Modulatory effects of dopamine on the excitability of the neural networks in the rat prefrontal cortex.

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The effects of 5-hydroxytryptamine (5-HT), noradrenaline (NA), dopamine (DA) and the muscarinic receptor agonist carbachol (CCh)on the voltage step-induced outward currents underlying afterhyperpolarization (AHP),consisting of a medium (I_<mAHP>) and slow (I_<sAHP>) component, were investigated in layer V pyramidal cells of the rat medial prefrontal cortex (mPFC). Whole-cell voltage clamp recordings were performed in vitro to quantitatively measure I_<mAHP> and I_<sAHP> and to examine their functional link to spike-frequency adaptation in the presence of agonists. CCh, 5-HT and NA all reduced the I_<sAHP> and the spike adaptation, and, in some cells, replaced the I_<sAHP> by the slow inward currents (I_<sADP>) underlying the slow afterdepolarization (sADP).DA, however, failed to increase the frequency despite its comparable inhibition of the I_<sAHP> over a range of concentrations. In order to test the neuromodulator agonists to see if they have additive actions on the I_<sAHP>, the effects of co-application of two agonists that increased spike-frequency, 5-HT+NA, CCh+5-HT and NA+CCh, all at the concentration 30 μM were examined.Specific combinations that included CCh showed additive effects on the slow afterpolarization currents, possibly via both inhibition of I_<sAHP> and generation of I_<sADP>. These findings suggest that neuromodulators have differential effects on the link between the I_<sAHP> modulation and spike-frequency adaptation, and that they could exert additive effects on the slow aftercurrents following a strong excitation and, therefore, regulate the repetitive firing properties of the output cells of the rat mPFC.