Role of the cyclic guanosine monophosphate pathway on the behavioral and neuronal plasticity induced by aversive stimuli in the sea hare, Aplysia californica

The ability to make decisions when in a state of trepidation is a universal and crucial component of organism survival. Studying behavior and the underlying cellular mechanisms in parallel is needed, but rarely achieved due to the complexity of the nervous system and the difficulty to link behaviors to cellular substrates. Therefore, the goal of this project was to examine both behavioral and neuronal plasticity using the marine mollusk Aplysia, an organism with quantifiable behaviors controlled by well-characterized neural circuitry. In Aplysia, exposure to aversive stimuli causes a learned suppression of a non-defensive behavior (i.e., feeding) and a learned enhancement of a defensive response (a form of learning called sensitization) of the tail-siphon withdrawal reflex (TSWR). Correspondingly, at the cellular level, exposure to the aversive stimuli causes a decrease in excitability of B51, a decision-making neuron controlling feeding, and an increase in excitability of tail sensory neurons (TSNs) responsible for the TSWR. The Cyclic Guanosine Monophosphate (cGMP) pathway dependent on protein kinase G (PKG) is involved in learning-dependent behavioral and neuronal plasticity associated with non-defensive and defensive responses in Aplysia. The aims of this thesis were: 1) to investigate the role of PKG in feeding suppression and sensitization in vivo and 2) to examine the role of PKG in neural correlates underlying feeding suppression via B51 excitability and sensitization via TSN excitability in vitro. Selective inhibitor KT5823 was used to block PKG activity. Findings from in vivo experiments indicate that KT5823 did not prevent either feeding suppression or sensitization induced by aversive stimuli. Concurrently, in vitro results determined that KT5823 did not prevent the learning-induced decreased excitability of B51 and also did not prevent the learning-induced increase in TSN excitability. These results suggest that PKG may not contribute to the behavioral or neuronal plasticity induced by aversive stimuli in Aplysia. Future directions include investigation of other potential downstream targets such as cyclic-nucleotide gated ion channels and phosphodiesterases.