Combien de neurons pour une sensation ?

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Orofacial Neuropathic Pain Leads to a Hyporesponsive Barrel Cortex with Enhanced Structural Synaptic Plasticity

International audienceChronic pain is a long-lasting debilitating condition that is particularly difficult to treat due to the lack of identified underlying mechanisms. Although several key contributing processes have been described at the level of the spinal cord, very few studies have investigated the supraspinal mechanisms underlying chronic pain. Using a combination of approaches (cortical intrinsic imaging, immunohistochemical and behavioural analysis), our study aimed to decipher the nature of functional and structural changes in a mouse model of orofacial neuropathic pain, focusing on cortical areas involved in various pain components. Our results show that chronic neuropathic orofacial pain is associated with decreased haemodynamic responsiveness to whisker stimulation in the barrel field cortex. This reduced functional activation is likely due to the increased basal neuronal activity (measured indirectly using cFos and phospho-ERK immunoreactivity) observed in several cortical areas, including the contralateral barrel field, motor and cingulate cortices. In the same animals, immunohistochemical analysis of markers for active pre-or postsynaptic elements (Piccolo and phosphoCofilin, respectively) revealed an increased immunofluorescence in deep cortical layers of the contralateral barrel field, motor and cingulate cortices. These results suggest that longlasting orofacial neuropathic pain is associated with exacerbated neuronal activity and synaptic plasticity at the cortical level

Supra-barrel Distribution of Directional Tuning for Global Motion in the Mouse Somatosensory Cortex

Summary: Rodents explore their environment with an array of whiskers, inducing complex patterns of whisker deflections. Cortical neuronal networks can extract global properties of tactile scenes. In the primary somatosensory cortex, the information relative to the global direction of a spatiotemporal sequence of whisker deflections can be extracted at the single neuron level. To further understand how the cortical network integrates multi-whisker inputs, we imaged and recorded the mouse barrel cortex activity evoked by sequences of multi-whisker deflections generating global motions in different directions. A majority of barrel-related cortical columns show a direction preference for global motions with an overall preference for caudo-ventral directions. Responses to global motions being highly sublinear, the identity of the first deflected whiskers is highly salient but does not seem to determine the global direction preference. Our results further demonstrate that the global direction preference is spatially organized throughout the barrel cortex at a supra-columnar scale. : Using voltage-sensitive dye imaging of the mouse barrel cortex, Vilarchao et al. demonstrate the presence of direction selectivity to global motion generated by multi-whisker stimuli. Selectivity to global motion is spatially organized at the supra-columnar scale with an overrepresentation of selectivity to caudo-ventral directions. Keywords: tactile sensory processing, multivibrissal stimulation, primary somatosensory cortex, barrel cortex, voltage-sensitive dye imaging, mouse, extracellular electrophysiological recording

5-HT 3 receptors mediate serotonergic fast synaptic excitation of neocortical vasoactive intestinal peptide/cholecystokinin interneurons

Neocortical neurons expressing the serotonin 5-HT 3 receptor (5-HT 3R) were characterized in rat acute slices by using patchclamp recordings combined with single-cell RT-PCR and histochemical labeling. The 5-HT 3A receptor subunit was expressed selectively in a subset of GABAergic interneurons coexpressing cholecystokinin (CCK) and vasoactive intestinal peptide (VIP). The 5-HT 3B subunit was never detected, indicating that 5-HT 3Rs expressed by neocortical interneurons did not contain this subunit. In 5-HT 3A-expressing VIP/CCK interneurons, serotonin induced fast membrane potential depolarizations by activating an inward current that was blocked by the selective 5-HT 3R antagonist tropisetron. Furthermore, we observed close appositions between serotonergic fibers and the dendrites and somata of 5-HT 3R-expressing neurons, suggestive of possible synaptic contacts. Indeed, in interneurons exhibitin

Intrinsic optical imaging reveals a decrease in sensory-evoked signals in the contralateral somatosensory cortex after ION ligation.

