CELLULAR, MOLECULAR AND DEVELOPMENTAL NEUROSCIENCEThe developmental regulation of glutamate receptor-mediated calcium signaling in primary cultured rat hippocampal neuronsGuo, Zhi Y.a; Li, Cheng Z.a; Li, Xiao J.a; Wang, Ya L.a; Mattson, Mark P.b; Lu, Cheng B.aAuthor Information aDepartment of Physiology and Neurobiology, Xinxiang Medical University, Xinxiang, People’s Republic of China bLaboratory of Neurosciences, National Institute on Aging Intramural Research Program, Baltimore, Maryland, USA Correspondence to Cheng B. Lu, MD, PhD, Department of Physiology and Neurobiology, The Key Lab for the Brain Research of Henan Province, Xinxiang Medical University, 453003 Xinxiang, People’s Republic of China Tel: +86 0373 3029104; fax: +86 0373 3029203; e-mails: [email protected], [email protected] Received March 8, 2013 Accepted April 5, 2013 NeuroReport: June 19, 2013 - Volume 24 - Issue 9 - p 492-497 doi: 10.1097/WNR.0b013e32836206b5 Buy Metrics Abstract We have studied the developmental changes of glutamate-induced calcium (Ca2+) response in primary cultured hippocampal neurons at three different stages of cultures, 3, 7–8, and 14–16 days in vitro (DIV), using fura-2 single-cell digital micro-fluorimetry. We found that glutamate-induced Ca2+ signaling was altered during development, and that two different ionotropic glutamate receptors, α-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptors (AMPARs) and N-methyl-D-aspartate receptors (NMDARs), were differently involved in the modulation of calcium response at different stages of neuronal culture. In the stages of culture at 3 and 8 DIV, glutamate-induced Ca2+ influx was mostly because of AMPAR activation and subsequent opening of voltage-dependent calcium channels, as Ca2+ response can be largely reduced by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and by nifedipine. In the advanced culture (14–17 DIV), glutamate-induced Ca2+ response was less sensitive to 6-cyano-7-nitroquinoxaline-2,3-dione and nifedipine. Furthermore, AMPA-induced Ca2+ response increased in a time-dependent manner during the cultures of 3–8 DIV and then reduced in the advanced culture of 14–17 DIV. NMDA-induced Ca2+ influx increased in a time-dependent manner, with a marked increase in the advanced culture (14–17 DIV). These results suggest that glutamate-induced Ca2+ signaling switched from AMPA-voltage-dependent calcium channel to NMDA-calcium signaling during development. © 2013 Lippincott Williams & Wilkins, Inc.