The mammalian olfactory system transmits respiration-entrained signals to widespread brain regions including the medial prefrontal cortex (mPFC), which critically regulates numerous cognitive functions. Breathing is dynamically modulated by metabolic needs, orofacial movements, and emotional states. It remains unclear how nasal breathing impacts the mPFC activity across behaviors and the underlying neural pathway(s). I will update our recent progress on this topic by discussing two ongoing projects in my lab. First, we recorded nasal breathing in mice via a pressure sensor across a broad spectrum of spontaneous, attractive odor-, stress-, and fear-induced behaviors, and extract respiratory features using BreathMetrics. Using K-means clustering, we grouped 11 well-defined behavioral states into four clusters with distinct key features. We then implemented the K nearest neighbor classifier and found that breathing patterns could predict these behaviors with an accuracy of 70%. These findings highlight the tight relationship between breathing and behavior. Second, several neural pathways can potentially transmit respiration-related signals, and we studied the potential contribution of the anterior olfactory nucleus/tenia tecta (AON/TT) – mPFC pathway. Using the CRISPR-cas9 gene-editing technique, we generated a new mouse line which allows genetic access to the AON/TT neurons. We characterized the synaptic properties of the AON/TT – mPFC pathway and monitored the neural activity of this pathway across different behaviors. Currently we are testing the effects of chemogenetic inactivation of the AON/TT - mPFC pathway on several behaviors. Our study may have important implications on how respiration-related olfactory inputs contribute to higher cognitive functions by influencing the mPFC activity.