@article{5afdcd63ba5f4edc9abf7660ee5d6d02,
title = "Labile calcium-permeable AMPA receptors constitute new glutamate synapses formed in hypothalamic neuroendocrine cells during salt loading",
abstract = "Magnocellular neuroendocrine cells (MNCs) of the hypothalamus play a critical role in the regulation of fluid and electrolyte homeostasis. They undergo a dramatic structural and functional plasticity under sustained hyperos-motic conditions, including an increase in afferent glutamatergic synaptic innervation. We tested for a postulated increase in glutamate AMPA receptor expression and signaling in magnocellular neurons of the male rat hypothalamic supraoptic nucleus (SON) induced by chronic salt loading. While without effect on GluA1-4 subunit mRNA, salt loading with 2% saline for 5–7 d resulted in a selective increase in AMPA receptor GluA1 protein expression in the SON, with no change in GluA2-4 protein expression, suggesting an increase in the ratio of GluA1 to GluA2 subunits. Salt loading induced a corresponding increase in EPSCs in both oxytocin (OT) and vasopressin (VP) neurons, with properties characteristic of calcium-permeable AMPA receptor-mediated currents. Unexpectedly, the emergent AMPA synaptic currents were silenced by blocking protein synthesis and mammalian target of rapamycin (mTOR) activity in the slices, suggesting that the new glutamate synapses induced by salt loading require continuous dendritic protein synthesis for maintenance. These findings indicate that chronic salt loading leads to the induction of highly labile glutamate synapses in OT and VP neurons that are comprised of calcium-permeable homomeric GluA1 AMPA receptors. The glutamate-induced calcium influx via calcium-permeable AMPA receptors would be expected to play a key role in the induction and/or maintenance of activity-dependent synaptic plasticity that occurs in the magnocellular neurons during chronic osmotic stimulation.",
keywords = "Excitability, Osmoregulation, Oxytocin, Paraventricular, Supraoptic, Vasopressin",
author = "Shi Di and Zhiying Jiang and Sen Wang and Harrison, {Laura M.} and Eduardo Castro-Echeverry and Stuart, {Thomas C.} and Wolf, {Marina E.} and Tasker, {Jeffrey G.}",
note = "Funding Information: Received March 22, 2019; accepted June 21, 2019; First published July 12, 2019. The authors declare no competing financial interests. Author contributions: S.D., Z.J., S.W., L.M.H., E.C.-E., and T.C.S. performed research; S.D., Z.J., S.W., L.M.H., E.C.-E., T.C.S., and J.G.T. analyzed data; S.D., M.E.W., and J.G.T. wrote the paper; T.C.S. and J.G.T. designed research; M.E.W. contributed unpublished reagents/analytic tools. This work was supported by National Institutes of Health Grants NS042081 (to J.G.T.) and DA009621 (to M.E.W.) and the Catherine and Hunter Pierson Chair in Neuroscience (J.G.T.). Z. Jiang{\textquoteright}s present address: Institute of Molecular Medicine, University of Texas Health Sciences Center, Houston, TX 77054. S. Wang{\textquoteright}s present address: Compeer Financial, Normal, IL 61761. E. Castro-Echeverry{\textquoteright}s present address: Baylor Scott and White Medical Center, Temple, TX 76508. T. C. Stuart{\textquoteright}s present address: PatentDive, Inc., New Orleans, LA 70119. M. E. Wolf{\textquoteright}s present address: Department of Behavioral Neuroscience, Oregon Health and Science University, Portland, OR 97239. Acknowledgements: We thank Dr. Katalin Smith and Mr. Mike Milovanovic for their expert technical assistance. We also thank the Department of Neuroscience of the Rosalind Franklin University of Medicine and Science for graciously hosting S.W. during the evacuation following hurricane Katrina. Correspondence should be addressed to Jeffrey G. Tasker at tasker@ tulane.edu. Publisher Copyright: {\textcopyright} 2019 Di et al.",
year = "2019",
month = jul,
day = "1",
doi = "10.1523/ENEURO.0112-19.2019",
language = "English (US)",
volume = "6",
journal = "eNeuro",
issn = "2373-2822",
publisher = "Society for Neuroscience",
number = "4",
}