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

Abstract

The cellular basis of depressive disorders is poorly understood. 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). LHb neurons project to, and modulate, dopamine-rich regions, such as the ventral tegmental area (VTA), that control reward-seeking behaviour and participate in depressive disorders. 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, 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.

Authors:
; ; ; ; ; ; ; ; ;
Publication Date:
Research Org.:
BROOKHAVEN NATIONAL LABORATORY (BNL)
Sponsoring Org.:
DOE - OFFICE OF SCIENCE
OSTI Identifier:
1014358
Report Number(s):
BNL-95032-2011-JA
Journal ID: ISSN 0028-0836; R&D Project: MO-085; YN1020000; TRN: US1102739
DOE Contract Number:  
DE-AC02-98CH10886
Resource Type:
Journal Article
Resource Relation:
Journal Name: Nature; Journal Volume: 470; Journal Issue: 7335
Country of Publication:
United States
Language:
English
Subject:
38 RADIATION CHEMISTRY, RADIOCHEMISTRY, AND NUCLEAR CHEMISTRY; ANIMALS; BIOLOGICAL MODELS; BRAIN; COMMUNICATIONS; MONKEYS; NERVE CELLS; PATIENTS; PROBABILITY; RODENTS; STIMULATION; models of depression; habenula neurons; synaptic potentiation; helplessness

Citation Formats

Li, B., Schulz, D., Li, B, Piriz, J., Mirrione, M., Chung, C.H., Proulx, C.D., Schulz, D., Henn, F., and Malinow, R. Synaptic potentiation onto habenula neurons in the learned helplessness model of depression. United States: N. p., 2011. Web. doi:10.1038/nature09742.
Li, B., Schulz, D., Li, B, Piriz, J., Mirrione, M., Chung, C.H., Proulx, C.D., Schulz, D., Henn, F., & Malinow, R. Synaptic potentiation onto habenula neurons in the learned helplessness model of depression. United States. doi:10.1038/nature09742.
Li, B., Schulz, D., Li, B, Piriz, J., Mirrione, M., Chung, C.H., Proulx, C.D., Schulz, D., Henn, F., and Malinow, R. Thu . "Synaptic potentiation onto habenula neurons in the learned helplessness model of depression". United States. doi:10.1038/nature09742.
@article{osti_1014358,
title = {Synaptic potentiation onto habenula neurons in the learned helplessness model of depression},
author = {Li, B. and Schulz, D. and Li, B and Piriz, J. and Mirrione, M. and Chung, C.H. and Proulx, C.D. and Schulz, D. and Henn, F. and Malinow, R.},
abstractNote = {The cellular basis of depressive disorders is poorly understood. 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). LHb neurons project to, and modulate, dopamine-rich regions, such as the ventral tegmental area (VTA), that control reward-seeking behaviour and participate in depressive disorders. 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, 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.},
doi = {10.1038/nature09742},
journal = {Nature},
number = 7335,
volume = 470,
place = {United States},
year = {Thu Feb 24 00:00:00 EST 2011},
month = {Thu Feb 24 00:00:00 EST 2011}
}