Disinhibition of somatostatin-positive GABAergic interneurons results in an anxiolytic and antidepressant-like brain state

Fuchs, T; Jefferson, S J; Hooper, A; Yee, P-HP; Maguire, J; Luscher, B

doi:10.1038/mp.2016.188

Cited by 204Treatment of Major DepressionNeuroscience and Neuropharmacology ResearchNeurotransmitter Receptor Influence on Behavior

Disinhibition of somatostatin-positive GABAergic interneurons results in an anxiolytic and antidepressant-like brain state

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Fuchs, T, Jefferson, S J, Hooper, A, Yee, P-HP, Maguire, J, Luscher, B·2017·Molecular Psychiatry

DOI 10.1038/mp.2016.188PMC PMC5422144

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Abstract

Major depressive disorder (MDD) is associated with reduced concentrations of γ-aminobutyric acid (GABA) that are normalized by antidepressant therapies. Moreover, depressive-like phenotypes of GABA A receptor mutant mice can be reversed by treatment with conventional antidepressants drugs, as well as by subanesthetic doses of ketamine. Thus GABAergic deficits may causally contribute to depressive disorders, while antidepressant therapies may enhance GABAergic synaptic transmission. Here we tested the hypothesis that sustained enhancement of GABAergic transmission alone is sufficient to elicit antidepressant-like behavior, using disinhibition of GABAergic interneurons. We focused on somatostatin-positive (SST + ) GABAergic interneurons because of evidence that their function is compromised in MDD. To disinhibit SST + interneurons, we inactivated the γ2 subunit gene of GABA A receptors selectively in these neurons (SSTCre:γ2 f/f mice). Loss of inhibitory synaptic input resulted in increased excitability of SST + interneurons. In turn, pyramidal cell targets of SST + neurons showed an increased frequency of spontaneous inhibitory postsynaptic currents. The behavior of SSTCre:γ2 f/f mice mimicked the effects of anxiolytic and antidepressant drugs in a number of behavioral tests, without affecting performance in a spatial learning- and memory-dependent task. Finally, brain extracts of SSTCre:γ2 f/f mice showed decreased phosphorylation of the eukaryotic elongation factor eEF2, reminiscent of the effects of ketamine. Importantly, these effects occurred without altered activity of the mammalian target of rapamycin pathway nor did they involve altered expression of SST. However, they were associated with reduced Ca 2+ /calmodulin-dependent auto-phosphorylation of eEF2 kinase, which controls the activity of eEF2 as its single target. Thus enhancing GABAergic inhibitory synaptic inputs from SST + interneurons to pyramidal cells and corresponding chronic reductions in the synaptic excitation:inhibition ratio represents a novel strategy for antidepressant therapies that reproduces behavioral and biochemical end points of rapidly acting antidepressants.

