Transient disruption of functional connectivity and depression of neural fluctuations in a mouse model of acute septic encephalopathy

Septic encephalopathy leads to major and costly burdens for a large percentage of admitted hospital patients. Elderly patients are at an increased risk, especially those with dementia. Current treatments are aimed at sedation to combat mental status changes and are not aimed at the underlying cause of encephalopathy. Indeed, the underlying pathology linking together peripheral infection and altered neural function has not been established, largely because good, acutely accessible readouts of encephalopathy in animal models do not exist. Behavioral testing in animals lasts multiple days, outlasting the time frame of acute encephalopathy. Here, we propose optical fluorescent imaging of neural functional connectivity (FC) as a readout of encephalopathy in a mouse model of acute sepsis. Imaging and basic behavioral assessment were performed at baseline, Hr8, Hr24, and Hr72 following injection of either lipopolysaccharide or phosphate buffered saline. Neural FC strength decreased at Hr8 and returned to baseline by Hr72 in motor, somatosensory, parietal, and visual cortical regions. Additionally, neural fluctuations transiently declined at Hr8 and returned to baseline by Hr72. Both FC strength and fluctuation tone correlated with neuroscore indicating this imaging methodology is a sensitive and acute readout of encephalopathy.