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Tsc1 represses parvalbumin expression and fast-spiking properties in somatostatin lineage cortical interneurons.


ABSTRACT: Medial ganglionic eminence (MGE)-derived somatostatin (SST)+ and parvalbumin (PV)+ cortical interneurons (CINs), have characteristic molecular, anatomical and physiological properties. However, mechanisms regulating their diversity remain poorly understood. Here, we show that conditional loss of the Tuberous Sclerosis Complex (TSC) gene, Tsc1, which inhibits the mammalian target of rapamycin (MTOR), causes a subset of SST+ CINs, to express PV and adopt fast-spiking (FS) properties, characteristic of PV+ CINs. Milder intermediate phenotypes also occur when only one allele of Tsc1 is deleted. Notably, treatment of adult mice with rapamycin, which inhibits MTOR, reverses the phenotypes. These data reveal novel functions of MTOR signaling in regulating PV expression and FS properties, which may contribute to TSC neuropsychiatric symptoms. Moreover, they suggest that CINs can exhibit properties intermediate between those classically associated with PV+ or SST+ CINs, which may be dynamically regulated by the MTOR signaling.

SUBMITTER: Malik R 

PROVIDER: S-EPMC6825152 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Tsc1 represses parvalbumin expression and fast-spiking properties in somatostatin lineage cortical interneurons.

Malik Ruchi R   Pai Emily Ling-Lin EL   Rubin Anna N AN   Stafford April M AM   Angara Kartik K   Minasi Petros P   Rubenstein John L JL   Sohal Vikaas S VS   Vogt Daniel D  

Nature communications 20191101 1


Medial ganglionic eminence (MGE)-derived somatostatin (SST)+ and parvalbumin (PV)+ cortical interneurons (CINs), have characteristic molecular, anatomical and physiological properties. However, mechanisms regulating their diversity remain poorly understood. Here, we show that conditional loss of the Tuberous Sclerosis Complex (TSC) gene, Tsc1, which inhibits the mammalian target of rapamycin (MTOR), causes a subset of SST+ CINs, to express PV and adopt fast-spiking (FS) properties, characteristi  ...[more]

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