Enhanced long-term microcircuit plasticity in the valproic Acid animal model of autism

A single intra-peritoneal injection of valproic acid (VPA) on embryonic day (ED) 11.5 to pregnant rats has been shown to produce severe autistic-like symptoms in the offspring. Previous studies showed that the microcircuitry is hyperreactive due to hyperconnectivity of glutamatergic synapses and hyperplastic due to over-expression of NMDA receptors. These changes were restricted to the dimensions of a minicolumn (

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Jean-Vincent Le Bé, Henry Markram, Kamila Markram, Imad Riachi, Tania Rinaldi, Guilherme Silva
2009
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https://infoscience.epfl.ch/record/183391?ln=fr

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Neurone

thumb|537x537px|Schéma complet d’un neurone. Un neurone, ou une cellule nerveuse, est une cellule excitable constituant l'unité fonctionnelle de la base du système nerveux. Les neurones assurent la

Cellule pyramidale

Les cellules pyramidales sont un certain type de neurone. Leur nom vient de la morphologie triangulaire de leur péricaryon. Elles possèdent en outre un arbre dendritique très développé qui reçoit un

Animal

vignette|upright=1.5|Biomasse animale totale (en gigatonne de carbone). Les Animaux (Animalia) (du latin animalis « animé, vivant, animal ») sont en biologie, selon la classification classique, des ê

Layer- and column-specific knockout of NMDA receptors in pyramidal neurons of the mouse barrel cortex

Rachel Aronoff, Carl Petersen

Viral vectors injected into the mouse brain offer the possibility for localized genetic modifications in a highly controlled manner. Lentivector injection into mouse neocortex transduces cells within a diameter of approximately 200mum, which closely matches the lateral scale of a column in barrel cortex. The depth and volume of the injection determines which cortical layer is transduced. Furthermore, transduced gene expression from the lentivector can be limited to predominantly pyramidal neurons by using a 1.3kb fragment of the alphaCaMKII promoter. This technique therefore allows genetic manipulation of a specific cell type in defined columns and layers of the neocortex. By expressing Cre recombinase from such a lentivector in gene-targeted mice carrying a floxed gene, highly specific genetic lesions can be induced. Here, we demonstrate the utility of this approach by specifically knocking out NMDA receptors (NMDARs) in pyramidal neurons in the somatosensory barrel cortex of gene-targeted mice carrying floxed NMDAR 1 genes. Neurons transduced with lentivector encoding GFP and Cre recombinase exhibit not only reductions in NMDAR 1 mRNA levels, but reduced NMDAR-dependent currents and pairing-induced synaptic potentiation. This technique for knockout of NMDARs in a cell type, column- and layer-specific manner in the mouse somatosensory cortex may help further our understanding of the functional roles of NMDARs in vivo during sensory perception and learning.

Frontiers Research Foundation2007

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Combined rehabilitation promotes recovery of motor functionality in a mouse model of stroke

Silvestro Micera, Maria Pasquini

Neuro-rehabilitative research is developing novel strategies to enhance the effectiveness of therapies after stroke by using a combination of physical and plasticizing treatments 1-3. Previous studies have shown that repeated optogenetics stimulation of neurons in the peri-lesioned area induces a significant improvement in cerebral blood flow and neurovascular coupling response 4-6. Up to now the mechanisms underneath the reshaping of brain circuitry induced by rehabilitation after stroke are widely unknown. To investigate how rehabilitative therapies shape new cortical maps in the peri-infarct region, we induce a photothrombotic stroke in the primary motor cortex and the expression of Channelrhodopsine 2 (ChR2) in the peri-infarct area on Thyl-GCaMP6f mice. To promote functional recovery after stroke we use both an optogenetic strategy to stimulate targeted excitatory neurons in the peri-lesional region and motor training on a robotic platform (M-Platform) 7. A 473 nm laser repeatedly stimulates ChR2-transfected neurons; the optostimulation is performed five days a week. The motor rehabilitation consists in a pulling task: after the forelimb is passively extended by the linear actuator of the M-platform, the animal has to pull back up to the resting position. By analysing the spatio-temporal calcium dynamic and the reshaping of cortical activation area during the movement throughout the treatment period, we found that the combined treatment restores cortical activation profiles during the forelimb movement. Through behavioural experiments, using Schallert test, we also evaluate changes of forelimb functionality during rehabilitation. Our combination of techniques allows obtaining unprecedented views on cortical plasticity induced by rehabilitative therapies.

SPIE-INT SOC OPTICAL ENGINEERING2019

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