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Selective knockout of γ2GABAARs in SST+ interneurons of the forebrain is anxiolytic.
“For instance, a recent study [52] showed that the selective knockout of γ2GABAARs in SST+ interneurons of the forebrain is anxiolytic.”
From An emerging circuit pharmacology of GABAA receptors (2018) · cites this paper as [52]
Selective knockout of γ2GABAARs on SST+ interneurons of the forebrain increases spontaneous and miniature IPSCs in CA1.
“Selective knockout of γ2GABAARs on SST+ interneurons of the forebrain, on the other hand, led to a subtler behavioral phenotype with no observed changes in spatial learning, despite increasing both spontaneous and miniature inhibitory postsynaptic currents (IPSCs) in CA1 [52].”
From An emerging circuit pharmacology of GABAA receptors (2018) · cites this paper as [52]
Conditional deletion of γ2 from SST+ interneurons in the forebrain disinhibits this interneuron population.
“More recently, conditional deletion of γ2 from SST+ interneurons in the forebrain was shown to disinhibit this interneuron population, in turn inhibiting excitatory pyramidal cells within CA1 of the hippocampus and layer 2/3 of the cingulate cortex and having anxiolytic- and antidepressant-like effects [52].”
From An emerging circuit pharmacology of GABAA receptors (2018) · cites this paper as [52]
This disinhibition inhibits excitatory pyramidal cells within CA1 of the hippocampus and layer 2/3 of the cingulate cortex.
“More recently, conditional deletion of γ2 from SST+ interneurons in the forebrain was shown to disinhibit this interneuron population, in turn inhibiting excitatory pyramidal cells within CA1 of the hippocampus and layer 2/3 of the cingulate cortex and having anxiolytic- and antidepressant-like effects [52].”
From An emerging circuit pharmacology of GABAA receptors (2018) · cites this paper as [52]
Potentiation of GABAergic inhibitory input to pyramidal cells via disinhibition of somatostatin-positive GABAergic interneurons induced sustained antidepressant-like effects in mice.
“Similarly, potentiation of GABAergic inhibitory input to pyramidal cells via a disinhibition of somatostatin-positive GABAergic interneurons induced sustained antidepressant-like effects in mice 54.”
From Mechanisms of ketamine action as an antidepressant (2018) · cites this paper as [54]

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Phosphorylation of elongation factor-2 kinase on serine 499 by cAMP-dependent protein kinase induces Ca2+/calmodulin-independent activity
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Benzodiazepine-dependent stabilization of GABAA receptors at synapses
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GABAergic Control of Critical Developmental Periods for Anxiety- and Depression-Related Behavior in Mice
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Activity-regulated Somatostatin Expression Reduces Dendritic Spine Density and Lowers Excitatory Synaptic Transmission via Postsynaptic Somatostatin Receptor 4
Hou, Z.-H., & Yu, X. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.419051 · Cited by 34 · see citing works

