On December 20th, the first issue of PLoS ONE published a report from ION entitled “Requirement of TORC1 for Late-Phase Long-Term Potentiation in the Hippocampus”. This work was done by graduate students Yang Zhou and Hao Wu, under the supervision of Dr. Zhi-qi Xiong.

Late-phase long-term potentiation (L-LTP) of synaptic transmission and long-term memory depend on the transcription of mRNA of CRE-driven genes and synthesis of proteins. However, how neurons convey synaptic signals to nuclear gene transcription is unclear. Recent work from Lab of Neurobiology of Disease headed by Dr. Zhi-Qi Xiong reported a new mechanism underlying CRE-dependent maintenance of long-term potentiation of synaptic transmission. They identified a new CREB coactivator, TORC1 (transducer of regulated CREB), in the central nervous system. They found that TORC1 underwent neuronal activity-dependent shuttling between cytoplasm and nucleus in responded to elevated intracellular Ca2+ and cAMP, a process required for CRE-dependent gene expression and L-LTP. Overexpressing a dominant-negative form of TORC1 or down-regulating TORC1 expression prevented activity-dependent transcription of CREB target genes in cultured hippocampal neurons, while overexpressing a wild-type form of TORC1 facilitated basal and activity-induced transcription of CREB target genes. Furthermore, overexpressing the dominant-negative form of TORC1 suppressed the maintenance of L-LTP without affecting early-phase LTP, while overexpressing the wild-type form of TORC1 facilitated the induction of L-LTP in hippocampal slices. These findings indicate that TORC1 functions as a cAMP- and Ca2+-sensitive coincidence detector and may play a critical role in neuronal development, synaptic plasticity, and memory formation, as well as in pathological states, such as drug addiction and axonal regeneration.