Genetic control of instrumental conditioning by striatopallidal neuron–specific S1P receptor Gpr6

Instrumental conditioning allows animals to learn about the consequences of their own actions, but the underpinning molecular mechanisms remain elusive. Here we show that the sphingosine-1-phosphate (S1P) receptor Gpr6 is selectively expressed in the striatopallidal neurons in the striatum. Gpr6-deficient mice showed reduced striatal cyclic AMP production in vitro and selective alterations in instrumental conditioning in vivo . Thus, Gpr6 is the first striatopallidal neuron–specific genetic regulator of instrumental conditioning in a mammal.