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Mechanisms of ketamine action as an antidepressant
Zanos, P., & Gould, T. D. (2018) · Molecular Psychiatry · doi:10.1038/mp.2017.255 · Cited by 1,127 · see citing works
Altered Connectivity in Depression: GABA and Glutamate Neurotransmitter Deficits and Reversal by Novel Treatments
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Brain-Derived Neurotrophic Factor Signaling in Depression and Antidepressant Action
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Cortical GABAergic Dysfunction in Stress and Depression: New Insights for Therapeutic Interventions
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GABA interneurons are the cellular trigger for ketamine's rapid antidepressant actions
Gerhard, D. M., Pothula, S., Liu, R.-J., Wu, M., Li, X.-Y., Girgenti, M. J., Taylor, S. R., Duman, C. H., Delpire, E., Picciotto, M., et al. (2020) · Journal of Clinical Investigation · doi:10.1172/jci130808 · Cited by 345 · see citing works
Somatostatin-Positive Gamma-Aminobutyric Acid Interneuron Deficits in Depression: Cortical Microcircuit and Therapeutic Perspectives
Fee, C., Banasr, M., & Sibille, E. (2017) · Biological Psychiatry · doi:10.1016/j.biopsych.2017.05.024 · Cited by 329 · see citing works
Inhibition in the amygdala anxiety circuitry
Babaev, O., Chatain, C. P., & Krueger‐Burg, D. (2018) · Experimental & Molecular Medicine · doi:10.1038/s12276-018-0063-8 · Cited by 312 · see citing works
GABAergic dysfunction in excitatory and inhibitory (E/I) imbalance drives the pathogenesis of Alzheimer's disease
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Altered GABA-mediated information processing and cognitive dysfunctions in depression and other brain disorders
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An emerging circuit pharmacology of GABAA receptors
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Inhibitory control of the excitatory/inhibitory balance in psychiatric disorders
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Prefrontal excitatory/inhibitory balance in stress and emotional disorders: Evidence for over-inhibition
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Fast-acting antidepressant activity of ketamine: Highlights on brain serotonin, glutamate, and GABA neurotransmission in preclinical studies
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Convergent molecular, cellular, and cortical neuroimaging signatures of major depressive disorder
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Convergent Mechanisms Underlying Rapid Antidepressant Action
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Neurobiology of rapid-acting antidepressants: convergent effects on GluA1-synaptic function
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Hippocampus: Molecular, Cellular, and Circuit Features in Anxiety
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Gene expression links functional networks across cortex and striatum
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Characterization of GABAergic Marker Expression in the Chronic Unpredictable Stress Model of Depression
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Inhibition of GABA interneurons in the mPFC is sufficient and necessary for rapid antidepressant responses
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Neurobiology and Therapeutic Potential of α5-GABA Type A Receptors
Jacob, T. C. (2019) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2019.00179 · Cited by 124 · see citing works
Transcriptional and imaging-genetic association of cortical interneurons, brain function, and schizophrenia risk
Anderson, K. M., Collins, M. A., Chin, R., Ge, T., Rosenberg, M. D., & Holmes, A. J. (2020) · Nature Communications · doi:10.1038/s41467-020-16710-x · Cited by 119 · see citing works
GABAA receptors as targets for treating affective and cognitive symptoms of depression
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Dual-transmitter systems regulating arousal, attention, learning and memory
