βCaMKII in lateral habenula mediates core symptoms of depression

Li, K., Zhou, T., Liao, L., Yang, Z., Wong, C., Henn, F., Malinow, R., Yates Iii, J. R., Hu, H. (August 2013) βCaMKII in lateral habenula mediates core symptoms of depression. Science, 341 (6149). pp. 1016-1020. ISSN 00368075 (ISSN)

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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 (βCaMKII) 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.

Item Type:	Paper
Subjects:	diseases & disorders diseases & disorders > mental disorders bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification organs, tissues, organelles, cell types and functions > organs types and functions > brain diseases & disorders > mental disorders > mood disorders > depression bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > kinase bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types
CSHL Authors:	Henn, Fritz A.
Communities:	CSHL labs > Henn lab
Depositing User:	Matt Covey
Date:	30 August 2013
Date Deposited:	25 Sep 2013 15:31
Last Modified:	19 Jul 2021 14:08
PMCID:	PMC3932364
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/28634

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