Spatial coding defects of hippocampal neural ensemble calcium activities in the triple-transgenic Alzheimer's disease mouse model.

Alzheimer's disease (AD) causes progressive age-related defects in memory and cognitive function and has emerged as a major health and socio-economic concern in the US and worldwide. To develop effective therapeutic treatments for AD, we need to better understand the neural mechanisms by which AD causes memory loss and cognitive deficits. Here we examine large-scale hippocampal neural population calcium activities imaged at single cell resolution in a triple-transgenic Alzheimer's disease mouse model (3xTg-AD) that presents both amyloid plaque and neurofibrillary pathological features along with age-related behavioral defects. To measure encoding of environmental location in hippocampal neural ensembles in the 3xTg-AD mice in vivo, we performed GCaMP6-based calcium imaging using head-mounted, miniature fluorescent microscopes ("miniscopes") on freely moving animals. We compared hippocampal CA1 excitatory neural ensemble activities during open-field exploration and track-based route-running behaviors in age-matched AD and control mice at young (3-6.5 months old) and old (18-21 months old) ages. During open-field exploration, 3xTg-AD CA1 excitatory cells display significantly higher calcium activity rates compared with Non-Tg controls for both the young and old age groups, suggesting that in vivo enhanced neuronal calcium ensemble activity is a disease feature. CA1 neuronal populations of 3xTg-AD mice show lower spatial information scores compared with control mice. The spatial firing of CA1 neurons of old 3xTg-AD mice also displays higher sparsity and spatial coherence, indicating less place specificity for spatial representation. We find locomotor speed significantly modulates the amplitude of hippocampal neural calcium ensemble activities to a greater extent in 3xTg-AD mice during open field exploration. Our data offer new and comprehensive information about age-dependent neural circuit activity changes in this important AD mouse model and provide strong evidence that spatial coding defects in the neuronal population activities are associated with AD pathology and AD-related memory behavioral deficits.

Ultrasound for Localization of Central Venous Catheter: A Good Alternative to Chest X-Ray?

BACKGROUND: Chest radiography after central venous catheter (CVC) insertion is the main method of verifying the catheter location. Despite the widespread use of radiography for detecting catheter position, x-ray may not always be readily available, especially in the operating room. OBJECTIVES: We aimed to compare contrast-enhanced ultrasonography (CEUS) and chest radiography for detecting the correct location of CVCs. METHODS: One hundred sixteen consecutive patients with indications for CVC before cardiac surgery were enrolled in this observational study. After catheter insertion, CEUS was performed. Portable radiography was obtained postoperatively in the intensive care unit. Sensitivity, specificity, and predictive values were determined by comparing the ultrasonography results with radiographic findings as a reference standard. RESULTS: Chest radiography revealed 16 CVC misplacements: two cases of intravascular and 14 cases of right atrium (RA) misplacement. CEUS detected 11 true catheter malpositionings in the RA, while it could not recognize seven catheter placements correctly. CEUS showed two false RA misplacements and five falsely correct CVC positions. A sensitivity of 98% and specificity of 69% were achieved for CEUS in detecting CVC misplacements. Positive and negative predictive values were 95% and 85%, respectively. The interrater agreement (kappa) between CEUS and radiography was 0.72 (P < 0.001). CONCLUSIONS: Despite close concordance between ultrasonography and chest radiography, CEUS is not a suitable alternative for standard chest radiography in detecting CVC location; however, considering its high sensitivity and acceptable specificity in our study, its usefulness as a triage method for detecting CVC location on a real-time basis in the operating room cannot be ignored.