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Brexanolone, a neurosteroid antidepressant, vindicates the GABAergic deficit hypothesis of depression and may foster resilience
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Catecholamines alter the intrinsic variability of cortical population activity and perception
Pfeffer, T. A., Avrămiea, A.-E., Nolte, G., Engel, A. K., Linkenkaer‐Hansen, K., & Donner, T. H. (2018) · PLoS Biology · doi:10.1371/journal.pbio.2003453 · Cited by 97 · see citing works
Ketamine rapidly reverses stress-induced impairments in GABAergic transmission in the prefrontal cortex in male rodents
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Diversity and Function of Somatostatin-Expressing Interneurons in the Cerebral Cortex
Riedemann, T. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20122952 · Cited by 94 · see citing works
Role of Leptin in Mood Disorder and Neurodegenerative Disease
Zou, X., Zhong, L., Zhu, C., Zhao, H., Zhao, F., Cui, R., Gao, S., & Li, B. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.00378 · Cited by 85 · see citing works
Electrophysiological biomarkers of antidepressant response to ketamine in treatment-resistant depression: Gamma power and long-term potentiation
Gilbert, J. R., & Zarate, C. A. (2020) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2020.172856 · Cited by 73 · see citing works
NMDA 2A receptors in parvalbumin cells mediate sex-specific rapid ketamine response on cortical activity
Picard, N., Takesian, A. E., Fagiolini, M., & Hensch, T. K. (2019) · Molecular Psychiatry · doi:10.1038/s41380-018-0341-9 · Cited by 71 · see citing works
Contribution of the GABAergic System to Non-Motor Manifestations in Premotor and Early Stages of Parkinson’s Disease
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Ahnak scaffolds p11/Anxa2 complex and L-type voltage-gated calcium channel and modulates depressive behavior
Jin, J., Bhatti, D. L., Lee, K.-W., Medrihan, L., Cheng, J., Wei, J., Zhong, P., Yan, Z., Kooiker, C. L., Song, C., et al. (2019) · Molecular Psychiatry · doi:10.1038/s41380-019-0371-y · Cited by 69 · see citing works
Hormonal regulation of circuit function: sex, systems and depression
Thériault, R.-K., & Perreault, M. L. (2019) · Biology of Sex Differences · doi:10.1186/s13293-019-0226-x · Cited by 68 · see citing works
Genetic insights into the neurobiology of anxiety
Koskinen, M.-K., & Hovatta, I. (2023) · Trends in Neurosciences · doi:10.1016/j.tins.2023.01.007 · Cited by 64 · see citing works
Chronic unpredictable stress promotes cell-specific plasticity in prefrontal cortex D1 and D2 pyramidal neurons
Anderson, E. M., Gomez, D. M., Caccamise, A. J., McPhail, D., & Hearing, M. C. (2019) · Neurobiology of Stress · doi:10.1016/j.ynstr.2019.100152 · Cited by 60 · see citing works
Reduced inhibition in depression impairs stimulus processing in human cortical microcircuits
Yao, H. K., Guet-McCreight, A., Mazza, F., Moradi Chameh, H., Prevot, T. D., Griffiths, J. D., Tripathy, S. J., Valiante, T. A., Sibille, E., & Hay, E. (2022) · Cell Reports · doi:10.1016/j.celrep.2021.110232 · Cited by 55 · see citing works
Somatostatin neurons control an alcohol binge drinking prelimbic microcircuit in mice
Dao, N. C., Brockway, D. F., Nair, M. S., Sicher, A. R., & Crowley, N. A. (2021) · Neuropsychopharmacology · doi:10.1038/s41386-021-01050-1 · Cited by 53 · see citing works
Maternal dietary patterns are associated with susceptibility to a depressive-like phenotype in rat offspring
Gawlińska, K., Gawliński, D., Korostyński, M., Borczyk, M., Frankowska, M., Piechota, M., Filip, M., & Przegaliński, E. (2020) · Developmental Cognitive Neuroscience · doi:10.1016/j.dcn.2020.100879 · Cited by 51 · see citing works
Understanding the effects of chronic benzodiazepine use in depression: a focus on neuropharmacology
Lim, B., Sproule, B. A., Zahra, Z., Sunderji, N., Kennedy, S. H., & Rizvi, S. J. (2020) · International Clinical Psychopharmacology · doi:10.1097/yic.0000000000000316 · Cited by 50 · see citing works
