PMID- 23873725 OWN - NLM STAT- MEDLINE DCOM- 20140528 LR - 20130916 IS - 1097-4547 (Electronic) IS - 0360-4012 (Linking) VI - 91 IP - 10 DP - 2013 Oct TI - N-methyl-D-aspartate receptors strongly regulate postsynaptic activity levels during optic nerve regeneration. PG - 1263-79 LID - 10.1002/jnr.23246 [doi] AB - During development, neuronal activity is used as a cue to guide synaptic rearrangements to refine connections. Many studies, especially in the visual system, have shown that the N-methyl-D-aspartate receptor (NMDAr) plays a key role in mediating activity-dependent refinement through long-term potentiation (LTP)-like processes. Adult goldfish can regenerate their optic nerve and utilize neuronal activity to generate precise topography in their projection onto tectum. Although the NMDAr has been implicated in this process, its precise role in regeneration has not been extensively studied. In examining NMDAr function during regeneration, we found salient differences compared with development. By using field excitatory postsynaptic potential (fEPSP) recordings, the contribution of the NMDAr at the primary optic synapse was measured. In contrast to development, no increase in NMDAr function was detectable during synaptic refinement. Unlike development, LTP could not be reliably elicited during regeneration. Unexpectedly, we found that NMDAr exerted a major effect on regulating ongoing tectal (postsynaptic) activity levels during regeneration. Blocking NMDAr strongly suppressed spontaneous activity during regeneration but had no significant effect in the normal projection. This difference could be attributed to an occlusion effect of strong optic drive in the normal projection, which dominated ongoing tectal activity. During regeneration, this optic drive is largely absent. Optic nerve stimulation further indicated that the NMDAr had little effect on the ability of optic fibers to evoke early postsynaptic impulse activity but was important for late network activity. These results indicate that, during regeneration, the NMDAr may play a critical role in the homeostatic regulation of ongoing activity and network excitability. CI - Copyright (c) 2013 Wiley Periodicals, Inc. FAU - Kolls, Brad J AU - Kolls BJ AD - Department of Developmental and Cell Biology, University of California Irvine, Irvine, California; Brain Injury Translational Research Center, Division of Neurology, Duke University Medical Center, Durham, North Carolina. FAU - Meyer, Ronald L AU - Meyer RL LA - eng PT - Journal Article DEP - 20130719 PL - United States TA - J Neurosci Res JT - Journal of neuroscience research JID - 7600111 RN - 0 (Receptors, N-Methyl-D-Aspartate) SB - IM MH - Animals MH - Electrophysiological Phenomena MH - Excitatory Postsynaptic Potentials/*physiology MH - Goldfish/*physiology MH - Nerve Regeneration/*physiology MH - Optic Nerve/*physiology MH - Receptors, N-Methyl-D-Aspartate/*physiology MH - Synapses/physiology OTO - NOTNLM OT - NMDA receptor OT - axonal remodeling OT - long-term potentiation OT - optic nerve OT - regeneration EDAT- 2013/07/23 06:00 MHDA- 2014/05/29 06:00 CRDT- 2013/07/23 06:00 PHST- 2012/11/29 00:00 [received] PHST- 2013/03/12 00:00 [revised] PHST- 2013/03/18 00:00 [accepted] PHST- 2013/07/23 06:00 [entrez] PHST- 2013/07/23 06:00 [pubmed] PHST- 2014/05/29 06:00 [medline] AID - 10.1002/jnr.23246 [doi] PST - ppublish SO - J Neurosci Res. 2013 Oct;91(10):1263-79. doi: 10.1002/jnr.23246. Epub 2013 Jul 19.