Serotonin (5-hydroxytryptamine, 5HT) is the neurotransmitter that mediates dishabituation in Aplysia. Serotonin mediates this behavioral change through the reversal of synaptic depression in sensory neurons (SNs). However, the 5HT receptors present in SNs and in particular, the receptor important for activation of protein kinase C (PKC) have not been fully identified. Using a recent genome assembly of Aplysia, we identified new receptors from the 5HT 2 , 5HT 4 , and 5HT 7 families. Using RT-PCR from isolated SNs, we found that three 5HT receptors, 5HT 1Apl(a) , 5HT 2Apl , and 5HT 7Apl were expressed in SNs. These receptors were cloned and expressed in a heterologous system. In this system, 5HT 2Apl could significantly translocate PKC Apl II in response to 5HT and this was blocked by pirenperone, a 5HT 2 receptor antagonist. Surprisingly, pirenperone did not block 5HT-mediated translocation of PKC Apl II in SNs, nor 5HT-mediated reversal of depression. Expression of 5HT 1Apl(a) in SNs or genistein, an inhibitor of tyrosine kinases inhibited both PKC translocation and reversal of depression. These results suggest a non-canonical mechanism for the translocation of PKC Apl II in SNs.

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