PV-IRES-Cre mouse line targets excitatory granule neurons in the cerebellum

Parvalbumin-expressing inhibitory neurons (PV-INs) are critical for the balance and fine-tuning of complex neuronal circuits. Studies of PV-IN biology require tools for their specific labeling, targeting and manipulation. Among these, the Cre/LoxP system is the most popular in mice, with the two commonly used PV-Cre lines cited over 5600 times. Here we report in the mouse cerebellar cortex that PV-Cre activity is not restricted to inhibitory neurons. Imaging of Cre-activated reporters demonstrated recombination in excitatory granule cells. We present evidence that PV-Cre recombination is: (1) spatially regulated and lobule specific; (2) detected in granule cells in the external and internal granule cell layers arising from strong, but transient Pvalb expression in progenitors between E13-E15; and (3) delayed in a subset of inhibitory interneurons, asynchronous with PV protein expression. Together, our findings establish the spatio-temporal patterns PV-Cre activation in the mouse cerebellum, raising considerations for conditional targeting of Pvalb-expressing inhibitory populations.