The striatum shows general topographic organization and regional differences in behavioral functions. How corticostriatal topography differs across cortical areas and cell types to support these distinct functions is unclear. This study contrasted corticostriatal projections from two layer 5 cell types, intratelencephalic (IT-type) and pyramidal tract (PT-type) neurons, using viral vectors expressing fluorescent reporters in Cre-driver mice. Corticostriatal projections from sensory and motor cortex are somatotopic, with a decreasing topographic specificity as injection sites move from sensory to motor and frontal areas. Topographic organization differs between IT-type and PT-type neurons, including injections in the same site, with IT-type neurons having higher topographic stereotypy than PT-type neurons. Furthermore, IT-type projections from interconnected cortical areas have stronger correlations in corticostriatal targeting than PT-type projections do. As predicted by a longstanding model, corticostriatal projections of interconnected cortical areas form parallel circuits in the basal ganglia.
Stereologic cell counting has had a major impact on the field of neuroscience. A major bottleneck in stereologic cell counting is that the user must manually decide whether or not each cell is counted according to three-dimensional (3D) stereologic counting rules by visual inspection within hundreds of microscopic fields-of-view per investigated brain or brain region. Reliance on visual inspection forces stereologic cell counting to be very labor-intensive and time-consuming, and is the main reason why biased, non-stereologic two-dimensional (2D) "cell counting" approaches have remained in widespread use. We present an evaluation of the performance of modern automated cell detection and segmentation algorithms as a potential alternative to the manual approach in stereologic cell counting. The image data used in this study were 3D microscopic images of thick brain tissue sections prepared with a variety of commonly used nuclear and cytoplasmic stains. The evaluation compared the numbers and locations of cells identified unambiguously and counted exhaustively by an expert observer with those found by three automated 3D cell detection algorithms: nuclei segmentation from the FARSIGHT toolkit, nuclei segmentation by 3D multiple level set methods, and the 3D object counter plug-in for ImageJ. Of these methods, FARSIGHT performed best, with true-positive detection rates between 38 and 99% and false-positive rates from 3.6 to 82%. The results demonstrate that the current automated methods suffer from lower detection rates and higher false-positive rates than are acceptable for obtaining valid estimates of cell numbers. Thus, at present, stereologic cell counting with manual decision for object inclusion according to unbiased stereologic counting rules remains the only adequate method for unbiased cell quantification in histologic tissue sections.
SUMMARYYoung loggerhead sea turtles (Caretta caretta) from the east coast of Florida, USA, undertake a transoceanic migration around the North Atlantic Gyre, the circular current system that flows around the Sargasso Sea. Previous experiments indicated that loggerhead hatchlings, when exposed to magnetic fields replicating those that exist at five widely separated locations along the migratory pathway, responded by swimming in directions that would, in each case, help turtles remain in the gyre and advance along the migratory route. In this study, hatchlings were exposed to several additional magnetic fields that exist along or outside of the gyre's northern boundary. Hatchlings responded to fields that exist within the gyre currents by swimming in directions consistent with their migratory route at each location, whereas turtles exposed to a field that exists north of the gyre had an orientation that was statistically indistinguishable from random. These results are consistent with the hypothesis that loggerhead turtles entering the sea for the first time possess a navigational system in which a series of regional magnetic fields sequentially trigger orientation responses that help steer turtles along the migratory route. By contrast, hatchlings may fail to respond to fields that exist in locations beyond the turtles' normal geographic range.
