Chronic Stress Induces Activity, Synaptic, and Transcriptional Remodeling of the Lateral Habenula Associated with Deficits in Motivated Behaviors

Cerniauskas, Ignas; Winterer, Jochen; de Jong, Johannes W.; Lukacsovich, David; Yang, Hongbin; Khan, Fawwad; Peck, James R.; Obayashi, Sophie K.; Lilascharoen, Varoth; Lim, Byung Kook; Földy, Csaba; Lammel, Stephan

doi:10.1016/j.neuron.2019.09.005

Cited by 187Neurotransmitter Receptor Influence on BehaviorNeuroscience and Neuropharmacology ResearchTreatment of Major Depression

Chronic Stress Induces Activity, Synaptic, and Transcriptional Remodeling of the Lateral Habenula Associated with Deficits in Motivated Behaviors

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Cerniauskas, Ignas, Winterer, Jochen, de Jong, Johannes W., Lukacsovich, David, Yang, Hongbin, Khan, Fawwad, Peck, James R., Obayashi, Sophie K. +4 more·2019·Neuron

DOI 10.1016/j.neuron.2019.09.005PMC PMC6895430

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Abstract

Chronic stress (CS) is a major risk factor for the development of depression. Here, we demonstrate that CS-induced hyperactivity in ventral tegmental area (VTA)-projecting lateral habenula (LHb) neurons is associated with increased passive coping (PC), but not anxiety or anhedonia. LHb→VTA neurons in mice with increased PC show increased burst and tonic firing as well as synaptic adaptations in excitatory inputs from the entopeduncular nucleus (EP). In vivo manipulations of EP→LHb or LHb→VTA neurons selectively alter PC and effort-related motivation. Conversely, dorsal raphe (DR)-projecting LHb neurons do not show CS-induced hyperactivity and are targeted indirectly by the EP. Using single-cell transcriptomics, we reveal a set of genes that can collectively serve as biomarkers to identify mice with increased PC and differentiate LHb→VTA from LHb→DR neurons. Together, we provide a set of biological markers at the level of genes, synapses, cells, and circuits that define a distinctive CS-induced behavioral phenotype.

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Lateral habenula neurons fire in response to aversive stimuli and the absence of an expected reward.
“LHb neurons fire in response to both aversive stimuli and the absence of an expected reward [257-260].”
From Plasticity of synapses and reward circuit function in the genesis and treatment of depression (2023) · cites this paper as [259]
Optogenetic activation of lateral habenula neurons via lateral hypothalamic projections triggers avoidance and escape behaviors, whereas optogenetic or pharmacological inhibition of lateral habenula discharge impairs avoidance and escape in response to aversive stimuli.
“Optogenetic activation of LHb neurons via projections from the lateral hypothalamic nucleus (LH) triggers avoidance and escape behaviors, whereas optogenetic or pharmacological inhibition of LHb cell discharge impairs avoidance and escape in response to aversive stimuli [258][259][260].”
From Plasticity of synapses and reward circuit function in the genesis and treatment of depression (2023) · cites this paper as [259]

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Measuring the Accuracy of Diagnostic Systems
Swets, J. A. (1988) · Science · doi:10.1126/science.3287615 · Cited by 10,058 · see citing works
Receiver-operating characteristic (ROC) plots: a fundamental evaluation tool in clinical medicine
ZWEIG, M. H., & Campbell, G. (1993) · Clinical Chemistry · doi:10.1093/clinchem/39.4.561 · Cited by 6,528 · see citing works
Basic principles of ROC analysis
Metz, C. E. (1978) · Seminars in Nuclear Medicine · doi:10.1016/s0001-2998(78)80014-2 · Cited by 6,058 · see citing works
Dopamine, learning and motivation.
Wise, R. A. (2004) · Nature Reviews Neuroscience · doi:10.1038/nrn1406 · Cited by 3,379 · cited 1× · see citing works
“Such behaviors are thought to be controlled by brain reward system which consists of circuits involving forebrain limbic system and its connections to the midbrain aminergic centers (Wise, 2004; Cools et al., 2011).”
Coping styles in animals: current status in behavior and stress-physiology
Koolhaas, J. M., Korte, S. M., De Boer, S. F., Van Der Vegt, B. J., Van Reenen, C. G., Hopster, H., De Jong, I. C., Ruis, M. A. W., & Blokhuis, H. J. (1999) · Neuroscience & Biobehavioral Reviews · doi:10.1016/s0149-7634(99)00026-3 · Cited by 2,875 · cited 1× · see citing works
“Mice initially attempt vigorous escape but then transition to a passive coping (PC) state (Koolhaas et al., 1999).”
Background
Molecular Adaptations Underlying Susceptibility and Resistance to Social Defeat in Brain Reward Regions
Krishnan, V., Han, M.-H., Graham, D. L., Berton, O., Renthal, W., Russo, S. J., LaPlant, Q., Graham, A., Lutter, M., Lagace, D. C., et al. (2007) · Cell · doi:10.1016/j.cell.2007.09.018 · Cited by 2,307 · cited 14× · see citing works
“(A) Schematic showing C57BL/6 mice in the tail suspension test (TST) and one week later in the forced swim test (FST).”
