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Is microcircuit wiring designed deterministically or probabilistically? Does geometric architecture predict functional dynamics of a given neuronal microcircuit? These questions were addressed in the visceral sensory microcircuit of the caudal nucleus of the tractus solitarius (NTS), which is generally thought to be homogeneous rather than laminar in cytoarchitecture. Using in situ hybridization histochemistry and whole-cell patch clamp recordings followed by neuronal reconstruction with biocytin filling, anatomical and functional organization of NTS microcircuitry was quantified to determine associative relationships. Morphologic and chemical features of NTS neurons displayed different patterns of process arborization and sub-nuclear localization according to neuronal types: smaller cells featured presynaptic local axons and GABAergic cells were aggregated specifically within the ventral NTS. The results suggested both a laminar organization and a spatial heterogeneity of NTS microcircuit connectivity. Geometric analysis of pre- and postsynaptic axodendritic arbor overlap of reconstructed neurons (according to parent somal distance) confirmed a heterogeneity of microcircuit connectivity that could underlie differential functional dynamics along the dorsoventral axis. Functional dynamics in terms of spontaneous and evoked postsynaptic current patterns behaved in a strongly location-specific manner according to the geometric dimension, suggesting a spatial laminar segregation of neuronal populations: a dorsal group of high excitation and a ventral group of balanced excitation and inhibition. Recurrent polysynaptic activity was also noted in a subpopulation of the ventral group. Such geometric and functional laminar organization seems to provide the NTS microcircuit with both reverberation capability and a differentiated projection system for appropriate computation of visceral sensory information.Electronic supplementary materialThe online version of this article (doi:10.1007/s00429-010-0294-5) contains supplementary material, which is available to authorized users.

Purpose To report the spectrum of ABCC6 variants in Japanese patients with angioid streaks (AS). Patients and Methods This was a single-center cohort study. The medical records of 20 patients with AS from 18 unrelated Japanese families were retrospectively reviewed. Screening of the ABCC6 gene (exons 1 to 31) was performed using PCR-based Sanger sequencing. Results Eight ABCC6 variants were identified as candidate disease-causing variants. These eight variants included five known variants (p.Q378X, p.R419Q, p.V848CfsX83, p.R1114C, and p.R1357W), one previously reported variant (p.N428S) of unknown significance, and two novel variants (c.1939C>T [p.H647Y] and c.3374C>T [p.S1125F]); the three latter variants were determined to be variants of significance. The following four variants were frequently identified: p.V848CfsX83 (14/40 alleles, 35.0%), p.Q378X (7/40 alleles, 17.5%), p.R1357W (6/40 alleles, 15.0%), and p.R419Q (4/40 alleles, 10.0%). The ABCC6 variants were identified in compound heterozygous or homozygous states in 13 of 18 probands. Two families showed a pseudodominant inheritance pattern. Pseudoxanthoma elasticum was seen in 15 of 17 patients (88.2%) who underwent dermatological examination. Conclusions We identified disease-causing ABCC6 variants that were in homozygous or compound heterozygous states in 13 of 18 families (72.2%). Our results indicated that ABCC6 variants play a significant role in patients with AS in the Japanese population.

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