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https://www.selleckchem.com/products/autophinib.html One way to assess a neuron's function is to describe all its inputs and outputs. With this goal in mind, we used serial section electron microscopy to map 899 synaptic inputs and 623 outputs in one inhibitory interneuron in a large volume of the mouse visual thalamus. This neuron innervated 256 thalamocortical cells spread across functionally distinct subregions of the visual thalamus. All but one of its neurites were bifunctional, innervating thalamocortical and local interneurons while also receiving synapses from the retina. We observed a wide variety of local synaptic motifs. While this neuron innervated many cells weakly, with single en passant synapses, it also deployed specialized branches that climbed along other dendrites to form strong multi-synaptic connections with a subset of partners. This neuron's diverse range of synaptic relationships allows it to participate in a mix of global and local processing but defies assigning it a single circuit function. Primary familial brain calcification (PFBC) is a rare neurodegenerative disorder characterized by a combination of neurological, psychiatric, and cognitive decline associated with calcium deposition on brain imaging. To date, mutations in five genes have been linked to PFBC. However, more than 50% of individuals affected by PFBC have no molecular diagnosis. We report four unrelated families presenting with initial learning difficulties and seizures and later psychiatric symptoms, cerebellar ataxia, extrapyramidal signs, and extensive calcifications on brain imaging. Through a combination of homozygosity mapping and exome sequencing, we mapped this phenotype to chromosome 21q21.3 and identified bi-allelic variants in JAM2. JAM2 encodes for the junctional-adhesion-molecule-2, a key tight-junction protein in blood-brain-barrier permeability. We show that JAM2 variants lead to reduction of JAM2 mRNA expression and absence of JAM2 protein in patient's fibrob

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