Although classical and operant conditioning are operationally distinct, it is unclear to what extent they are mechanistically similar or different. Feeding behavior in the mollusk Aplysia californica is a useful model system to analyze these two ubiquitous forms of associative learning and compare the underlying neuronal mechanisms. Here, we review studies that have analyzed and compared the mechanisms underlying classical and operant conditioning at the circuit, single-cell, and molecular levels. These analyses reveal similarities and intriguing differences. Both forms of learning lead to increased biting in vivo and fictive ingestion in vitro and also share a common reinforcement pathway, which uses dopamine as the reinforcement transmitter. Although the identified neuron B51 is a locus of plasticity common to both classical and operant conditioning, its activity is altered in opposite ways by these two forms of learning. B51 excitability is increased by operant conditioning, whereas it is decreased by classical conditioning.
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