Anoxia-Mediated Electrical Suppression in the Cerebral Cortex of the Western Painted Turtle (Chrysemys picta bellii): Role of the Mitochondrion

The vertebrate brain is one of the most oxygen-demanding organs of the body. In animals that are intolerant to severe hypoxia or anoxia, the brain undergoes irreparable harm within minutes of insufficient oxygen supply. The western painted turtle (Chrysemys picta bellii) has evolved the ability to survive winter months without access to air and does not experience any apparent neurological damage. It is able to achieve this by reducing energetically-demanding cellular processes and the overall electrical activity of the brain to match the reduction in energy availability, effectively balancing energetic supply and demand during anoxic periods. The aim of my research was to understand how the signal of lowered oxygen tension is translated to a reduction in electrical activity with specific focus on the involvement of mitochondria, which are oxygen-consuming organelles that provide the cell with energy in the form of adenosine triphosphate (ATP). Since mitochondria are functionally associated with oxygen availability, I hypothesized that mitochondria serve as oxygen sensors in the anoxia-tolerant brain and initiate signaling cascades that ultimately reduce energy consumption. In the following body of work, I demonstrated that: 1) anoxia leads to depolarization of the mitochondrial membrane potential, which is required for mitochondrial calcium release and glutamatergic channel arrest, and occurs via ATP-sensitive potassium channel opening balanced by proton efflux via the ATP synthase; 2) the mitochondrial depolarization event occurs independently of the enzyme protein kinase C epsilon; and 3) the anoxia-mediated reduction in mitochondrially-derived reactive oxygen species results in increased activity in fast-spiking GABAergic interneurons and elevated extracellular [GABA]. Together, this research contributes to our understanding of neuroprotective mechanisms in anoxia-tolerant organisms and demonstrates the importance of mitochondrial function during the early phases of the anoxic response.

Department dc:contributor.department

Cell and Systems Biology

Year dc:date.issued

2018

Author dc:creator

• Hawrysh, Peter John

Advisor dc:contributor.advisor

• Buck, Leslie T

• Anoxia tolerance
• Channel arrest
• Mitochondria
• Spike arrest
• Stellate neurons
• Western painted turtle

Handle dc:identifier.uri

http://hdl.handle.net/1807/95650

OAI identifier oai:identifier

oai:utoronto.scholaris.ca:1807/95650