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From circuits to behaviour in the amygdala
Open accessAbstract
The amygdala has long been associated with emotion and motivation, playing an essential part in processing both fearful and rewarding environmental stimuli. How can a single structure be crucial for such different functions? With recent technological advances that allow for causal investigations of specific neural circuit elements, we can now begin to map the complex anatomical connections of the amygdala onto behavioural function. Understanding how the amygdala contributes to a wide array of behaviours requires the study of distinct amygdala circuits.
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In the citing paper
“More recently, more in-depth research has illustrated that alterations in the HPA axis have been associated with the process of dealing with stress, especially toxic stress-induced negative health outcomes (83).”
From Epigenetic Modifications in Stress Response Genes Associated With Childhood Trauma (2019) · cites this paper as [83]
Experimental — accuracy not yet measuredIn the citing paper
“A growing appreciation for the complexity of the amygdala complex has resulted in a more nuanced understanding of this region’s role in fear learning, appetitive learning, and value encoding (Janak and Tye, 2015), and it is clear that the amygdala promotes adaptive behavioral responses to both positive and negative environmental stimuli.”
From A framework for understanding the emerging role of corticolimbic-ventral striatal networks in OCD-associated repetitive behaviors (2015) · cites this paper as Janak and Tye, 2015
In the citing paper
“In addition to a role in fear and threat conditioning, the amygdala also regulates anxiety.”
From A framework for understanding the emerging role of corticolimbic-ventral striatal networks in OCD-associated repetitive behaviors (2015) · cites this paper as Janak and Tye, 2015
In the citing paper
“Since the amygdala is central to processing these forms of information (Janak and Tye, 2015), aberrant communication of anxiety-related information from amygdala to VS could mediate anxiety-driven compulsive behavior.”
From A framework for understanding the emerging role of corticolimbic-ventral striatal networks in OCD-associated repetitive behaviors (2015) · cites this paper as Janak and Tye, 2015
In the citing paper
“The BNST and the CeA have been implicated in diverse behavioral functions (Davis et al., 2010, Janak and Tye, 2015, Kim et al., 2013)”
From Dorsal raphe dopamine neurons represent the experience of social isolation (2016) · cites this paper as Janak and Tye, 2015
In the citing paper
“In particular, given its access to primary sensory information, the CeA could orchestrate appropriate behavioral responses to salient stimuli with different valences [88,93].”
From Oxytocin Signaling in the Central Amygdala Modulates Emotion Discrimination in Mice (2019) · cites this paper as [93]
In the citing paper
“Processing of this sensory information in the BLA results in the formation of associations between neutral predictive stimuli and outcomes of positive or negative valence56 via Hebbian mechanisms57-59.”
From Resolving the neural circuits of anxiety (2015) · cites this paper as [56]
In the citing paper
“This interpretation is in part dictated by the individual’s previous experience and includes the assignment of valence to the stimulus via BLA circuits56.”
From Resolving the neural circuits of anxiety (2015) · cites this paper as [56]
In the citing paper
“the valence detection function of BLA projection neurons56 fits within the interpretation circuits described here, helping to determine whether a given stimulus is threatening or appetitive.”
From Resolving the neural circuits of anxiety (2015) · cites this paper as [56]
In the citing paper
“The BLA is critical for associative learning”
From Infraslow histaminergic dynamics govern priming states to gate moment-to-moment memory accessibility (2026) · cites this paper as [30]
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Citations
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“The BLA contains a critical node of network for valence encoding and assigning valence to sensory stimuli 55,56 .”
