Decoding Depression: Insights from Glial and Ketamine Regulation of Neuronal Burst Firing in Lateral Habenula

  1. Hailan Hu1,2,3,4
  1. 1Center for Neuroscience and Department of Psychiatry of First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China
  2. 2NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University, Hangzhou 310058, China
  3. 3Interdisciplinary Institute of Neuroscience and Technology, Qiushi Academy for Advanced Studies, Zhejiang University, Hangzhou 310058, China
  4. 4Mental Health Center, Zhejiang University, Hangzhou 310013, China
  1. Correspondence: huhailan{at}zju.edu.cn

Abstract

The rapid antidepressant effect of ketamine is arguably one of the most significant advances in the mental health field in the last half century. However, its mechanism of action has remained elusive. Here, we describe our latest discovery on how ketamine blocks N-methyl-D-aspartate receptor (NMDAR)-dependent burst firing of an “antireward” center in the brain, the lateral habenula (LHb), to mediate its antidepressant effects. We also discuss a novel structure–function mechanism at the glia–neuron interface to account for the enhanced LHb bursting during depression. These results reveal new molecular targets for the therapeutic intervention of major depression.

This article is distributed under the terms of the Creative Commons Attribution-NonCommercial License, which permits reuse and redistribution, except for commercial purposes, provided that the original author and source are credited.

| Table of Contents