The lateral habenular nucleus mediates signal transduction from the insular cortex in OSA rats

The insular cortex (Ic) and habenular nuclei (Hb) of the limbic system are associated with human and animal dyspnea by regulating 5-hydroxytryptamine (5-HT) release in the raphe nuclei (RN). However, the Hb are composed of the medial habenular nucleus (MHb) and the lateral habenular nucleus (LHb). Therefore, it is still unclear whether the Ic signal is conducted through the MHb or LHb. This study aimed to investigate the role of the Hb and Ic in obstructive sleep apnea syndrome (OSA) and the functional relationship between these two structures.

We monitored multiple indicators, including the respiration movement curve, neuronal activity in the MHb and LHb, and arterial blood gas, when stimulating the anterior Ic of Wistar rats. We compared the results with the control group (stimulating the surrounding cortex).

Electrical stimulation of the Ic in the rat brain caused respiratory disturbances, apnea, reduced blood pH, and aggravated base deficit (more negative base excess value) compared to control animals (p < 0.05). It also reduced the spontaneous firing of the MHb neurons but increased that of the LHb neurons. Electrical stimulation of the Ic induces apnea in rats in a similar manner to human OSA. The Ic and the Hb are functionally linked. Stimulation of the Ic inhibits the MHb, but activates the LHb. It induces OSA-like symptoms by enhancing LHb-mediated inhibition of the RN.

This study illustrates the mechanism by which an animal model of OSA is created by stimulating the Ic and promotes understanding of OSA pathogenesis.