The role of the basolateral amygdala in the perception of faces in natural contexts
Hortensius, R., Terburg, D., Morgan, B. E., Stein, D. J., van Honk, J., & de Gelder, B. (2016) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2015.0376 · Cited by 29
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“From these studies investigating the molecular mechanisms underlying reconsolidation emerges a central role played by the amygdala and interconnections with brain areas involved in emotional and appetitive processing such as the medial prefrontal cortex (mPFC), with opposite functions of prelimbic and infralimbic port…”
BackgroundUnconscious psychological treatments for physiological survival circuits
Taschereau‐Dumouchel, V., Liu, K., & Lau, H. C. (2018) · Current Opinion in Behavioral Sciences · doi:10.1016/j.cobeha.2018.04.010 · Cited by 26
Opposing roles for amygdala and vmPFC in the return of appetitive conditioned responses in humans
Ebrahimi, C., Koch, S., Pietrock, C., Fydrich, T., Heinz, A., & Schlagenhauf, F. (2019) · Translational Psychiatry · doi:10.1038/s41398-019-0482-x · Cited by 28
CGRP-dependent sensitization of PKC-δ positive neurons in central amygdala mediates chronic migraine
Chou, T.-M., Lee, Z.-F., Wang, S., Lien, C., & Chen, S. (2022) · The Journal of Headache and Pain · doi:10.1186/s10194-022-01531-8 · Cited by 27
“As the CeA primarily comprises heterogeneous GABAergic subpopulations of interneurons [44–46], we further investigated whether these pERK positive neurons were protein kinase C-delta (PKC-δ) or somatostatin (SOM) positive neurons, two major non-overlapping cell types in the CeA [44, 46, 47], with immunofluorescent co-…”
BackgroundMolecular neurobiology of loss: a role for basolateral amygdala extracellular matrix
Smail, M. A., Smith, B. L., Shukla, R., Alganem, K., Eby, H., Bollinger, J. L., Parikh, R. K., Chambers, J. B., Reigle, J. K., Moloney, R. D., et al. (2023) · Molecular Psychiatry · doi:10.1038/s41380-023-02231-8 · Cited by 27
“PNNs help regulate PV cell physiology [19, 20, 35], so the present ER-related increase in PNNs could impact the BLA ’ s inhibitory tone via changes to PV characteristics [13, 40], an effect that could substantially impact ER behaviors.”
BackgroundMethodInfluentialPain in Parkinson's disease: a neuroanatomy-based approach
Nardelli, D., Gambioli, F., Bartolo, M. I. D., Mancinelli, R., Biagioni, F., Carotti, S., Falato, E., Leodori, G., Puglisi‐Allegra, S., Vivacqua, G., et al. (2024) · Brain Communications · doi:10.1093/braincomms/fcae210 · Cited by 31
Basolateral amygdala neurons are activated during threat expectation
Amir, A., Kyriazi, P., Lee, S.-C., Headley, D. B., & Paré, D. (2019) · Journal of Neurophysiology · doi:10.1152/jn.00807.2018 · Cited by 25
“A long series of studies have established that the basolateral complex of the amygdala (BLA) plays an essential role in the acquisition and expression of appetitive and aversive conditioned behaviors (Janak and Tye 2015; Maren and Quirk 2004; Pape and Paré 2010).”
BackgroundIndividual susceptibility or resistance to posttraumatic stress disorder-like behaviours
Skórzewska, A., Lehner, M., Wisłowska-Stanek, A., Turzyńska, D., Sobolewska, A., Krząścik, P., Szyndler, J., Maciejak, P., Chmielewska, N., Kołosowska, K., et al. (2020) · Behavioural Brain Research · doi:10.1016/j.bbr.2020.112591 · Cited by 29
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“These regions that are highly connected and play an important role in memory formation and in the regulation of emotions (Janak & Tye, 2015; Kitamura et al., 2017; Leal et al., 2017).”
BackgroundNeurobiology of maternal mental illness
Maguire, J., McCormack, C., Mitchell, A., & Monk, C. E. (2020) · Handbook of clinical neurology · doi:10.1016/b978-0-444-64239-4.00005-9 · Cited by 28
“Our current understanding surrounding the function of the amygdala in reward, anxiety, and valence processing (Janak and Tye, 2015) suggests that these pathological features involving the amygdala (summarized earlier) are associated with the primary pathology of major depressive disorder.”
BackgroundLong term effects of early life stress on HPA circuit in rodent models
Babicola, L., Ventura, R., D’Addario, S. L., Ielpo, D., Andolina, D., & Segni, M. D. (2020) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2020.111125 · Cited by 31
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Glutamatergic Neurons in the Amygdala Are Involved in Paclitaxel-Induced Pain and Anxiety
Liu, J., Li, D., Huang, J., Cao, J., Cai, G., Guo, Y., Wang, G., Zhao, S., Wang, X., & Wu, S. (2022) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2022.869544 · Cited by 28
Toward a systems-oriented approach to the role of the extended amygdala in adaptive responding
Waraczynski, M. A. (2016) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2016.05.015 · Cited by 28
Orsini, C. A., Hernandez, C. M., Bizon, J. L., & Setlow, B. (2018) · Cognitive Affective & Behavioral Neuroscience · doi:10.3758/s13415-018-00649-0 · Cited by 28
Nadig, A., Reardon, P. K., Seidlitz, J., McDermott, C. L., Blumenthal, J. D., CLASEN, L. S., Lalonde, F. M., Lerch, J. P., Chakravarty, M. M., & Raznahan, A. (2018) · eNeuro · doi:10.1523/eneuro.0265-18.2018 · Cited by 29
“2018 eNeuro.org microarchitectural gradients of the limbic system (Janak and Tye, 2015).”
