Effects of stroke on cortical synaptic function

缺血性中风是指流向部分大脑的血液流动受阻，是世界范围内导致残疾和死亡的主要原因。在中风幸存者中，缺血核心的神经元死亡伴随着备用脑区的功能变化。这些备用区域的突触变化可能会导致缺陷和/或反映自发恢复的机制，但缺乏中风后突触如何、何时和在哪里修改的完整图景。在典型情况下，分别对突触后和突触前进行调节。在突触后，对尖峰频率的慢性改变会导致代偿性改变，使放电频率自稳态地恢复到基线水平。在突触前，睡眠/清醒状态调节兴奋性和抑制性突触传递，但方向相反：睡眠减少兴奋，增加抑制，推动兴奋/抑制(E/I)比在24小时内振荡。中风后，神经元活动水平和行为睡眠/觉醒状态都会发生变化，这增加了这些变化驱动代偿性或病理性突触修改的可能性。在这项计划中，我们将研究改变的尖峰活动和行为唤醒状态如何影响多个脑区和不同时间点的突触功能在小鼠光血栓卒中后。

Ischemic stroke, in which blood flow to part of the brain is blocked, is a leading cause of disability and death worldwide. In stroke survivors, neuronal death in the ischemic core is accompanied by functional alterations to spared brain regions. Synaptic changes in these spared regions may contribute to deficits and/or reflect mechanisms of spontaneous recovery, but a complete picture of how, when, and where synapses are modified after stroke is lacking. Under typical conditions, regulate synapses post and pre synaptically respectively. Post-synaptically, chronic changes to spike rate induce compensatory changes that homeostatically return firing rates to baseline levels. Pre-synaptically, sleep/wake states regulate both excitatory and inhibitory synaptic transmission, but in opposite directions: sleep decreases excitation and increases inhibition, driving an oscillation of the excitation/inhibition (E/I) ratio across the 24h day. Neuronal activity levels and behavioral sleep/wake states are both altered following stroke, raising the possibility that these changes drive synaptic modifications that are either compensatory or pathological. In this proposal, we will investigate how altered spiking activity and behavioral arousal states impact synaptic function in multiple brain regions and at different time points following photothrombotic stroke in mice.