Inducible NMDA Receptor Knockdown Reveals a Maintenance Phase in Dendritic Refinement of Barrel Cortex Neurons

Ayane Nihashi, Naoki Nakagawa, Takuya Sato, Mariko Yamamoto, Luwei Wang, Rieko Ajima, Yumiko Saga, Yumiko Yoshimura, Masato T. Kanemaki, Takuji Iwasato^*
* Corresponding Author

iScience (2025) DOI:10.1016/j.isci.2025.113229

Press release (In Japanese only)

The temporal mechanisms of activity-dependent dendritic patterning during postnatal development remain unclear because appropriate technology is lacking. Here, we demonstrate that the auxin-inducible degron 2 technology enables the rapid knockdown of target proteins at specific time points in the postnatal mouse brain. When N-methyl-D-aspartate-type glutamate receptor (NMDAR) depletion was induced from postnatal day (P)3, barrel cortex layer 4 spiny stellate neurons (barrel cells) failed to form strong asymmetry and a high tree-length variance in the dendritic patterns. Intriguingly, these unique dendritic patterns of barrel cells formed by P6 were rapidly canceled by NMDAR depletion from P6 but not from P12. NMDAR depletion from P6 also extinguished the existing Golgi apparatus’ lateral polarity. These results suggest that the barrel cells’ dendritic refinement involves not only formation but also “maintenance” of specific dendritic patterns during early postnatal development, in which NMDARs play a critical role, likely by regulating the Golgi polarity.