콘텐츠로 건너뛰기
Merck
  • Emergence of non-canonical parvalbumin-containing interneurons in hippocampus of a murine model of type I lissencephaly.

Emergence of non-canonical parvalbumin-containing interneurons in hippocampus of a murine model of type I lissencephaly.

eLife (2020-11-06)
Tyler G Ekins, Vivek Mahadevan, Yajun Zhang, James A D'Amour, Gülcan Akgül, Timothy J Petros, Chris J McBain
초록

Type I lissencephaly is a neuronal migration disorder caused by haploinsuffiency of the PAFAH1B1 (mouse: Pafah1b1) gene and is characterized by brain malformation, developmental delays, and epilepsy. Here, we investigate the impact of Pafah1b1 mutation on the cellular migration, morphophysiology, microcircuitry, and transcriptomics of mouse hippocampal CA1 parvalbumin-containing inhibitory interneurons (PV+INTs). We find that WT PV+INTs consist of two physiological subtypes (80% fast-spiking (FS), 20% non-fast-spiking (NFS)) and four morphological subtypes. We find that cell-autonomous mutations within interneurons disrupts morphophysiological development of PV+INTs and results in the emergence of a non-canonical 'intermediate spiking (IS)' subset of PV+INTs. We also find that now dominant IS/NFS cells are prone to entering depolarization block, causing them to temporarily lose the ability to initiate action potentials and control network excitation, potentially promoting seizures. Finally, single-cell nuclear RNAsequencing of PV+INTs revealed several misregulated genes related to morphogenesis, cellular excitability, and synapse formation.

MATERIALS
제품 번호
브랜드
제품 설명

Sigma-Aldrich
Nuclei Isolation Kit: Nuclei PURE Prep, sufficient for 15 nuclei preparations (~1-10×107 cells or 1g of tissue per preparation)