Hierarchical organization of cortical and thalamic connectivity.

The mammalian cortex is a laminar structure containing many areas and cell types that are densely interconnected in complex ways, and for which generalizable principles of organization remain mostly unknown. Here we describe a major expansion of the Allen Mouse Brain Connectivity Atlas resource1, involving around a thousand new tracer experiments in the cortex and its main satellite structure, the thalamus. We used Cre driver lines (mice expressing Cre recombinase) to comprehensively and selectively label brain-wide connections by layer and class of projection neuron. Through observations of axon termination patterns, we have derived a set of generalized anatomical rules to describe corticocortical, thalamocortical and corticothalamic projections. We have built a model to assign connection patterns between areas as either feedforward or feedback, and generated testable predictions of hierarchical positions for individual cortical and thalamic areas and for cortical network modules. Our results show that cell-class-specific connections are organized in a shallow hierarchy within the mouse corticothalamic network.

Shared and distinct transcriptomic cell types across neocortical areas.

The neocortex contains a multitude of cell types that are segregated into layers and functionally distinct areas. To investigate the diversity of cell types across the mouse neocortex, here we analysed 23,822 cells from two areas at distant poles of the mouse neocortex: the primary visual cortex and the anterior lateral motor cortex. We define 133 transcriptomic cell types by deep, single-cell RNA sequencing. Nearly all types of GABA (γ-aminobutyric acid)-containing neurons are shared across both areas, whereas most types of glutamatergic neurons were found in one of the two areas. By combining single-cell RNA sequencing and retrograde labelling, we match transcriptomic types of glutamatergic neurons to their long-range projection specificity. Our study establishes a combined transcriptomic and projectional taxonomy of cortical cell types from functionally distinct areas of the adult mouse cortex.

Ultrasound imaging of the trapeziometacarpal articular cavity to investigate the presence of intraarticular gas bubbles after chiropractic manipulation.

OBJECTIVE: The purpose of this study was to investigate the presence of intraarticular gas bubbles in the trapeziometacarpal joint cavity after chiropractic manipulation with audible cavitation and to assess the state of the gas bubbles after a 20-minute refractory period. METHODS: This investigation included 18 asymptomatic male and female participants between the ages of 21 and 26 years. High-resolution (15 MHz) sonograms of the trapeziometacarpal articular cavity were obtained by an experienced musculoskeletal ultrasonographer at 3 intervals: premanipulation, within 30 seconds postmanipulation, and at 20 minutes postmanipulation. The sonograms were saved as digital copies for subsequent reports that were correlated with reports compiled during dynamic visualization of the articular cavity. Data were extracted from the reports for analysis. RESULTS: The premanipulative sonograms showed that 27.78% of joints contained minute gas bubbles, also known as microcavities, within the synovial fluid before the joint was manipulated. The remaining 72.22% of joints contained no intraarticular microcavities. All of the postmanipulative sonograms revealed numerous large conspicuous gas bubbles within the synovial fluid. The postrefractory sonograms showed that, in 66.66% of the synovial fluid, gas bubbles were still visible, whereas the remaining 33.34% had no presence of gas bubbles or microcavities, and the synovial fluid had returned to its premanipulative state. CONCLUSION: The findings of this study suggest that synovial fluid may contain intraarticular microcavities even before a manipulation is performed. Numerous large intraarticular gas bubbles are formed during manipulation due to cavitation of the synovial fluid and were observed in the absence of an axial distractive load at the time of imaging. In most cases, these gas bubbles remained within the joint for longer than 20 minutes.

A mesoscale connectome of the mouse brain.

Comprehensive knowledge of the brain's wiring diagram is fundamental for understanding how the nervous system processes information at both local and global scales. However, with the singular exception of the C. elegans microscale connectome, there are no complete connectivity data sets in other species. Here we report a brain-wide, cellular-level, mesoscale connectome for the mouse. The Allen Mouse Brain Connectivity Atlas uses enhanced green fluorescent protein (EGFP)-expressing adeno-associated viral vectors to trace axonal projections from defined regions and cell types, and high-throughput serial two-photon tomography to image the EGFP-labelled axons throughout the brain. This systematic and standardized approach allows spatial registration of individual experiments into a common three dimensional (3D) reference space, resulting in a whole-brain connectivity matrix. A computational model yields insights into connectional strength distribution, symmetry and other network properties. Virtual tractography illustrates 3D topography among interconnected regions. Cortico-thalamic pathway analysis demonstrates segregation and integration of parallel pathways. The Allen Mouse Brain Connectivity Atlas is a freely available, foundational resource for structural and functional investigations into the neural circuits that support behavioural and cognitive processes in health and disease.