Researchers map nose-to-brain anxiety circuit

Researchers reported in a PNAS paper published online on August 18 that they identified a mouse neural pathway linking nasal airflow to anxiety-like behavior. The study traced signals from airflow-sensitive olfactory sensory neurons in the nose through the olfactory bulb and perirhinal cortex to the posterior basolateral amygdala, a limbic region involved in emotional processing. The authors said the circuit bidirectionally regulated anxiety in a frequency-dependent way, with low-frequency nasal input reducing anxiety-like behavior and high-frequency input producing the opposite effect. ScienceAlert amplified the findings in a Sept. 7 report and an X post shared visuals from the study on Sept. 6. ### Which circuit did the researchers say they found? The PNAS paper, titled “A nose-to-brain circuit underlies anxiety regulation by nasal afferent frequency in mice,” identified a pathway from olfactory sensory neurons in the nasal cavity to mitral cells in the olfactory bulb, then to parvalbumin-positive long-projecting interneurons in the perirhinal cortex, and then to glutamatergic neurons in the posterior basolateral amygdala. The paper listed Xinsong Guo, Mengyan Liu, Qingcheng Xiong and colleagues as authors, with affiliations including Fudan University, Hainan University, Xuzhou Medical University, the Chinese Academy of Sciences’ Shenzhen Institutes of Advanced Technology, and the University of Pennsylvania. (pubmed.ncbi.nlm.nih.gov) ### What did the mouse experiments show about breathing frequency? The authors reported that low-frequency nasal airflow, or optogenetic stimulation of olfactory sensory neurons at low frequency, produced anxiolytic effects in mice and increased high-gamma power in the perirhinal cortex. The same experiments showed that high-frequency stimulation had the opposite effect, which the paper described as anxiogenic and associated with reduced perirhinal high-gamma activity. (pubmed.ncbi.nlm.nih.gov) A chemogenetic silencing experiment then tested whether the middle leg of the pathway mattered. The paper said silencing the olfactory bulb-to-perirhinal cortex pathway eliminated the frequency-dependent regulation of anxiety-like behaviors driven by olfactory sensory neuron stimulation. Selective activation or inhibition of the identified circuit also generated opposing behavioral effects, the authors wrote. ### Where do the amygdala and other anxiety-related brain signals fit in? (pubmed.ncbi.nlm.nih.gov) The posterior basolateral amygdala was the downstream limbic target named in the paper, and the authors said glutamatergic neurons there were part of the circuit that translated nasal input into anxiety-related effects. The study summary available through PubMed and PNAS does not describe a prefrontal cortex node as part of the newly mapped pathway; instead, it centers on the perirhinal cortex and posterior basolateral amygdala. (pubmed.ncbi.nlm.nih.gov) ScienceAlert’s Sept. 7 write-up said the work may help explain why slow nasal breathing can influence emotional states. That report also noted earlier research showing breathing rhythms can synchronize brain oscillations in humans and rodents, but said the precise nose-to-limbic pathway had remained unclear before this mouse study. ### Did the researchers test anything beyond short-term stimulation? (pubmed.ncbi.nlm.nih.gov) The PNAS paper said a two-week regimen of low-frequency nasal airflow or low-frequency optogenetic stimulation ameliorated anxiety-like behaviors in a mouse anxiety model. The same regimen restored perirhinal high-gamma activity, according to the abstract. The authors said those results point to “potential interventional strategies and targets for anxiety disorders,” but the work was done in mice. (sciencealert.com) Neither the paper abstract nor the ScienceAlert report described a human trial or clinical testing. ### What should readers be careful not to overstate? The Aug. 25 PNAS publication studied mice, not people, and the available abstract does not show that breathing exercises in humans act through the same pathway. (pubmed.ncbi.nlm.nih.gov) The paper also identifies a specific circuit involving the perirhinal cortex and posterior basolateral amygdala, rather than establishing a broad prefrontal mechanism. The next place to watch is the full PNAS paper and any follow-up work from the listed research groups at Fudan University and their collaborators, after the article’s Aug. 18 online publication and Aug. 25 issue date. (pubmed.ncbi.nlm.nih.gov)