A study published in *Nature Neuroscience* (2012) investigates the distinct roles of direct and indirect pathway striatal neurons in reinforcement learning. The research used optogenetics to activate dopamine D1- and D2-receptor-expressing striatal projection neurons in mice. Stimulation of D1-expressing neurons (direct pathway) induced persistent reinforcement, while stimulation of D2-expressing neurons (indirect pathway) induced transient punishment. These findings suggest that direct pathway neurons mediate reinforcement, while indirect pathway neurons mediate punishment. The study used channelrhodopsin-2 (ChR2) to selectively activate direct (dMSNs) and indirect (iMSNs) striatal neurons. In vivo electrophysiology showed that dMSNs were identified based on increased firing rates in response to laser stimulation. Mice expressing ChR2 in dMSNs or iMSNs were tested in operant tasks. dMSN-ChR2 mice showed a persistent preference for the laser-paired trigger, while iMSN-ChR2 mice showed a transient preference. This difference was evident even after extinction, with dMSN-ChR2 mice maintaining their preference, while iMSN-ChR2 mice lost it. The study also tested the effect of dopamine antagonists on trigger preference. DA antagonists reduced movement but did not affect the acquisition or expression of trigger preferences. This suggests that dopamine is not essential for the expression of trigger bias. The results were consistent across operant and place preference tasks, showing that reinforcement is more effective than punishment in modifying long-term behavior. The study highlights the distinct roles of direct and indirect pathway neurons in reinforcement and punishment. These findings have implications for understanding psychiatric disorders, where dysfunction in these processes is implicated. The results suggest that targeting specific neuronal populations could be a potential therapeutic approach for disorders involving impaired reinforcement or punishment.A study published in *Nature Neuroscience* (2012) investigates the distinct roles of direct and indirect pathway striatal neurons in reinforcement learning. The research used optogenetics to activate dopamine D1- and D2-receptor-expressing striatal projection neurons in mice. Stimulation of D1-expressing neurons (direct pathway) induced persistent reinforcement, while stimulation of D2-expressing neurons (indirect pathway) induced transient punishment. These findings suggest that direct pathway neurons mediate reinforcement, while indirect pathway neurons mediate punishment. The study used channelrhodopsin-2 (ChR2) to selectively activate direct (dMSNs) and indirect (iMSNs) striatal neurons. In vivo electrophysiology showed that dMSNs were identified based on increased firing rates in response to laser stimulation. Mice expressing ChR2 in dMSNs or iMSNs were tested in operant tasks. dMSN-ChR2 mice showed a persistent preference for the laser-paired trigger, while iMSN-ChR2 mice showed a transient preference. This difference was evident even after extinction, with dMSN-ChR2 mice maintaining their preference, while iMSN-ChR2 mice lost it. The study also tested the effect of dopamine antagonists on trigger preference. DA antagonists reduced movement but did not affect the acquisition or expression of trigger preferences. This suggests that dopamine is not essential for the expression of trigger bias. The results were consistent across operant and place preference tasks, showing that reinforcement is more effective than punishment in modifying long-term behavior. The study highlights the distinct roles of direct and indirect pathway neurons in reinforcement and punishment. These findings have implications for understanding psychiatric disorders, where dysfunction in these processes is implicated. The results suggest that targeting specific neuronal populations could be a potential therapeutic approach for disorders involving impaired reinforcement or punishment.