(A) Intrinsic properties. Schematics depicting electrophysiological differences. PT neurons have more hyperpolarization-activated current (Ih), appeared as “sag” of the membrane potential during steps of injected current (top row, right). Action potentials are relatively wide (long duration) in IT neurons (middle row, left, arrows), and narrow (fast, short duration) in PT neurons (middle row, right, arrows). Repetitive firing in IT neurons typically follows an adapting (phasic) pattern (bottom row, left), but in PT neurons often follows a more non-adapting (tonic, sustained) pattern , , . (B) Neuromodulation. Left, Schematic depicting PT-specific increase in the transfer function relating synaptic input to spiking output, observed or inferred for NE, DA, and ACh (dashed lines) -. Right, serotonin (5HT) has an opposite effect on PT neurons, increasing the excitability of IT neurons . These schematics, although greatly oversimplified, are intended to convey a sense of the diverse and either opposing or augmenting actions of neuromodulators on IT and PT neurons. (C) Molecular expression. IT neurons (left) express the transcription factor Satb2, the calcium-binding protein p11, the receptor tyrosine kinase Met, protein kinase A (PKA), types 1B-, 2A-, and 4-5HT receptor, and D1 dopamine receptors. PT neurons (right) express the transcription factors Ctip2 and Fezf2, muscarinic mAChR receptors, 5HT-1A receptors, D2 dopamine receptors, L-type voltage gated calcium channels (L-VGCC), calcium-activated non-selective cation channels (CAN), Kv1 potassium channels, HCN1 and Trip8b channel subunits, type A2 adrenoreceptors, and sonic hedgehog (shh), which interacts with Boc in presynaptic axons from layer 2/3 neurons. Whereas most of the molecules shown here are expressed differentially in IT and PT neurons, others, particularly ion channels such as L-VGCC, may be expressed in both IT and PT neurons, but are likely regulated by distinct signaling mechanisms. This schematic represents a simplified view of current information, with varying degrees of experimental support for the various features, and in some cases not fully capturing the complexity of the available data; for example, Kv1 channel expression is high in PT neurons in motor but not somatosensory cortex . This graphical summary is intended as a starting pointing for further refinement as new information about the types and subcellular distributions of molecules and signaling pathways is gained.