Bidirectional Influence of Limbic GIRK Channel Activation on Innate Avoidance Behavior
Open accessAbstract
Systemic administration of ML297, a selective activator of G-protein-gated inwardly rectifying K+ (GIRK) channels, decreases innate avoidance behavior in male C57BL/6J mice. The cellular mechanisms mediating the ML297-induced suppression of avoidance behavior are unknown. Here, we show that systemic ML297 administration suppresses elevated plus maze (EPM)-induced neuronal activation in the ventral hippocampus (vHPC) and basolateral amygdala (BLA) and that ML297 activates GIRK1-containing GIRK channels in these limbic structures. While intracranial infusion of ML297 into the vHPC suppressed avoidance behavior in the EPM test, mirroring the effect of systemic ML297, intra-BLA administration of ML297 provoked the opposite effect. Using neuron-specific viral genetic and chemogenetic approaches, we found that the combined inhibition of excitatory neurons in CA3 and dentate gyrus (DG) subregions of the vHPC was sufficient to decrease innate avoidance behavior in the EPM, open-field, and light-dark tests in male C57BL/6J mice, while performance in the marble-burying test was not impacted. Furthermore, genetic ablation of GIRK channels in CA3/DG excitatory neurons precluded the suppression of avoidance behavior evoked by systemic ML297 in the EPM test. Thus, acute inhibition of excitatory neurons in the ventral CA3 and DG subregions of the vHPC is necessary for the apparent anxiolytic efficacy of systemic ML297 and is sufficient to decrease innate avoidance behavior in male C57BL/6J mice. SIGNIFICANCE STATEMENT We interrogated the cellular mechanisms underlying the apparent anxiolytic efficacy of ML297, a selective activator of G-protein-gated inwardly rectifying K+ (GIRK) channels and promising lead compound. Intracranial infusion of ML297 into the ventral hippocampus (vHPC) and basolateral amygdala (BLA) complex exerted opposing influence on innate avoidance behavior in male C57BL/6J mice, the former recapitulating the suppression of avoidance behavior evoked by systemic ML297. Using viral genetic and chemogenetic approaches, we showed that combined inhibition of excitatory neurons in CA3 and dentate gyrus (DG) subregions of the vHPC is sufficient to decrease innate avoidance behavior in male mice and mediates the decrease in avoidance behavior evoked by systemic ML297. These findings establish a foundation for future investigations into the therapeutic potential of GIRK channel modulation in anxiety disorders.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Selective GIRK1/2 channel openers including ML297 and GAT1508 hyperpolarize principal neurons, reduce avoidance and anxiety-like behaviors, and facilitate extinction of conditioned fear without motor or cardiac liabilities.
“Selective GIRK1/2 channel openers, including ML297, a prototype small-molecule GIRK1/2 activator, and GAT1508, a next-generation brain-penetrant GIRK1/2 modulator, hyperpolarize principal neurons, reduce avoidance and anxiety-like behaviors, and facilitate extinction of conditioned fear without motor or cardiac liabilities”
From Synaptic Plasticity—Intrinsic Excitability and Antidepressant Discovery (2026) · cites this paper as [314]
The Introduction (page not provided) identifies ML297 as a GIRK1-containing channel activator and reports reduced innate avoidance without altered motor activity. The results section on intracranial ML297 (page not provided) qualifies that finding: infusion into the ventral hippocampus reduced avoidance, whereas infusion into the basal amygdala increased it. Our copy reports ML297-induced currents in excitatory neurons, but does not establish the claim about GAT1508, conditioned-fear extinction, or absence of cardiac liabilities. (LLM, conf=0.88)
Experimental — accuracy not yet measuredPharmacological activation of GIRK channels delivers a coherent anti-agitation profile by lowering pyramidal cell gain and stabilizing limbic rhythms.
“Pharmacological activation of GIRK channels delivers a coherent anti-agitation profile by lowering pyramidal cell gain and stabilizing limbic rhythms [305,314].”
