Ionotropic Glutamate Receptors in Aplysia californica and Molecular Changes in the Aging Nervous System

Aplysia californica is a marine snail with well-defined neural circuits and a relatively short life span of one year, making it a useful model for studies of neural function and aging. Many of these neural circuits likely use L-Glutamate as the excitatory neurotransmitter. The goal of this dissertation was to molecularly characterize ionotropic L-Glutamate receptors in A. californica, and describe molecular changes in these receptors during aging in well-defined neural circuits. The evolutionary relationship between ionotropic L-Glutamate receptors of A. californica and vertebrates was first studied to evaluate the relevance of A. californica as a model of ionotropic L-Glutamate receptor function. Genes belonging to the N-methyl-D-aspartate receptor (NMDAR) and α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) subtypes were found to be particularly well-conserved between A. californica and vertebrates. Both subtypes are critical for synaptic plasticity underlying learning and memory. These results suggest conserved function of NMDAR and AMPAR over large evolutionary distances, thus making A. californica a suitable model for studying their function. Expression of all identified ionotropic L-Glutamate receptors in all A. californica nervous system tissues emphasized their important role in the nervous system. Next, age-related changes in L-Glutamate receptor expression were examined in two sensory neuron clusters. Several NMDAR subtype genes exhibited reduced expression in aged animals compared to sexually mature animals. This suggested that reduced NMDAR in sensory neurons may contribute to previously described declines in L-Glutamate current amplitude and reduced reflexes of aged animals. Finally, whole transcriptome expression changes in aged sensory neurons were studied using RNASeq. Transcription of ion channel genes and genes related to nervous system function were significantly affected in aged compared to mature animals. These alterations may negatively affect synaptic transmission and contribute to previously observed deficits in nervous system function of aged A. californica