Molecular substrates of action control in cortico-striatal circuits

The purpose of this review is to describe the molecular mechanisms in the striatum that mediate reward-based learning and action control during instrumental conditioning. Experiments assessing the neural bases of instrumental conditioning have uncovered functional circuits in the striatum, including dorsal and ventral striatal sub-regions, involved in action–outcome learning, stimulus–response learning, and the motivational control of action by reward-associated cues. Integration of dopamine (DA) and glutamate neurotransmission within these striatal sub-regions is hypothesized to enable learning and action control through its role in shaping synaptic plasticity and cellular excitability. The extracellular signal regulated kinase (ERK) appears to be particularly important for reward-based learning and action control due to its sensitivity to combined DA and glutamate receptor activation and its involvement in a range of cellular functions. ERK activation in striatal neurons is proposed to have a dual role in both the learning and performance factors that contribute to instrumental conditioning through its regulation of plasticity-related transcription factors and its modulation of intrinsic cellular excitability. Furthermore, perturbation of ERK activation by drugs of abuse may give rise to behavioral disorders such as addiction.

► Distinct functional circuits in striatum mediate goal-directed actions, habits and motivation.
► The integration of dopamine and glutamate activity in striatum enables these functions.
► Dopamine and glutamate integration shapes both synaptic plasticity and cellular excitability.
► ERK is an important kinase sensitive to combined DA and glutamate receptor activation.
► ERK activation in striatal neurons plays a role in both instrumental learning and performance.