A Developmental Gene (Tolloid/BMP-1) Is Regulated in Aplysia Neurons by Treatments that Induce Long-Term Sensitization

Long-term sensitization training, or procedures that mimic the training, produces long-term facilitation of sensory-motor neu-ron synapses in Aplysia. The long-term effects of these proce-dures require mRNA and protein synthesis (Montarolo et al., 1986; Castellucci et al., 1989). Using the techniques of differ-ential display reverse transcription PCR (DDRT-PCR) and ribo-nuclease protection assays (RPA), we identified a cDNA whose mRNA level was increased significantly in sensory neurons by treatments of isolated pleural-pedal ganglia with serotonin for 1.5 hr or by long-term behavioral training of Aplysia. The effects of serotonin and behavioral training on this mRNA were mim-icked by treatments that elevate cAMP. The Aplysia mRNA increased by serotonin and behavioral training was 41–45% identical to a developmentally regulated gene family which includes Drosophila tolloid and human bone morphogenetic protein-1 (BMP-1). Both tolloid and BMP-1 encode metallopro-teases that might activate TGF-b (transforming growth factor b)-like molecules or process procollagens. Aplysia tolloid/BMP-1-like protein (apTBL-1) might regulate the morphology and efficacy of synaptic connections between sensory and motor neurons, which are associated with long-term sensitization. Key words: Aplysia; tolloid; metalloprotease; sensitization; learning; memory; TGF-b Sensitization of defensive withdrawal reflexes in Aplysia is a sim-ple form of nonassociative learning in that the response to a test stimulus is enhanced by a noxious stimulus (Kandel and Schwartz, 1982; Byrne, 1987). Enhancement of the reflex responses is me-diated, at least in part, by presynaptic facilitation of the connec-tions between sensory neurons and motor neurons (Castellucc