eNMDAR
2022-05-01: reference:
- @Extrasynaptic NMDARs oppose synaptic NMDARs by triggering CREB shut-off and cell death pathways (2002)
- @The Role of the Tripartite Glutamatergic Synapse in the Pathophysiology of Alzheimer’s Disease (Rudy et al)
Extrasynaptic NMDAR #
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Specifically, they are found on the spine neck, dendritic shaft, or soma. They require much higher glutamate concentration than typical sNMDAR. However, they may be adjacent to glia, resulting in their activation if they release glutamate.
- Somatic is worse than dendritic.
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Instead of modulating cognition/plasticity, they signal death and are responsible for glutamatergic Excitotoxicity: JNK, CDK5, Nitric Oxide (via NOS, duh), GSK-3β; cell death. Downregulates LTP and pCREB.
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Extrasynaptic NMDA receptor dependent long-term potentiation of hippocampal CA1 pyramidal neurons
- It was at some point regarded that NR2B was exclusively segregated to extrasynaptic receptors and NR2A for synaptic, but as I well know, either can be anywhere.
- LTP cannot be induced when Synaptic NMDARs are selectively blocked.
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Ok so hold up, Ca-Calmodulin can activate PDE which breaks down cAMP, but ca-calmodulin can also sitmulate many adenylyl cyclase isoforms. Is there an intermediate here that balances these things out?