From Synaptic Plasticity—Intrinsic Excitability and Antidepressant Discovery (2026) · cites this paper as [314]
The electrophysiology results report GIRK-dependent currents in ventral hippocampal pyramidal neurons, and the Discussion reports that GIRK activation in the ventral hippocampus decreased innate avoidance in male mice. But activation in the basal amygdala increased avoidance, so the behavioral effect is not uniformly anti-agitation. The paper does not report stabilization of limbic rhythms, and innate avoidance in mice is not the same outcome as agitation. (LLM, conf=0.88)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Genome-wide atlas of gene expression in the adult mouse brain
Lein, E. S., Hawrylycz, M. J., Ao, N., Ayres, M., Bensinger, A., Bernard, A., Boe, A. F., Boguski, M. S., Brockway, K. S., Byrnes, E. J., et al. (2007) · Nature · doi:10.1038/nature05453 · Cited by 5,572 · see citing works
Are the Dorsal and Ventral Hippocampus Functionally Distinct Structures?
Fanselow, M. S., & Dong, H.-W. (2010) · Neuron · doi:10.1016/j.neuron.2009.11.031 · Cited by 3,358 · see citing works
From circuits to behaviour in the amygdala
Janak, P. H., & Tye, K. M. (2015) · Nature · doi:10.1038/nature14188 · Cited by 2,011 · cited 4× · see citing works
“1I,J), which shares reciprocal connections with the vHPC and other brain regions implicated in anxiety and avoidance behavior (Calhoon and Tye, 2015; Janak and Tye, 2015). c-Fos labeling in the lateral (LA) subregion of the BLA complex was not significantly impacted by EPM exposure (p = 0.2468;…”
BackgroundInfluentialOptogenetics in neural systems
Yizhar, O., Fenno, L. E., Davidson, T. J., Mogri, M., & Deisseroth, K. (2011) · Neuron · doi:10.1016/j.neuron.2011.06.004 · Cited by 1,881 · see citing works
Rapid, reversible activation of AgRP neurons drives feeding behavior in mice
Krashes, M. J., Koda, S., Ye, C., Rogan, S. C., Adams, A. C., Cusher, D. S., Maratos-Flier, E., Roth, B. L., & Lowell, B. B. (2011) · Journal of Clinical Investigation · doi:10.1172/jci46229 · Cited by 1,578 · 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
Tamamaki, N., Yanagawa, Y., Tomioka, R., Miyazaki, J., Obata, K., & Kaneko, T. (2003) · The Journal of Comparative Neurology · doi:10.1002/cne.10905 · Cited by 1,277 · see citing works
Requirement for Hippocampal CA3 NMDA Receptors in Associative Memory Recall
Nakazawa, K., Quirk, M. C., Chitwood, R. A., Watanabe, M., Yeckel, M. F., Sun, L. D., Kato, A., Carr, C. A., Johnston, D., Wilson, M. A., et al. (2002) · Science · doi:10.1126/science.1071795 · Cited by 1,090 · see citing works
Reduced fear expression after lesions of the ventral hippocampus
Kjelstrup, K. G., Tuvnes, F. A., Steffenach, H.-A., Murison, R., Moser, E. I., & Moser, M.-B. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.152112399 · Cited by 912 · see citing works
Resolving the neural circuits of anxiety
Calhoon, G. G., & Tye, K. M. (2015) · Nature Neuroscience · doi:10.1038/nn.4101 · Cited by 766 · see citing works
Lüscher, C., Jan, L. Y., Stoffel, M., Malenka, R. C., & Nicoll, R. A. (1997) · Neuron · doi:10.1016/s0896-6273(00)80381-5 · Cited by 762 · see citing works
Adhikari, A., Topiwala, M. A., & Gordon, J. A. (2010) · Neuron · doi:10.1016/j.neuron.2009.12.002 · Cited by 729 · see citing works
Differential Control of Learning and Anxiety along the Dorsoventral Axis of the Dentate Gyrus
Kheirbek, M. A., Drew, L. J., Burghardt, N. S., Costantini, D. O., Tannenholz, L., Ahmari, S. E., Zeng, H., Fenton, A. A., & Hen, R. (2013) · Neuron · doi:10.1016/j.neuron.2012.12.038 · Cited by 713 · see citing works
