Regulation of emotional memory by hydrogen sulfide: role of GluN2B‐containing NMDA receptor in the amygdala

As an endogenous gaseous molecule, hydrogen sulfide (H 2 S) has attracted extensive attention because of its multiple biological effects. However, the effect of H 2 S on amygdala‐mediated emotional memory has not been elucidated. Here, by employing Pavlovian fear conditioning, an animal model widely used to explore the neural substrates of emotion, we determined whether H 2 S could regulate emotional memory. It was shown that the H 2 S levels in the amygdala of rats were significantly elevated after cued fear conditioning. Both intraamygdala and systemic administrations of H 2 S markedly enhanced amygdala‐dependent cued fear memory in rats. Moreover, it was found that H 2 S selectively increased the surface expression and currents of NMDA‐type glutamate receptor subunit 2B (GluN2B)‐containing NMDA receptors ( NMDAR s) in lateral amygdala of rats, whereas blockade of GluN2B‐containing NMDAR s in lateral amygdala eliminated the effects of H 2 S to enhance amygdalar long‐term potentiation and cued fear memory. These results demonstrate that H 2 S can regulate amygdala‐dependent emotional memory by promoting the function of GluN2B‐containing NMDAR s in amygdala, suggesting that H 2 S‐associated signaling may hold potential as a new target for the treatment of emotional disorders.In our study, the effect of hydrogen sulfide (H 2 S) on amygdala‐mediated emotional memory was investigated. It was found that H 2 S could enhance amygdala‐dependent emotional memory and long‐term potentiation (LTP) in rats by selectively increasing the function of GluN2B‐containing NMDA receptors in the amygdala. These results suggest that H 2 S‐associated signaling may be a new target for the treatment of emotional disorders.