BackgroundResultInfluential
Resting-state connectivity biomarkers define neurophysiological subtypes of depression
Drysdale, A. T., Grosenick, L., Downar, J., Dunlop, K., Mansouri, F., Meng, Y., Fetcho, R. N., Zebley, B., Oathes, D. J., Etkin, A., et al. (2017) · Nature Medicine · doi:10.1038/nm.4246 · Cited by 2,170 · see citing works
The mesolimbic dopamine reward circuit in depression
Nestler, E. J., & Carlezon, W. A. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2005.09.018 · Cited by 2,059 · see citing works
Animal models of neuropsychiatric disorders
Nestler, E. J., & Hyman, S. E. (2010) · Nature Neuroscience · doi:10.1038/nn.2647 · Cited by 2,023 · see citing works
Validity, reliability and utility of the chronic mild stress model of depression: a 10-year review and evaluation
Willner, P. (1997) · Psychopharmacology · doi:10.1007/s002130050456 · Cited by 1,832 · see citing works
Stress, Depression, and Neuroplasticity: A Convergence of Mechanisms
Pittenger, C., & Duman, R. S. (2008) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301574 · Cited by 1,795 · see citing works
Chronic Mild Stress (CMS) Revisited: Consistency and Behavioural-Neurobiological Concordance in the Effects of CMS
Willner, P. (2005) · Neuropsychobiology · doi:10.1159/000087097 · Cited by 1,605 · see citing works
New approaches to antidepressant drug discovery: beyond monoamines
Berton, O., & Nestler, E. J. (2006) · Nature Reviews Neuroscience · doi:10.1038/nrn1846 · Cited by 1,589 · see citing works
A step-by-step workflow for low-level analysis of single-cell RNA-seq data with Bioconductor
Lun, A. T. L., McCarthy, D. J., & Marioni, J. C. (2016) · F1000Research · doi:10.12688/f1000research.9501.2 · Cited by 1,586 · see citing works
Receiver-operating characteristic analysis for evaluating diagnostic tests and predictive models
Zou, K. H., O’Malley, A. J., & Mauri, L. (2007) · Circulation · doi:10.1161/circulationaha.105.594929 · Cited by 1,473 · see citing works
Ca2 + Permeability of KA-AMPA—Gated Glutamate Receptor Channels Depends on Subunit Composition
Hollmann, M., Hartley, M., & Heinemann, S. F. (1991) · Science · doi:10.1126/science.1709304 · Cited by 1,450 · see citing works
Progressive ratio schedules in drug self-administration studies in rats: a method to evaluate reinforcing efficacy
Richardson, N. R., & Roberts, D. C. S. (1996) · Journal of Neuroscience Methods · doi:10.1016/0165-0270(95)00153-0 · Cited by 1,357 · see citing works
Input-specific control of reward and aversion in the ventral tegmental area
Lammel, S., Lim, B. K., Ran, C., Huang, K. W., Betley, M. J., Tye, K. M., Deisseroth, K., & Malenka, R. C. (2012) · Nature · doi:10.1038/nature11527 · Cited by 1,300 · see citing works
Self-citation
Lateral habenula as a source of negative reward signals in dopamine neurons
Matsumoto, M., & Hikosaka, O. (2007) · Nature · doi:10.1038/nature05860 · Cited by 1,292 · see citing works
Amygdala circuitry mediating reversible and bidirectional control of anxiety
Tye, K. M., Prakash, R., Kim, S.-Y., Fenno, L. E., Grosenick, L., Zarabi, H., Thompson, K. R., Gradinaru, V., Ramakrishnan, C., & Deisseroth, K. (2011) · Nature · doi:10.1038/nature09820 · Cited by 1,289 · see citing works
Paxinos and Franklin's the Mouse Brain in Stereotaxic Coordinates
Paxinos, G., & Franklin, K. B. J. (2012) · Cited by 1,267 · see citing works
Chronic mild stress-induced anhedonia: A realistic animal model of depression
Willner, P., Muscat, R., & Papp, M. (1992) · Neuroscience & Biobehavioral Reviews · doi:10.1016/s0149-7634(05)80194-0 · Cited by 1,160 · cited 3× · see citing works
“anhedonia, social withdrawal), which are thought to reflect some of the core symptoms seen in depressed humans (Berton et al., 2012; Monteggia et al., 2018; Nestler and Hyman, 2010; Willner et al., 1992).”
BackgroundMethod
Progressive Ratio as a Measure of Reward Strength
Hodos, W. (1961) · Science · doi:10.1126/science.134.3483.943 · Cited by 1,147 · see citing works
Dopamine neurons modulate neural encoding and expression of depression-related behaviour
Tye, K. M., Mirzabekov, J. J., Warden, M. R., Ferenczi, E. A., Tsai, H.-C., Finkelstein, J., Kim, S.-Y., Adhikari, A., Thompson, K. R., Andalman, A. S., et al. (2013) · Nature · doi:10.1038/nature11740 · Cited by 1,073 · see citing works
The subcellular organization of neocortical excitatory connections
Petreanu, L., Mao, T., Sternson, S. M., & Svoboda, K. (2009) · Nature · doi:10.1038/nature07709 · Cited by 1,047 · see citing works
Ketamine blocks bursting in the lateral habenula to rapidly relieve depression
Yang, Y., Cui, Y., Sang, K., Dong, Y., Ni, Z., Ma, S., & Hu, H. (2018) · Nature · doi:10.1038/nature25509 · Cited by 1,036 · see citing works
The chronic mild stress (CMS) model of depression: History, evaluation and usage
Willner, P. (2017) · Neurobiology of Stress · doi:10.1016/j.ynstr.2016.08.002 · Cited by 959 · see citing works
Afferent connections of the habenular nuclei in the rat. A horseradish peroxidase study, with a note on the fiber‐of‐passage problem
Herkenham, M. A., & Nauta, W. J. H. (1977) · The Journal of Comparative Neurology · doi:10.1002/cne.901730107 · Cited by 798 · see citing works
Skeletal Muscle PGC-1α1 Modulates Kynurenine Metabolism and Mediates Resilience to Stress-Induced Depression
Agudelo, L. Z., Femenía, T., Orhan, F., Porsmyr-Palmertz, M., Goiny, M., Martinez-Redondo, V., Correia, J. C., Izadi, M., Bhat, M., Schuppe-Koistinen, I., et al. (2014) · Cell · doi:10.1016/j.cell.2014.07.051 · Cited by 739 · see citing works
Rodent Models of Depression: Forced Swim and Tail Suspension Behavioral Despair Tests in Rats and Mice
Castagné, V., Moser, P., Roux, S., & Porsolt, R. D. (2011) · Current Protocols in Neuroscience · doi:10.1002/0471142301.ns0810as55 · Cited by 702 · see citing works
The rostromedial tegmental nucleus (RMTg), a GABAergic afferent to midbrain dopamine neurons, encodes aversive stimuli and inhibits motor responses.