BackgroundEstradiol and progesterone in female reward-learning, addiction, and therapeutic interventions
Hilz, E. N., & Lee, H. J. (2022) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2022.101043 · Cited by 29
Plasticity of Fear and Safety Neurons of the Amygdala in Response to Fear Extinction
Sangha, S. (2015) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2015.00354 · Cited by 28
“The amygdala has been consistently implicated in processing and regulating a myriad of emotional responses (for review see Janak and Tye, 2015).”
Primate amygdala neurons evaluate the progress of self-defined economic choice sequences
Fabian Grabenhorst, B., Hernádi, I., & Schultz, W. (2016) · eLife · doi:10.7554/elife.18731 · Cited by 26
“…imaging studies (De Martino et al., 2006; Grabenhorst et al., 2013), and with features of amygdala inhibitory microcircuits (Duvarci and Pare, 2014; Janak and Tye, 2015) that could support neural choice mechanisms by winner-take-all competition through mutual inhibition (Deco et al., 2013; Wang,…”
BackgroundInfluentialCorticolimbic circuitry in the modulation of chronic pain and substance abuse
Taylor, A. M. W. (2017) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2017.05.009 · Cited by 26
“In this context, the CeA is primarily involved in mediating behavioral output (Janak and Tye, 2015).”
Acute Stress-Induced Epigenetic Modulations and Their Potential Protective Role Toward Depression
Rusconi, F., & Battaglioli, E. (2018) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2018.00184 · Cited by 29
“Either acute or chronic stress can transiently or stably modify dendritic spine density and arborization (Golden et al., 2013; Maras et al., 2014; Chattarji et al., 2015; Janak and Tye, 2015), suggesting that adaptive structural modification of corticolimbic areas can also correspond to a neutral behavioral response.”
BackgroundImaging of Posttraumatic Stress Disorder
Kamiya, K., & Abe, O. (2019) · Neuroimaging Clinics of North America · doi:10.1016/j.nic.2019.09.010 · Cited by 29
Hu, B., Boyle, C. A., & Lei, S. (2020) · The Journal of Physiology · doi:10.1113/jp279457 · Cited by 29
“The amygdala is an important structure involved in modulating emotion (Ressler, 2010; Tye et al. 2011; Dejean et al. 2015; Janak & Tye, 2015), pain (Neugebauer et al. 2004; Veinante et al. 2013; Neugebauer, 2015), alcohol use (Silberman et al. 2008; Gilpin et al. 2015) and appetite (Petrovich,…”
BackgroundNahman‐Averbuch, H., Schneider, V. J., Chamberlin, L. A., Diest, A. M. K. V., Peugh, J., Lee, G. R., Radhakrishnan, R., Hershey, A. D., Powers, S. W., Coghill, R. C., et al. (2020) · Pain · doi:10.1097/j.pain.0000000000002029 · Cited by 25
Roles of the bed nucleus of the stria terminalis and amygdala in fear reactions
Hulsman, A. M., Terburg, D., Roelofs, K., & Klumpers, F. (2021) · Handbook of clinical neurology · doi:10.1016/b978-0-12-819975-6.00027-3 · Cited by 29
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“It is therefore possible that anxious traits recruit amygdalarelated circuitry and interfere with food approach [60].”
BackgroundAn NTS-CeA projection modulates depression-like behaviors in a mouse model of chronic pain
He, S., Huang, X., Zheng, J., Zhang, Y., & Ruan, X. (2022) · Neurobiology of Disease · doi:10.1016/j.nbd.2022.105893 · Cited by 27
“The CeA is a well-known hub that modulates sensory and mental information (Janak and Tye, 2015; Sanders et al., 2019; Zhou et al., 2019).”
BackgroundLactobacillus reuteri normalizes altered fear memory in male Cntnap4 knockout mice
Zhang, W., Huang, J., Gao, F., You, Q.-L., Ding, L., Gong, J., Zhang, M., Ma, R., Zheng, S., Sun, X., et al. (2022) · EBioMedicine · doi:10.1016/j.ebiom.2022.104323 · Cited by 29
“The amygdala is critical for input and processing of emotional memories, especially including fear memory acquisition, consolidation and extinction, 11,65 – 67 and amygdala projection neurons are primarily innervated by GABAergic interneurons.”
Cortical kainate receptors and behavioral anxiety
Zhuo, M. (2017) · Molecular Brain · doi:10.1186/s13041-017-0297-8 · Cited by 27
Chen, L., Song, L., Cai, J., Wei, T., Liu, L., Zhao, H., Liu, B.-H., Jing, H., Jin, Z., Liu, M., et al. (2017) · Behavioural Brain Research · doi:10.1016/j.bbr.2017.10.027 · Cited by 26
“The LA/BLA receive highly processed sensory information via cortical afferents coursing into the region from the external capsule (EC) [5], and subsequently transmit to the CeA, the output nucleus for major amygdala functions [6], to drive stress-related mood disorders like fear, anxiety and depression [7,8].”
