In silico investigation of the puzzling dopamine effects on excitability and synaptic plasticity in hippocampal CA1 pyramidal neurons

It has been shown that in the CA1 region of the hippocampus, dopamine modulates memory functions by influencing spike-timing-dependent plasticity (STDP) and intrinsic neuronal properties. Although experimental findings have suggested potential mechanisms, their detailed interplay remains incompletely understood. Here, using a realistic CA1 pyramidal neuron model, we have investigated the possible effects of dopaminergic modulation on a neuron's signal integration and synaptic plasticity processes. The results suggest a physiological plausible explanation for the puzzling experimental observation that long-term potentiation (LTP) increases in spite of a reduction in the neuron's excitability, and explains why physiological dopamine levels are necessary for LTP induction. The model suggests experimentally testable predictions on which ion channel kinetic properties can modulate the interplay between synaptic plasticity and neuronal excitability, thereby identifying potential molecular targets for therapeutic intervention.