Expression of the developmental transcription factor Fezf2 identifies a distinct subpopulation of layer 5...

The transcription factor encoded by Fez family zinc finger 2 (Fezf2) is necessary for normal development of the cerebral cortex. However, Fezf2 continues to be expressed in the mature brain, indicating that it might also be necessary for cortical function throughout life. Here, we show a unique identity of Fezf2-expressing intratelencephalic-projection neurons (IT-PNs) in layer 5 of the mature mouse motor cortex, using a Fezf2-Gfp reporter mouse, in vivo retrograde labeling, whole-cell electrophysiology with morphology reconstruction, and cluster analysis. Fezf2-expressing IT-PNs occupy layer 5A and display an apical dendritic tuft; functionally, they fire broad, adapting action potentials and exhibit an Ih-mediated voltage sag that influences their synaptic properties. In contrast, IT-PNs without Fezf2 expression mainly occupy layer 5B, do not display a tuft, and exhibit regular action potential firing and little sag. Both groups of IT-PNs demonstrated distinct frequency-selective synaptic responses to commissural inputs, indicating unique contributions within the cortical microcircuitry. Our findings establish a new, distinct physiological identity of Fezf2-expressing neurons within mature motor cortex.