| Although the mechanistic details of central respiratory chemosensitivity have been studied for a long time, the emergence of central chemosensitivity in embryos remains largely out of reach. In this dissertation research project, I used the altricial zebra finch embryo to study the neurogenesis of breathing-related motor activity spanning the time period when the microcircuits are not yet required for respiration in ovo, through the establishment of continuous air-breathing. The present research encompasses three aims. The first aim was to describe the sensitivity of avian embryo hindbrainmotorrhythms to metabolic and respiratory acidic/alkaline conditions. Using this approach, I discovered a neurodevelopmental switch in pH chemosensitivity on rhythmic frequency bookmarked near embryonic(E) day 11. Previous work in the Pilarski Laboratory shows that ~E11 defines a shift in the role of chloride(Cl-)neurotransmission from excitatory to the more typical adult role of inhibition (Pickett et al., 2018).Accordingly, the second aim was to test whether Cl-played a role in the age-dependent pH response. By lowering pH in combination with antagonists for aCl-ion channel and a Cl-transporter, as well as using Cl-free artificial cerebrospinal fluid (aCSF), results showed that the age-dependent effects of pH on rhythm frequency we irreversible. These findings suggest the Cl-concentration gradient is a critical factor determining thepH response of rhythm frequency. The final aim was to assess whether Cl-contributed to motor rhythm recovery often observed during low
xxpH exposure and determine whether this effect was age-dependent. Results showed that rebound or recovery was blocked by disrupting Cl-transport and removing extracellular Cl-. Understanding the rules of developingcentralcircuits that support homeostatic control of the electrochemical environment could help elucidate how early experiences shape functional outcomes. Newborns are prone to ventilatory control issues that impair breathing and threaten life (Carroll and Agarwal, 2010)and avian embryos in the wild are subject to fluctuating temperature and pH conditions as incubating parents periodically leave the nest (MacDonald et al., 2014). My dissertation research could provide some insights that help inform future investigations in these clinical and ecological contexts. Key Words: development, motor rhythm, pH, neural activity, zebra finch, avian |