Normal breathing, termed ?eupnea?, is periodically interrupted by larger breaths known as sighs. Sighs occur at regular intervals to re-inflate collapsed alveoli and are essential to prevent spontaneous atelectasis. During sleep, sighs also function to trigger arousal to hypoxia and are common during transitions between different sleep states. Indeed, reduced sighing has been reported in infants who have died from Sudden Infant Death Syndrome (SIDS). Sighing is also linked to higher-order brain functions and emotions such as love, stress, exasperation, and is clinically tied to anxiety disorders. The rhythmogenic circuit in the brain that produces eupnea and sighs is the preBtzinger Complex, located bilaterally in the ventrolateral medulla. However, despite its physiological importance, the specific mechanisms that generate sighs are not well understood. Moreover, whether the same microcircuit can simultaneously generate both a fast eupneic breathing rhythm and a much slower sigh rhythm is a matter of debate. Based on our intriguing preliminary observations, we hypothesize that sighs are generated by the interaction between neurons and astrocytes in the preBtzinger Complex. Here, we propose to test this hypothesis using in vitro and in vivo mouse preparations and a combination of optogenetic, electrophysiological, calcium imaging, pharmacological, and histological approaches.
Sighing is an element of normal breathing that has vital physiological functions and is also involved in higher- order brain functions. Despite the importance of sighing, we do not have a complete understanding of how sighs and normal breathing might be generated by the same microcircuit, the preBtzinger Complex. This proposal uses modern experimental techniques including optogenetics, calcium imaging, and electrophysiology to investigate the role that astrocytes play in this vital physiological process.
