanism for exploration during action selection.
抑制导致负面结果的行动并探索替代行动的能力对于最佳决策至关重要。尽管基底神经节已被牵涉到这些过程中，但行动选择和探索的回路机制仍不清楚。在这里，我们使用简单的侧化舔食任务表明，基底神经节中的间接纹状体投射神经元（iSPN）通过调节上丘（SC）来促进这些过程。光遗传学激活 iSPN 可抑制对侧舔食并促进同侧舔食。来自基底神经节下游的外侧上丘（lSC）的活动对于任务表现是必要的，并预测舔食方向。此外，iSPN 激活抑制同侧 lSC，但令人惊讶的是兴奋对侧 lSC，解释了同侧舔食的出现。光遗传学失活揭示了脑桥间的竞争，其中上丘的每一侧半球都抑制另一侧半球，从而允许间接途径去抑制对侧 lSC 并引发舔食。最后，失活 iSPN 会损害对先前奖励但贬值的舔食的抑制，并减少探索性舔食。我们的结果表明，iSPN 参与了 lSC 半球之间的竞争相互作用，以触发运动动作，并为行动选择过程中的探索提供了一般的电路机制。
