MBF Bioscience (United States)

The impact of alcohol abuse on Alzheimer's disease (AD) is poorly understood. Here, we show that the onset of neurocognitive impairment in a mouse model of AD is hastened by repeated alcohol intoxication through exposure to alcohol vapor, and we provide a comprehensive gene expression dataset of the prefrontal cortex by the single-nucleus RNA sequencing of 113,242 cells. We observed a broad dysregulation of gene expression that involves neuronal excitability, neurodegeneration, and inflammation, including interferon genes. Several genes previously associated with AD in humans by genome-wide association studies were differentially regulated in specific neuronal populations. The gene expression signatures of AD mice with a history of alcohol intoxication showed greater similarity to the signatures of older AD mice with advanced disease and cognitive impairment than did the gene expression signatures of AD mice not exposed to alcohol, suggesting that alcohol promotes transcriptional changes consistent with AD progression. Our gene expression dataset at the single-cell level provides a unique resource for investigations of the molecular bases of the detrimental role of excessive alcohol intake in AD.

The neurophysiology of cells and tissues are monitored electrophysiologically and optically in diverse experiments and species, ranging from flies to humans. Understanding the brain requires integration of data across this diversity, and thus these data must be findable, accessible, interoperable, and reusable (FAIR). This requires a standard language for data and metadata that can coevolve with neuroscience. We describe design and implementation principles for a language for neurophysiology data. Our open-source software (Neurodata Without Borders, NWB) defines and modularizes the interdependent, yet separable, components of a data language. We demonstrate NWB’s impact through unified description of neurophysiology data across diverse modalities and species. NWB exists in an ecosystem, which includes data management, analysis, visualization, and archive tools. Thus, the NWB data language enables reproduction, interchange, and reuse of diverse neurophysiology data. More broadly, the design principles of NWB are generally applicable to enhance discovery across biology through data FAIRness.

SummaryWe developed and analyzed a single cell scale anatomical map of the rat intrinsic cardiac nervous system (ICNS) across 4 male and 3 female hearts. We find the ICNS has a reliable structural organizational plan across individuals that may provide the foundation for further analyses of the ICNS in cardiac function and disease. The distribution of the ICNS was evaluated by 3D visualization and using data-driven clustering. The pattern, distribution and clustering of ICNS neurons across all male and female rat hearts is highly conserved, demonstrating a coherent organizational plan in which distinct clusters of neurons are consistently localized. Female hearts had fewer neurons, lower packing density and slightly reduced distribution, but with the same localization. We registered the anatomical data from each heart to a geometric scaffold, normalizing their 3D coordinates for the standardization of common anatomical planes and providing the path where multiple experimental results and data types can be integrated and compared.

Advances in molecular neuroanatomical tools have expanded the ability to map in detail connections of specific neuron subtypes in the context of behaviorally driven patterns of neuronal activity. Analysis of such data across the whole mouse brain, registered to a reference atlas, aids in understanding the functional organization of brain circuits related to behavior. A process is described to image mouse brain sections labeled with standard histochemical techniques, reconstruct those images into a whole brain image volume and register those images to the Allen Mouse Brain Common Coordinate Framework. Image analysis tools automate detection of cell bodies and quantification of axon density labeling in the structures in the annotated reference atlas. Examples of analysis are provided for mapping the axonal projections of layer-specific cortical neurons using Cre-dependent AAV vectors and for mapping inputs to such neurons using retrograde transsynaptic tracing with modified rabies viral vectors.

The cognitive capacities of a human agent are significantly impoverished when operating under severe temporal and emotional stress. Currently, human-machine interaction under these circumstances is being informed by classical cognitive models, which treat the human agent as having a repertoire of undiminished cognitive capacities consisting of semantic, symbolic, and inferential reasoning abilities. Such an approach is unsuited when an agent’s mental capacities are reduced to simple perception-action mechanisms, due to functional decortication, under severe stress. Gibson’s direct perception provides a partial answer to this problem. This paper attempts to provide a more robust answer by putting direct perception under the light of recent advances made in human-machine interaction design and theory, neurosciences and embodied cognition. This resulted in the development of a model for human-machine interaction called Direct Perception-Action Coupling (DPAC). This model can be applied to inform the design of critical human-machine interactions that need to be flawlessly performed, often times under stress, to prevent catastrophic outcomes.

The carotid intima-media thickness (IMT) is a validated marker of cerebrovascular disease risk. This paper presents a new parameter, the IMT variability (IMTV), and compares it between symptomatic and asymptomatic patients taken from a cohort of Italian population. One hundred forty-two patients were analyzed (age 59 ± 112 years, 59% males), 42 of these patients suffered from TIA or minor stroke. The lumen-intima (LI) and media-adventitia (MA) interfaces of the far wall were manually traced by a Reader. We also used a computer-based automated system (called AutoEdge) to obtain the LI/MA interfaces. The LI/MA interfaces were used to measure the IMT and the IMTV along the distal wall of the common carotid artery. Wilcoxon and Pearson correlation analyses were performed. The agreement between the Reader's IMT and the AutoEdge IMT values was 98.7% for the symptomatic (0.83 ± 0.44 mm for Reader, 0.82 ± 0.35 mm for AutoEdge) and 94.9% for the asymptomatic patients (0.78 ± 0.45 mm for Reader, 0.74 ± 0.30 mm for AutoEdge). Correlation was 65% for symptomatic and 68% for asymptomatic patients, respectively. The IMT measured using AutoEdge was 1.2% lower compared to manual measurements in symptomatic population, while 5.12% lower in asymptomatic. The IMTV was 11% higher in symptomatic patients compared to asymptomatic when using manual delineations, 8% higher when using AutoEdge. There was no statistical difference between the manual and automated IMTV measurements (Wilcoxon signed rank, P > 0.7). We conclude that the IMT and IMTV values were very similar between Reader and AutoEdge software when studying symptomatic and asymptomatic patients in Italian population.