Jhou, T. C., Fields, H. L., Baxter, M. G., Saper, C. B., & Holland, P. C. (2009) · Neuron · doi:10.1016/j.neuron.2009.02.001 · Cited by 696 · see citing works
Untitled work
(2000) · PubMed · Cited by 685 · see citing works
SSRI Antidepressant Medications: Adverse Effects and Tolerability
Ferguson, J. M. (2001) · The Primary Care Companion For CNS Disorders · doi:10.4088/pcc.v03n0105 · Cited by 669 · cited 1× · see citing works
“Moreover, treatment with antidepressants has numerous side effects, such as fatigue, sleep disturbances, weight and appetite, and sexual dysfunction (Fergusson, 2001).”
The Tail Suspension Test
Can, A., Dao, D. T., Terrillion, C. E., Piantadosi, S. C., Bhat, S., & Gould, T. D. (2011) · Journal of Visualized Experiments · doi:10.3791/3769 · Cited by 657 · see citing works
A prefrontal cortex–brainstem neuronal projection that controls response to behavioural challenge
Warden, M. R., Selimbeyoglu, A., Mirzabekov, J. J., Lo, M., Thompson, K. R., Kim, S.-Y., Adhikari, A., Tye, K. M., Frank, L. M., & Deisseroth, K. (2012) · Nature · doi:10.1038/nature11617 · Cited by 645 · see citing works
“Behavioural despair” in rats and mice: Strain differences and the effects of imipramine
Porsolt, R. D., Bertin, A., & Jalfre, M. (1978) · European Journal of Pharmacology · doi:10.1016/0014-2999(78)90414-4 · Cited by 640 · see citing works
Synaptic potentiation onto habenula neurons in the learned helplessness model of depression
Li, B., Piriz, J., Mirrione, M., Chung, C., Proulx, C. D., Schulz, D., Henn, F., & Malinow, R. (2011) · Nature · doi:10.1038/nature09742 · Cited by 634 · cited 10× · see citing works
“On the other hand, LHb neurons are mainly glutamatergic as demonstrated by extensive expression of vesicular glutamate transporter VGlut2 (Li et al., 2011; Lammel et al., 2012).”
BackgroundMethodResultInfluential
The Mouse Forced Swim Test
Can, A., Dao, D. T., Arad, M., Terrillion, C. E., Piantadosi, S. C., & Gould, T. D. (2011) · Journal of Visualized Experiments · doi:10.3791/3638 · Cited by 616 · see citing works
Remission of major depression under deep brain stimulation of the lateral habenula in a therapy-refractory patient
Sartorius, A., Kiening, K. L., Kirsch, P., von Gall, C. C., Haberkorn, U., Unterberg, A. W., Henn, F. A., & Meyer-Lindenberg, A. (2010) · Biological Psychiatry · doi:10.1016/j.biopsych.2009.08.027 · Cited by 611 · see citing works
Dopamine reward prediction error coding
Schultz, W. (2016) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2016.18.1/wschultz · Cited by 597 · see citing works
Astroglial Kir4.1 in the lateral habenula drives neuronal bursts in depression
Cui, Y., Yang, Y., Ni, Z., Dong, Y., Cai, G., Foncelle, A., Ma, S., Sang, K., Tang, S., Li, Y., et al. (2018) · Nature · doi:10.1038/nature25752 · Cited by 597 · see citing works
Activation of lateral habenula inputs to the ventral midbrain promotes behavioral avoidance
Stamatakis, A. M., & Stuber, G. D. (2012) · Nature Neuroscience · doi:10.1038/nn.3145 · Cited by 564 · see citing works
Ca2+-permeable AMPA receptors in synaptic plasticity and neuronal death
Liu, S. J., & Zukin, R. S. (2007) · Trends in Neurosciences · doi:10.1016/j.tins.2007.01.006 · Cited by 530 · see citing works
The neurobiology of depression and antidepressant action
Willner, P., Scheel-Krüger, J., & Belzung, C. (2013) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2012.12.007 · Cited by 519 · see citing works
Calcium Control of Neurotransmitter Release
Sudhof, T. C. (2012) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a011353 · Cited by 502 · see citing works
The Inhibitory Circuit Architecture of the Lateral Hypothalamus Orchestrates Feeding
Jennings, J. H., Rizzi, G., Stamatakis, A. M., Ung, R. L., & Stuber, G. D. (2013) · Science · doi:10.1126/science.1241812 · Cited by 493 · see citing works
Molecular Neurobiology for Practicing Psychiatrists, Part 5: How a Leucine Zipper Can Turn On Genes: Immediate-Early Genes Activate Late-Gene Expression in the Brain.
Stahl, S. M. (2000) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.v61n0103 · Cited by 490 · see citing works
Error Monitoring Using External Feedback: Specific Roles of the Habenular Complex, the Reward System, and the Cingulate Motor Area Revealed by Functional Magnetic Resonance Imaging
Ullsperger, M., & von Cramon, D. Y. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-10-04308.2003 · Cited by 484 · see citing works
Rodent Models of Depression: Forced Swim and Tail Suspension Behavioral Despair Tests in Rats and Mice
Castagné, V., Moser, P. C., Roux, S., & Porsolt, R. D. (2010) · Current Protocols in Pharmacology · doi:10.1002/0471141755.ph0508s49 · Cited by 468 · see citing works
Serotonin and dopamine: unifying affective, activational, and decision functions.
