Separate functional properties of NMDARs regulate distinct aspects of spatial cognition
| Autor: | Mohima Sanyal, Kevin Zhao, Alyssa Kozma, Jane Pyon, Theodore C. Dumas, Erin M. Sanders, Matthew J. Keith, Hong Hong Liao Liao, Akua O. Nyarko-Odoom, Daniel G. McHail, Michael Nguyen |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Memory Long-Term Cognitive Neuroscience Protein subunit Protein domain Spatial Behavior Morris water navigation task Mice Transgenic Receptors N-Methyl-D-Aspartate 03 medical and health sciences Cellular and Molecular Neuroscience Prosencephalon 0302 clinical medicine Protein Domains Animals Amino Acid Sequence RNA Messenger Maze Learning Neurons Memory Disorders Learning Disabilities Chemistry Research Transmembrane domain 030104 developmental biology Neuropsychology and Physiological Psychology Synaptic plasticity Excitatory postsynaptic potential NMDA receptor Neuroscience 030217 neurology & neurosurgery Ionotropic effect |
| Zdroj: | Learning & Memory. 25:264-272 |
| ISSN: | 1549-5485 |
| DOI: | 10.1101/lm.047290.118 |
| Popis: | N-methyl-d-aspartate receptors (NMDARs) at excitatory synapses are central to activity-dependent synaptic plasticity and learning and memory. NMDARs act as ionotropic and metabotropic receptors by elevating postsynaptic calcium concentrations and by direct intracellular protein signaling. In the forebrain, these properties are controlled largely by the auxiliary GluN2 subunits, GluN2A and GluN2B. While calcium conductance through NMDAR channels and intracellular protein signaling make separate contributions to synaptic plasticity, it is not known if these properties individually influence learning and memory. To address this issue, we created chimeric GluN2 subunits containing the amino-terminal domain and transmembrane domains from GluN2A or GluN2B fused to the carboxy-terminal domain of GluN2B (termed ABc) or GluN2A ATD (termed BAc), respectively, and expressed these mutated GluN2 subunits in transgenic mice. Expression was confirmed at the mRNA level and protein subunit translation and translocation into dendrites were observed in forebrain neurons. In the spatial version of the Morris water maze, BAc mice displayed signs of a learning deficit. In contrast, ABc animals performed similarly to wild-types during training, but showed a more direct approach to the goal location during a long-term memory test. There was no effect of ABc or BAc expression in a nonspatial water escape task. Since background expression is predominantly GluN2A in mature animals, the results suggest that spatial learning is more sensitive to manipulations of the amino-terminal domain and transmembrane domains (calcium conductance) and long-term memory is regulated more by the carboxy-terminal domain (intracellular protein signaling). |
| Databáze: | OpenAIRE |
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