title: NMDA receptor-dependent LTD is required for consolidation but not acquisition of fear memory.
abstract: NMDA receptor-dependent long-term depression (NMDAR-LTD) is a form of synaptic plasticity leading to long-lasting decreases in synaptic strength. NMDAR-LTD is essential for spatial and working memory, but its role in hippocampus-dependent fear memory has yet to be determined. Induction of NMDAR-LTD requires the activation of caspase-3 by cytochrome c. Cytochrome c normally resides in mitochondria and during NMDAR-LTD is released from mitochondria, a process promoted by Bax (Bcl-2-associated X protein). Bax induces cell death in apoptosis, but it plays a nonapoptotic role in NMDAR-LTD. Here, we investigated the role of NMDAR-LTD in fear memory in CA1-specific Bax knock-out mice. In hippocampal slices from these knock-out mice, while long-term potentiation of synaptic transmission, basal synaptic transmission, and paired-pulse ratio are intact, LTD in both young and fear-conditioned adult mice is obliterated. Interestingly, in CA1-specific Bax knock-out mice, long-term contextual fear memory is impaired, but the acquisition of fear memory and innate fear are normal. Moreover, these conditional Bax knock-out mice exhibit less behavioral despair. These findings indicate that NMDAR-LTD is required for consolidation, but not the acquisition of fear memory. Our study also shows that Bax plays an important role in depressive behavior.
authors: Unit on Synapse Development and Plasticity, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892, and The State Key Laboratory of Medical Neurobiology and Pharmacology Research Center, Shanghai Medical College and Institutes of Brain Science, Fudan University, Shanghai 200032, People's Republic of China.
authors: Xing
authors: X
authors: Liu
authors: Unit on Synapse Development and Plasticity, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892, and.
authors: Qin-Hua
authors: QH
authors: Gu
authors: Unit on Synapse Development and Plasticity, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892, and.
authors: Kaizheng
authors: K
authors: Duan
authors: Unit on Synapse Development and Plasticity, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892, and lizheng2@mail.nih.gov.
authors: Zheng
authors: Z
authors: Li
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000378:metabolism / Q000502:physiology*; D005239:Fear / Q000502:physiology*; D017774:Long-Term Potentiation / Q000502:physiology; D036881:Long-Term Synaptic Depression / Q000502:physiology*; D008568:Memory / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; D051028:bcl-2-Associated X Protein
keywords: Bax; LTD; NMDA receptor; depressive behavior; fear memory; memory consolidation