Individual and additive effects of neuromodulators on the slow components of afterhyperpolarization currents in layer V pyramidal cells of the rat medial prefrontal cortex

The effects of 5-hydyoxytryptamine (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 uitro to quantitatively measure ImAHp 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 IsAHp 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, 5-HT+CCh and CCh+NA, all at the concentration 30 mu M 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. (C) 2008 Elsevier B.V. All rights reserved.