Non-monosynaptic group I and group II excitation of human lower limb motoneurones was investigated. Changes in the firing probability of individual voluntarily activated motor units belonging to various muscles (soleus, gastrocnemius medialis, tibialis anterior, peroneus brevis, quadriceps and biceps femoris) were investigated after stimulation of various nerves (posterior tibial, common peroneal and femoral nerves) with weak (0.4-0.6x motor threshold) electrical stimuli. In all investigated motor nuclei, stimulation of the "homonymous" nerve evoked a peak of increased firing probability with a latency that was 3-7 ms longer than the monosynaptic Ia latency. The more caudal the motor nucleus explored, the greater the central delay. This strongly suggests a transmission through neurones located above the lumbar enlargement. If one excepts the sural-induced excitation of peroneus brevis units, which seems to be mediated through a particular pathway, the main peripheral input to neurones mediating non-monosynaptic excitation evoked by these weak stimuli is group I in origin. The pattern of distribution of non-monosynaptic group I excitation was very diffuse, since stimulation of each nerve was able to evoke excitation in all investigated nuclei. In most cases, non-monosynaptic excitation evoked in a given motor unit by stimulation of one nerve was depressed on combined stimulation of two nerves, and evidence is presented that this lateral inhibition is exerted at a premotoneuronal level. By contrast, there was no evidence that increasing the afferent input in a given pathway evokes an "autogenetic" inhibition in this pathway. The negative correlation found between non-monosynaptic group I-induced and late group II-induced facilitation of the quadriceps H-reflex when using high stimulus intensities applied on the common peroneal nerve suggests that these two effects could be mediated through common interneurones.

Summary:Despite the efforts employed, understanding the genetic architecture underlying epilepsy remains difficult. To reach this aim, convulsive epilepsies are classically modeled in mice, where genetic studies are less constricting than in humans. Pharmacogenetic approaches are one major source of investigation where kainic acid, pentylenetetrazol, and the ß-carboline family represent compounds that are used extensively. Several quantitative trait loci (QTLs) influencing the convulsant effects of these drugs have been mapped using either recombinant inbred strains (RIS) or segregating F2 populations (or both). In our laboratory, we have recently mapped two QTLs for methyl 6, 7-dimethoxy-4-ethyl-ß-carboline-3-carboxylate (DMCM), and seizure response using an F2 method. One is located on the distal part of Chromosome 1, a region implicated in a number of other studies. Here, we address the general importance of this chromosomal fragment for influencing seizure susceptibility.

The diaphragm muscle is essential for breathing in mammals. Its asymmetric elevation during contraction correlates with morphological features suggestive of inherent left–right (L/R) asymmetry. Whether this asymmetry is due to L versus R differences in the muscle or in the phrenic nerve activity is unknown. Here, we have combined the analysis of genetically modified mouse models with transcriptomic analysis to show that both the diaphragm muscle and phrenic nerves have asymmetries, which can be established independently of each other during early embryogenesis in pathway instructed by Nodal, a morphogen that also conveys asymmetry in other organs. We further found that phrenic motoneurons receive an early L/R genetic imprint, with L versus R differences both in Slit/Robo signaling and MMP2 activity and in the contribution of both pathways to establish phrenic nerve asymmetry. Our study therefore demonstrates L–R imprinting of spinal motoneurons and describes how L/R modulation of axon guidance signaling helps to match neural circuit formation to organ asymmetry.DOI: http://dx.doi.org/10.7554/eLife.18481.001

The mutation extra-toes (Gli3Xt-J) on chromosome (Chr) 13 of the mouse is known to be involved in the development of the skeleton. The only visible manifestation is the presence of an extra digit on each hind foot. Here we report evidence from several experiments that Gli3XtJ/+ mice weigh more than littermate Gli3+/+ mice, suggesting an effect on body weight of Gli3 or of a gene tightly linked to it on Chr 13. Four independent experiments in different environments were conducted on mice with different genetic backgrounds derived from the C3XtEso Gli3Xt-J/+ Eso/+ linkage testing strain and the JE/Le strain at adult age. The analyses have shown an association between the Gli3Xt-J allele and a body weight increase of about 6.5%. This effect is genetically dominant. It would appear that if the gene of interest is not Gli3 itself, it must be very close to this locus. Indeed, the expected size for this fragment is 7.9 ± 5.3 cM. The manifestation of this gene, observed in two animal facilities and on different genetic backgrounds, is consistent with the idea that the effect of the gene(s) is displayed in a stable manner. It accounts for a variation of 6.5% of body weight.