Dopamine modulates cortical circuit activity, in part, through its actions on GABAergic interneurons, including increasing the excitability of fast-spiking interneurons. Though such effects have been demonstrated in single cells, there are no studies that examine how such mechanisms may lead to the effects of dopamine at a neural network level. With this motivation, we investigated the effects of dopamine on synchronization in a simulated neural network, composed of excitatory and fast-spiking inhibitory Wang-Buzsaki neurons. The effects of dopamine were implemented through varying leak K+ conductance of the fast-spiking interneurons and the network synchronization within gamma band (~40 Hz) was analyzed. Parametrically varying the leak K+ conductance revealed an inverted-U shaped relationship, with low gamma band power at both low and high conductance levels, and optimal synchronization at intermediate conductance levels. We also examined the effects of modulating excitability of the inhibitory neurons more generically using an idealized model with theta neurons, with similar findings. Moreover, such relationship holds both when the external input is tonic vs. periodic. Our computational results mirror our empirical study of dopamine modulation in schizophrenia and healthy controls, which showed that amphetamine administration increased gamma power in patients but decreased it in controls. Together, our computational and empirical investigations indicate that dopamine can modulate cortical gamma band synchrony in an inverted-U fashion, and that the physiologic effects of dopamine on single fast-spiking interneurons can give rise to such non-monotonic effects at the network level.
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