BackgroundAlternations in functional connectivity of amygdalar subregions under acute social stress
Chang, J., & Yu, R. (2018) · Neurobiology of Stress · doi:10.1016/j.ynstr.2018.06.001 · Cited by 27
“When the BLA was lesioned and thus the inhibition from BLA to intact CMA was impaired, a BLA-damaged patient showed hyper-vigilance to fearful and threatening stimuli (Janak and Tye, 2015a; Terburg et al., 2012; Tye et al., 2011; Wang et al., 2017).”
BackgroundOxytocin for learning calm and safety
Eckstein, M., de Minas, A. C. A., Scheele, D., Kreuder, A., Hurlemann, R., Grinevich, V., & Ditzen, B. (2018) · International Journal of Psychophysiology · doi:10.1016/j.ijpsycho.2018.06.004 · Cited by 28
Inhibition of Pyramidal Neurons in the Basal Amygdala Promotes Fear Learning
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“…the importance of the amygdala to the formation and extinction of fear memories (LeDoux, 2000; Pape and Pare, 2010; Johansen et al., 2011; Janak and Tye, 2015), including identifying specific roles for the various subnuclei of the amygdala in these processes (Duvarci and Pare, 2014;…”
BackgroundInfluentialConnecting Childhood Wariness to Adolescent Social Anxiety through the Brain and Peer Experiences
Jarcho, J. M., Grossman, H., Guyer, A. E., Quarmley, M., Smith, A. R., Fox, N. A., Leibenluft, E., Pine, D. S., & Nelson, E. E. (2019) · Research on Child and Adolescent Psychopathology · doi:10.1007/s10802-019-00543-4 · Cited by 28
“…is often implicated in reward learning, the amygdala is also implicated in coding for salience of positive and negative prediction error outcomes (Belova et al. 2007; Metereau and Dreher 2013), and is necessary for successful reinforcement learning in unpredictable contexts (Janak and Tye 2015).”
BackgroundLoBue, V., Kim, E., & Delgado, M. R. (2019) · Springer eBooks · doi:10.1007/978-3-030-17332-6_11 · Cited by 25
Ge, M.-J., Chen, G., Zhang, Z., Yu, Z.-H., Shen, J., Pan, C., Han, F., Xu, H., Zhu, X.-L., & Lu, Y.-P. (2024) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2024.110981 · Cited by 25
“A large number of studies have proved that there are reciprocally connections between mPFC and amygdala (H, 2000, Chang et al., 2013, Ruff, 2014, DeNardo et al., 2015, Janak and Tye, 2015, Chen and Hong, 2018, Wittmann et al., 2018, ¨ et al. 2019, Gang-opadhyay et al., 2021, Bhattarai et al., 2022).”
Beattie, M. C., Maldonado‐Devincci, A. M., Porcu, P., O’Buckley, T. K., Daunais, J. B., Grant, K. A., & Morrow, A. L. (2015) · Addiction Biology · doi:10.1111/adb.12326 · Cited by 26
“The amygdala plays an important role in drug seeking and is associated with affective behaviors that contribute to the abuse of drugs, including ethanol (Janak & Tye 2015).”
BackgroundThe anterior medial temporal lobes: Their role in food intake and body weight regulation
Coppin, G. (2016) · Physiology & Behavior · doi:10.1016/j.physbeh.2016.08.028 · Cited by 27
Chick, C. F., Rolle, C. E., Trivedi, H. M., Monuszko, K. A., & Etkin, A. (2019) · Psychiatry Research · doi:10.1016/j.psychres.2019.112515 · Cited by 25
Li, K., He, M., Ye, W., Simms, J. A., Gill, M., Xiang, X., Jan, Y. N., & Jan, L. Y. (2019) · eLife · doi:10.7554/elife.47106 · Cited by 26
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Chávez-Pichardo, M. E., Reyes-Bravo, D. Y., Mendoza-Trejo, M. S., Marín-López, A. G., Giòrdano, M., Hernández‐Chan, N. G., Domínguez-Marchan, K., Ortega-Rosales, L. C., & Rodríguez, V. M. (2020) · Archives of Toxicology · doi:10.1007/s00204-020-02806-2 · Cited by 25
Elorette, C., Aguilar, B. L., Novak, V., Forcelli, P. A., & Málková, L. (2020) · Neuropharmacology · doi:10.1016/j.neuropharm.2020.108275 · Cited by 24
“The study of separable neural circuits both within the amygdala and in the amygdala’s projections to other brain regions is a growing field in the rodent (Janak and Tye, 2015), but has remained understudied in the non-human primate.”