The role of the excitation:inhibition functional balance in the mPFC in the onset of antidepressants
Yin, Y., Wang, Y., Liu, W., Yao, J.-Q., Yuan, J., Li, Z.-H., Ran, Y., Zhang, L., & Li, Y. (2021) · Neuropharmacology · doi:10.1016/j.neuropharm.2021.108573 · Cited by 48 · see citing works
Oxytocin Exerts Antidepressant-like effect by potentiating dopaminergic synaptic transmission in the mPFC
Li, Q., Zhang, B., Cao, H., Liu, W., Guo, F., Shen, F., Ye, B., Liu, H., Li, Y., & Liu, Z. (2020) · Neuropharmacology · doi:10.1016/j.neuropharm.2019.107836 · Cited by 47 · see citing works
Somatostatin and Somatostatin-Containing Interneurons—From Plasticity to Pathology
Liguz‐Lecznar, M., Dobrzański, G., & Kossut, M. M. (2022) · Biomolecules · doi:10.3390/biom12020312 · Cited by 46 · see citing works
Behavioral Deficits Induced by Somatostatin-Positive GABA Neuron Silencing Are Rescued by Alpha 5 GABA-A Receptor Potentiation
Fee, C., Prévot, T. D., Misquitta, K. A., Knutson, D. E., Li, G., Mondal, P., Cook, J. M., Banasr, M., & Sibille, E. L. (2021) · The International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyab002 · Cited by 45 · see citing works
The claustrum-prelimbic cortex circuit through dynorphin/κ-opioid receptor signaling underlies depression-like behaviors associated with social stress etiology
Wang, Y., Zan, G., Xu, C., Li, X., Shu, X., Yao, S.-Y., Xu, X.-S., Qiu, X., Chen, Y., Jin, K., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-43636-x · Cited by 44 · see citing works
Forced Abstinence From Alcohol Induces Sex-Specific Depression-Like Behavioral and Neural Adaptations in Somatostatin Neurons in Cortical and Amygdalar Regions
Dao, N. C., Nair, M. S., Magee, S. N., Moyer, J. B., Sendao, V., Brockway, D. F., & Crowley, N. A. (2020) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2020.00086 · Cited by 43 · see citing works
Engaging homeostatic plasticity to treat depression
Workman, E. R., Niere, F., & Raab‐Graham, K. F. (2017) · Molecular Psychiatry · doi:10.1038/mp.2017.225 · Cited by 42 · see citing works
Effect of Ketamine on Limbic GABA and Glutamate: A Human In Vivo Multivoxel Magnetic Resonance Spectroscopy Study
Silberbauer, L., Spurny‐Dworak, B., Handschuh, P. A., Klöbl, M., Bednařík, P., Reiter, B., Ritter, V., Trost, P., Konadu, M. E., Windpassinger, M., et al. (2020) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2020.549903 · Cited by 42 · see citing works
Antidepressant mechanisms of ketamine: Focus on GABAergic inhibition
Lüscher, B., Feng, M., & Jefferson, S. J. (2020) · Advances in pharmacology · doi:10.1016/bs.apha.2020.03.002 · Cited by 41 · see citing works
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Chronic activation of the relaxin‐3 receptor on GABA neurons in rat ventral hippocampus promotes anxiety and social avoidance
Rytova, V., Ganella, D. E., Hawkes, D. J., Bathgate, R. A. D., Ma, S., & Gundlach, A. L. (2019) · Hippocampus · doi:10.1002/hipo.23089 · Cited by 40 · see citing works
GABAergic System in Stress: Implications of GABAergic Neuron Subpopulations and the Gut-Vagus-Brain Pathway
Hou, X., Rong, C., Wang, F., Liu, X., Sun, Y., & Zhang, H. (2020) · Neural Plasticity · doi:10.1155/2020/8858415 · Cited by 41 · see citing works
Basolateral amygdala parvalbumin and cholecystokinin-expressing GABAergic neurons modulate depressive and anxiety-like behaviors
Asim, M., Wang, H., Waris, A., & He, J. (2024) · Translational Psychiatry · doi:10.1038/s41398-024-03135-z · Cited by 39 · see citing works
Fluoxetine Suppresses Glutamate- and GABA-Mediated Neurotransmission by Altering SNARE Complex
Lazarevic, V., Mantas, I., Flais, I., & Svenningsson, P. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20174247 · Cited by 39 · see citing works
Loss of liver X receptor β in astrocytes leads to anxiety-like behaviors via regulating synaptic transmission in the medial prefrontal cortex in mice
Li, X., Zhong, H., Wang, Z., Xiao, R., Antonson, P., Liu, T., Chuan, W., Zou, J., Wang, L. Y., Nalvarte, I., et al. (2021) · Molecular Psychiatry · doi:10.1038/s41380-021-01139-5 · Cited by 37 · see citing works
