The learning abilities and the relatively simple central nervous system of gastropod mollusks have provided us with insight into the richness of cellular correlates of learning behavior, such as a classical conditioning. In the pond snail Lymnaea stagnalis, conditioned taste aversion (CTA) learning can be acquired and stored as long term memory, and the neurons involved in this behavioral plasticity are identified. Using the identified neurons, we here discuss the neuronal and molecular substrates for memory formation of associative learning at a single cell level.
  Cyclic AMP-responsive element binding protein (CREB) is universally accepted to be necessary for specific transcription in long-term memory formation. In the key neuron of CTA learning in Lymnaea, we first showed the inhibition of CREB function blocked the expression of cAMP-induced synaptic plasticity. We then characterized the CREB genes in Lymnaea central nervous system (CNS), including transcriptional activator CREB1 and repressor CREB2. Interestingly, CREB1 transcripts included the repressor isoforms as well as the activator ones. The interaction between the activator and the repressor CREB1 proteins was demonstrated in co-transfected HeLa cells using dual color fluorescence cross-correlation spectroscopy (FCCS). Quantitative RT-PCR experiments showed the transcriptional repressor CREB1 isoforms and CREB2 were constitutively expressed at large amount, as well as activator CREB1. The copy number of CREB2 mRNA was changed according to training paradigm and their behavior, at a single cell level. These results suggest that the transcriptional ability of CREB is regulated by altering the ratio between the transcriptional activator and repressor proteins, and thereby changing the synaptic plasticity. In this review, we also introduce the recent reports for learning behavior and its molecular mechanism for the gill withdrawal reflex in Aplysia, and the EST (expressed sequence tag) projects in gastropods.

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Recording neuronal activity in animal models give us important clues to understand the pathophysiology of movement disorders. Dystonia is one of the basal ganglia disorders characterized by sustained or repetitive involuntary muscle contractions and abnormal postures. A major group of early-onset generalized dystonia arises from a mutation in the DYT1 gene, which encodes torsinA protein. To understand the pathophysiology of dystonia, we recorded neuronal activity of basal ganglia in a mouse model overexpressing mutant torsinA, in awake state. Reduced spontaneous activity with bursts and pauses were observed in both the internal (GPi) and external segments of the globus. Motor cortical stimulation evoked abnormal responses with long-lasting inhibition, which were never observed in the normal mice. In addition, somatotopic arrangements in both pallidal segments were disorganized. Long-lasting inhibition induced by cortical inputs in GPi may disinhibit thalamic and cortical activity, resulting in the involuntary movements observed in the mouse model.

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