BackgroundA Role for the Amygdala in Impairments of Affective Behaviors Following Mild Traumatic Brain Injury
McCorkle, T. A., Barson, J. R., & Raghupathi, R. (2021) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2021.601275 · Cited by 25
“Threatening cues induce anxiogenic behavior because of increased activation of the CeA and the BNST, whereas hyperexcitation within the CeA promotes arousal and hypervigilance and leads to the association of nonthreatening factors with potential danger (Calhoon and Tye, 2015).”
BackgroundMethodInfluentialModular Network between Postrhinal Visual Cortex, Amygdala, and Entorhinal Cortex
Meier, A. M., Wang, Q., Ji, W., Ganachaud, J., & Burkhalter, A. (2021) · Journal of Neuroscience · doi:10.1523/jneurosci.2185-20.2021 · Cited by 33
“For this, animals rely on neural circuits connecting multiple brain structures including the amygdala, which drives flight, freezing, and approach (Janak and Tye, 2015); and areas of the limbic and sensory cortex (LeDoux, 2012).”
BackgroundZeng, N., Cutts, E. J., Lopez, C. B., Kaur, S., Duran, M., VIRKUS, S., & Hardaway, J. A. (2021) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2021.724030 · Cited by 25
Prenatal stress and its association with amygdala-related structural covariance patterns in youth
Marečková, K., Miles, A. E., Liao, Z., Andrýsková, L., Brázdil, M., Paus, T., & Nikolova, Y. S. (2022) · NeuroImage Clinical · doi:10.1016/j.nicl.2022.102976 · Cited by 29
Wronski, M., Geisler, D., Bernardoni, F., Seidel, M., Bahnsen, K., Doose, A., Steinhäuser, J. L., Gronow, F., Böldt, L. V., Plessow, F., et al. (2022) · Psychological Medicine · doi:10.1017/s0033291722003609 · Cited by 29
“…emotional learning, regulation of aversive and appetitive behavioral responses to sensory including olfactory and gustatory stimuli, and evaluation of affective situations (Baxter & Murray, 2002; Davis & Whalen, 2001; Janak & Tye, 2015; Kim et al., 2017; Petrovich, 2011; Smitka et al., 2012).”
InfluentialUltra-high field imaging of the amygdala – A narrative review
Kirstein, C. F., Güntürkün, O., & Ocklenburg, S. (2023) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2023.105245 · Cited by 25
“Other authors suggest categorizing it into a lateral, basolateral, medial, and central nuclei complex (Janak and Tye, 2015).”
BackgroundEvidence of estrogen modulation on memory processes for emotional content in healthy young women
Pompili, A., Arnone, B., D'Amico, M., Federico, P., & Gasbarri, A. (2015) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2015.12.013 · Cited by 25
de Borst, A. W., & de Gelder, B. (2016) · Social Cognitive and Affective Neuroscience · doi:10.1093/scan/nsw039 · Cited by 24
“As stated by Janak and Tye (2015), behaviours of opposite valence do not necessarily arise from activity in different pathways, but may be modulated by connections between the same regions.”
BackgroundMethodInfluentialKimura, E., Endo, T., Yoshioka, W., Ding, Y., Ujita, W., Kakeyama, M., & Tohyama, C. (2016) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2016.05.048 · Cited by 25
Kovner, R., Souaiaia, T., Fox, A. S., French, D. A., Goss, C. E., Roseboom, P. H., Oler, J. A., Riedel, M. K., Fekete, E. M., Fudge, J. L., et al. (2020) · Biological Psychiatry · doi:10.1016/j.biopsych.2020.05.009 · Cited by 25
Tian, Y., Yang, X.-W., Chen, L., Xi, K., Cai, S.-Q., Cai, J., Yang, X.-M., Wang, Z., Li, M., & Xing, G. (2024) · Journal of Pain · doi:10.1016/j.jpain.2024.02.009 · Cited by 25
A brainstem circuit amplifies aversion
Liang, J., Zhou, Y., Feng, Q., Zhou, Y., Jia, X., Ren, M., Jia, X., Gong, H., Di, R., Jiao, P., et al. (2024) · Neuron · doi:10.1016/j.neuron.2024.08.010 · Cited by 28
The Mechanisms and Boundary Conditions of Drug Memory Reconsolidation
Chen, L., He, Y., Wang, Y., He, Z., Leng, Q., Huang, S., Wu, F., Feng, X., & Yan, J. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.717956 · Cited by 23
“, 2001) and that is actively involved in processing rewarding environmental stimuli (Janak and Tye, 2015).”