Hippocampal synaptic plasticity, spatial memory and anxiety
Bannerman, D. M., Sprengel, R., Sanderson, D. J., McHugh, S. B., Rawlins, J. N. P., Monyer, H., & Seeburg, P. H. (2014) · Nature Reviews Neuroscience · doi:10.1038/nrn3677 · Cited by 688 · see citing works
Ventral CA1 neurons store social memory
Okuyama, T., Kitamura, T., Roy, D. S., Itohara, S., & Tonegawa, S. (2016) · Science · doi:10.1126/science.aaf7003 · Cited by 657 · see citing works
Lüscher, C., & Slesinger, P. A. (2010) · Nature Reviews Neuroscience · doi:10.1038/nrn2834 · Cited by 617 · see citing works
Anxiety Cells in a Hippocampal-Hypothalamic Circuit
Jimenez, J., Su, K., Goldberg, A., Luna, V. M., Biane, J. S., Ordek, G., Zhou, P., Ong, S. K., Wright, M. A., Zweifel, L. S., et al. (2018) · Neuron · doi:10.1016/j.neuron.2018.01.016 · Cited by 606 · see citing works
Hippocampal neurogenesis confers stress resilience by inhibiting the ventral dentate gyrus
Anacker, C., Luna, V. M., Stevens, G. S., Millette, A., Shores, R., Jimenez, J. C., Chen, B., & Hen, R. (2018) · Nature · doi:10.1038/s41586-018-0262-4 · Cited by 605 · see citing works
BLA to vHPC inputs modulate anxiety-related behaviors
Felix-Ortiz, A. C., Beyeler, A., Seo, C., Leppla, C. A., Wildes, C. P., & Tye, K. M. (2013) · Neuron · doi:10.1016/j.neuron.2013.06.016 · Cited by 592 · see citing works
A viral strategy for targeting and manipulating interneurons across vertebrate species
Dimidschstein, J., Chen, Q., Tremblay, R., Rogers, S. L., Saldi, G.-A., Guo, L., Xu, Q., Liu, R., Lu, C., Chu, J., et al. (2016) · Nature Neuroscience · doi:10.1038/nn.4430 · Cited by 541 · see citing works
Ventral hippocampal lesions affect anxiety but not spatial learning
Bannerman, D. M., Grubb, M., Deacon, R. M. J., Yee, B. K., Feldon, J., & Rawlins, J. N. P. (2003) · Behavioural Brain Research · doi:10.1016/s0166-4328(02)00268-1 · Cited by 530 · see citing works
Cell type–specific genetic and optogenetic tools reveal hippocampal CA2 circuits
Kohara, K., Pignatelli, M., Rivest, A. J., Jung, H.-Y., Kitamura, T., Suh, J., Frank, D., Kajikawa, K., Mise, N., Obata, Y., et al. (2014) · Nature Neuroscience · doi:10.1038/nn.3614 · Cited by 528 · see citing works
Basomedial amygdala mediates top-down control of anxiety and fear
Adhikari, A., Lerner, T. N., Finkelstein, J., Pak, S., Jennings, J. H., Davidson, T. J., Ferenczi, E., Gunaydin, L. A., Mirzabekov, J. J., Ye, L., et al. (2015) · Nature · doi:10.1038/nature15698 · Cited by 485 · see citing works
Padilla-Coreano, N., Bolkan, S. S., Pierce, G. M., Blackman, D. R., Hardin, W. D., Garcia-Garcia, A. L., Spellman, T. J., & Gordon, J. A. (2016) · Neuron · doi:10.1016/j.neuron.2016.01.011 · Cited by 463 · see citing works
Estrous cycle influences the response of female rats in the elevated plus-maze test
Marcondes, F. K., Miguel, K. J., Melo, L. L., & Spadari-Bratfisch, R. C. (2001) · Physiology & Behavior · doi:10.1016/s0031-9384(01)00593-5 · Cited by 449 · see citing works
Karschin, C., Dißmann, E., Stühmer, W., & Karschin, A. (1996) · Journal of Neuroscience · doi:10.1523/jneurosci.16-11-03559.1996 · Cited by 449 · see citing works
Felix‐Ortiz, A. C., Burgos-Robles, A., Bhagat, N. D., Leppla, C. A., & Tye, K. M. (2015) · Neuroscience · doi:10.1016/j.neuroscience.2015.07.041 · Cited by 414 · see citing works
Selective information routing by ventral hippocampal CA1 projection neurons
Ciocchi, S., Passecker, J., Malagon‐Vina, H., Mikuš, N., & Klausberger, T. (2015) · Science · doi:10.1126/science.aaa3245 · Cited by 344 · see citing works
