The distribution of postsynaptic glutamate receptors has been shown to be regula ted by proimmunocytokine tumor necrosis factor (TNF-)

) sign ling. The role of TNF- receptor subtypes in medi ting glut m te receptor expression, tr fficking, nd f unction still rem ins uncle r. Here, we report th t TNF receptor subtypes (TNFR1 nd TNFR2) differenti lly modul te - mino-3-hydroxy-5-methyl-4-isox zole propion ic cid receptor (AMPAR) clustering nd function in cultured cortic l neurons. W e find th t genetic deletion of TNFR1 decre ses surf ce expression nd syn ptic loc liz tion of the AMPAR GluA1 subunit, reduces the frequency of mini ture exci t tory postsyn ptic current (mEPSC), nd reduces AMPA-induced m xim l whole-cell current. In ddition, these results re not observed in TNFR2-deleted neurons. The decre sed AMPAR expression nd function in TNFR1-deleted cells re not signi fic ntly restored by short (2 h) or long (24 h) term exposure to TNF-. In TNFR2-d eleted cells, TNF- promotes AMPAR tr fficking to the syn pse nd incre ses mEPSC frequency. In the present study, we find no signific nt ch nge in the GluN1 subu nit of NMDAR clusters, loc tion, nd mEPSC. This includes pplying or withholdin g the TNF- tre tment in both TNFR1- nd TNFR2-deleted neurons. Our results indic te th t TNF receptor subtype 1 but not 2 pl ys critic l role in modul ting AMP AR clustering, suggesting th t t rgeting TNFR1 gene might be novel ppro ch to preventing neuron l AMPAR-medi ted excitotoxicity.-He, P., Liu, Q., Wu, J., She n, Y. Genetic deletion of TNF receptor suppresses excit tory syn ptic tr nsmissi on vi reducing AMPA receptor syn ptic loc liz tion in cortic l neurons. for more inform tion on the Rosk mp Institute nd Alzheimers ple se visit: http://www.mull n lzheimer.com http://www.mull n lzheimer.info www.rfdn.org