Cystathionine-β-synthase-derived hydrogen sulfide is required for amygdalar long-term potentiation and cued fear memory in rats.

Hydrogen sulfide (HS) is an endogenous gaseous molecule that functions as a neuromodulator in the brain. We previously reported that HS regulated amygdalar synaptic plasticity and cued fear memory in rats. However, whether endogenous HS is required for amygdalar long-term potentiation (LTP) induction and cued fear memory formation remains unclear. Here, we show that cystathionine-β-synthase (CBS), the predominant HS-producing enzyme in the brain, was highly expressed in the amygdala of rats. Suppressing CBS activity by inhibitor prevented activity-triggered generation of HS in the lateral amygdala (LA) region. Incubating brain slices with CBS inhibitor significantly prevented the induction of NMDA receptors (NMDARs)-dependent LTP in the thalamo-LA pathway, and intra-LA infusion of CBS inhibitor impaired cued fear memory in rats. Notably, treatment with HS donor, but not CBS activator, significantly reversed the impairments of LTP and fear memory caused by CBS inhibition. Mechanismly, inhibition of CBS activity led to a reduction in NMDAR-mediated synaptic response in the thalamo-LA pathway, and treatment with HS donor restored the function of NMDARs. Collectively, these results indicate that CBS-derived HS is required for amygdalar synaptic plasticity and cued fear memory in rats, and the effects of endogenous HS might involve the regulation of NMDAR function.