Cools, R., Nakamura, K., & Daw, N. D. (2011) · Neuropsychopharmacology · doi:10.1038/npp.2010.121 · Cited by 464 · see citing works
Reward processing by the lateral habenula in normal and depressive behaviors
Proulx, C. D., Hikosaka, O., & Malinow, R. (2014) · Nature Neuroscience · doi:10.1038/nn.3779 · Cited by 461 · see citing works
Function of Specific K <sup>+</sup> Channels in Sustained High-Frequency Firing of Fast-Spiking Neocortical Interneurons
Erisir, A., Lau, D., Rudy, B., & Leonard, C. S. (1999) · Journal of Neurophysiology · doi:10.1152/jn.1999.82.5.2476 · Cited by 458 · see citing works
Treatment resistant depression: A multi-scale, systems biology approach
Akil, H., Gordon, J. A., Hen, R., Javitch, J. A., Mayberg, H. S., McEwen, B. S., Meaney, M. J., & Nestler, E. J. (2017) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2017.08.019 · Cited by 443 · see citing works
Habenula: crossroad between the basal ganglia and the limbic system
Hikosaka, O., Sesack, S. R., Lecourtier, L., & Shepard, P. D. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.3463-08.2008 · Cited by 432 · see citing works
Neurobiology of chronic mild stress: parallels to major depression
Hill, M. N., Hellemans, K. G. C., Verma, P., Gorzalka, B. B., & Weinberg, J. (2012) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2012.07.001 · Cited by 420 · see citing works
Physiological Evidence for Habenula as Major Link Between Forebrain and Midbrain Raphe
Wang, R. Y., & Aghajanian, G. K. (1977) · Science · doi:10.1126/science.194312 · Cited by 411 · see citing works
βCaMKII in Lateral Habenula Mediates Core Symptoms of Depression
Li, K., Zhou, T., Liao, L., Yang, Z., Wong, C., Henn, F., Malinow, R., Yates, J. R., & Hu, H. (2013) · Science · doi:10.1126/science.1240729 · Cited by 411 · see citing works
Animal models of major depression and their clinical implications
Czéh, B., Fuchs, E., Wiborg, O., & Simon, M. (2016) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2015.04.004 · Cited by 375 · cited 1× · see citing works
“This has led to the development of several animal models of depression that have been extensively used in basic research over the last few decades (Czéh et al., 2016; Nestler and Hyman, 2010; Willner, 2017).”
Method
Activating positive memory engrams suppresses depression-like behaviour
Ramirez, S., Liu, X., MacDonald, C. J., Moffa, A., Zhou, J. Y., Redondo, R. L., & Tonegawa, S. (2015) · Nature · doi:10.1038/nature14514 · Cited by 373 · see citing works
GABA/glutamate co-release controls habenula output and is modified by antidepressant treatment
Shabel, S. J., Proulx, C. D., Piriz, J., & Malinow, R. (2014) · Science · doi:10.1126/science.1250469 · Cited by 369 · see citing works
Synaptic Encoding of Fear Extinction in mPFC-amygdala Circuits
Cho, J.-H., Deisseroth, K. A., & Bolshakov, V. Y. (2013) · Neuron · doi:10.1016/j.neuron.2013.09.025 · Cited by 367 · see citing works
A unique population of ventral tegmental area neurons inhibits the lateral habenula to promote reward
Stamatakis, A. M., Jennings, J. H., Ung, R. L., Blair, G. A., Weinberg, R. J., Neve, R. L., Boyce, F., Mattis, J., Ramakrishnan, C., Deisseroth, K., et al. (2013) · Neuron · doi:10.1016/j.neuron.2013.08.023 · Cited by 364 · see citing works
STAR*D: What Have We Learned?
Rush, A. J. (2007) · American Journal of Psychiatry · doi:10.1176/ajp.2007.164.2.201 · Cited by 353 · see citing works
Single rodent mesohabenular axons release glutamate and GABA
Root, D. H., Mejias-Aponte, C. A., Zhang, S., Wang, H.-L., Hoffman, A. F., Lupica, C. R., & Morales, M. (2014) · Nature Neuroscience · doi:10.1038/nn.3823 · Cited by 349 · see citing works
Afferents to the GABAergic tail of the ventral tegmental area in the rat
Kaufling, J., Veinante, P., Pawlowski, S. A., Freund‐Mercier, M., & Barrot, M. (2009) · Journal of Comparative Neurology · doi:10.1002/cne.21983 · Cited by 347 · see citing works
The globus pallidus sends reward-related signals to the lateral habenula
Hong, S., & Hikosaka, O. (2008) · Neuron · doi:10.1016/j.neuron.2008.09.035 · Cited by 346 · see citing works
Diversity of Transgenic Mouse Models for Selective Targeting of Midbrain Dopamine Neurons
Lammel, S., Steinberg, E. E., Földy, C., Wall, N. R., Beier, K. T., Luo, L., & Malenka, R. C. (2015) · Neuron · doi:10.1016/j.neuron.2014.12.036 · Cited by 345 · see citing works
Self-citation
Input to the lateral habenula from the basal ganglia is excitatory, aversive, and suppressed by serotonin
Shabel, S. J., Proulx, C. D., Trias, A., Murphy, R. T., & Malinow, R. (2012) · Neuron · doi:10.1016/j.neuron.2012.02.037 · Cited by 334 · see citing works
Circuit-wide Transcriptional Profiling Reveals Brain Region-Specific Gene Networks Regulating Depression Susceptibility
