We all sigh, whether due to exasperation, sadness, or relief. But how does our brain make it happen? Sighing is an irregular breathing pattern, which involves the intake of twice as much air . Therefore there must be away to override normal breathing to allow a sigh, to happen. To determine how sighing is controlled, Li et al.  worked to determine the molecular basis of sighing in the brain. They did this using mice as a model, as they sigh twice as much as we do, and therefore are perfect test subjects.
The researchers did a large scale gene expression screen of embryonic mouse brains’ hindbrain, the region of the brain that maintains our unconscious processes, such as breathing, blood circulation, and sleep patterns .This gene screen was done to determine what genes were more highly expressed in the breathing control centerin the medulla portion of the hindbrain compared to other regions. This screen resulted in the discovery that two genes,Neuromedin B (Nmb) and gastrin-releasing peptide (Grp), were heavily expressed in the breathing control centers. These neuropeptides, small proteins which are used as signaling molecules, were injected into the mice, and were able to induce sighing as much as 17 times the normal level. The neuropeptides also induced neuronal activity in isolated tissue samples from the breathing centers of mouse brain. The researchers then knocked out the receptors for these neuropeptides individually in mice and found sighing was reduced by as much as half, while normal breathing was unaltered. If both receptors were removed at the same time, or the neurons that expressed them were destroyed, sighing essentially ceased to occur.
This showed for the first time that neuropeptides, Nmb and Grp, specifically control sighing in the breathing centers of the brain. They appear to do so by causing a second inhalation immediately after a normal breath, causing the deep breath needed for a sigh. This is why loss of these neuropeptide signaling doesn’t affect normal breathing; they don’t alter breathing, they simply add to it to make a sigh. So breathe deep, and let out a sigh of relief that your NMB and GRP work properly.