Role of Nitric Oxide in Short-Term Potentiation and Long-Term Facilitation

Abstract

It has been well documented that increases in breathing in response to a variety of stimuli may often outlast the actual period of stimulation in various species (see references^{1, 2}). For instance, after a brief hypoxic challenge, ventilation slowly returns to baseline values over a period of minutes, a phenomenon often termed as “short-term potentiation (STP).” On the other hand, after episodes of recurrent hypoxic challenges, depending on species, breathing may remain elevated as long as an hotir. This long lasting enhancement of respiration that follows recurrent episodes of hypoxia is referred to as “long-term facilitation (LTF).” It has been proposed that STP and LTF are critical for maintaining stability of breathing, especially in situations involving acute changes in arterial blood gases², and may involve brainstem neurons^1,2. Recent studies on hippocampal neurons suggest that nitric oxide (NO) is critical for the development of long term potentiation (LTP) associated with learning and memory^3,4. Given that NOS-1, the enzyme that generates NO, is co-localized with 5-HT in raphe neurons^{5, 6}, which has been shown to be important for the generation of LTF², as well as our recent observation that NOS-1 mutant mice exhibit breathing instability during hypoxia⁷, prompted us to examine whether NO generated by NOS-1 plays a role in the development STP and/or LTF.