Rapamycin-Sensitive Late-LTP is Enhanced in the Hippocampus of IL-6 Transgenic Mice

• Published in: Neuroscience Vol. 367; pp. 200 - 210
• Main Authors: Olde Engberink, Anneke, Hernandez, Ruben, de Graan, Pierre, Gruol, Donna L.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Ltd 26-12-2017
• Subjects: Animals; astrocyte; cytokine; Electric Stimulation; Female; Glial Fibrillary Acidic Protein - metabolism; Hippocampus - cytology; Hippocampus - drug effects; Immunosuppressive Agents - pharmacology; In Vitro Techniques; Interleukin-6 - genetics; Interleukin-6 - metabolism; Long-Term Potentiation - drug effects; Long-Term Potentiation - genetics; Male; Mice; Mice, Transgenic; mTOR; neuroimmune; Neurons - drug effects; Sirolimus - pharmacology; Statistics, Nonparametric; synaptic function; synaptic plasticity; Time Factors; TOR Serine-Threonine Kinases - metabolism; L-LTP; PS; PPF; I/O; CNS; LTP; fEPSP; PPR; HFS; ANOVA; synaptic function; mTOR; astrocyte; cytokine; IL-6R; neuroimmune; STAT3; ACSF; MAPK; IL-6; non-tg; JAK; DNA; synaptic plasticity; ERK
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2017.10.040

•Elevated CNS expression of IL-6 increases the late form of LTP in the hippocampus.•Rapamycin, an antagonist of mTOR, reduced genotypic differences in L-LTP.•Rapamycin reduced synaptic responses during LTP induction in IL-6-tg hippocampus.
The neuroimmune factor IL-6 has been shown to regulate hippocampal long-term potentiation (LTP), an activity-dependent enhancement of synaptic transmission that plays a central role in memory and learning. This IL-6 action was demonstrated with relatively short IL-6 exposure, and may reflect physiological actions of IL-6. IL-6 is also expressed chronically at elevated levels in the central nervous system (CNS) under pathological conditions such as neurological disorders. Little is known about the effects IL-6 on LTP under such conditions, an issue that we are addressing by electrophysiological recordings from CA1 pyramidal neurons of hippocampal slices from transgenic mice that persistently express elevated levels of IL-6 in the CNS (IL-6 tg). The current studies examined the long-lasting phase of LTP (late LTP; L-LTP) and the potential involvement mammalian target of rapamycin (mTOR), a known regulator of L-LTP and a downstream partner of IL-6 signal transduction pathways. Results show that basal synaptic transmission and L-LTP were increased in hippocampal slices from IL-6 tg mice compared to slices from non-transgenic (non-tg) control mice. An inhibitor of mTOR, rapamycin, reduced L-LTP in slices from both genotypes, and eliminated the difference in magnitude of L-LTP between IL-6 and non-tg hippocampus. There were no genotypic effect of rapamycin on basal synaptic transmission, but synaptic responses during the LTP induction protocol were reduced in IL-6 tg slices, an effect that could contribute to the reduction of L-LTP in the IL-6 tg slices. These results indicate that persistently increased levels of IL-6 can lead to alterations in mTOR regulation of L-LTP, possibly affecting learning and memory.