Immediate Early Genes, Memory and Psychiatric Disorders: Focus on c-Fos, Egr1 and Arc
Gallo, F. T., Katche, C., Morici, J. F., Medina, J. H., & Weisstaub, N. (2018) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2018.00079 · Cited by 339 · see citing works
Rethinking avoidance: Toward a balanced approach to avoidance in treating anxiety disorders
Hofmann, S. G., & Hay, A. C. (2018) · Journal of Anxiety Disorders · doi:10.1016/j.janxdis.2018.03.004 · Cited by 315 · see citing works
Fear and safety engage competing patterns of theta-gamma coupling in the basolateral amygdala
Stujenske, J. M., Likhtik, E., Topiwala, M. A., & Gordon, J. A. (2014) · Neuron · doi:10.1016/j.neuron.2014.07.026 · Cited by 303 · see citing works
From Structure to Behavior in Basolateral Amygdala-Hippocampus Circuits
Yang, Y., & Wang, J. (2017) · Frontiers in Neural Circuits · doi:10.3389/fncir.2017.00086 · Cited by 301 · see citing works
Adhikari, A., Topiwala, M. A., & Gordon, J. A. (2011) · Neuron · doi:10.1016/j.neuron.2011.07.027 · Cited by 285 · see citing works
Current diagnosis and treatment of anxiety disorders.
Bystritsky, A., Khalsa, S. S., Cameron, M., & Schiffman, J. E. (2013) · Europe PMC (PubMed Central) · Cited by 249 · see citing works
The Corticohippocampal Circuit, Synaptic Plasticity, and MemoryPreprint
Basu, J., & Siegelbaum, S. A. (2015) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a021733 · Cited by 244 · see citing works
Long-term disability in anxiety disorders
Hendriks, S. M., Spijker, J., Licht, C. M. M., Hardeveld, F., de Graaf, R., Batelaan, N. M., Penninx, B. W. J. H., & Beekman, A. T. F. (2016) · BMC Psychiatry · doi:10.1186/s12888-016-0946-y · Cited by 234 · cited 1× · see citing works
“Anxiety is a state of apprehension and enhanced vigilance, triggered by anticipation of a future threat or internally generated, that often results in avoidance behavior (Hendriks et al., 2016; Arnaudova et al., 2017; Hofmann and Hay, 2018).”
BackgroundInduction of Fos immunoreactivity in the brain by exposure to the elevated plus-maze
Silveira, M. C. L., Sandner, G., & Graeff, F. G. (1993) · Behavioural Brain Research · doi:10.1016/0166-4328(93)90028-o · Cited by 231 · see citing works
Parfitt, G. M., Nguyen, R., Bang, J. Y., Aqrabawi, A. J., Tran, M. M., Seo, D. K., Richards, B. A., & Kim, J. C. (2017) · Neuropsychopharmacology · doi:10.1038/npp.2017.56 · Cited by 229 · see citing works
Strawn, J. R., Geracioti, L., Rajdev, N., Clemenza, K., & Levine, A. (2018) · Expert Opinion on Pharmacotherapy · doi:10.1080/14656566.2018.1491966 · Cited by 214 · see citing works
Amygdalar and hippocampal substrates of anxious temperament differ in their heritability
Oler, J. A., Fox, A. S., Shelton, S. E., Rogers, J., Dyer, T. D., Davidson, R. J., Shelledy, W., Oakes, T. R., Blangero, J., & Kalin, N. H. (2010) · Nature · doi:10.1038/nature09282 · Cited by 208 · see citing works
Strain and Sex Differences in Anxiety-Like and Social Behaviors in C57BL/6J and BALB/cJ Mice
An, X., Jun-Xian, Z. O. U., Wu, R., Yang, Y., Tai, F., Zeng, S., Jia, R., Zhang, X., Liu, E., & Broders, H. G. (2011) · EXPERIMENTAL ANIMALS · doi:10.1538/expanim.60.111 · Cited by 203 · see citing works
Molecular and Cellular Diversity of Neuronal G-Protein-Gated Potassium Channels
Koyrakh, L., Luján, R., Colón, J., Karschin, C., Kurachi, Y., Karschin, A., & Wickman, K. D. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.3484-05.2005 · Cited by 199 · see citing works
Self-citationLecca, 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
Animal models for screening anxiolytic-like drugs: a perspective.
