A Kinetic Model of Dopamine- and Calcium-Dependent Striatal Synaptic Plasticity

Takashi Nakano, Tomokazu Doi, Junichiro Yoshimoto, Kenji Doya

Abstract: Author Summary Recent brain imaging and neurophysiological studies suggest that the striatum, the start of the basal ganglia circuit, plays a major role in value-based decision making and behavioral disorders such as drug addiction. The plasticity of synaptic input from the cerebral cortex to output neurons of the striatum, which are medium spiny neurons, depends on interactions between glutamate input from the cortex and dopaminergic input from the midbrain. It also links sensory and cognitive states in the cortex with reward-oriented action outputs. The mechanisms involved in molecular cascades that transmit glutamate and dopamine inputs to changes in postsynaptic glutamate receptors are very complex and it is difficult to intuitively understand the mechanism. Therefore, a biochemical network model was constructed, and computer simulations were performed. The model reproduced dopamine-dependent and calcium-dependent forms of long-term depression (LTD) and potentiation (LTP) of corticostriatal synapses. Further in silico experiments revealed that a positive feedback loop formed by proteins, the protein specifically expressed in the striatum, served as the major switch for inducing LTD and LTP. This model could allow us to understand dynamic constraints in reward-dependent learning, as well as causes and therapies of dopamine-related disorders such as drug addiction.