Musculotopic organization of the motor neurons supplying the mouse hindlimb muscles: a quantitative study using Fluoro-Gold retrograde tracing

We have mapped the motor neurons (MNs) supplying the major hindlimb muscles of transgenic (C57/BL6J-ChAT-EGFP) and wild-type (C57/BL6J) mice. The fluorescent retrograde tracer Fluoro-Gold was injected into 19 hindlimb muscles. Consecutive transverse spinal cord sections were harvested, the MNs counted, and the MN columns reconstructed in 3D. Three longitudinal MN columns were identified. The dorsolateral column extends from L4 to L6 and consists of MNs innervating the crural muscles and the foot. The ventrolateral column extends from L1 to L6 and accommodates MNs supplying the iliopsoas, gluteal, and quadriceps femoris muscles. The middle part of the ventral horn hosts the central MN column, which extends between L2–L6 and consists of MNs for the thigh adductor, hamstring, and quadratus femoris muscles. Within these longitudinal columns, the arrangement of the different MN groups reflects their somatotopic organization. MNs innervating muscles developing from the dorsal (e.g., quadriceps) and ventral muscle mass (e.g., hamstring) are situated in the lateral and medial part of the ventral gray, respectively.MN pools belonging to proximal muscles (e.g., quadratus femoris and iliopsoas) are situatedventral to those supplying more distal ones (e.g., plantar muscles). Finally, MNs innervatingflexors (e.g., posterior crural muscles) are more medial than those belonging to extensors ofthe same joint (e.g., anterior crural muscles). These data extend and modify the MN maps in the recently published atlas of the mouse spinal cord and may help when assessing neuronal loss associated with MN diseases

Combinatorial Mismatch Scan (CMS) for loci associated with dementia in the Amish

BACKGROUND: Population heterogeneity may be a significant confounding factor hampering detection and verification of late onset Alzheimer's disease (LOAD) susceptibility genes. The Amish communities located in Indiana and Ohio are relatively isolated populations that may have increased power to detect disease susceptibility genes. METHODS: We recently performed a genome scan of dementia in this population that detected several potential loci. However, analyses of these data are complicated by the highly consanguineous nature of these Amish pedigrees. Therefore we applied the Combinatorial Mismatch Scanning (CMS) method that compares identity by state (IBS) (under the presumption of identity by descent (IBD)) sharing in distantly related individuals from such populations where standard linkage and association analyses are difficult to implement. CMS compares allele sharing between individuals in affected and unaffected groups from founder populations. Comparisons between cases and controls were done using two Fisher's exact tests, one testing for excess in IBS allele frequency and the other testing for excess in IBS genotype frequency for 407 microsatellite markers. RESULTS: In all, 13 dementia cases and 14 normal controls were identified who were not related at least through the grandparental generation. The examination of allele frequencies identified 24 markers (6%) nominally (p ≤ 0.05) associated with dementia; the most interesting (empiric p ≤ 0.005) markers were D3S1262, D5S211, and D19S1165. The examination of genotype frequencies identified 21 markers (5%) nominally (p ≤ 0.05) associated with dementia; the most significant markers were both located on chromosome 5 (D5S1480 and D5S211). Notably, one of these markers (D5S211) demonstrated differences (empiric p ≤ 0.005) under both tests. CONCLUSION: Our results provide the initial groundwork for identifying genes involved in late-onset Alzheimer's disease within the Amish community. Genes identified within this isolated population will likely play a role in a subset of late-onset AD cases across more general populations. Regions highlighted by markers demonstrating suggestive allelic and/or genotypic differences will be the focus of more detailed examination to characterize their involvement in dementia

Man on His Nature

Sherrington, C. Man on his Nature. New York: The Macmillan Company; Cambridge, Eng.: The University Press,1941 Sir Charles Sherrington in his Gifford Lectures takes the task of natural theology to be a survey of the nature of man and his place in the universe from the point of view of the natural sciences, but with the addition of an evaluation of the conclusions in terms of man\u27s moral intuitions: intuitions that lie outside the scope of natural science. The interest in the survey is greatly increased by his comparing his own with one made in the sixteenth century by Jean Pernel, the greatest physician of his day, and mathematician and philosopher besides. Medical science for Fernel was still about where Galen had left it, though Fernel himself was a man of independent judgment and a good observer not prepared to follow blindly after Galen or any other authority. But of course, he was still confined to what he could see with the naked eye. Since physics and chemistry were as yet non-existent, not only was there no basis for physiology but the concept of matter was vague. The principle of life, that which distinguishes the living from the lifeless, was conceived as a kind of fire and might be corporeal or incorporeal or something intermediate. Today it is possible to speak more definitely. The most fundamental category of the physical world seems to be energy, and the structure of things to be ‘granular’, as though made up of separate but similar packets; the quantum of action, the electron, the atom, the molecule. At the level of living organisms, there is a similar ‘granularity’ in cell structure and the nervous impulse. There does not appear to be anything incorporeal about living organisms as such. The kind of physical and chemical process they exhibit is complex and peculiar, but still physical and chemical. There is no basic difference in the stuff they are made of, only in certain special arrangements of that stuff (Ritchie, A. Man on his Nature. Nature 147, 127–129 (1941))https://digitalcommons.rockefeller.edu/jason-brown-library/1058/thumbnail.jp