Effects of stroke on cortical synaptic function

在缺血性中风中，流向大脑部分的血液被阻断，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，缺血性核心的神经元死亡伴随着备用脑区域的功能改变。这些空闲区域的突触变化可能导致缺陷和/或反映自发恢复的机制，但缺乏中风后突触如何、何时以及在何处被修改的完整图景。在典型条件下，分别调控突触后和突触前。突触后，脉冲速率的慢性变化诱导代偿性变化，使放电速率稳态地恢复到基线水平。突触前，睡眠/觉醒状态调节兴奋性和抑制性突触传递，但方向相反：睡眠减少兴奋性，增加抑制性，驱动24小时内兴奋/抑制（E/I）比的振荡。神经元活动水平和行为睡眠/清醒状态在中风后都发生改变，这提高了这些变化驱动代偿性或病理性突触修饰的可能性。在本研究中，我们将研究小鼠光血栓性中风后不同时间点的尖峰活动和行为唤醒状态的改变如何影响大脑多个区域的突触功能。

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.