Deriving striatal projection neurons from human pluripotent stem cells with Activin A

The striatum is the main input structure of the basal ganglia and is involved in voluntary motor control,habit learning and reward processing.Medium spiny neurons（MSNs）comprise80%and 95%of striatal neurons in primates and rodents,respectively.

The Secondary Motor Cortex-striatum Circuit Contributes to Suppressing Inappropriate Responses in Perceptual Decision Behavior

The secondary motor cortex(M2)encodes choice-related information and plays an important role in cue-guided actions.M2 neurons innervate the dorsal striatum(DS),which also contributes to decision-making behavior,yet how M2 modulates signals in the DS to influence perceptual decision-making is unclear.Using mice performing a visual Go/No-Go task,we showed that inactivating M2 projections to the DS impaired performance by increasing the false alarm(FA)rate to the reward-irrelevant No-Go stimulus.The choice signal of M2 neurons correlated with behavioral performance,and the inactivation of M2 neurons projecting to the DS reduced the choice signal in the DS.By measuring and manipulating the responses of direct or indirect pathway striatal neurons defined by M2 inputs,we found that the indirect pathway neurons exhibited a shorter response latency to the No-Go stimulus,and inactivating their early responses increased the FA rate.These results demonstrate that the M2-to-DS pathway is crucial for suppressing inappropriate responses in perceptual decision behavior.