Dopaminergic Modulation of Glutamatergic Signaling in Striatal Medium Spiny Neurons

Abstract

Dopamine (DA) controls a wide variety of striatal functions, including action selection and associative learning. This is achieved by modulating cortical and thalamic glutamatergic synapses formed on principal medium spiny neurons (MSNs) and the way in which these signals are processed. Accumulating evidence suggests that D1 receptor signaling enhances dendritic excitability and glutamater- gic signaling in striatonigral MSNs, whereas D2 receptor signaling exerts the opposite effect in striatopallidal MSNs. The functional antagonism between these two major striatal DA receptors extends to the regulation of synaptic plasticity. Using brain slices from DA receptor transgenicmice, recent studies have uncovered important differences between MSNs that shape long-term alterations in glutamater- gic signaling with experience. These results are consistent with network models of striatal function, suggesting that DA acts in a push–pull fashion in action selec- tion. Work in models of Parkinson’s disease has shown this bidirectionality is lost following DA depletion, pointing to the mechanisms underlying network dysfunc- tion in this disease as well as in others with strong DA determinants like drug abuse.