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J Neurosci. 2012 Oct 31;32(44):15476-88. doi: 10.1523/JNEUROSCI.2429-12.2012.

Oxytocin promotes long-term potentiation by enhancing epidermal growth factor receptor-mediated local translation of protein kinase Mζ.

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Department of Pharmacology, and Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan.


In addition to triggering the birthing process and milk release, the hypothalamic neuropeptide oxytocin (OXT) plays an important role in the regulation of complex social cognition and behavior. Previous work has shown that OXT can regulate hippocampal synaptic plasticity and improve hippocampus-dependent cognitive functions in the female mice, but the underlying mechanisms remain largely unclear. Here, we demonstrate that OXT promotes the maintenance of long-term potentiation (LTP) induced by one train of tetanic stimulation (TS) in the CA1 region of hippocampal slices from both nulliparous female and male rats through a previously unknown mechanism involving OXT receptor (OXTR)-dependent and epidermal growth factor receptor (EGFR)-mediated local translation of an atypical protein kinase C isoform, protein kinase Mζ (PKMζ), in dendrites. Using pharmacological and biochemical approaches, we show that both the conventional OXTR-associated signaling pathway (G(q/11)-coupled phospholipase C) and the transactivated EGFR downstream signaling pathways (phosphatidylinositol 3 kinase and extracellular signal-regulated kinase 1/2) are involved in the regulation of OXT. In addition, OXT stimulates local dendritic PKMζ mRNA translation via activation of a mammalian target of rapamycin-regulated mechanism. Furthermore, blockade of OXTR results in a modest decrease in the ability to maintain late-phase LTP induced by three trains of TS. These results reveal a novel OXTR-to-EGFR communication to regulate the new synthesis of PKMζ, which functions to promote the maintenance of LTP at hippocampal CA1 synapses.

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