title: Nogo-66 Restricts Synaptic Strengthening via Lingo1 and the ROCK2-Cofilin Pathway to Control Actin Dynamics.
abstract: Nogo-A restricts long-term potentiation (LTP) at the Schaffer collateral-CA1 pathway in the adult hippocampus via 2 extracellular domains: Nogo-A-Δ20 and Nogo-66. Nogo-66 signals via Nogo Receptor 1 (NgR1) to regulate synaptic function. Whether the NgR1 coreceptors Lingo1 and p75NTR are involved in the signaling in this context is still not known. Moreover, the intracellular cascade mediating the activity of Nogo-66 in restricting LTP is unexplored. We combine electrophysiology and biochemistry in acute hippocampal slices and demonstrate that a loss of function for Lingo1 results in a significant increase in LTP levels at the Schaffer collateral-CA1 pathway, and that Lingo1 is the NgR1 coreceptor mediating the role of Nogo-66 in restricting LTP. Our data show that p75NTR is not involved in mediating the Nogo-66 effect on LTP. Moreover, loss of function for p75NTR and NgR1 equally attenuate LTD, suggesting that p75NTR might mediate the NgR1-dependent regulation of LTD, independently of Nogo-66. Finally, our results indicate that Nogo-66 signaling limits LTP via the ROCK2-Cofilin pathway to control the dynamics of the actin cytoskeleton. The present results elucidate the signaling pathway activated by Nogo-66 to control LTP and contribute to the understanding of how Nogo-A stabilizes the neural circuits to limit activity-dependent plasticity events in the mature hippocampus.
authors.affiliation: Zoological Institute, Division of Cellular Neurobiology, TU Braunschweig, 38106, Braunschweig, Germany.
authors.forename: Cristina
authors.initials: C
authors.lastname: Iobbi
authors.affiliation: Zoological Institute, Division of Cellular Neurobiology, TU Braunschweig, 38106, Braunschweig, Germany.|Helmholtz Centre for Infection Research, AG NIND, 38124, Braunschweig, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Korte
authors.affiliation: Zoological Institute, Division of Cellular Neurobiology, TU Braunschweig, 38106, Braunschweig, Germany.
authors.forename: Marta
authors.initials: M
authors.lastname: Zagrebelsky
mesh_terms: D051339:Actin Depolymerizing Factors / Q000235:genetics / Q000378:metabolism*; D000199:Actins / Q000378:metabolism*; D000577:Amides / Q000494:pharmacology; D000818:Animals; D001703:Biophysics; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006624:Hippocampus; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D000070798:Nogo Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D011725:Pyridines / Q000494:pharmacology; D020800:Receptor, Nerve Growth Factor / Q000172:deficiency / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D051339:Actin Depolymerizing Factors; D000199:Actins; D000577:Amides; D004791:Enzyme Inhibitors; D000070798:Nogo Proteins; D010455:Peptides; D011725:Pyridines; D020800:Receptor, Nerve Growth Factor; C108830:Y 27632; C515855:Rock2 protein, mouse; D054460:rho-Associated Kinases
keywords: LTP; Nogo-A; actin; cofilin; hippocampus; plasticity