Related Experiment Video
Updated: May 8, 2026

Animal Models of Depression - Chronic Despair Model (CDM)
Published on: September 23, 2021
βCaMKII in lateral habenula mediates core symptoms of depression
Kun Li1, Tao Zhou, Lujian Liao
1Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, P R China.
Abstract:
The lateral habenula (LHb) has recently emerged as a key brain region in the pathophysiology of depression. However, the molecular mechanism by which LHb becomes hyperactive in depression remains unknown. Through a quantitative proteomic screen, we found that expression of the β form of calcium/calmodulin-dependent protein kinase type II (βCaMΚΙΙ) was significantly up-regulated in the LHb of animal models of depression and down-regulated by antidepressants. Increasing β-, but not α-, CaMKII in the LHb strongly enhanced the synaptic efficacy and spike output of LHb neurons and was sufficient to produce profound depressive symptoms, including anhedonia and behavioral despair. Down-regulation of βCaMKII levels, blocking its activity or its target molecule the glutamate receptor GluR1 reversed the depressive symptoms. These results identify βCaMKII as a powerful regulator of LHb neuron function and a key molecular determinant of depression.
Related Concept Videos
Depression: Overview
Long-term Depression
Long-term Depression
Calcium Ion Concentration Mechanism
If over time, all...
cAMP-dependent Protein Kinase Pathways
G-protein Coupled Receptors
Calmodulin-dependent Signaling
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...

