title: Ketamine Protects Gamma Oscillations by Inhibiting Hippocampal LTD.
abstract: NMDA receptors have been widely reported to be involved in the regulation of synaptic plasticity through effects on long-term potentiation (LTP) and long-term depression (LTD). LTP and LTD have been implicated in learning and memory processes. Besides synaptic plasticity, it is known that the phenomenon of gamma oscillations is critical in cognitive functions. Synaptic plasticity has been widely studied, however it is still not clear, to what degree synaptic plasticity regulates the oscillations of neuronal networks. Two NMDA receptor antagonists, ketamine and memantine, have been shown to regulate LTP and LTD, to promote cognitive functions, and have even been reported to bring therapeutic effects in major depression and Alzheimer's disease respectively. These compounds allow us to investigate the putative interrelationship between network oscillations and synaptic plasticity and to learn more about the mechanisms of their therapeutic effects. In the present study, we have identified that ketamine and memantine could inhibit LTD, without impairing LTP in the CA1 region of mouse hippocampus, which may underlie the mechanism of these drugs' therapeutic effects. Our results suggest that NMDA-induced LTD caused a marked loss in the gamma power, and pretreatment with 10 μM ketamine prevented the oscillatory loss via its inhibitory effect on LTD. Our study provides a new understanding of the role of NMDA receptors on hippocampal plasticity and oscillations.
authors.affiliation: Neurodegeneration Discovery Performance Unit, GSK, R&D Shanghai, Building 1, 917 Halei Road, Zhangjiang Hi-tech Park, Pudong, Shanghai, China.|Stem Cell Translational Research Center, Tongji Hospital, School of Medicine, Collaborative Innovation Center for Brain Science, Tongji University, Shanghai, China.
authors.forename: Lanting
authors.initials: L
authors.lastname: Huang
authors.affiliation: Neurodegeneration Discovery Performance Unit, GSK, R&D Shanghai, Building 1, 917 Halei Road, Zhangjiang Hi-tech Park, Pudong, Shanghai, China.
authors.forename: Xiu-Juan
authors.initials: XJ
authors.lastname: Yang
authors.affiliation: Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Stem Cell Translational Research Center, Tongji Hospital, School of Medicine, Collaborative Innovation Center for Brain Science, Tongji University, Shanghai, China.
authors.forename: Eve Y
authors.initials: EY
authors.lastname: Sun
authors.affiliation: Neurodegeneration Discovery Performance Unit, GSK, R&D Shanghai, Building 1, 917 Halei Road, Zhangjiang Hi-tech Park, Pudong, Shanghai, China.
authors.forename: Mu
authors.identifier: http://orcid.org/0000-0001-8261-3705
authors.initials: M
authors.lastname: Sun
mesh_terms: D000818:Animals; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D007649:Ketamine / Q000494:pharmacology*; D036881:Long-Term Synaptic Depression / Q000187:drug effects*; D008297:Male; D008559:Memantine / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D055366:Synaptic Potentials / Q000187:drug effects
chemical_list: D007649:Ketamine; D008559:Memantine