TGF-β1-Induced Long-Term Changes in Neuronal Excitability in<i>Aplysia</i>Sensory Neurons Depend on MAPK

Abstract

Transforming growth factor beta-1 (TGF-beta1) 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-beta1 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-beta1-induced long-term changes in neuronal excitability. Prolonged (6 h) exposure to TGF-beta1 induced long-term increases in excitability. We confirmed this finding and now report that exposure to TGF-beta1 was sufficient to activate MAPK and increase nuclear levels of active MAPK. Moreover, TGF-beta1 enhanced phosphorylation of the Aplysia transcriptional activator cAMP response element binding protein (CREB)1, a homologue to vertebrate CREB. Both the TGF-beta1-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.