<p>A: Intrinsic optical signals were recorded through the intact skull, on the right posteromedial barrel subfield of the primary omatosensory cortex (S1BF; the black dotted line designates the borders of the imaging chamber). Variation in the reflected light (at 570 nm) induced by repetitive C1 whisker deflections (1 s at 100 Hz) is shown for a sham-operated (left) and an ION-ligated mouse (right). The results obtained before surgery (Baseline: BL, upper images) or 2 and 4 weeks after the surgery (2W and 4W, respectively, lower images) are expressed as R-R₀/R₀, with R representing the averaged reflected light measured over 1 s immediately after the stimulus presentation and R₀ representing the reflected light averaged over 1 s before the stimulus presentation. B: Spatial profiles of the reflected light measured along the rostro-caudal axis, using the region of interest indicated in A by the light grey rectangle. Note the absence of signal variation for the ION-ligated mouse at 2W and 4W. C: Quantification of the evoked signals was performed by looking for the minimal values of the spatial profiles (with examples shown in B). The ION ligation resulted in a significant decrease in evoked signals that persisted from the first week after the surgery through the following weeks. *p<0.05 and **p<0.01 ***p<0.001 <i>vs</i>. sham mice; #p<0.05 and ##p<0.01 <i>vs</i>. BL (n = 6 sham, n = 6 ION). All data are expressed as means ± SEM.</p

ION ligation induces the upregulation of p-Erk in different cortical areas.

<p>A-B: Representative examples of p-Erk staining in the barrel field cortex (S1BF) in sham (A) and ION (B) mice 5 weeks after the lesion/sham operation. Scale bars = 50μm. C: Quantification of the numbers of p-Erk-labelled cells in the S1BF, motor and cingulate cortices. ION ligation induced the upregulation of p-Erk+ cells. (F_1,26 = 29.571; p<0.001, n = 6 sham, n = 5 ION)</p

ION ligation induces synaptic plasticity in the S1BF, motor and cingulate cortices.

<p>A-B: Representative examples of Piccolo staining (arrow heads) in the deep laminae of the S1BF cortex in sham (A) and ION (B) mice 5 weeks after surgery. Scale bar = 50μm. C-D: Representative examples of p-Cofilin staining (arrow heads) in the deep laminae of the S1BF cortex in sham (C) and ION (D) mice. Scale bar = 50μm. E: Double immunostaining showing NeuN (green)/p-Cofilin (red) positive neurons in the S1BF (arrows). The arrow head point at a NeuN positive neuron negative for pcofilin. Scale bar = 25μm. F: Quantification of Piccolo staining in the S1BF, motor and cingulate cortices in deep and superficial laminae. ION ligation induced the upregulation of Piccolo staining in deep laminae in the S1BF and the motor cortex. Data are expressed as means ± SEM. *p<0.05 and **p<0.01 ***p<0.001 <i>vs</i>. sham mice, (n = 5 sham, n = 5 ION).</p

Upregulation of ATF3 in sensory neurons of the trigeminal ganglion after ION ligation.

<p>A-C: Double immunostaining showing ATF3 (green)/βIII tubulin (blue) positive neurons in the ipsilateral (A) and contralateral TG (B) of a representative ION animal, and the ipsilateral TG of a sham animal (C). D: Quantification of the percentage of ATF3-positive neurons in sham and ION (animals that received a ligation of the Infraorbitrary nerve) mice, 5 weeks after surgery, in the ipsilateral (ipsi) and contralateral (contra) sides of the lesion. Nerve ligation induced a statistically significant upregulation of ATF3 in the ipsilateral TG of ION animals (F_1,21 = 15.927; p<0.001). Scale bars = 50μm. ** p<0.01 ION <i>vs</i>. sham animals (n = 6 sham, n = 5 ION). Data are expressed as means ± SEM.</p

Asymmetric synthesis of a highly functionalized enantioenriched system close to thapsigargin framework

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