This article investigates the relationship between neuronal hyperactivity and specialized rod-shaped microglia in a mouse model of TDP-43-related neurodegeneration, a condition relevant to Amyotrophic Lateral Sclerosis (ALS). The authors use advanced techniques, including spatial and single-cell RNA sequencing and in vivo calcium imaging, to demonstrate that early cortical hyperactivity induces the formation of these rod-shaped microglia. Crucially, the paper proposes that these specialized microglia interact with neuronal dendrites to remodel inputs, suggesting a neuroprotective role by attenuating cortical excitability. Furthermore, the study identifies the TREM2/DAP12 axis as a regulator for the formation of these protective microglia, linking this signaling pathway to the observed neuroprotection.

References:

• Xie M, Liang Y, Miller A S, et al. Rod-shaped microglia interact with neuronal dendrites to attenuate cortical excitability during TDP-43-related neurodegeneration[J]. Immunity, 2025.