The DOI matches its Crossref record; 84 of the 84 references it cites were found in a registry or an index.
Glial Dysfunction in the Mouse Habenula Causes Depressive-Like Behaviors and Sleep Disturbance
Open accessAbstract
The lateral habenula (LHb) regulates the activity of monoaminergic neurons in the brainstem. This area has recently attracted a surge of interest in psychiatry because studies have reported the pathological activation of the habenula in patients with major depression and in animal models. The LHb plays a significant role in the pathophysiology of depression; however, how habenular neurons are activated to cause various depression symptoms, such as reduced motivation and sleep disturbance, remain unclear. We hypothesized that dysfunctional astrocytes may cause LHb hyperactivity due to the defective uptake activity of extracellular glutamate, which induces depressive-like behaviors. We examined the activity of neurons in habenular pathways and performed behavioral and sleep analyses in mice with pharmacological and genetic inhibition of the activity of the glial glutamate transporter GLT-1 in the LHb. The habenula-specific inhibition of GLT-1 increased the neuronal firing rate and the level of c-Fos expression in the LHb. Mice with reduced GLT-1 activity in the habenula exhibited a depressive-like phenotype in the tail suspension and novelty-suppressed feeding tests. These animals also displayed increased susceptibility to chronic stress, displaying more frequent avoidant behavior without affecting locomotor activity in the open-field test. Intriguingly, the mice showed disinhibition of rapid eye movement sleep, which is a characteristic sleep pattern in patients with depression. These results provide evidence that disrupting glutamate clearance in habenular astrocytes increases neuronal excitability and depressive-like phenotypes in behaviors and sleep.
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“As glutamate clearance modulates neuronal excitability [200] and glutamatergic synapse strength contributes to depression [202], how astrocytic glutamate clearance contributes to excitatory synapse strength and subsequent depressive behavior is also worth further investigation in the reward circuit.”
From The molecular and cellular mechanisms of depression: a focus on reward circuitry (2019) · cites this paper as [200]
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“Mice with reduced glutamate transporter GLT-1 expression in habenular astrocytes are more stress-susceptible and exhibit increased tail-suspension immobility at baseline [200], in agreement with reduced glutamate transporter expression in learned helpless rats [201].”
From The molecular and cellular mechanisms of depression: a focus on reward circuitry (2019) · cites this paper as [200]
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Cites
Molecular Mechanisms of Depression: Perspectives on New Treatment Strategies
Lang, U. E., & Borgwardt, S. (2013) · Cellular Physiology and Biochemistry · doi:10.1159/000350094 · Cited by 8,526
Glutamate neurotoxicity and diseases of the nervous system
Choi, D. W. (1988) · Neuron · doi:10.1016/0896-6273(88)90162-6 · Cited by 8,188
Kessler, R. C., Berglund, P., Demler, O., Jin, R., Koretz, D., Merikangas, K. R., Rush, A. J., Walters, E. E., & Wang, P. S. (2003) · JAMA · doi:10.1001/jama.289.23.3095 · Cited by 7,988
Selective Cortical Undercutting As a Means of Modifying and Studying Frontal Lobe Function in Man
Scoville, W. B. (1949) · Journal of neurosurgery · doi:10.3171/jns.1949.6.1.0065 · Cited by 7,374
Requirement of hippocampal neurogenesis for the behavioral effects of antidepressants
Santarelli, L., Saxe, M., Gross, C., Surget, A., Battaglia, F., Dulawa, S., Weisstaub, N., Lee, J., Duman, R., Arancio, O., et al. (2003) · Science · doi:10.1126/science.1083328 · Cited by 4,321
Dopamine, learning and motivation.
Wise, R. A. (2004) · Nature Reviews Neuroscience · doi:10.1038/nrn1406 · Cited by 3,379 · cited 2×
“In contrast, impairments in dopaminergic transmission also suppress motor behavior (Wise, 2004), and repetitive stressors, such as aversive stimuli, sensitize LHb neurons and increase baseline activity, which may lead to persistent reductions in the firing activity of midbrain dopaminergic neurons and decreased motor…”
BackgroundCircStat : A MATLAB Toolbox for Circular Statistics
Berens, P. (2009) · Journal of Statistical Software · doi:10.18637/jss.v031.i10 · Cited by 3,099
Cellular Scaling Rules for the Brains of Marsupials: Not as “Primitive” as Expected
Santos, S. E. D., Porfírio, J., Cunha, F., Manger, P. R., Tavares, W. C., Pessôa, L. M., Raghanti, M. A., Sherwood, C. C., & Herculano‐Houzel, S. (2017) · Brain Behavior and Evolution · doi:10.1159/000452856 · Cited by 2,652
NeuN, a neuronal specific nuclear protein in vertebratesxs
Mullen, R. J., Buck, C. R., & Smith, A. M. (1992) · Development · doi:10.1242/dev.116.1.201 · Cited by 2,351
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 1×
“The interaction ratio was calculated as 100 (interaction time, unfamiliar aggressor)/(interaction time, empty cage) (Krishnan et al., 2007).”
Method
Research works printed but not linked: 1
- Paxinos G Franklin KB (2008) The mouse brain in stereotaxic coordinates, compact (Elsevier Academic, Amsterdam), Ed 3.
Cited by
Sorted by citations
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
Pathogenesis of depression: Insights from human and rodent studies
Ménard, C., Hodes, G. E., & Russo, S. J. (2016) · Neuroscience · doi:10.1016/j.neuroscience.2015.05.053 · Cited by 593
Circuits and functions of the lateral habenula in health and in disease
Hu, H., Cui, Y., & Yang, Y. (2020) · Nature reviews. Neuroscience · doi:10.1038/s41583-020-0292-4 · Cited by 489
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
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 253
Metadata
- Authors
- Cui, W., Mizukami, H., Yanagisawa, M., Aida, T., Nomura, M., Isomura, Y., Takayanagi, R., Ozawa, K., Tanaka, K., & Aizawa, H.
- Affiliations
- Jichi Medical University (JP)
- Kyushu University (JP)
- Tamagawa University (JP)
- Tokyo Medical and Dental University (JP)
- ORCID
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2014-12-03
- Volume
- 34
- Issue
- 49
- Pages
- 16273-16285
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6608483
- OpenAlex
- W2052808411
- Cited by
- 139
- References
- 84
- Citations by year
- 2026: 5 · 2025: 11 · 2024: 8 · 2023: 7 · 2022: 10 · 2021: 13 · 2020: 16 · 2019: 19 · 2018: 12 · 2017: 18 · 2016: 9 · 2015: 11
- FWCI
- 9.23
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Naito Foundation
- Suzuken Memorial Foundation
- Uehara Memorial Foundation
- Brain Science Foundation
- Ministry of Education, Culture, Sports, Science and Technology
- Inamori Foundation
- Kanae Foundation for the Promotion of Medical Science
- Japan Society for the Promotion of Science (24390247, 26430008)
- Japan Science and Technology Agency
- Core Research for Evolutional Science and Technology
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- lateral habenula, glial dysfunction, astrocytes, GLT-1, glutamate uptake, major depressive disorder, depression-like behavior, sleep disorders, chronic stress, neuronal excitability, c-fos
- MeSH terms
- Action Potentials, Animals, Astrocytes, Behavior, Animal, Depression, Mice, Transgenic, Microinjections, Neurons, Pyrones, Sleep, REM, Neurotransmitter Uptake Inhibitors, Habenula, Excitatory Amino Acid Transporter 2, Mice
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