Bagot, R. C., Cates, H. M., Purushothaman, I., Lorsch, Z. S., Walker, D. M., Wang, J., Huang, X., Schlüter, O. M., Maze, I., Peña, C. J., et al. (2016) · Neuron · doi:10.1016/j.neuron.2016.04.015 · Cited by 333 · see citing works
Data-driven subtypes of major depressive disorder: a systematic review
van Loo, H. M., de Jonge, P., Romeijn, J., Kessler, R. C., & Schoevers, R. A. (2012) · BMC Medicine · doi:10.1186/1741-7015-10-156 · Cited by 320 · see citing works
Lateral Hypothalamic Area Glutamatergic Neurons and Their Projections to the Lateral Habenula Regulate Feeding and Reward
Stamatakis, A. M., van Swieten, M. M. H., Basiri, M. L., Blair, G. A., Kantak, P. A., & Stuber, G. D. (2016) · Journal of Neuroscience · doi:10.1523/jneurosci.1202-15.2016 · Cited by 317 · see citing works
Receiver-operating characteristic curve analysis in diagnostic, prognostic and predictive biomarker research
Søreide, K. (2008) · Journal of Clinical Pathology · doi:10.1136/jcp.2008.061010 · Cited by 301 · see citing works
Design and generation of recombinant rabies virus vectors
Osakada, F., & Callaway, E. M. (2013) · Nature Protocols · doi:10.1038/nprot.2013.094 · Cited by 296 · see citing works
Covariation of activity in habenula and dorsal raphe nuclei following tryptophan depletion
Morris, J. S., Smith, K. A., Cowen, P. J., Friston, K. J., & Dolan, R. J. (1999) · NeuroImage · doi:10.1006/nimg.1999.0455 · Cited by 288 · see citing works
Asymmetry in the epithalamus of vertebrates
Concha, M. L., & Wilson, S. W. (2001) · Journal of Anatomy · doi:10.1046/j.1469-7580.2001.19910063.x · Cited by 279 · see citing works
Distinct Ventral Pallidal Neural Populations Mediate Separate Symptoms of Depression
Knowland, D., Lilascharoen, V., Pacia, C. P., Shin, S., Wang, E. H.-J., & Lim, B. K. (2017) · Cell · doi:10.1016/j.cell.2017.06.015 · Cited by 273 · see citing works
Self-citation
An excitatory synapse hypothesis of depression
Thompson, S. M., Kallarackal, A. J., Kvarta, M. D., Van Dyke, A. M., LeGates, T. A., & Cai, X. (2015) · Trends in Neurosciences · doi:10.1016/j.tins.2015.03.003 · Cited by 265 · see citing works
Optogenetic Dissection of Entorhinal-Hippocampal Functional Connectivity
Zhang, S., Ye, J., Miao, C., Tsao, A., Cerniauskas, I., Ledergerber, D., Moser, M., & Moser, E. I. (2013) · Science · doi:10.1126/science.1232627 · Cited by 256 · see citing works
Self-citation
Lateral habenula in the pathophysiology of depression
Yang, Y., Wang, H., Hu, J., & Hu, H. (2018) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2017.10.024 · Cited by 254 · see citing works
Deep brain stimulation of the lateral habenula in treatment resistant major depression
Sartorius, A., & Henn, F. A. (2007) · Medical Hypotheses · doi:10.1016/j.mehy.2007.03.021 · Cited by 251 · see citing works
Developmental expression and functional characterization of the potassium-channel subunit Kv3.1b in parvalbumin-containing interneurons of the rat hippocampus
Du, J., Zhang, L., Weiser, M., Rudy, B., & McBain, C. (1996) · The Journal of Neuroscience · doi:10.1523/jneurosci.16-02-00506.1996 · Cited by 246 · see citing works
Neuronal Dynamics Regulating Brain and Behavioral State Transitions
Andalman, A. S., Burns, V. M., Lovett-Barron, M., Broxton, M. J., Poole, B., Yang, S., Grosenick, L., Lerner, T. N., Chen, R., Benster, T., et al. (2019) · Cell · doi:10.1016/j.cell.2019.02.037 · Cited by 246 · see citing works
The potassium channel subunit KV3.1b is localized to somatic and axonal membranes of specific populations of CNS neurons
Weiser, M., Bueno, E., Sekirnjak, C., Martone, M. E., Baker, H., Hillman, D. E., Chen, S., Thornhill, W. B., Ellisman, M. H., & Rudy, B. (1995) · Journal of Neuroscience · doi:10.1523/jneurosci.15-06-04298.1995 · Cited by 241 · see citing works
Basal forebrain projections to the lateral habenula modulate aggression reward
Golden, S. A., Heshmati, M., Flanigan, M. E., Christoffel, D. J., Guise, K. G., Pfau, M. L., Aleyasin, H., Ménard, C., Zhang, H., Hodes, G. E., et al. (2016) · Nature · doi:10.1038/nature18601 · Cited by 241 · see citing works
Lateral habenula lesions improve the behavioral response in depressed rats via increasing the serotonin level in dorsal raphe nucleus
Yang, L.-M., Hu, B., Xia, Y.-H., Zhang, B.-L., & Zhao, H. (2008) · Behavioural Brain Research · doi:10.1016/j.bbr.2007.10.022 · Cited by 236 · see citing works
Opposite metabolic changes in the habenula and ventral tegmental area of a genetic model of helpless behavior
Shumake, J., Edwards, E., & Gonzalez-Lima, F. (2003) · Brain Research · doi:10.1016/s0006-8993(02)04048-9 · Cited by 232 · see citing works
Moving forward: how depression heterogeneity hinders progress in treatment and research
Fried, E. (2017) · Expert Review of Neurotherapeutics · doi:10.1080/14737175.2017.1307737 · Cited by 220 · cited 1× · see citing works
“This heterogeneity of depression hinders both research and treatment of this highly prevalent disorder (Fried, 2017).”
