Measuring macroscopic brain connections in vivo

Decades of detailed anatomical tracer studies in non-human animals point to a rich and complex organization of long-range white matter connections in the brain. State-of-the art in vivo imaging techniques are striving to achieve a similar level of detail in humans, but multiple technical factors can limit their sensitivity and fidelity. In this review, we mostly focus on magnetic resonance imaging of the brain. We highlight some of the key challenges in analyzing and interpreting in vivo connectomics data, particularly in relation to what is known from classical neuroanatomy in laboratory animals. We further illustrate that, despite the challenges, in vivo imaging methods can be very powerful and provide information on connections that is not available by any other means

A First- and Second-Order Motion Energy Analysis of Peripheral Motion Illusions Leads to Further Evidence of “Feature Blur” in Peripheral Vision

Anatomical and physiological differences between the central and peripheral visual systems are well documented. Recent findings have suggested that vision in the periphery is not just a scaled version of foveal vision, but rather is relatively poor at representing spatial and temporal phase and other visual features. Shapiro, Lu, Huang, Knight, and Ennis (2010) have recently examined a motion stimulus (the “curveball illusion”) in which the shift from foveal to peripheral viewing results in a dramatic spatial/temporal discontinuity. Here, we apply a similar analysis to a range of other spatial/temporal configurations that create perceptual conflict between foveal and peripheral vision.To elucidate how the differences between foveal and peripheral vision affect super-threshold vision, we created a series of complex visual displays that contain opposing sources of motion information. The displays (referred to as the peripheral escalator illusion, peripheral acceleration and deceleration illusions, rotating reversals illusion, and disappearing squares illusion) create dramatically different perceptions when viewed foveally versus peripherally. We compute the first-order and second-order directional motion energy available in the displays using a three-dimensional Fourier analysis in the (x, y, t) space. The peripheral escalator, acceleration and deceleration illusions and rotating reversals illusion all show a similar trend: in the fovea, the first-order motion energy and second-order motion energy can be perceptually separated from each other; in the periphery, the perception seems to correspond to a combination of the multiple sources of motion information. The disappearing squares illusion shows that the ability to assemble the features of Kanisza squares becomes slower in the periphery.The results lead us to hypothesize “feature blur” in the periphery (i.e., the peripheral visual system combines features that the foveal visual system can separate). Feature blur is of general importance because humans are frequently bringing the information in the periphery to the fovea and vice versa

Building connectomes using diffusion MRI: why, how and but

Why has diffusion MRI become a principal modality for mapping connectomes in vivo? How do different image acquisition parameters, fiber tracking algorithms and other methodological choices affect connectome estimation? What are the main factors that dictate the success and failure of connectome reconstruction? These are some of the key questions that we aim to address in this review. We provide an overview of the key methods that can be used to estimate the nodes and edges of macroscale connectomes, and we discuss open problems and inherent limitations. We argue that diffusion MRI-based connectome mapping methods are still in their infancy and caution against blind application of deep white matter tractography due to the challenges inherent to connectome reconstruction. We review a number of studies that provide evidence of useful microstructural and network properties that can be extracted in various independent and biologically-relevant contexts. Finally, we highlight some of the key deficiencies of current macroscale connectome mapping methodologies and motivate future developments

RNA delivery by extracellular vesicles in mammalian cells and its applications.

The term 'extracellular vesicles' refers to a heterogeneous population of vesicular bodies of cellular origin that derive either from the endosomal compartment (exosomes) or as a result of shedding from the plasma membrane (microvesicles, oncosomes and apoptotic bodies). Extracellular vesicles carry a variety of cargo, including RNAs, proteins, lipids and DNA, which can be taken up by other cells, both in the direct vicinity of the source cell and at distant sites in the body via biofluids, and elicit a variety of phenotypic responses. Owing to their unique biology and roles in cell-cell communication, extracellular vesicles have attracted strong interest, which is further enhanced by their potential clinical utility. Because extracellular vesicles derive their cargo from the contents of the cells that produce them, they are attractive sources of biomarkers for a variety of diseases. Furthermore, studies demonstrating phenotypic effects of specific extracellular vesicle-associated cargo on target cells have stoked interest in extracellular vesicles as therapeutic vehicles. There is particularly strong evidence that the RNA cargo of extracellular vesicles can alter recipient cell gene expression and function. During the past decade, extracellular vesicles and their RNA cargo have become better defined, but many aspects of extracellular vesicle biology remain to be elucidated. These include selective cargo loading resulting in substantial differences between the composition of extracellular vesicles and source cells; heterogeneity in extracellular vesicle size and composition; and undefined mechanisms for the uptake of extracellular vesicles into recipient cells and the fates of their cargo. Further progress in unravelling the basic mechanisms of extracellular vesicle biogenesis, transport, and cargo delivery and function is needed for successful clinical implementation. This Review focuses on the current state of knowledge pertaining to packaging, transport and function of RNAs in extracellular vesicles and outlines the progress made thus far towards their clinical applications