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

Publication date: 19 June 2018
Source:Cell Reports, Volume 23, Issue 12
Author(s): Yuqiang Liu, Cui Chen, Yunlong Liu, Wei Li, Zhihong Wang, Qifeng Sun, Hang Zhou, Xiangjun Chen, Yongchun Yu, Yun Wang, Nashat Abumaria
The TRPM7 chanzyme 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 TRPM7 knockdown in hippocampal neurons reduces structural synapse density. The synapse density is rescued by the α-kinase domain in the C terminus but not by the ion channel region of TRPM7 or by increasing extracellular concentrations of Mg²⁺ or Zn²⁺. Early postnatal conditional knockout of TRPM7 in mice impairs learning and memory and reduces synapse density and plasticity. TRPM7 knockdown in the hippocampus of adult rats also impairs learning and memory and reduces synapse density and synaptic plasticity. In knockout mice, restoring expression of the α-kinase domain in the brain rescues synapse density/plasticity and memory, probably by interacting with and phosphorylating cofilin. These results suggest that brain TRPM7 is important for having normal synaptic and cognitive functions under physiological, non-pathological conditions.

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Liu et al. find that TRPM7 regulates synapse density/plasticity and memory functions across different species and that this regulation depends on the α-kinase domain. These results add to our understanding of TRPM7 functions in the mammalian brain and implicate TRPM7 in the pathologies of some cognitive disorders.


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