The role of neurochemical modulation in learning.

Tsukahara creatively exploited the advantages of a "simple system" approach in a vertebrate context to gain cellular insights into the learning process. The molluscs Aplysia and Hermissenda have provided useful invertebrate examples of this approach. For classical conditioning of Hermissenda a temporal sequence of cellular transformations has been found to correspond to and to substantially account for a learning-specific behavioral transformation. For at least days after the conditioning a biophysical record persists: two voltage-dependent K+ currents, IA and ICa2+-K+, remain reduced in amplitude and at least IA shows an increased rate of inactivation. More recently, a similar biophysical record of associative memory has been identified in the mammalian brain (Disterhoft et al., 1986). Other experiments suggest that a synergistic interaction of C-kinase activation with Ca2+/CaM-kinase activation enhances and prolongs Ca2+-mediated K+ current reduction. The effects of alpha-receptor agonists to enhance depolarization of type B cells (a site of visual-vestibular convergence) and in turn acquisition of classical conditioning are in contrast to the effects of serotonin which can hyperpolarize and thereby reduce depolarization during the acquisition process. For both LTP and LTD, application of a neurotransmitter itself is not sufficient to produce long-lasting neural modification. In this respect, both the LTP and LTD models are more similar to the biochemical sequence implicated in Hermissenda conditioning than to the mechanism initiated by serotonin-like substances proposed for Aplysia sensitization.