5-HT5A−/− mice display a selective upregulation of layer V 5-HT1A currents, but not of prefrontal 5-HT1A protein content. A, In the absence of antagonists, the amplitude of the 5-HT outward current is significantly larger in layer V neurons from 5-HT5A−/− mice compared with layer V neurons from 5-HT5A+/+ mice or layer II/III neurons from either 5-HT5A+/+ or 5-HT5A−/− mice (two-way ANOVA, significant interaction; **p = 0.01). B, Voltage clamp traces illustrate that the larger 5-HT outward current observed in 5-HT5A−/− mice (1.) is completely suppressed by the selective 5-HT1A receptor antagonist, WAY-100635 (2.). C, Representative immunolabeling from two 5-HT5A+/+ and two 5-HT5A−/− mice illustrating that prefrontal 5-HT1A protein content is not significantly affected by genotype.