{"id":115666,"date":"2020-01-30T11:24:10","date_gmt":"2020-01-30T10:24:10","guid":{"rendered":"https:\/\/www.bordeaux-neurocampus.fr\/?p=115666"},"modified":"2020-01-30T15:33:36","modified_gmt":"2020-01-30T14:33:36","slug":"pascal-branchereau-et-al-in-elife","status":"publish","type":"post","link":"https:\/\/www.bordeaux-neurocampus.fr\/en\/pascal-branchereau-et-al-in-elife\/","title":{"rendered":"Pascal Branchereau et al. in eLife<\/em>"},"content":{"rendered":"
\n

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease affecting motor neurons (MNs) during late adulthood. Here, with the aim of identifying early changes underpinning ALS neurodegeneration, we analyzed the GABAergic\/glycinergic inputs to E17.5 fetal MNs from SOD1G93A<\/sup> (SOD) mice in parallel with chloride homeostasis. Our results show that IPSCs are less frequent in SOD animals in accordance with a reduction of synaptic VIAAT-positive terminals. SOD MNs exhibited an EGABAAR<\/sub>10 mV more depolarized than in WT MNs associated with a KCC2 reduction. Interestingly, SOD GABAergic\/glycinergic IPSCs and evoked GABAA<\/sub>R-currents exhibited a slower decay correlated to elevated [Cl–<\/sup>]i<\/sub>. Computer simulations revealed that a slower relaxation of synaptic inhibitory events acts as compensatory mechanism to strengthen GABA\/glycine inhibition when EGABAAR<\/sub> is more depolarized. How such mechanisms evolve during pathophysiological processes remain to be determined, but our data indicate that at least SOD1 familial ALS may be considered as a neurodevelopmental disease.<\/p>\n<\/div>\n

\"\"
Schematic drawing summarizing the altered inhibitory inputs to fetal SOD MNs. [Cl-]i is higher in SOD MNs (A1) than in WT MNs (A2) because of a KCC2 down-regulation, leading to an increased GABA\/Gly-induced depolarizing effect (see insets). B, Consequence of increasing taudecay on the GABA\/gly inhibitory effect in SOD-like MNs. Due to an accumulation in the intracellular compartment, EGABAAR exerts a strong depolarizing effect. A burst of spikes generated by MNs is hardly blocked by a barrage of GABA\/gly events (see blue traces) when taudecay is set to 20 ms. Increasing taudecay to 25 ms allows a better summation of the shunting component of the depolarizing GABA\/gly post-synaptic event leading to a better clamp of Em towards EGABAAR and to the blockade of MN discharge (see green traces).<\/figcaption><\/figure>\n

Article<\/h2>\n

Relaxation of synaptic inhibitory events as a compensatory mechanism in fetal SOD spinal motor networks.<\/strong><\/em> Branchereau P, Martin E, Allain AE, Cazenave W, Supiot L, Hodeib F, Laup\u00e9nie A, Dalvi U, Zhu H, Cattaert D. Elife<\/em>. 2019 Dec 23;8. pii: e51402.
\ndoi: 10.7554\/eLife.51402<\/a><\/p>\n

\"Pascal<\/a>
Pascal Branchereau<\/figcaption><\/figure>\n

Contact :<\/strong>
\nPascal Branchereau<\/a>
\nINCIA
\npascal.brancheau@u-bordeaux.fr<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"

Relaxation of synaptic inhibitory events as a compensatory mechanism in fetal SOD spinal motor networks.<\/p>\n","protected":false},"author":108,"featured_media":115665,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[71],"tags":[],"class_list":["post-115666","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-highlight-en"],"_links":{"self":[{"href":"https:\/\/www.bordeaux-neurocampus.fr\/en\/wp-json\/wp\/v2\/posts\/115666","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.bordeaux-neurocampus.fr\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.bordeaux-neurocampus.fr\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.bordeaux-neurocampus.fr\/en\/wp-json\/wp\/v2\/users\/108"}],"replies":[{"embeddable":true,"href":"https:\/\/www.bordeaux-neurocampus.fr\/en\/wp-json\/wp\/v2\/comments?post=115666"}],"version-history":[{"count":0,"href":"https:\/\/www.bordeaux-neurocampus.fr\/en\/wp-json\/wp\/v2\/posts\/115666\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.bordeaux-neurocampus.fr\/en\/wp-json\/wp\/v2\/media\/115665"}],"wp:attachment":[{"href":"https:\/\/www.bordeaux-neurocampus.fr\/en\/wp-json\/wp\/v2\/media?parent=115666"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.bordeaux-neurocampus.fr\/en\/wp-json\/wp\/v2\/categories?post=115666"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.bordeaux-neurocampus.fr\/en\/wp-json\/wp\/v2\/tags?post=115666"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}