Transcription factors (TFs) play a pivotal role in the plastic changes of the brain. Measuring TF activity in vivo and uncovering changes under various physiological and pathophysiological conditions provide valuable insights into brain mechanisms. This protocol outlines a detailed procedure for measuring TF activity in the brain by using lentiviral vector (LV)-based TF reporters. The protocol covers the preparation of LV, injection of the vector into the mouse brain, mRNA processing from the tissue, and quantitative PCR-based calculation of TF activity.