Synaptic potentiation onto habenula neurons in the learned helplessness model of depression

Li, B., Piriz, J., Mirrione, M., Chung, C. H., Proulx, C. D., Schulz, D., Henn, F. A., Malinow, R. (2011) Synaptic potentiation onto habenula neurons in the learned helplessness model of depression. Nature, 470 (7335). 535-U125. ISSN 0028-0836

URL: http://www.ncbi.nlm.nih.gov/pubmed/21350486
DOI: 10.1038/nature09742

Abstract

The cellular basis of depressive disorders is poorly understood(1). Recent studies in monkeys indicate that neurons in the lateral habenula (LHb), a nucleus that mediates communication between forebrain and midbrain structures, can increase their activity when an animal fails to receive an expected positive reward or receives a stimulus that predicts aversive conditions (that is, disappointment or anticipation of a negative outcome)(2-4). LHb neurons project to, and modulate, dopamine-rich regions, such as the ventral tegmental area (VTA)(2,5), that control reward-seeking behaviour(6) and participate in depressive disorders(7). Here we show that in two learned helplessness models of depression, excitatory synapses onto LHb neurons projecting to the VTA are potentiated. Synaptic potentiation correlates with an animal's helplessness behaviour and is due to an enhanced presynaptic release probability. Depleting transmitter release by repeated electrical stimulation of LHb afferents, using a protocol that can be effective for patients who are depressed(8,9), markedly suppresses synaptic drive onto VTA-projecting LHb neurons in brain slices and can significantly reduce learned helplessness behaviour in rats. Our results indicate that increased presynaptic action onto LHb neurons contributes to the rodent learned helplessness model of depression.

Item Type: Paper
Uncontrolled Keywords: midbrain dopamine neurons dorsal raphe nucleus lateral habenula animal-model tryptophan depletion responses behavior stress rat stimulation
Subjects: diseases & disorders
diseases & disorders > mental disorders
diseases & disorders > mental disorders > mood disorders
organism description > animal
organs, tissues, organelles, cell types and functions > cell types and functions > cell functions
organs, tissues, organelles, cell types and functions > cell types and functions > cell types
organs, tissues, organelles, cell types and functions > cell types and functions > cell types
organs, tissues, organelles, cell types and functions > cell types and functions > cell types

organs, tissues, organelles, cell types and functions > cell types and functions
diseases & disorders > mental disorders > mood disorders > depression
organism description > animal > mammal
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons

organism description > animal > mammal > rodent > rat
organism description > animal > mammal > rodent > rat

organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > synaptic transmission
CSHL Authors:
Communities: CSHL labs > Henn lab
CSHL labs > Li lab
CSHL Post Doctoral Fellows
CSHL labs > Malinow lab
Depositing User: Matt Covey
Date Deposited: 06 Feb 2013 20:24
Last Modified: 02 May 2013 20:44
PMCID: PMC3285101
Related URLs:
URI: http://repository.cshl.edu/id/eprint/27154

Actions (login required)

Administrator's edit/view item Administrator's edit/view item
CSHL HomeAbout CSHLResearchEducationNews & FeaturesCampus & Public EventsCareersGiving