Bourin, M. (2015) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2015.17.3/mbourin · Cited by 163 · see citing works
Kaufmann, K. W., Romaine, I. M., Days, E., Pascual, C., Malik, A., Yang, L., Zou, B., Du, Y., Sliwoski, G. R., Morrison, R. D., et al. (2013) · ACS Chemical Neuroscience · doi:10.1021/cn400062a · Cited by 155 · see citing works
Hippocampal-Prefrontal Theta Transmission Regulates Avoidance Behavior
Padilla-Coreano, N., Canetta, S., Mikofsky, R. M., Alway, E., Passecker, J., Myroshnychenko, M., Garcia‐García, Á. L., Warren, R., Teboul, E., Blackman, D. R., et al. (2019) · Neuron · doi:10.1016/j.neuron.2019.08.006 · Cited by 134 · see citing works
An elevated plus-maze in mixed reality for studying human anxiety-related behavior
Biedermann, S., Biedermann, D., Wenzlaff, F., Kurjak, T., Nouri, S., Auer, M., Wiedemann, K., Briken, P., Haaker, J., Lonsdorf, T., et al. (2017) · BMC Biology · doi:10.1186/s12915-017-0463-6 · Cited by 129 · see citing works
New insights into the therapeutic potential of Girk channels
Luján, R., de Velasco, E. M. F., Aguado, C., & Wickman, K. (2013) · Trends in Neurosciences · doi:10.1016/j.tins.2013.10.006 · Cited by 122 · see citing works
Self-citationRepeated Cocaine Weakens GABAB-Girk Signaling in Layer 5/6 Pyramidal Neurons in the Prelimbic Cortex
Hearing, M. C., Kotecki, L., de Velasco, E. M. F., Fajardo‐Serrano, A., Chung, H. J., Luján, R., & Wickman, K. D. (2013) · Neuron · doi:10.1016/j.neuron.2013.07.019 · Cited by 117 · see citing works
Self-citationPathways towards the proliferation of avoidance in anxiety and implications for treatment.
Arnaudova, I., Kindt, M., Fanselow, M., & Beckers, T. (2017) · Behaviour Research and Therapy · doi:10.1016/j.brat.2017.04.004 · Cited by 111 · see citing works
Wydeven, N., Marron Fernandez de Velasco, E., Du, Y., Benneyworth, M. A., Hearing, M. C., Fischer, R. A., Thomas, M. J., Weaver, C. D., & Wickman, K. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1405190111 · Cited by 109 · see citing works
Self-citationLinden, A.-M., Greene, S. J., Bergeron, M., & Schoepp, D. D. (2003) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300321 · Cited by 106 · see citing works
Contribution of the Kir3.1 Subunit to the Muscarinic-gated Atrial Potassium Channel IKACh
Bettahi, I., Marker, C. L., Roman, M. I., & Wickman, K. D. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m209599200 · Cited by 101 · see citing works
Self-citationSchumacher, A., Villaruel, F. R., Ussling, A., Riaz, S., Lee, A. C. H., & Ito, R. (2018) · Current Biology · doi:10.1016/j.cub.2018.03.012 · Cited by 101 · see citing works
Modulation of anxiety and fear via distinct intrahippocampal circuits
Engin, E., Smith, K. S., Gao, Y., Nagy, D., Foster, R. A., Tsvetkov, E., Keist, R., Crestani, F., Fritschy, J.-M., Bolshakov, V. Y., et al. (2016) · eLife · doi:10.7554/elife.14120 · Cited by 91 · see citing works
Behavioral characterization of mice lacking GIRK/Kir3 channel subunits
Pravetoni, M., & Wickman, K. D. (2008) · Genes Brain & Behavior · doi:10.1111/j.1601-183x.2008.00388.x · Cited by 84 · see citing works
Self-citationThe role of the ventral dentate gyrus in anxiety-based behaviors
Weeden, C. S. S., Roberts, J. M., Kamm, A. M., & Kesner, R. P. (2015) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2014.12.002 · Cited by 80 · see citing works
