Integrating neurotransmission in striatal medium spiny neurons

The striatum is a major entry structure of the basal ganglia. Its role in information processing in close interaction with the cerebral cortex and thalamus has various behavioral consequences depending on the regions concerned, including control of body movements and motivation. A general feature of striatal information processing is the control by reward-related dopamine signals of glutamatergic striatal inputs and of their plasticity. This relies on specific sets of receptors and signaling proteins in medium-sized spiny neurons which belong to two groups, striatonigral and striatopallidal neurons. Some signaling pathways are activated only by dopamine or glutamate, but many provide multiple levels of interactions. For example, the cAMP pathway is mostly regulated by dopamine D1 receptors in striatonigral neurons, whereas the ERK pathway detects a combination of glutamate and dopamine signals and is essential for long-lasting modifications. These adaptations require changes in gene expression, and the signaling pathways linking synaptic activity to nuclear function and epigenetic changes are beginning to be deciphered. Their alteration underlies many aspects of striatal dysfunction in pathological conditions which include a decrease or an increase in dopamine transmission, as encountered in Parkinson's disease or exposure to addictive drugs, respectively.