BackgroundZhang, R., Zhao, W., Qi, Z., Xu, T., Zhou, F., & Becker, B. (2022) · Biological Psychiatry Cognitive Neuroscience and Neuroimaging · doi:10.1016/j.bpsc.2022.09.008 · Cited by 21
A striatal circuit balances learned fear in the presence and absence of sensory cues
Kintscher, M., Kochubey, O., & Schneggenburger, R. (2023) · eLife · doi:10.7554/elife.75703 · Cited by 23
“As such, fear learning is necessary for the survival of animals (Phelps and LeDoux, 2005; Janak and Tye, 2015).”
BackgroundDomi, E., Xu, L. X., Toivainen, S., Wiskerke, J., Coppola, A., Holm, L., Augier, E., Petrella, M., & Heilig, M. A. (2023) · Neuropsychopharmacology · doi:10.1038/s41386-023-01543-1 · Cited by 26
“Our fi ndings are broadly consistent with, and expand on an extensive literature of human and animal studies suggesting a key role for CeA in alcohol dependence [10, 11, 41 – 44].”
Dynamic fluctuations in ascending heart-to-brain communication under mental stress
Candia‐Rivera, D., Norouzi, K., Ramsøy, T. Z., & Valenza, G. (2023) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00251.2022 · Cited by 29
Prepulse inhibition in euthymic bipolar disorder patients in comparison with control subjects
Sánchez‐Morla, E. M., Mateo, J., Aparicio, A., García-Jiménez, M. Á., Jiménez, E., & Santos, J. L. (2016) · Acta Psychiatrica Scandinavica · doi:10.1111/acps.12604 · Cited by 24
“The amygdala plays an important role in processing emotions, such that amygdala damage can lead to deficits in tasks related to social cognition (67, 68).”
BackgroundAghakhanyan, G., Bonanni, P., Randazzo, G., Nappi, S., Tessarotto, F., Martin, L. D., Frijia, F., Marchi, D. D., Masi, F. D., Kuppers, B., et al. (2016) · PLoS ONE · doi:10.1371/journal.pone.0162817 · Cited by 24
Russell, A. L., Grimes, J. M., Larco, D. O., Cruthirds, D. F., Westerfield, J., Wooten, L., Keil, M. F., Weiser, M. J., Landauer, M. R., Handa, R. J., et al. (2017) · Neuroscience Letters · doi:10.1016/j.neulet.2017.01.011 · Cited by 25
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Functional coupling of Tmem74 and HCN1 channels regulates anxiety-like behavior in BLA neurons
Shao, L.-X., Jiang, Q., Liu, X., Gong, D.-M., Yin, Y., Wu, G., Sun, N.-H., Wang, C.-K., Chen, Q., Yu, C., et al. (2019) · Molecular Psychiatry · doi:10.1038/s41380-019-0402-8 · Cited by 23
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“Amygdalae are critical for social interaction, fear memory, and anxious behaviors (Janak and Tye, 2015; LeDoux et al., 2017; Tovote et al., 2015).”
BackgroundVarlinskaya, E. I., Johnson, J. M., Przybysz, K. R., Terrence Deak, B., & Diaz, M. R. (2019) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2019.109812 · Cited by 24
Sikora, J., Leddy, J., Gulinello, M. E., & Walkley, S. U. (2015) · Disease Models & Mechanisms · doi:10.1242/dmm.022780 · Cited by 24
“Molecular, structural and, most importantly, functional/connectivity characteristics (Capogna, 2014; Janak and Tye, 2015) of these neurons, the determinants of their sphingolipid pathology and its contribution to the overall phenotype remain to be established.”
McMurray, K. M. J., Du, X., Brownlee, M., & Palmer, A. A. (2015) · Behavioural Brain Research · doi:10.1016/j.bbr.2015.12.026 · Cited by 24
Acute Food Deprivation Rapidly Modifies Valence-Coding Microcircuits in the AmygdalaPreprint
Calhoon, G. G., Sutton, A. K., Chang, C.-J., Libster, A. M., Glober, G. F., Lévêque, C. L., Murphy, G., Namburi, P., Leppla, C. A., Siciliano, C. A., et al. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/285189 · Cited by 26
“The basolateral amygdala (BLA) is a nucleus poised to decipher the predictive value of environmental events and to integrate that information with signals indicating internal state (Burgess et al., 2017; Janak and Tye, 2015; Meyer et al., 2014).”