Ion Channel Dysfunction and Neuroinflammation in Migraine and Depression
Eren‐Koçak, E., & Dalkara, T. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.777607 · Cited by 39 · see citing works
Ketamine normalizes binge drinking-induced defects in glutamatergic synaptic transmission and ethanol drinking behavior in female but not male mice
Crowley, N. A., Magee, S. N., Feng, M., Jefferson, S. J., Morris, C., Dao, N. C., Brockway, D. F., & Lüscher, B. (2019) · Neuropharmacology · doi:10.1016/j.neuropharm.2019.02.003 · Cited by 34 · see citing works
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Effects of ketamine on GABAergic and glutamatergic activity in the mPFC: biphasic recruitment of GABA function in antidepressant-like responses
Fogaça, M. V., Daher, F., & Picciotto, M. R. (2024) · Neuropsychopharmacology · doi:10.1038/s41386-024-02002-1 · Cited by 34 · see citing works
Loss of Foxg1 Impairs the Development of Cortical SST-Interneurons Leading to Abnormal Emotional and Social Behaviors
Chen, D., Wang, C., Li, M., She, X., Yuan, Y., Chen, H., Zhang, W., & Zhao, C. (2019) · Cerebral Cortex · doi:10.1093/cercor/bhz114 · Cited by 32 · see citing works
Loss of SST and PV positive interneurons in the ventral hippocampus results in anxiety-like behavior in 5xFAD mice
Li, H., Zhao, J., Lai, L., Xia, Y., Wan, C., Wei, S., Liang, J., Chen, Y., & Xu, N. (2022) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2022.05.013 · Cited by 34 · see citing works
Mechanism underlying NMDA blockade-induced inhibition of aggression in post-weaning socially isolated mice
Chang, C., Su, C.-L., & Gean, P. (2018) · Neuropharmacology · doi:10.1016/j.neuropharm.2018.09.019 · Cited by 34 · see citing works
Arid1b haploinsufficiency in parvalbumin- or somatostatin-expressing interneurons leads to distinct ASD-like and ID-like behavior
Smith, A. L., Jung, E., Jeon, B. T., & Kim, W.-Y. (2020) · Scientific Reports · doi:10.1038/s41598-020-64066-5 · Cited by 33 · see citing works
Weakened effective connectivity between salience network and default mode network during resting state in adolescent depression
Willinger, D., Häberling, I. S., Ilioska, I., Berger, G. E., Walitza, S., & Brem, S. (2024) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2024.1386984 · Cited by 30 · see citing works
Loss of Glutamate Decarboxylase 67 in Somatostatin-Expressing Neurons Leads to Anxiety-Like Behavior and Alteration in the Akt/GSK3β Signaling Pathway
Miyata, S., Kumagaya, R., Kakizaki, T., Fujihara, K., Wakamatsu, K., & Yanagawa, Y. (2019) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2019.00131 · Cited by 30 · see citing works
A role for the neuropeptide somatostatin in the neurobiology of behaviors associated with substances abuse and affective disorders
Robinson, S. L., & Thiele, T. E. (2020) · Neuropharmacology · doi:10.1016/j.neuropharm.2020.107983 · Cited by 30 · see citing works
The Role of Glutamate Underlying Treatment-resistant Depression
Kim, J., Kim, T.-E., Lee, S., & Koo, J. W. (2023) · Clinical Psychopharmacology and Neuroscience · doi:10.9758/cpn.22.1034 · Cited by 30 · see citing works
NMDAR hypofunction and somatostatin-expressing GABAergic interneurons and receptors: A newly identified correlation and its effects in schizophrenia
Alherz, F. A., Alherz, M., & Almusawi, H. M. (2017) · Schizophrenia Research Cognition · doi:10.1016/j.scog.2017.02.001 · Cited by 29 · see citing works
Mu opioid receptors on hippocampal GABAergic interneurons are critical for the antidepressant effects of tianeptine
Han, J., Andreu, V., Langreck, C. B., Pekarskaya, E. A., Grinnell, S. G., Allain, F., Magalong, V. M., Pintar, J. E., Kieffer, B. L., Harris, A. Z., et al. (2021) · Neuropsychopharmacology · doi:10.1038/s41386-021-01192-2 · Cited by 28 · see citing works
Npas4 regulates IQSEC3 expression in hippocampal somatostatin interneurons to mediate anxiety-like behavior
