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

Abstract

Hydrogen sulfide (H₂S) is an endogenous gaseous molecule that functions as a neuromodulator in the brain. We previously reported that H₂S regulated amygdalar synaptic plasticity and cued fear memory in rats. However, whether endogenous H₂S 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 H₂S-producing enzyme in the brain, was highly expressed in the amygdala of rats. Suppressing CBS activity by inhibitor prevented activity-triggered generation of H₂S 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 H₂S 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 H₂S donor restored the function of NMDARs. Collectively, these results indicate that CBS-derived H₂S is required for amygdalar synaptic plasticity and cued fear memory in rats, and the effects of endogenous H₂S might involve the regulation of NMDAR function.

Keywords: Amygdala; Cystathionine-β-synthase; Fear memory; Hydrogen sulfide; Long-term potentiation; NMDA receptors.