Neurons in the Amygdala with Response-Selectivity for Anxiety in Two Ethologically Based Tests
Wang, D. V., Wang, F., Liu, J., Zhang, L., Wang, Z., & Lin, L. (2011) · PLoS ONE · doi:10.1371/journal.pone.0018739 · Cited by 78 · see citing works
Andy’s Algorithms: new automated digital image analysis pipelines for FIJI
Law, A. M. K., Yin, J. X. M., Castillo, L. E., Young, A. I. J., Blyth, C., Rogers, S., Caldon, C. E., Burgess, A., Millar, E. K. A., O’Toole, S. A., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-15885-6 · Cited by 67 · see citing works
Blednov, Y. A., Stoffel, M., Chang, S., & Harris, R. A. (2001) · Physiology & Behavior · doi:10.1016/s0031-9384(01)00555-8 · Cited by 65 · see citing works
Localization and Targeting of GIRK Channels in Mammalian Central Neurons
Luján, R., & Aguado, C. (2015) · International review of neurobiology · doi:10.1016/bs.irn.2015.05.009 · Cited by 60 · see citing works
GIRK Channels Modulate Opioid-Induced Motor Activity in a Cell Type- and Subunit-Dependent Manner
Kotecki, L., Hearing, M. C., McCall, N. M., de Velasco, E. M. F., Pravetoni, M., Arora, D. S., Victoria, N. C., Munoz, M. B., Xia, Z., Slesinger, P. A., et al. (2015) · Journal of Neuroscience · doi:10.1523/jneurosci.5051-14.2015 · Cited by 56 · see citing works
Self-citationD'Souza, D., & Sadananda, M. (2017) · Annals of Neurosciences · doi:10.1159/000477151 · Cited by 50 · see citing works
Victoria, N. C., de Velasco, E. M. F., Ostrovskaya, O. I., Metzger, S., Xia, Z., Kotecki, L., Benneyworth, M. A., Zink, A. N., Martemyanov, K. A., & Wickman, K. (2015) · Biological Psychiatry · doi:10.1016/j.biopsych.2015.10.004 · Cited by 38 · see citing works
Self-citationYohn, C. N., Shifman, S. G., Garino, A., Diethorn, E. J., Bokka, L., Ashamalla, S. A., & Samuels, B. A. (2020) · Psychopharmacology · doi:10.1007/s00213-020-05456-5 · Cited by 35 · see citing works
Manassero, E., Renna, A., Milano, L., & Sacchetti, B. (2018) · Scientific Reports · doi:10.1038/s41598-017-19074-3 · Cited by 31 · see citing works
Ventral Hippocampus Modulates Anxiety-Like Behavior in Male But Not Female C57BL/6 J Mice
Wang, C., Zhang, Y., Shao, S. H., Cui, S., Wan, Y., & Yi, M. (2019) · Neuroscience · doi:10.1016/j.neuroscience.2019.08.032 · Cited by 28 · see citing works
Amygdaloid involvement in the defensive behavior of mice exposed to the open elevated plus-maze
Sorregotti, T., Cipriano, A. C., Cruz, F. C., Mascarenhas, D. C., Rodgers, R. J., & Nunes‐de‐Souza, R. L. (2017) · Behavioural Brain Research · doi:10.1016/j.bbr.2017.10.022 · Cited by 26 · see citing works
Inhibition of Pyramidal Neurons in the Basal Amygdala Promotes Fear Learning
Tipps, M. E., de Velasco, E. M. F., Schaeffer, A., & Wickman, K. (2018) · eNeuro · doi:10.1523/eneuro.0272-18.2018 · Cited by 24 · see citing works
Self-citationVo, B. N., Abney, K. K., Anderson, A., de Velasco, E. M. F., Benneyworth, M. A., Daniels, J. S., Morrison, R. D., Hopkins, C. R., Weaver, C. D., & Wickman, K. D. (2019) · British Journal of Pharmacology · doi:10.1111/bph.14671 · Cited by 16 · see citing works
Self-citationMaestas-Olguin, C. R., Fennelly, J. W., & Pentkowski, N. S. (2021) · Neuroscience Letters · doi:10.1016/j.neulet.2021.135777 · Cited by 15 · see citing works