BackgroundSelf-citationPeng, X., Mao, Y., Liu, Y., Dai, Q., Tai, Y., Luo, B., Liang, Y., Guan, R., Zhou, W., Chen, L., et al. (2024) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.14674 · Cited by 24
“26 Despite extensive research on the reciprocal connection between auditory brain areas and the amygdala in fear conditioning, 20,27–29 the role of the amygdala in mediating noise-related anxiety has not been thoroughly defined.”
BackgroundThe case for hemispheric lateralization of the human amygdala in fear processing
Xie, T., van Rooij, S. J. H., Inman, C. S., Wang, S., Brunner, P., & Willie, J. T. (2025) · Molecular Psychiatry · doi:10.1038/s41380-025-02940-2 · Cited by 26
“The BLA is reciprocally connected with the hippocampus and medial prefrontal cortices [5], and it has been particularly implicated in fear acquisition [1].”
Flores‐Cuadrado, A., Úbeda‐Bañón, I., Saiz‐Sánchez, D., & Martı́nez-Marcos, A. (2017) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/nlx054 · Cited by 23
Hu, K. (2018) · Neuropsychologia · doi:10.1016/j.neuropsychologia.2018.07.004 · Cited by 26
“Previous work on threat processing has identified a number of regions involved in threat anticipation, including vmPFC, rACC, VS, and other regions (Bishop et al., 2004; Bishop, 2009; Davis, 1992; Hare et al., 2008; Janak and Tye, 2015; Kinnison et al., 2012; Straube et al., 2009).”
Zhang, W., Llera, A., Hashemi, M. M., Kaldewaij, R., Koch, S. B. J., Beckmann, C. F., Klumpers, F., & Karin Roelofs, A. (2020) · Human Brain Mapping · doi:10.1002/hbm.25000 · Cited by 23
“Since the amygdala is not included in the FIND atlas while mounting evidence suggests its engagement in stress-related processing (Janak & Tye, 2015; Ressler, 2010; Zhang et al., 2018; also see review by McEwen & Gianaros, 2010), we further augmented the set of functional units with three amygdala…”
BackgroundYu, W., Wang, L., Yang, L., Li, Y., Wang, M., Qiu, C., Yang, Q., Li, X., Huang, Y., Liu, R., et al. (2020) · Neurotherapeutics · doi:10.1007/s13311-020-00857-y · Cited by 23
Glutamatergic lateral hypothalamus promotes defensive behaviors
Chen, L., Cai, P., Wang, R.-F., Lu, Y., Chen, H., Guo, Y.-R., Huang, S., Hu, L., Chen, J., Zheng, Z.-H., et al. (2020) · Neuropharmacology · doi:10.1016/j.neuropharm.2020.108239 · Cited by 23
Altered behaviour, dopamine and norepinephrine regulation in stressed mice heterozygous in TPH2 gene
Strekalova, T. V., Svirin, E. P., Waider, J., Вячеславовна, Г. А., Cespuglio, R., Kalueff, A. V., Анатольевич, П. И., Schmitt-Böhrer, A. G., Lesch, K., & Anthony, D. C. (2020) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2020.110155 · Cited by 24
Nakagawa, H., & Ishiwata, T. (2021) · Journal of Thermal Biology · doi:10.1016/j.jtherbio.2021.102923 · Cited by 22
Farkas, S., Szabó, A., Török, B., Sólyomvári, C., Fazekas, C. L., Bánrévi, K., Correia, P., Chaves, T., & Zelena, D. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.985424 · Cited by 25
Synaptic plasticity in two cell types of central amygdala for regulation of emotion and pain
Ge, J., Cai, Y., & Pan, Z. Z. (2022) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2022.997360 · Cited by 22
“The amygdala is a key limbic structure for regulation of the brain’s emotional responses, including negative emotions such as anxiety, depression and pain, and positive emotions in reward (Janak and Tye, 2015; de Guglielmo et al., 2017; Wang et al., 2017; Nation et al., 2018; Neugebauer et al., 2020; Samineni et al.,…”
BackgroundA sex difference in mouse dopaminergic projections from the midbrain to basolateral amygdala
Manion, M. T. C., Glasper, E. R., & Wang, K. H. (2022) · Biology of Sex Differences · doi:10.1186/s13293-022-00486-4 · Cited by 25
Zheng, Z.-H., Lin, X.-C., Lu, Y., Cao, S.-R., Liu, X.-K., Dong, L., Yang, F.-H., Zhang, Y.-B., Tu, J., Pan, B., et al. (2023) · International Immunopharmacology · doi:10.1016/j.intimp.2023.110208 · Cited by 25
A multiple hits hypothesis for memory dysfunction in Parkinson disease
Citro, S., Lazzaro, G. D., Cimmino, A. T., Giuffrè, G. M., Marra, C., & Calabresi, P. (2023) · Nature Reviews Neurology · doi:10.1038/s41582-023-00905-z · Cited by 23
“The amygdala plays a key part in processing both fearful and rewarding stimuli, thus determining emotional influence on memory and motivation 100 .”
