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bioRxiv · 10.1101/2020.08.19.258269

Non-ionotropic NMDA receptor signaling gates bidirectional structural plasticity of dendritic spines

Stein, I. S.·Park, D. K.·Claiborne, N.·Zito, K.
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Abstract

Experience-dependent refinement of neuronal connections is critically important for brain development and learning. Here we show that ion flow-independent NMDAR signaling is required for the long-term dendritic spine growth that is a vital component of brain circuit plasticity. We found that inhibition of p38 MAPK, shown to be downstream of non-ionotropic NMDAR signaling in LTD and spine shrinkage, blocked LTP-induced spine growth but not LTP. We hypothesized that non-ionotropic NMDAR signaling drives the cytoskeletal changes that support bidirectional spine structural plasticity. Indeed, we found that key signaling components downstream of non-ionotropic NMDAR function in LTD-induced spine shrinkage also are necessary for LTP-induced spine growth. Furthermore, NMDAR conformational signaling with coincident Ca2+ influx is sufficient to drive CaMKII-dependent long-term spine growth, even when Ca2+ is artificially driven through voltage-gated Ca2+ channels. Our results support a model in which non-ionotropic NMDAR signaling gates the bidirectional spine structural changes vital for brain plasticity.

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Stein, I. S., Park, D. K., Claiborne, N., Zito, K.. 2020-08-19. Non-ionotropic NMDA receptor signaling gates bidirectional structural plasticity of dendritic spines. https://doi.org/10.1101/2020.08.19.258269

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