de Velasco, E. M. F., Carlblom, N., Xia, Z., & Wickman, K. (2017) · Neuropharmacology · doi:10.1016/j.neuropharm.2017.01.021 · Cited by 13 · see citing works
Self-citationStructure to Function of G Protein-Gated Inwardly Rectifying (GIRK) Channels
(2015) · International review of neurobiology · doi:10.1016/s0074-7742(15)x0005-5 · Cited by 9 · see citing works
Schumacher, A., Villaruel, F. R., Riaz, S., et al. (2017) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/180513 · Cited by 8 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
The Neuropsychology of Anxiety
McNaughton, N., & Gray, J. A. (2024) · doi:10.1093/oso/9780198843313.001.0001 · Cited by 98 · see citing works
Neuronal G protein-gated K<sup>+</sup> channels
Luo, H., Marron Fernandez de Velasco, E., & Wickman, K. (2022) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00102.2022 · Cited by 62 · see citing works
Self-citationLuo, H., de Velasco, E. M. F., Gansemer, B. M., Frederick, M. H., Aguado, C., Luján, R., Thayer, S. A., & Wickman, K. D. (2024) · Science Signaling · doi:10.1126/scisignal.ado4132 · Cited by 11 · see citing works
Self-citationJenkins, B. W., Moore, C. F., Jantzie, L. L., & Weerts, E. M. (2025) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2025.106207 · Cited by 13 · see citing works
Mitten, E. H., Souders, A., de Velasco, E. M. F., Aguado, C., Luján, R., & Wickman, K. D. (2024) · British Journal of Pharmacology · doi:10.1111/bph.17335 · Cited by 9 · see citing works
Self-citationLiu, X., Liu, R., Sun, Y., Wang, H., Wang, H., Wang, T., Ma, Y., Li, X., Wang, Q., Su, Y., et al. (2024) · Neuropsychopharmacology · doi:10.1038/s41386-024-01848-9 · Cited by 7 · see citing works
Luo, P., Liu, W. D., Zhou, M. L., Li, Y., & Lin, K. (2022) · Current Neurovascular Research · doi:10.2174/1567202620666221025152325 · Cited by 5 · see citing works
Luo, H., Frederick, M. H., de Velasco, E. M. F., Oltmanns, J. R. O., Wright, C. J., & Wickman, K. D. (2024) · Learning & Memory · doi:10.1101/lm.054022.124 · Cited by 4 · see citing works
Self-citationCollins, H. M., Gullino, L. S., Fuller, C., Pinacho, R., Bannerman, D. M., & Sharp, T. (2025) · Neuropharmacology · doi:10.1016/j.neuropharm.2025.110541 · Cited by 3 · see citing works
McNaughton, N., & Gray, J. A. (2024) · Oxford University Press eBooks · doi:10.1093/oso/9780198843313.003.0012 · Cited by 2 · see citing works
Soto, C., Orihuela, L. P., Apostol, G., & Vivar, C. (2025) · European Journal of Neuroscience · doi:10.1111/ejn.70084 · Cited by 1 · see citing works
Fundamentals of the septo-hippocampal system
McNaughton, N., & Gray, J. A. (2024) · Oxford University Press eBooks · doi:10.1093/oso/9780198843313.003.0009 · Cited by 1 · see citing works
Memory and the septo-hippocampal system
McNaughton, N., & Gray, J. A. (2024) · Oxford University Press eBooks · doi:10.1093/oso/9780198843313.003.0008 · Cited by 1 · see citing works
Bonilla, P., McBride, D., Shanks, A., Kartik, J., Bhan, A., & Porcu, A. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.01.31.635947 · Cited by 2 · see citing works
Synaptic Plasticity—Intrinsic Excitability and Antidepressant Discovery
Tanaka, M. (2026) · Biomedicines · doi:10.3390/biomedicines14061265
What do hippocampal cell fields represent?
