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.

A mesoscale connectome of the mouse brain

Pd-catalyzed cross-coupling reactions that form C–N bonds have become useful methods to synthesize anilines and aniline derivatives, an important class of compounds throughout chemical research. A key factor in the widespread adoption of these methods has been the continued development of reliable and versatile catalysts that function under operationally simple, user-friendly conditions. This review provides an overview of Pd-catalyzed N-arylation reactions found in both basic and applied chemical research from 2008 to the present. Selected examples of C–N cross-coupling reactions between nine classes of nitrogen-based coupling partners and (pseudo)aryl halides are described for the synthesis of heterocycles, medicinally relevant compounds, natural products, organic materials, and catalysts.

Applications of Palladium-Catalyzed C–N Cross-Coupling Reactions

Specific labeling of biomolecules with bright fluorophores is the keystone of fluorescence microscopy. Genetically encoded self-labeling tag proteins can be coupled to synthetic dyes inside living cells, resulting in brighter reporters than fluorescent proteins. Intracellular labeling using these techniques requires cell-permeable fluorescent ligands, however, limiting utility to a small number of classic fluorophores. Here we describe a simple structural modification that improves the brightness and photostability of dyes while preserving spectral properties and cell permeability. Inspired by molecular modeling, we replaced the N,N-dimethylamino substituents in tetramethylrhodamine with four-membered azetidine rings. This addition of two carbon atoms doubles the quantum efficiency and improves the photon yield of the dye in applications ranging from in vitro single-molecule measurements to super-resolution imaging. The novel substitution is generalizable, yielding a palette of chemical dyes with improved quantum efficiencies that spans the UV and visible range.

/pdf/a-general-method-to-improve-fluorophores-for-live-cell-and-56mvzhhh2n.pdf

A general method to improve fluorophores for live-cell and single-molecule microscopy

Transgenic mice for intersectional targeting of neural sensors and effectors with high specificity and performance.

We identified the neurons comprising the Drosophila mushroom body (MB), an associative center in invertebrate brains, and provide a comprehensive map describing their potential connections. Each of the 21 MB output neuron (MBON) types elaborates segregated dendritic arbors along the parallel axons of ∼2000 Kenyon cells, forming 15 compartments that collectively tile the MB lobes. MBON axons project to five discrete neuropils outside of the MB and three MBON types form a feedforward network in the lobes. Each of the 20 dopaminergic neuron (DAN) types projects axons to one, or at most two, of the MBON compartments. Convergence of DAN axons on compartmentalized Kenyon cell-MBON synapses creates a highly ordered unit that can support learning to impose valence on sensory representations. The elucidation of the complement of neurons of the MB provides a comprehensive anatomical substrate from which one can infer a functional logic of associative olfactory learning and memory.

/pdf/the-neuronal-architecture-of-the-mushroom-body-provides-a-4jan707nqc.pdf

The neuronal architecture of the mushroom body provides a logic for associative learning

https://www.cell.com/cell-reports/pdf/S2211-1247(12)00292-6.pdf

A GAL4-Driver Line Resource for Drosophila Neurobiology

Fluorogenic molecules are important tools for advanced biochemical and biological experiments The extant collection of fluorogenic probes is incomplete, however, leaving regions of the electromagnetic spectrum unutilized Here, we synthesize green-excited fluorescent and fluorogenic analogues of the classic fluorescein and rhodamine 110 fluorophores by replacement of the xanthene oxygen with a quaternary carbon These anthracenyl “carbofluorescein” and “carborhodamine 110” fluorophores exhibit excellent fluorescent properties and can be masked with enzyme- and photolabile groups to prepare high-contrast fluorogenic molecules useful for live cell imaging experiments and super-resolution microscopy Our divergent approach to these red-shifted dye scaffolds will enable the preparation of numerous novel fluorogenic probes with high biological utility

http://pubs.acs.org/doi/pdf/10.1021/cb4000822

Carbofluoresceins and carborhodamines as scaffolds for high-contrast fluorogenic probes.

Dent disease has multiple defects attributed to proximal tubule malfunction including low-molecular-weight proteinuria, aminoaciduria, phosphaturia, and glycosuria. To understand the changes in kidney function of the Clc5 chloride/proton exchanger gene knockout mouse model of Dent disease, we examined gene expression profiles from proximal S1 and S2 tubules of mouse kidneys. We found many changes in gene expression not known previously to be altered in this disease. Genes involved in lipid metabolism, organ development, and organismal physiological processes had the greatest number of significantly changed transcripts. In addition, genes of catalytic activity and transporter activity also had a great number of changed transcripts. Overall, 720 genes are expressed differentially in the proximal tubules of the Dent Clcn5 knockout mouse model compared with those of control wild-type mice. The fingerprint of these gene changes may help us to understand the phenotype of Dent disease.

Phuson Hulamm

Papers

A GAL4-Driver Line Resource for Drosophila Neurobiology

Carbofluoresceins and carborhodamines as scaffolds for high-contrast fluorogenic probes.

Transcriptional adaptation to Clcn5 knockout in proximal tubules of mouse kidney

Chloride channel (Clc)-5 is necessary for exocytic trafficking of Na+/H+ exchanger 3 (NHE3).