Cellular interactions in the striatum involving neuronal systems using "classical" neurotransmitters: possible functional implications.

The neostriatum contains a wide variety of neuroactive substances associated with several well-defined functional neuronal systems. This structure, which is the seat of numerous neurological pathological disorders, is commonly used as a model for studying the basic mechanisms of neurotransmitter interactions in the brain and their putative involvement in striatal functions. Increasing interest has been focusing lately on the cellular interactions that may occur between the corticostriatal putatively glutamatergic system and the nigrostriatal dopaminergic input. Current evidence suggests that the activatory corticostriatal glutamatergic input may play a more crucial role in regulating striatal functions than was formerly assumed in comparison with the dopaminergic input. The key role of cholinergic interneurons in the striatum may therefore be attributable to the fact that they modulate the glutamatergic transmission to GABA striatal efferent neurons. Likewise, dopamine may actually act indirectly in the striatum by "tuning down" the cortical excitation of striatal neurons. Consequently, an impairment of the dopaminergic transmission such as that occurring in Parkinsonism may lead to an increase in the corticostriatal glutamatergic transmission, which may further contribute towards reinforcing the "imbalance" between subsets of striatal neuronal systems controlling the output of the basal ganglia.