Hydrogen sulfide is produced in response to neuronal excitation.

Although hydrogen sulfide (H2S) is generally thought of in terms of a poisonous gas, it is endogenously produced in the brain. Physiological concentrations of H2S selectively enhance NMDA receptor-mediated responses and alter the induction of hippocampal long-term potentiation (LTP). Here we use cystathionine beta-synthase (CBS) knock-out mice to clearly show that CBS produces endogenous H2S in the brain and that H2S production is greatly enhanced by the excitatory neurotransmitter l-glutamate, as well as by electrical stimulation. This increased CBS activity is regulated by a pathway involving Ca2+/calmodulin. In addition, LTP is altered in CBS knock-out mice. These observations suggest that H2S is produced by CBS in response to neuronal excitation and that it may regulate some aspects of synaptic activity.