Effects of stroke on cortical synaptic function

中风对皮质突触功能的影响

• 批准号: 10761388
• 负责人: Michelle Bridi
• 金额: $ 19.7万
• 依托单位: WEST VIRGINIA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-01-05 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10761388
• 关键词: Effects; stroke; cortical; synaptic; function

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.

缺血性中风，其中血液流向大脑的一部分被阻塞，是世界范围内残疾和死亡的主要原因。在中风幸存者中，缺血核心区的神经元死亡伴随着备用脑区的功能改变。这些备用区域的突触变化可能导致缺陷和/或反映自发恢复的机制，但缺乏卒中后突触如何、何时以及在何处被修改的完整图片。在典型条件下，分别调节突触后和突触前。突触后，尖峰频率的慢性变化诱导代偿性变化，使放电率稳态地返回到基线水平。在突触前，睡眠/觉醒状态调节兴奋性和抑制性突触传递，但方向相反：睡眠减少兴奋并增加抑制，驱动24小时内兴奋/抑制（E/I）比率的振荡。神经元活动水平和行为睡眠/觉醒状态在中风后都发生了改变，这增加了这些变化驱动突触修饰的可能性，这些突触修饰是补偿性的或病理性的。在这项提案中，我们将研究如何改变尖峰活动和行为唤醒状态影响突触功能在多个大脑区域和在不同的时间点后，小鼠光血栓中风。