Spiking neurons, dopamine, and plasticity: timing is everything, but concentration also matters.

While both dopamine (DA) fluctuations and spike-timing-dependent plasticity (STDP) are known to influence long-term corticostriatal plasticity, little attention has been devoted to the interaction between these two fundamental mechanisms. Here, a theoretical framework is proposed to account for experimental results specifying the role of presynaptic activation, postsynaptic activation, and concentrations of extracellular DA in synaptic plasticity. Our starting point was an explicitly-implemented multiplicative rule linking STDP to Michaelis-Menton equations that models the dynamics of extracellular DA fluctuations. This rule captures a wide range of results on conditions leading to long-term potentiation and depression in simulations that manipulate the frequency of induced corticostriatal stimulation and DA release. A well-documented biphasic function relating DA concentrations to synaptic plasticity emerges naturally from simulations involving a multiplicative rule linking DA and neural activity. This biphasic function is found consistently across different neural coding schemes employed (voltage-based vs. spike-based models). By comparison, an additive rule fails to capture these results. The proposed framework is the first to generate testable predictions on the dual influence of DA concentrations and STDP on long-term plasticity, suggesting a way in which the biphasic influence of DA concentrations can modulate the direction and magnitude of change induced by STDP, and raising the possibility that DA concentrations may inverse the LTP/LTD components of the STDP rule.