D1 Receptor Modulation of Action Potential Firing in a Subpopulation of Layer 5 Pyramidal Neurons in the Prefrontal Cortex

Dopamine modulation in the prefrontal cortex is important for cognitive processing and disrupted in diverse neuropsychiatric diseases. Activation of D1 receptors is thought to enable working memory by enhancing the firing properties of pyramidal neurons. However, these receptors are only sparsely expressed in the prefrontal cortex, and how they impact individual neurons remains unknown. Here we study D1 receptor modulation of layer 5 pyramidal neurons in acute slices of the mouse prefrontal cortex. Using whole-cell recordings and two-photon microscopy, we show that neurons expressing D1 receptors have unique morphological and physiological properties. We then demonstrate that activation of these receptors selectively enhances the firing of these neurons by signaling via the protein kinase A pathway. This finding of robust D1 receptor modulation in only a subpopulation of neurons has important implications for cognitive function and disease.