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. 2018 Feb 8;11:19. doi: 10.3389/fnmol.2018.00019

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Copyright © 2018 Tröster, Haseleu, Petersen, Drees, Schmidtko, Schwaller, Lewin, Ter-Avetisyan, Winter, Peters, Feil, Feil, Rathjen and Schmidt.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Receptive fields of spinal terminations of tactile afferents from the hindpaw in wild type and Npr2-deficient conditional mice. (A) Subcutaneous injection of 0.3 μl of CTB conjugated to AL594 into the second digit of the left hind paw in order to label the terminal fields of cutaneous myelinated afferents in the spinal cord dorsal horn. A fluorescent micrograph of the left hind paw is shown. Scale bar, 1 mm. (B) Heat maps of averaged summed projections of spinal terminal fields in Npr2^fl/fl;Wnt1^Cre and Npr2^fl/fl control mice. Terminal fields of fibers innervating the second digit of the left hind paw appear different in Npr2^fl/fl;Wnt1^Cre mice (n = 6) than in Npr2^fl/fl mice (n = 6) in dorsoventral, mediolateral, and rostrocaudal projections. The ImageJ color lookup table “16 Colors” was applied (see color map). The color code in each pixel denotes the number of voxels found in corresponding positions along different axes averaged across mice. Scale bars, 100 μm. (C) In Npr2^fl/fl;Wnt1^Cre mice, the number of voxels representing CTB-labeled fibers is significantly lower compared to those in Npr2^fl/fl mice. (D–F) Morphometrics of spinal terminal fields in Npr2^fl/fl;Wnt1^Cre and Npr2^fl/fl control mice. Spinal terminal fields of fibers innervating the second digit of the left hind paw span similarly far in the (D) RC dimension but in a significantly different range in the (E) ML and further in the (F) DV dimension in Npr2^fl/fl;Wnt1^Cre (red, n = 6) as compared to Npr2^fl/fl (blue, n = 6) mice. (G–I) Areal densities of spinal terminal fields in Npr2^fl/fl and Npr2^fl/fl;Wnt1^Cre mice. The areal densities of terminal fields innervating the second digit of the left hind paw digit were significantly lower in (G) the dorsoventral projection, (H) the mediolateral projection, and (I) the rostrocaudal projection in Npr2^fl/fl;Wnt1^Cre (red, n = 6) as compared to Npr2^fl/fl (blue, n = 6) mice. Individual data points and mean values ± SEM are shown. Each data set was compared using a two-tailed unpaired t-test (^*p < 0.05; ^**p < 0.01; ^***p < 0.001). CTB, cholera toxin subunit B; WT, wild type; M, medial; V, ventral; C, caudal; D, dorsal; RC, rostrocaudal; ML, mediolateral; DV, dorsoventral.