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. (February 2011) Synaptic potentiation onto habenula neurons in the learned helplessness model of depression. Nature, 470 (7335). 535-U125. ISSN 0028-0836

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:	Henn, Fritz A. Li, Bo Mirrione, Martine M.
Communities:	CSHL labs > Henn lab CSHL labs > Li lab CSHL Post Doctoral Fellows CSHL labs > Malinow lab
Depositing User:	Matt Covey
Date:	February 2011
Date Deposited:	06 Feb 2013 20:24
Last Modified:	02 May 2013 20:44
PMCID:	PMC3285101
Related URLs:	http://www.nature.com/nature/journal/v47...
URI:	https://repository.cshl.edu/id/eprint/27154

Actions (login required)

Administrator's edit/view item