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

Nat Commun. 2019 Nov 1;10(1):4994. doi: 10.1038/s41467-019-12962-4.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Action Potentials / physiology
  • Animals
  • Cerebral Cortex / cytology
  • Cerebral Cortex / physiology*
  • Female
  • Interneurons / metabolism
  • Interneurons / physiology*
  • Male
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Parvalbumins / genetics
  • Parvalbumins / metabolism*
  • Patch-Clamp Techniques
  • Signal Transduction / drug effects
  • Sirolimus / pharmacology
  • Somatostatin / genetics
  • Somatostatin / metabolism*
  • TOR Serine-Threonine Kinases / antagonists & inhibitors
  • TOR Serine-Threonine Kinases / metabolism
  • Tuberous Sclerosis Complex 1 Protein / genetics
  • Tuberous Sclerosis Complex 1 Protein / metabolism*


  • Parvalbumins
  • Tsc1 protein, mouse
  • Tuberous Sclerosis Complex 1 Protein
  • Somatostatin
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Sirolimus