Subtypes of depression in a nationally representative sample
Carragher, N., Adamson, G., Bunting, B. P., & McCann, S. (2008) · Journal of Affective Disorders · doi:10.1016/j.jad.2008.05.015 · Cited by 218 · see citing works
A basal ganglia circuit for evaluating action outcomes
Stephenson‐Jones, M., Yu, K., Ahrens, S., Tucciarone, J., van Huijstee, A. N., Mejia, L. A., Penzo, M. A., Tai, L.-H., Wilbrecht, L., & Li, B. (2016) · Nature · doi:10.1038/nature19845 · Cited by 217 · see citing works
Role of Glutamatergic Projections from Ventral Tegmental Area to Lateral Habenula in Aversive Conditioning
Root, D. H., Mejías-Aponte, C. A., Qi, J., & Morales, M. (2014) · Journal of Neuroscience · doi:10.1523/jneurosci.2029-14.2014 · Cited by 213 · see citing works
Genetically distinct parallel pathways in the entopeduncular nucleus for limbic and sensorimotor output of the basal ganglia
Wallace, M. L., Saunders, A., Huang, K. W., Philson, A. C., Goldman, M., Macosko, E. Z., McCarroll, S. A., & Sabatini, B. L. (2017) · Neuron · doi:10.1016/j.neuron.2017.03.017 · Cited by 205 · see citing works
Prolonged effect of an anesthetic dose of ketamine on behavioral despair
Yılmaz, A., Schulz, D., Aksoy‐Aksel, A., & Canbeyli, R. S. (2002) · Pharmacology Biochemistry and Behavior · doi:10.1016/s0091-3057(01)00693-1 · Cited by 199 · see citing works
Cocaine Drives Aversive Conditioning via Delayed Activation of Dopamine-Responsive Habenular and Midbrain Pathways
Jhou, T. C., Good, C. H., Rowley, C. S., Xu, S., Wang, H., Burnham, N. W., Hoffman, A. F., Lupica, C. R., & Ikemoto, S. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.3634-12.2013 · Cited by 198 · see citing works
The lateral habenula in addiction and depression: an anatomical, synaptic and behavioral overview
Lecca, S., Meye, F. J., & Mameli, M. (2014) · European Journal of Neuroscience · doi:10.1111/ejn.12480 · Cited by 196 · see citing works
Single-cell RNAseq reveals cell adhesion molecule profiles in electrophysiologically defined neurons
Földy, C., Darmanis, S., Aoto, J., Malenka, R. C., Quake, S. R., & Südhof, T. C. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1610155113 · Cited by 179 · see citing works
Self-citation
Rescue of GABAB and GIRK function in the lateral habenula by protein phosphatase 2A inhibition ameliorates depression-like phenotypes in mice
Lecca, S., Pelosi, A., Tchenio, A., Moutkine, I., Lujan, R., Hervé, D., & Mameli, M. (2016) · Nature Medicine · doi:10.1038/nm.4037 · Cited by 176 · see citing works
Efferent Pathways of the Mouse Lateral Habenula
Quina, L. A., Tempest, L., Ng, L., Harris, J. A., Ferguson, S. M., Jhou, T. C., & Turner, E. E. (2014) · The Journal of Comparative Neurology · doi:10.1002/cne.23662 · Cited by 165 · see citing works
Dendritic morphology, local circuitry, and intrinsic electrophysiology of neurons in the rat medial and lateral habenular nuclei of the epithalamus
Kim, U., & Chang, S.-Y. (2005) · The Journal of Comparative Neurology · doi:10.1002/cne.20410 · Cited by 159 · see citing works
Are We Getting Closer to Valid Translational Models for Major Depression?
Berton, O., Hahn, C.-G., & Thase, M. E. (2012) · Science · doi:10.1126/science.1222940 · Cited by 148 · see citing works
Orexin signaling in GABAergic lateral habenula neurons modulates aggressive behavior in male mice
Flanigan, M. E., Aleyasin, H., Li, L., Burnett, C. J., Chan, K. L., LeClair, K. B., Lucas, E. K., Matikainen‐Ankney, B. A., Cuttoli, R. D.-D., Takahashi, A., et al. (2020) · Nature Neuroscience · doi:10.1038/s41593-020-0617-7 · Cited by 147 · see citing works
Pharmacological inhibition of the lateral habenula improves depressive-like behavior in an animal model of treatment resistant depression
Winter, C., Vollmayr, B., Djodari-Irani, A., Klein, J., & Sartorius, A. (2011) · Behavioural Brain Research · doi:10.1016/j.bbr.2010.07.034 · Cited by 145 · see citing works
Caveats and pitfalls of ROC analysis in clinical microarray research (and how to avoid them)
Berrar, D., & Flach, P. (2012) · Briefings in Bioinformatics · doi:10.1093/bib/bbr008 · Cited by 136 · see citing works
Chronic Mild Stress (CMS) in Mice: Of Anhedonia, ‘Anomalous Anxiolysis’ and Activity
Schweizer, M. C., Henniger, M. S. H., & Sillaber, I. (2009) · PLoS ONE · doi:10.1371/journal.pone.0004326 · Cited by 133 · see citing works
The medial habenula: still neglected
Viswanath, H., Carter, A. Q., Baldwin, P. R., Molfese, D. L., & Salas, R. (2014) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2013.00931 · Cited by 133 · see citing works
Topography of descending projections from anterior insular and medial prefrontal regions to the lateral habenula of the epithalamus in the rat
Kim, U., & Lee, T. (2012) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2012.08030.x · Cited by 133 · see citing works
Lateral habenula and the rostromedial tegmental nucleus innervate neurochemically distinct subdivisions of the dorsal raphe nucleus in the rat
Sego, C., Gonçalves, L., Lima, L. B., Furigo, I. C., Donato, J., & Metzger, M. (2013) · The Journal of Comparative Neurology · doi:10.1002/cne.23533 · Cited by 126 · see citing works
A GABAergic cell type in the lateral habenula links hypothalamic homeostatic and midbrain motivation circuits with sex steroid signaling
Zhang, L., Hernández, V. S., Swinny, J. D., Verma, A. K., Giesecke, T., Emery, A. C., Mutig, K., García‐Segura, L. M., & Eiden, L. E. (2018) · Translational Psychiatry · doi:10.1038/s41398-018-0099-5 · Cited by 121 · see citing works
