TGF- 1-Induced Long-Term Changes in Neuronal Excitability in Aplysia Sensory Neurons Depend on MAPK

Chin, Jeannie, Rong-Yu Liu, Leonard J. Cleary, Arnold Eskin, and John H. Byrne. TGF1-induced long-term changes in neuronal excitability in Aplysia sensory neurons depend on MAPK. J Neurophysiol 95: 3286–3290, 2006; doi:10.1152/jn.00770.2005. Transforming growth factor beta-1 (TGF1) 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, TGF1 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 TGF1-induced long-term changes in neuronal excitability. Prolonged (6 h) exposure to TGF1 induced long-term increases in excitability. We confirmed this finding and now report that exposure to TGF1 was sufficient to activate MAPK and increase nuclear levels of active MAPK. Moreover, TGF1 enhanced phosphorylation of the Aplysia transcriptional activator cAMP response element binding protein (CREB)1, a homologue to vertebrate CREB. Both the TGF1-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.