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

Autor: Zorrilla de San Martin J; Institut du Cerveau (ICM), CNRS UMR 7225 - Inserm U1127, Sorbonne Université, Paris, France., Donato C; Institut du Cerveau (ICM), CNRS UMR 7225 - Inserm U1127, Sorbonne Université, Paris, France., Peixoto J; Institut du Cerveau (ICM), CNRS UMR 7225 - Inserm U1127, Sorbonne Université, Paris, France., Aguirre A; Institut du Cerveau (ICM), CNRS UMR 7225 - Inserm U1127, Sorbonne Université, Paris, France., Choudhary V; Institut du Cerveau (ICM), CNRS UMR 7225 - Inserm U1127, Sorbonne Université, Paris, France., De Stasi AM; Institut du Cerveau (ICM), CNRS UMR 7225 - Inserm U1127, Sorbonne Université, Paris, France., Lourenço J; Institut du Cerveau (ICM), CNRS UMR 7225 - Inserm U1127, Sorbonne Université, Paris, France., Potier MC; Institut du Cerveau (ICM), CNRS UMR 7225 - Inserm U1127, Sorbonne Université, Paris, France., Bacci A; Institut du Cerveau (ICM), CNRS UMR 7225 - Inserm U1127, Sorbonne Université, Paris, France.
Jazyk: angličtina
Zdroj: ELife [Elife] 2020 Aug 12; Vol. 9. Date of Electronic Publication: 2020 Aug 12.
DOI: 10.7554/eLife.58731
Abstrakt: Down syndrome (DS) results in various degrees of cognitive deficits. In DS mouse models, recovery of behavioral and neurophysiological deficits using GABA A R 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.
Competing Interests: JZ, CD, JP, AA, VC, AD, JL, MP, AB No competing interests declared
(© 2020, Zorrilla de San Martin et al.)
Databáze: MEDLINE
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