TY - JOUR T1 - Cooperative Activation of D<sub>1</sub> and D<sub>2</sub> Dopamine Receptors Enhances a Hyperpolarization-Activated Inward Current in Layer I Interneurons JF - The Journal of Neuroscience JO - J. Neurosci. SP - 6322 LP - 6328 DO - 10.1523/JNEUROSCI.1405-05.2005 VL - 25 IS - 27 AU - JianPing Wu AU - John J. Hablitz Y1 - 2005/07/06 UR - http://www.jneurosci.org/content/25/27/6322.abstract N2 - Layer I of the neocortex comprises axonal processes from widespread regions of the brain and a unique population of GABAergic interneurons. Dopamine is known to directly depolarize layer I interneurons, but the underlying mechanism is unclear. Using whole-cell recording techniques in neocortical brain slices, we have examined how dopamine increases excitability of layer I interneurons in postnatal day 7-11 rats. Dopamine (30 μm) caused a 10 mV depolarization of layer I neurons. Paradoxically, neither the D1-like receptor agonist 6-chloro-2,3,4,5-tetrahydro-1-phenyl-1H-3-benzazepine hydrobromide (SKF81297) (1-10 μm) nor the D2-like agonist quinpirole (10 μm) produced a significant depolarization. Depolarization was observed when SKF81297 and quinpirole were coapplied. When G-protein βγ subunits were included in the recording pipette, D1 but not D2 agonists depolarized layer I neurons. Bath application of 4-ethylphenylamino-1,2-dimethyl-6-methylaminopyrimidinium chloride, a specific blocker of inwardly rectifying hyperpolarization-activated current (Ih) channels, hyperpolarized the neurons and occluded the action of dopamine. Voltage-clamp analysis demonstrated that dopamine increased the amplitude and shifted the voltage dependence of activation of Ih. These results indicate that Ih contributes to the resting potential of layer I interneurons and is subject to modulation by dopamine. ER -