A neural pathway controlling motivation to exert effort
Proulx, C. D., Aronson, S., Milivojevic, D., Molina, C., Loi, A., Monk, B., Shabel, S. J., & Malinow, R. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1801837115 · Cited by 119 · see citing works
Organization of Functional Long-Range Circuits Controlling the Activity of Serotonergic Neurons in the Dorsal Raphe Nucleus
Zhou, L., Liu, M., Li, Q., Deng, J., Mu, D., & Sun, Y.-G. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.02.077 · Cited by 116 · see citing works
Chronic deep brain stimulation of the lateral habenula nucleus in a rat model of depression
Meng, H., Wang, Y., Huang, M. H., Lin, W., Wang, S., & Zhang, B. (2011) · Brain Research · doi:10.1016/j.brainres.2011.08.041 · Cited by 113 · see citing works
Lateral Habenular Burst Firing as a Target of the Rapid Antidepressant Effects of Ketamine
Cui, Y., Hu, S., & Hu, H. (2019) · Trends in Neurosciences · doi:10.1016/j.tins.2018.12.002 · Cited by 105 · see citing works
Individual neurons in the rat lateral habenular complex project mostly to the dopaminergic ventral tegmental area or to the serotonergic raphe nuclei
Bernard, R., & Veh, R. W. (2012) · The Journal of Comparative Neurology · doi:10.1002/cne.23080 · Cited by 103 · see citing works
Limiting habenular hyperactivity ameliorates maternal separation-driven depressive-like symptoms
Tchenio, A., Lecca, S., Valentinova, K., & Mameli, M. (2017) · Nature Communications · doi:10.1038/s41467-017-01192-1 · Cited by 103 · see citing works
Morphological and electrophysiological characteristics of neurons within identified subnuclei of the lateral habenula in rat brain slices
Weiss, T., & Veh, R. W. (2010) · Neuroscience · doi:10.1016/j.neuroscience.2010.10.047 · Cited by 100 · see citing works
Progress in understanding mood disorders: optogenetic dissection of neural circuits
Lammel, S., Tye, K. M., & Warden, M. R. (2014) · Genes, Brain and Behavior · doi:10.1111/gbb.12049 · Cited by 98 · see citing works
Self-citation
Involvement of Infralimbic Prefrontal Cortex but not Lateral Habenula in Dopamine Attenuation After Chronic Mild Stress
Moreines, J. L., Owrutsky, Z. L., & Grace, A. A. (2017) · Neuropsychopharmacology · doi:10.1038/npp.2016.249 · Cited by 93 · see citing works
Habenula-Induced Inhibition of Midbrain Dopamine Neurons Is Diminished by Lesions of the Rostromedial Tegmental Nucleus
Brown, P. L., Palacorolla, H., Brady, D. L., Riegger, K. E., Elmer, G. I., & Shepard, P. D. (2016) · Journal of Neuroscience · doi:10.1523/jneurosci.1353-16.2016 · Cited by 90 · see citing works
An Unpredictable Chronic Mild Stress Protocol for Instigating Depressive Symptoms, Behavioral Changes and Negative Health Outcomes in Rodents
Frisbee, J. C., Brooks, S., Stanley, S., & d’Audiffret, A. C. (2015) · Journal of Visualized Experiments · doi:10.3791/53109 · Cited by 89 · see citing works
Increased metabolic activity in the septum and habenula during stress is linked to subsequent expression of learned helplessness behavior
Mirrione, M. M., Schulz, D., Lapidus, K. A. B., Zhang, S., Goodman, W. K., & Henn, F. A. (2014) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2014.00029 · Cited by 86 · see citing works
Dopaminergic projections from the VTA substantially contribute to the mesohabenular pathway in the rat
Gruber, C., Kahl, A., Lebenheim, L., Kowski, A. B., Dittgen, A., & Veh, R. W. (2007) · Neuroscience Letters · doi:10.1016/j.neulet.2007.09.016 · Cited by 85 · see citing works
Dopamine D 4 Receptor Excitation of Lateral Habenula Neurons via Multiple Cellular Mechanisms
Good, C. H., Wang, H., Chen, Y.-H., Mejías-Aponte, C. A., Hoffman, A. F., & Lupica, C. R. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.1844-13.2013 · Cited by 80 · see citing works
A glutamatergic projection from the lateral hypothalamus targets VTA-projecting neurons in the lateral habenula of the rat
Poller, W. C., Madai, V. I., Bernard, R., Laube, G., & Veh, R. W. (2013) · Brain Research · doi:10.1016/j.brainres.2013.01.029 · Cited by 77 · see citing works
Elevation of p11 in lateral habenula mediates depression-like behavior
Seo, J.-S., Zhong, P., Liu, A., Yan, Z., & Greengard, P. (2017) · Molecular Psychiatry · doi:10.1038/mp.2017.96 · Cited by 77 · see citing works
A nonparametric approach for detection of bursts in spike trains
Gourévitch, B., & Eggermont, J. J. (2006) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2006.09.024 · Cited by 74 · see citing works
A new translational target for deep brain stimulation to treat depression
Kiening, K., & Sartorius, A. (2013) · EMBO Molecular Medicine · doi:10.1002/emmm.201302947 · Cited by 70 · see citing works
The identification of symptom-based subtypes of depression: A nationally representative cohort study
ten Have, M., Lamers, F., Wardenaar, K. J., Beekman, A. T. F., de Jonge, P., van Dorsselaer, S., Tuithof, M., Kleinjan, M., & de Graaf, R. (2015) · Journal of Affective Disorders · doi:10.1016/j.jad.2015.10.040 · Cited by 64 · see citing works
β Ca 2+ /CaM-dependent kinase type II triggers upregulation of GluA1 to coordinate adaptation to synaptic inactivity in hippocampal neurons
Groth, R. D., Lindskog, M., Thiagarajan, T. C., Li, L., & Tsien, R. W. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1018022108 · Cited by 64 · see citing works
Meeting report: can we make animal models of human mental illness?
