Sensing of extracellular matrix in motor circuit remodelling: a novel target for neuroplasticity-promoting stroke therapies?

该项目假设细胞外基质(ECM)的降解重新打开了缺血性卒中后有助于运动协调恢复的神经可塑性窗口。作为一个潜在的机制，我们将描述机械感受器在控制星形细胞和神经元网络重构中的作用。我们假设，机械转导的下调是缺血后ECM降解减少星形胶质细胞钙振荡和功能偶联的关键机制。星形细胞网络活动的减少将放松对神经传递的调节，同时促进突触指导分子的释放。因此，神经元网络的活性将得到增强，新突触的建立将成为可能。随着实验的计划，我们希望建立大脑的ECM作为促进可塑性中风治疗的新靶点。

This project postulates that extracellular matrix (ECM) degradation re-opens a neuroplasticity window following ischemic stroke that contributes to motor-coordination recovery. As an underlying mechanism, we will characterize the role of mechanoreceptors in controlling astrocytic and neuronal network remodeling. We hypothesize that the downregulation of mechanotransduction represents a key mechanism via which post-ischemic ECM degradation reduces calcium oscillations and functional coupling in astrocytes. The reduction of astrocytic network activity will deregulate neurotransmission, at the same time facilitating the release of synaptic guidance molecules. Accordingly, the activity of neuronal networks will be enhanced, and the establishment of new synapses will be enabled. With the experiments planned, we hope to establish the brain’s ECM as novel target for plasticity-promoting stroke therapies.