McNaughton, N., & Gray, J. A. (2024) · Oxford University Press eBooks · doi:10.1093/oso/9780198843313.003.0007
McNaughton, N., & Gray, J. A. (2024) · Oxford University Press eBooks · doi:10.1093/oso/9780198843313.003.0001
The neurology of anxiety—planning circuits
McNaughton, N., & Gray, J. A. (2024) · Oxford University Press eBooks · doi:10.1093/oso/9780198843313.003.0011
A theory of the septo-hippocampal system (SHS)
McNaughton, N., & Gray, J. A. (2024) · Oxford University Press eBooks · doi:10.1093/oso/9780198843313.003.0010
Symptoms and syndromes of anxiety
McNaughton, N., & Gray, J. A. (2024) · Oxford University Press eBooks · doi:10.1093/oso/9780198843313.003.0013
The neurology of anxiety—survival circuits
McNaughton, N., & Gray, J. A. (2024) · Oxford University Press eBooks · doi:10.1093/oso/9780198843313.003.0006
McNaughton, N., & Gray, J. A. (2024) · Oxford University Press eBooks · doi:10.1093/oso/9780198843313.003.0002
The treatment of anxiety and fear disorders
McNaughton, N., & Gray, J. A. (2024) · Oxford University Press eBooks · doi:10.1093/oso/9780198843313.003.0014
McNaughton, N., & Gray, J. A. (2024) · Oxford University Press eBooks · doi:10.1093/oso/9780198843313.002.0011
McNaughton, N., & Gray, J. A. (2024) · Oxford University Press eBooks · doi:10.1093/oso/9780198843313.003.0015
McNaughton, N., & Gray, J. A. (2024) · Oxford University Press eBooks · doi:10.1093/oso/9780198843313.002.0009
The anxiolytic drugs—our key tool
McNaughton, N., & Gray, J. A. (2024) · Oxford University Press eBooks · doi:10.1093/oso/9780198843313.003.0004
McNaughton, N., & Gray, J. A. (2024) · Oxford University Press eBooks · doi:10.1093/oso/9780198843313.003.0003
List of online appendices and reviews
McNaughton, N., & Gray, J. A. (2024) · Oxford University Press eBooks · doi:10.1093/oso/9780198843313.002.0010
A conceptual theory of the goal inhibition system
McNaughton, N., & Gray, J. A. (2024) · Oxford University Press eBooks · doi:10.1093/oso/9780198843313.003.0005
McNaughton, N., & Gray, J. A. (2024) · Oxford University Press eBooks · doi:10.1093/oso/9780198843313.002.0006
McNaughton, N., & Gray, J. A. (2024) · Oxford University Press eBooks · doi:10.1093/oso/9780198843313.002.0004
McNaughton, N., & Gray, J. A. (2024) · Oxford University Press eBooks · doi:10.1093/oso/9780198843313.002.0005
- Authors
- Vo, B. N., Marron Fernandez de Velasco, E., Rose, T. R., Oberle, H., Luo, H., Hopkins, C. R., & Wickman, K.
- Affiliations
- University of Minnesota (US)
- University of Nebraska Medical Center (US)
- ORCID
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2021-05-26
- Volume
- 41
- Issue
- 27
- Pages
- 5809-5821
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC8265807
- OpenAlex
- W3165477014
- Cited by
- 33
- References
- 73
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 26 · 2022: 2
- FWCI
- 3.23
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (DA007234)
- National Institute on Alcohol Abuse and Alcoholism (R01AA027544)
- National Institute of Mental Health (R01MH107399)
- National Institute on Drug Abuse (R01DA034696, T32DA007234)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Keywords
- G protein-coupled inwardly rectifying potassium channels, GIRK1, anxiolytic efficacy, ventral hippocampus, basolateral amygdala, CA3, dentate gyrus, excitatory neurons, elevated plus maze, chemogenetic inhibition, viral gene delivery, marble-burying behavior
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
