Dopamine Receptor Modulation of Glutamatergic Neurotransmission

Abstract

Dopamine (DA), a prominent neuromodulator in the brain, regulates neuronal excitability and synaptic transmission. These actions are effected through diverse DA receptor subtypes whose effects vary as a function of a number of factors including pre- or postsynaptic localization and the intracellular signaling cascades they activate. We have chosen the corticostriatal synapse as a model to study the interactions between DA and glutamate, the major excitatory neurotransmitter for striatal inputs. In the striatum, DA receptors modulate glutamate release via presynaptic mechanisms and synaptic responses mediated by activation of postsynaptic glutamate receptors through alterations in voltage-gated channels, phosphorylation of glutamate receptor subunits, as well as physical interactions with other receptors. The outcomes of these actions are diverse and can lead to opposite or synergistic effects. These multiple effects are important to keep the balance between striatal output pathways to coordinate sensorimotor integration.