title: MHC class I immune proteins are critical for hippocampus-dependent memory and gate NMDAR-dependent hippocampal long-term depression.
abstract: Memory impairment is a common feature of conditions that involve changes in inflammatory signaling in the brain, including traumatic brain injury, infection, neurodegenerative disorders, and normal aging. However, the causal importance of inflammatory mediators in cognitive impairments in these conditions remains unclear. Here we show that specific immune proteins, members of the major histocompatibility complex class I (MHC class I), are essential for normal hippocampus-dependent memory, and are specifically required for NMDAR-dependent forms of long-term depression (LTD) in the healthy adult hippocampus. In β2m(-/-)TAP(-/-)mice, which lack stable cell-surface expression of most MHC class I proteins, NMDAR-dependent LTD in area CA1 of adult hippocampus is abolished, while NMDAR-independent forms of potentiation, facilitation, and depression are unaffected. Altered NMDAR-dependent synaptic plasticity in the hippocampus of β2m(-/-)TAP(-/-)mice is accompanied by pervasive deficits in hippocampus-dependent memory, including contextual fear memory, object recognition memory, and social recognition memory. Thus normal MHC class I expression is essential for NMDAR-dependent hippocampal synaptic depression and hippocampus-dependent memory. These results suggest that changes in MHC class I expression could be an unexpected cause of disrupted synaptic plasticity and cognitive deficits in the aging, damaged, and diseased brain.
authors: Department of Neuroscience, University of California, San Diego, La Jolla, California 92093, USA.
authors: P Austin
authors: PA
authors: Nelson
authors: Jennifer R
authors: JR
authors: Sage
authors: Suzanne C
authors: SC
authors: Wood
authors: Christopher M
authors: CM
authors: Davenport
authors: Stephan G
authors: SG
authors: Anagnostaras
authors: Lisa M
authors: LM
authors: Boulanger
mesh_terms: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000818:Animals; D005260:Female; D006624:Hippocampus / Q000502:physiology*; D015395:Histocompatibility Antigens Class I / Q000502:physiology*; D017774:Long-Term Potentiation; D036881:Long-Term Synaptic Depression; D008297:Male; D008568:Memory / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D001613:beta 2-Microglobulin / Q000235:genetics
chemical_list: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D015395:Histocompatibility Antigens Class I; D016194:Receptors, N-Methyl-D-Aspartate; C486171:Tap1 protein, mouse; D001613:beta 2-Microglobulin
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