Identification and delineation of brain regions in histologic mouse brain sections is especially pivotal for many neurogenomics, transcriptomics, proteomics, and connectomics studies, yet this process is prone to observer error and bias. Here we present a novel brain navigation system, named NeuroInfo, whose general principle is similar to that of a global positioning system (GPS) in a car. NeuroInfo automatically navigates an investigator through the complex microscopic anatomy of histologic sections of mouse brains (thereafter: “experimental mouse brain sections”). This is achieved by automatically registering a digital image of an experimental mouse brain section with a three‐dimensional (3D) digital mouse brain atlas that is essentially based on the third version of the Allen Mouse Brain Common Coordinate Framework (CCF v3), retrieving graphical region delineations and annotations from the 3D digital mouse brain atlas, and superimposing this information onto the digital image of the experimental mouse brain section on a computer screen. By doing so, NeuroInfo helps in solving the long‐standing problem faced by researchers investigating experimental mouse brain sections under a light microscope—that of correctly identifying the distinct brain regions contained within the experimental mouse brain sections. Specifically, NeuroInfo provides an intuitive, readily‐available computer microscopy tool to enhance researchers' ability to correctly identify specific brain regions in experimental mouse brain sections. Extensive validation studies of NeuroInfo demonstrated that this novel technology performs remarkably well in accurately delineating regions that are large and/or located in the dorsal parts of mouse brains, independent on whether the sections were imaged with fluorescence or bright‐field microscopy. This novel navigation system provides a highly efficient way for registering a digital image of an experimental mouse brain section with the 3D digital mouse brain atlas in a minute and accurate delineation of the image in real‐time.
Fibrin polymerizes into the fibrous network that is the major structural component of blood clots and thrombi. We demonstrate that fibrin from three different species can also spontaneously polymerize into extensive, molecularly thin, 2D sheets. Sheet assembly occurs in physiologic buffers on both hydrophobic and hydrophilic surfaces, but is routinely observed only when polymerized using very low concentrations of fibrinogen and thrombin. Sheets may have been missed in previous studies because they may be very short-lived at higher concentrations of fibrinogen and thrombin, and their thinness makes them very difficult to detect. We were able to distinguish fluorescently labeled fibrin sheets by polymerizing fibrin onto micropatterned structured surfaces that suspended polymers 10 m above and parallel to the cover-glass surface. We used a combined fluorescence/atomic force microscope system to determine that sheets were Ϸ5 nm thick, flat, elastic and mechanically continuous. Video microscopy of assembling sheets showed that they could polymerize across 25-m channels at hundreds of m 2 /sec (Ϸ10 13 subunits/s⅐M), an apparent rate constant many times greater than those of other protein polymers. Structural transitions from sheets to fibers were observed by fluorescence, transmission, and scanning electron microscopy. Sheets appeared to fold and roll up into larger fibers, and also to develop oval holes to form fiber networks that were ''preattached'' to the substrate and other fibers. We propose a model of fiber formation from sheets and compare it with current models of end-wise polymerization from protofibrils. Sheets could be an unanticipated factor in clot formation and adhesion in vivo, and are a unique material in their own right.clot ͉ fiber ͉ monomolecular sheet ͉ network ͉ thrombus B ecause of the central role of fibrin in the clotting of blood during wound healing and in the formation of pathogenic vascular thrombi, the polymerization of fibrin has been actively studied since the mid-19th century (1). The parent protein, fibrinogen, is an elongated, sausage-shaped dimeric molecule with symmetry around a central globular domain (2-6). Cleavage and removal of the small peptides-fibrinopeptide A and later B-from fibrinogen by the enzyme thrombin expose specific binding sites (''knobs'') on fibrin that allow binding to corresponding regions (''holes'') on neighboring fibrin molecules (7-11). Fibrin can then self-associate to form elongated, sometimes twisted, often highly branched fibers and fiber networks that, together with platelets and blood cells, form clots in response to vascular injury (1,(12)(13)(14)(15). Fibrin fibers are elastic and adhesive and show very high extensibility (16,17). Recent studies suggest that these properties derive, at least in part, from the properties of the fibrin molecule itself (18-21). Exhaustive studies of fibrin polymerization in vitro have been carried out with purified components since the 1940s (e.g., 22, 23), but several details of fibrin assembly into fibers and fibe...
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