Neurobiological Substrates of Age-Associated Decline in Neuronal Excitability - Lipid Peroxidation-Dependent Modulation of Transient Potassium Current Inactivation?

Abstract

Aging is a universal phenomenon that is observed in almost all organisms within the animal kingdom, yet the biological substrates that underlie the onset and progression of aging are not entirely understood. While aging produces dysfunction in all organ systems, aging of the nervous system can result in severe consequences including age-associated cognitive impairment and deficiencies in learning and memory formation. Long term memory formation often involves repetitive, high frequency periods activity and therefore is affected by electrophysiological properties of the nervous system, including neuronal excitability: excitability of the nervous system declines with age and this may contribute to age-associated cognitive dysfunction. This thesis will investigate age-associated intrinsic neuronal excitability decline in the model system Lymnaea stagnalis, investigate the ionic mechanisms underlying this dysfunction with a focus on voltage gated potassium channels, and seek to implicate oxidative stress and lipid peroxidation with the aging process in these neurons.