Effects of stroke on cortical synaptic function

点击翻译按钮获取中文摘要

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.