TGF-β1-induced long-term changes in neuronal excitability in Aplysia sensory neurons depend on MAPK

Transforming growth factor beta-1 (TGF-beta 1) plays important roles in the early development of the nervous system and has been implicated in neuronal plasticity in adult organisms. It induces long-term increases in sensory neuron excitability in Aplysia as well as a long-term enhancement of synaptic efficacy at sensorimotor synapses. In addition, TGF-beta 1 acutely regulates synapsin phosphorylation and reduces synaptic depression induced by low-frequency stimuli. Because of the critical role of MAPK in other forms of long-term plasticity in Aplysia, we examined the role of MAPK in TGF-beta 1-induced long-term changes in neuronal excitability. Prolonged ( 6 h) exposure to TGF-beta 1 induced long-term increases in excitability. We confirmed this finding and now report that exposure to TGF-beta 1 was sufficient to activate MAPK and increase nuclear levels of active MAPK. Moreover, TGF-beta 1 enhanced phosphorylation of the Aplysia transcriptional activator cAMP response element binding protein ( CREB) 1, a homologue to vertebrate CREB. Both the TGF-beta 1-induced long-term changes in neuronal excitability and the phosphorylation of CREB1 were blocked in the presence of an inhibitor of the MAPK cascade, confirming a role for MAPK in long-term modulation of sensory neuron function.