Astrocytic Piezo1-mediated mechanotransduction determines adult neurogenesis and cognitive functions

Adult brain activities are generally believed to be dominated by chemical and electrical transduction mech-anisms. However, the importance of mechanotransduction mediated by mechano-gated ion channels in brain functions is less appreciated. Here, we show that the mechano-gated Piezo1 channel is expressed in the exploratory processes of astrocytes and utilizes its mechanosensitivity to mediate mechanically evoked Ca2+ responses and ATP release, establishing Piezo1-mediated mechano-chemo transduction in as-trocytes. Piezo1 deletion in astrocytes causes a striking reduction of hippocampal volume and brain weight and severely impaired (but ATP-rescuable) adult neurogenesis in vivo, and it abolishes ATP-dependent potentiation of neural stem cell (NSC) proliferation in vitro. Piezo1-deficient mice show impaired hippocampal long-term potentiation (LTP) and learning and memory behaviors. By contrast, overexpression of Piezo1 in astrocytes sufficiently enhances mechanotransduction, LTP, and learning and memory performance. Thus, astrocytes utilize Piezo1-mediated mechanotransduction mechanisms to robustly regulate adult neu-rogenesis and cognitive functions, conceptually highlighting the importance of mechanotransduction in brain structure and function.

Automated summary

This study reveals the importance of mechanotransduction mediated by Piezo1 in astrocytes for adult neurogenesis and cognitive functions. Piezo1 in astrocytes mediates mechanically evoked calcium responses and ATP release, and its deficiency leads to severe impairment in brain structure and function.