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  Alterations of specific cortical GABAergic circuits underlie abnormal network activity in a mouse model of Down syndrome

Zorrilla de San Martin, J., Donato, C., Peixoto, J., Aguirre, A., Choudhary, V., De Stasi, A., et al. (2020). Alterations of specific cortical GABAergic circuits underlie abnormal network activity in a mouse model of Down syndrome. eLife, 9, 1-23. doi:10.7554/eLife.58731.

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Zorrilla de San Martin, J, Author
Donato, C, Author
Peixoto, J, Author
Aguirre, A, Author
Choudhary, V1, Author           
De Stasi, AM, Author
Lourenço , J, Author
Potier, M-C, Author
Bacco, A, Author
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1External Organizations, ou_persistent22              

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 Abstract: Down syndrome (DS) results in various degrees of cognitive deficits. In DS mouse models, recovery of behavioral and neurophysiological deficits using GABAAR antagonists led to hypothesize an excessive activity of inhibitory circuits in this condition. Nonetheless, whether over-inhibition is present in DS and whether this is due to specific alterations of distinct GABAergic circuits is unknown. In the prefrontal cortex of Ts65Dn mice (a well-established DS model), we found that the dendritic synaptic inhibitory loop formed by somatostatin-positive Martinotti cells (MCs) and pyramidal neurons (PNs) was strongly enhanced, with no alteration in their excitability. Conversely, perisomatic inhibition from parvalbumin-positive (PV) interneurons was unaltered, but PV cells of DS mice lost their classical fast-spiking phenotype and exhibited increased excitability. These microcircuit alterations resulted in reduced pyramidal-neuron firing and increased phase locking to cognitive-relevant network oscillations in vivo. These results define important synaptic and circuit mechanisms underlying cognitive dysfunctions in DS.

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 Dates: 2020-08
 Publication Status: Published online
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 Identifiers: DOI: 10.7554/eLife.58731
eDoc: e58731
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Title: eLife
Source Genre: Journal
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Publ. Info: Cambridge : eLife Sciences Publications
Pages: - Volume / Issue: 9 Sequence Number: - Start / End Page: 1 - 23 Identifier: ISSN: 2050-084X
CoNE: https://pure.mpg.de/cone/journals/resource/2050-084X