The contributions and mechanisms of changes in excitability during simple forms of learning in Aplysia

Learning and memory have long been thought to involve changes in synaptic connections between neurons. However, in many cases learning-related plasticity also involves changes in the excitability of neurons. These findings have raised questions about the relative importance of these two types of mechanisms to behavioral learning, and also about the extent to which they involve shared or unique molecular mechanisms. We have taken a reductionist approach to these questions by addressing them in a simple model organism, Aplysia californica. Studies of a semi-intact Aplysia siphon withdrawal preparation suggest that classical conditioning involves an increase in the evoked firing of sensory neurons (SNs) as well as facilitation of the monosynaptic PSP to motor neurons (MNs). Furthermore, these two mechanisms may act cooperatively at the cellular level: increased SN firing produces more PSPs, each of which is facilitated, leading to a multiplicative increase in depolarization of the MN and siphon withdrawal. The changes in SN firing and the monosynaptic PSP also share several mechanisms at the molecular level, suggesting that they may both be due in part to a decrease in K⁺ current that causes an increase in SN excitability as well as an increase in SN spike width and thus increased transmitter release. However, changes in the monosynaptic PSP also involve additional mechanisms that are not shared and may affect different aspects of synaptic transmission as well. Studies of operant conditioning of feeding suggest that it involves similar mechanisms as classical conditioning of siphon withdrawal. In particular, for both types of associative learning adenylyl cyclase appears to serve as a molecular coincidence detector that leads to increased activation of PKA and changes in excitability of key neurons in the neural circuit. Furthermore, in both cases those changes in excitability make an important contribution to the behavioral learning.