Kim, S., Park, D., Kim, J., Kim, D., Kim, H., Mori, T., Jung, H., Lee, D., Hong, S., Jeon, J., et al. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109417 · Cited by 30 · see citing works
M1 acetylcholine receptors in somatostatin interneurons contribute to GABAergic and glutamatergic plasticity in the mPFC and antidepressant-like responses
Fogaça, M. V., Wu, M., Li, C., Li, X., Duman, R. S., & Picciotto, M. R. (2023) · Neuropsychopharmacology · doi:10.1038/s41386-023-01583-7 · Cited by 28 · see citing works
In Vitro Optogenetic Characterization of Neuropeptide Release from Prefrontal Cortical Somatostatin Neurons
Dao, N. C., Brockway, D. F., & Crowley, N. A. (2019) · Neuroscience · doi:10.1016/j.neuroscience.2019.08.014 · Cited by 26 · see citing works
An integrative view on the cell-type-specific mechanisms of ketamine's antidepressant actions
Lewis, V., Rurak, G. M., Salmaso, N., & Aguilar‐Valles, A. (2024) · Trends in Neurosciences · doi:10.1016/j.tins.2023.12.004 · Cited by 27 · see citing works
De Novo Protein Synthesis Mediated by the Eukaryotic Elongation Factor 2 Is Required for the Anxiolytic Effect of Oxytocin
Martinetz, S., Meinung, C.-P., Jurek, B., von Schack, D., van den Burg, E. H., Slattery, D. A., & Neumann, I. D. (2019) · Biological Psychiatry · doi:10.1016/j.biopsych.2019.01.010 · Cited by 25 · see citing works
Synaptic inhibition in the neocortex: Orchestration and computation through canonical circuits and variations on the theme
Lourenço, J., Koukouli, F., & Bacci, A. (2020) · Cortex · doi:10.1016/j.cortex.2020.08.015 · Cited by 22 · see citing works
Development, Diversity, and Death of MGE-Derived Cortical Interneurons
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Magnetic seizure therapy and electroconvulsive therapy increase aperiodic activity
Smith, S. E., Kosik, E. L., van Engen, Q., Kohn, J. N., Hill, A. T., Zomorrodi, R., Blumberger, D. M., Daskalakis, Z. J., Hadas, I., & Voytek, B. (2023) · Translational Psychiatry · doi:10.1038/s41398-023-02631-y · Cited by 24 · see citing works
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Authors: Fuchs, T., Jefferson, S. J., Hooper, A., Yee, P.-H., Maguire, J., & Luscher, B.
Affiliations: Pennsylvania State University (US)
Tufts University (US)
ORCID: Jefferson, S J
Hooper, A
Maguire, J
Venue: Molecular Psychiatry
Publisher: Springer Science and Business Media LLC
Published: 2016-11-08
Volume: 22
Issue: 6
Pages: 920-930
ISSN: 1359-4184 (ISSN-L)
1476-5578
DOI: 10.1038/mp.2016.188
PMC: PMC5422144
OpenAlex: W2556544290
Cited by: 204
References: 82
Citations by year: 2026: 14 · 2025: 22 · 2024: 23 · 2023: 21 · 2022: 14 · 2021: 24 · 2020: 27 · 2019: 36 · 2018: 14 · 2017: 9
FWCI: 15.90
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc-sa
creativecommons.org/licenses/by-nc-sa/4.0 (tdm)
Locations: Molecular Psychiatry (publishedVersion, cc-by-nc-sa)
Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
PubMed Central (publishedVersion, cc-by-nc-sa)
PubMed (publishedVersion)
Funders: National Institute of Mental Health (R21MH097247, R01MH099851, MH099851, MH097247)
National Institute of Neurological Disorders and Stroke (T32NS061764, R56 NS073574, R01NS073574, NS073574, R01NS102937)
Topics: Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords: GABAergic disinhibition, major depressive disorder, antidepressant-like behavior, anxiolytic behavior, GABA-A receptor gamma2 subunit, eEF2 phosphorylation, eEF2 kinase, calcium/calmodulin-dependent protein kinase, excitation-inhibition balance, inhibitory postsynaptic currents, pyramidal neurons, ketamine, synaptic transmission
MeSH terms: Animals, Antidepressive Agents, Brain, Major Depressive Disorder, gamma-Aminobutyric Acid, Interneurons, Ketamine, Mice, Transgenic, Synaptic Transmission, Receptors, GABA-A, Somatostatin, Anti-Anxiety Agents, GABA Agents, Mice, Inhibitory Postsynaptic Potentials, GABAergic Neurons

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Disinhibition of somatostatin-positive GABAergic interneurons results in an anxiolytic and antidepressant-like brain state

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