Monteggia, L. M., Heimer, H., & Nestler, E. J. (2018) · Biological Psychiatry · doi:10.1016/j.biopsych.2018.02.010 · Cited by 60 · see citing works
Subtypes of depression and their overlap in a naturalistic inpatient sample of major depressive disorder
Musil, R., Seemüller, F., Meyer, S., Spellmann, I., Adli, M., Bauer, M., Kronmüller, K., Brieger, P., Laux, G., Bender, W., et al. (2017) · International Journal of Methods in Psychiatric Research · doi:10.1002/mpr.1569 · Cited by 54 · see citing works
A model of risk for major depression: Effects of life stress and cognitive style vary by age
Mazure, C. M., & Maciejewski, P. K. (2003) · Depression and Anxiety · doi:10.1002/da.10081 · Cited by 49 · see citing works
Balanced Activity between Kv3 and Nav Channels Determines Fast-Spiking in Mammalian Central Neurons
Gu, Y., Servello, D., Han, Z., Lalchandani, R. R., Ding, J., Huang, K., & Gu, C. (2018) · iScience · doi:10.1016/j.isci.2018.10.014 · Cited by 39 · see citing works
Habenular neuron responses to noxious input are modified by dorsal raphe stimulation
Dafny, N., & Qiao, J.-T. (1990) · Neurological Research · doi:10.1080/01616412.1990.11739929 · Cited by 37 · see citing works
Substance P receptor antagonist in lateral habenula improves rat depression-like behavior
Yang, L.-M., Yu, L., Jin, H., & Zhao, H. (2013) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2013.10.007 · Cited by 36 · see citing works
Choosing Medications for Treatment-Resistant Depression Based on Mechanism of Action
Thase, M. E., & Schwartz, T. L. (2015) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.14052ah2c · Cited by 29 · see citing works
Tooth pulp stimulation induces c-fos expression in the lateral habenular nucleus of the cat
Matsumoto, N., Yahata, F., Kawarada, K., et al. (1994) · Neuroreport · doi:10.1097/00001756-199411000-00046 · Cited by 16 · see citing works
Brain-Based Biomarkers for the Treatment of Depression: Evolution of an Idea
Waters, A. C., & Mayberg, H. S. (2017) · Journal of the International Neuropsychological Society · doi:10.1017/s1355617717000881 · Cited by 13 · see citing works
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Wills, L., & Kenny, P. J. (2021) · Journal of Neurochemistry · doi:10.1111/jnc.15356 · Cited by 61 · see citing works
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Thompson, S. M. (2023) · Neuropsychopharmacology · doi:10.1038/s41386-022-01422-1 · Cited by 40 · see citing works
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Xu, C., Sun, Y., Cai, X., You, T., Zhao, H., Li, Y., & Zhao, H. (2018) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2018.00238 · Cited by 62 · see citing works
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Neckers, L., Schwartz, J. P., Wyatt, R. J., & Speciale, S. G. (1979) · Experimental Brain Research · doi:10.1007/bf00236830 · Cited by 77 · see citing works

Authors: Cerniauskas, I., Winterer, J., de Jong, J. W., Lukacsovich, D., Yang, H., Khan, F., Peck, J. R., Obayashi, S. K., Lilascharoen, V., Lim, B. K., Földy, C., & Lammel, S.
Affiliations: University of California, Berkeley (US)
University of Zurich (CH)
University of California San Diego (US)
Corresponding author: Földy, Csaba
Lammel, Stephan
ORCID: Winterer, Jochen
Lukacsovich, David
Yang, Hongbin
Khan, Fawwad
Obayashi, Sophie K.
Lilascharoen, Varoth
Lim, Byung Kook
Földy, Csaba
Lammel, Stephan
Venue: Neuron
Publisher: Elsevier BV
Published: 2019-12
Volume: 104
Issue: 5
Pages: 899-915.e8
ISSN: 0896-6273 (ISSN-L)
DOI: 10.1016/j.neuron.2019.09.005
PMC: PMC6895430
OpenAlex: W2981981976
Cited by: 187
References: 137
Citations by year: 2026: 23 · 2025: 31 · 2024: 50 · 2023: 25 · 2022: 26 · 2021: 20 · 2020: 10 · 2019: 2
FWCI: 6.93
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 369 d)
Locations: Neuron (publishedVersion)
PubMed (publishedVersion)
Zurich Open Repository and Archive (University of Zurich) (acceptedVersion)
PubMed Central (acceptedVersion)
eScholarship (California Digital Library) (submittedVersion)
Zurich Open Repository and Archive (University of Zurich) (submittedVersion)
Zurich Open Repository and Archive (University of Zurich)
Funders: Wayne and Gladys Valley Foundation
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (CRETP3_166815)
Shurl and Kay Curci Foundation
National Institute of Mental Health (R01MH112721, R01MH107742)
Center for Outcomes Research and Evaluation, Yale School of Medicine
Rita Allen Foundation
University of North Carolina
Valley Foundation
Hellman Foundation
Boehringer Ingelheim Stiftung
Whitehall Foundation (2015-12-69)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
Keywords: chronic stress, lateral habenula, ventral tegmental area, entopeduncular nucleus, dorsal raphe nucleus, passive coping, depression, synaptic plasticity, neuronal firing patterns, single-cell transcriptomics, biomarkers, neural circuits
MeSH terms: Psychological Distress, Animals, Behavior, Animal, Depression, Male, Mice, Inbred C57BL, Motivation, Neurons, Phenotype, Habenula, Mice

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Chronic Stress Induces Activity, Synaptic, and Transcriptional Remodeling of the Lateral Habenula Associated with Deficits in Motivated Behaviors

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