Abstract
The study of brain aging is complicated by the complexity of mammalian nervous systems and lifespans not conductive to practical study design. The goal of this work was to characterize aging in a simple, functionally defined neural circuit in cohorts of the marine snail Aplysia californica. Each cohort was studied at maturity and again throughout the aging process of this annual animal. First, basic reflex responses such as tail withdrawal and biting and the physiological responses exhibited by their associated neural circuits were compared during aging. Reflexes were weaker in amplitude and slower in duration in aged animals. These impaired responses corresponded to decreased excitability in sensory and motor neurons known to be involved in the reflex circuit. Behavioral and morphological signposts were used to identify three stages of aging in adult Aplysia: Mature, Aged I and Aged II. Next, behavioral and neuronal proxies for learning and memory were investigated during aging. Simple forms of nonassociative learning, including behavioral sensitization and habituation, were impaired in aged animals. These deficiencies corresponded to specific defects in synaptic plasticity in associated neural circuit, such as reduced facilitation between sensory-motor neuronal synapses. Finally, molecular pathways known to be involved in age-related memory loss were investigated. Activators of the second messengers protein kinases A and C restored physiological function in isolated aged sensory neurons, suggesting possible molecular targets with the potential to restore age-related memory impairment in this model system.