Postnatal Transcriptional Activity Regulates Functional Properties of PV Interneurons

Overview

Journal iScience

Publisher Cell Press

Date 2021 Jan 25

PMID 33490907

Citations 7

Authors

Donald J Joseph

Markus von Deimling

Yuiko Hasegawa

Ana G Cristancho

Rebecca C Ahrens-Nicklas

Stephanie L Rogers

Rashmi Risbud

Almedia J McCoy

Eric D Marsh

Affiliations

Soon will be listed here.

Abstract

The transcription factor Aristaless-related X-linked gene () is a monogenic factor in early onset epileptic encephalopathies (EOEEs) and a fundamental regulator of early stages of brain development. However, expression persists in mature GABAergic neurons with an unknown role. To address this issue, we generated a conditional knockout (CKO) mouse in which postnatal was ablated in parvalbumin interneurons (PVIs). Electroencephalogram (EEG) recordings in CKO mice revealed an increase in theta oscillations and the occurrence of occasional seizures. Behavioral analysis uncovered an increase in anxiety. Genome-wide sequencing of fluorescence activated cell sorted (FACS) PVIs revealed that impinged on network excitability via genes primarily associated with synaptic and extracellular matrix pathways. Whole-cell recordings revealed prominent hypoexcitability of various intrinsic and synaptic properties. These results revealed important roles for postnatal expression in PVIs in the control of neural circuits and that dysfunction in those roles alone can cause EOEE-like network abnormalities.

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