Evolutionary Specializations of the Human Limbic System
Lew, C. H., & Semendeferi, K. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-804042-3.00115-9 · Cited by 24
Heesink, L., Gladwin, T. E., Vink, M., van Honk, J., Kleber, R. J., & Geuze, E. (2017) · European Psychiatry · doi:10.1016/j.eurpsy.2017.09.002 · Cited by 23
“The amygdala consists of distinct subnuclei [9,10].”
Anatomy and Function of the Hypothalamus
Pop, M. G., Crivii, C. B., & Opincariu, I. (2018) · IntechOpen eBooks · doi:10.5772/intechopen.80728 · Cited by 30
“It is involved in body’s response to fear and rewards but also in memory [21].”
BackgroundTzovara, A., Meyer, S. S., Bonaiuto, J. J., Abivardi, A., Dolan, R. J., Barnes, G. R., & Bach, D. R. (2019) · Human Brain Mapping · doi:10.1002/hbm.24689 · Cited by 25
“These latter areas are directly connected to subnuclei of the amygdala (Abivardi & Bach, 2017; Felix-Ortiz et al., 2013; Janak & Tye, 2015; Lithari, Moratti, & Weisz, 2016; Sah, Faber, Armentia, & Power, 2003) and communicate with amygdala through synchronised firing of neuronal populations (Fries,…”
Neural Circuit Mechanism Underlying the Feeding Controlled by Insula-Central Amygdala Pathway
Zhang-Molina, C., Schmit, M. B., & Cai, H. (2020) · iScience · doi:10.1016/j.isci.2020.101033 · Cited by 24
Neural mechanisms underlying heterogeneous expression of threat-related attention in social anxiety
Evans, T. C., Bar‐Haim, Y., Fox, N. A., Pine, D. S., & Britton, J. C. (2020) · Behaviour Research and Therapy · doi:10.1016/j.brat.2020.103657 · Cited by 25
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“The LA receives afferent input from sensory thalamic and cortical sources, as well as inputs from the ventral tegmental area, orbitofrontal, and medial prefrontal cortex, and therefore functions to integrate information during cue-associated learning (Janak and Tye, 2015; Maren, 2016).”
BackgroundMolecular biology of serotonergic systems in avian brains
Fujita, T., Aoki, N., Mori, C., Homma, K. J., & Yamaguchi, S. (2023) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2023.1226645 · Cited by 22
“In this circuit, the LA receives sensory projections from outside of the amygdala and projects to the BA, which projects to the central nucleus of the amygdala (CeA) to provide output to the brainstem (LeDoux, 2000; Duvarci and Pare, 2014; Janak and Tye, 2015; Tovote et al., 2015).”
Background
Metadata
- Authors
- Janak, P. H., & Tye, K. M.
- Affiliations
- Johns Hopkins University (US)
- Massachusetts Institute of Technology (US)
- Corresponding author
- Janak, Patricia H.
- Tye, Kay M.
- Venue
- Nature
- Published
- 2015-01-14
- Volume
- 517
- Issue
- 7534
- Pages
- 284-292
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC4565157
- OpenAlex
- W1989982790
- Cited by
- 2,011
- References
- 126
- Citations by year
- 2026: 149 · 2025: 193 · 2024: 198 · 2023: 210 · 2022: 207 · 2021: 234 · 2020: 225 · 2019: 172 · 2018: 132 · 2017: 119 · 2016: 114 · 2015: 56
- FWCI
- 13.69
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc-sa)
- PMC
- Funders
- New York Stem Cell Foundation
- JPB Foundation
- National Institutes of Health
- National Institute on Alcohol Abuse and Alcoholism (R01AA014925, AA17072, AA014925, P50AA017072, R01AA016835)
- National Institute of Mental Health (R01MH102441, MH102441, R37MH102441)
- National Institute on Drug Abuse (DA015096, R01DA015096, R01DA035943)
- National Institute of Diabetes and Digestive and Kidney Diseases (DP2DK102256)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- amygdala, neural circuits, emotions, motivation, fear, reward, behavioural function, structural connectivity, causal manipulation
- MeSH terms
- Amygdala, Animals, Behavior, Biological Evolution, Fear, Humans, Memory, Neural Pathways, Reward
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