Description
In developing brains, activity-dependent remodeling facilitates the formation of precise neuronal connectivity. Synaptic competition is known to facilitate synapse elimination; however, it has remained unknown how different synapses compete with one another within a post-synaptic cell. Here, the authors investigate how a mitral cell in the mouse olfactory bulb prunes all but one primary dendrite during the developmental remodeling process. They find that spontaneous activity generated within the olfactory bulb is essential. They show that strong glutamatergic inputs to one dendrite trigger branch-specific changes in RhoA activity to facilitate the pruning of the remaining dendrites: NMDAR-dependent local signals suppress RhoA to protect it from pruning; however, the subsequent neuronal depolarization induces neuron-wide activation of RhoA to prune non-protected dendrites. NMDAR-RhoA signals are also essential for the synaptic competition in the mouse barrel cortex. These results demonstrate a general principle whereby activity-dependent lateral inhibition across synapses establishes a discrete receptive field of a neuron.
Funding Information
This work was supported by grants from the PRESTO and CREST (JPMJCR2021 to T.I.) programs of the Japan Science and Technology Agency (JST) (T.I.), AMED (JP20dm0207055 and JP23wm0525012 to T.I.), the JSPS KAKENHI (JP23680038, JP15H05572, JP15K14336, JP16K14568, JP16H06456, JP17H06261, JP21H00205, JP21H05696, JP23H02577, and JP23H04236 to T.I.; JP15K14327, JP17K14944, and JP19K06886 to S.F.; JP17K14946 to M.N.L.; and JP18J10215 to S.A.), Mitsubishi Foundation (T.I.), Sumitomo Foundation (T.I.), Nakajima Foundation (T.I.), the Mochida Memorial Foundation for Medical and Pharmaceutical Research, the Uehara Memorial Foundation (T.I.), and a RIKEN CDB intramural grant (T.I.). S.A. was a junior research associate at RIKEN and a predoctoral research fellow (DC2) of JSPS.