Upregulation of TASK-3 Underlies Retraction of Spontaneous Activity in the Developing Mouse Hindbrain

Abstract

The cessation of spontaneous activity (SA) is an important characteristic of this immature form of cellular excitability. While we have extensively documented the precise timing and patterning of mouse hindbrain SA, the mechanism behind its termination remained a mystery. For my thesis project, I sought to elucidate the molecular mechanism behind hindbrain SA retraction and subsequent termination. I hypothesized that a class of background leak potassium channels, K2P channels, were upregulated in the same spatiotemporal manner as SA retraction, allowing for the hyperpolarization of resting membrane potential that leads to the silencing of cellular activity. By pharmacologically targeting the precise K2P channel I identified to be upregulated, TASK-3, I was able to reactivate cells that had already been silenced. Finally, I utilized open-source transcriptome data to explore plausible biological pathways that might be linked to hindbrain SA regulation.