REVIEW article
Front. Syst. Neurosci.
This article is part of the Research TopicBrain Injury after Hypoxia/Ischemia: Mechanisms, Pathogenesis, and Potential Therapeutic InterventionsView all articles
When the Gatekeeper is Absent: Thalamic Reticular Nucleus in Development and Hypoxic-Ischemic Injury After Cardiac Arrest
Provisionally accepted
- 1Children’s Research Institute, Children’s National Hospital, Washington DC, United States
- 2George Washington University School of Medicine and Health Sciences, Washington, United States
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
The thalamic reticular nucleus orchestrates thalamocortical oscillations and sensory gating. Its early development features a unique confluence of depolarizing GABA signaling, immature chloride regulation, and transient electrical coupling via connexin-36 gap junctions. These developmental specializations, essential for synchronizing cortical maturation, also render thalamocortical networks vulnerable to hypoxic–ischemic insults such as perinatal asphyxia or pediatric cardiac arrest. Following cellular ATP depletion, rapid chloride imbalance eliminates fast synaptic inhibition, permitting abnormal network activity to propagate via gap-junction coupling that persists when chemical inhibition collapses. The resulting electrical hypersynchrony, exacerbated by depolarizing GABAergic currents and impaired chloride extrusion, promotes excitotoxicity and thalamocortical dysrhythmia. This review synthesizes recent evidence to establish a framework that accounts for the selective vulnerability of the immature brain. Understanding these mechanisms may inform strategies to preserve developmental integrity and promote circuit resilience after pediatric asphyxial events.
Keywords: Cardiac arrest, chloride homeostasis, connexin-36, developmental neurophysiology, GABAA receptor, hypoxia–ischemia, network synchrony, Thalamic reticular nucleus
Received: 24 Nov 2025; Accepted: 13 Feb 2026.
Copyright: © 2026 Hsiao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Kuangfu Hsiao
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.