TRPM7 Is Required for Normal Synapse Density, Learning, and Memory at Different Developmental Stages

Summary The TRPM7chanzyme contributes to several biological and pathological processes in different tissues. However, its role in the CNS under physiological conditions remains unclear. Here, we show that TRPM7knockdown in hippocampal neurons reduces structural synapsedensity. The synapsedensity is rescued by the α-kinase domain in the C terminusbut not by the ion channel region of TRPM7or by increasing extracellular concentrations of Mg 2+ or Zn 2+ . Early postnatal conditional knockout of TRPM7in mice impairs learning and memory and reduces synapsedensity and plasticity. TRPM7knockdown in the hippocampus of adult rats also impairs learning and memory and reduces synapsedensity and synaptic plasticity. In knockout mice, restoring expression of the α-kinase domain in the brain rescues synapsedensity/plasticity and memory, probably by interacting with and phosphorylating cofilin. These results suggest that brain TRPM7is important for having normal synaptic and cognitive functions under physiological, non-pathological conditions.