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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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“This form of learning depends on neural connections in the amygdala (LeDoux, 2000; Goosens and Maren, 2001; Fanselow and Poulos, 2005; Maren, 2005; Herry and Johansen, 2014; Lüthi and Lüscher, 2014; Janak and Tye, 2015).”
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“It should be noted that the amygdala itself is a complex formation consisting of many conjoined parts, with each giving rise to unclear but varied behaviour [23], [31], [34], [36].”
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BackgroundResultSpecialization of amygdala subregions in emotion processing
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“However, the view that the amygdala specializes in fear processing has been challenged (Janak & Tye, 2015), with evidence suggesting a role for the amygdala in the processing of a range of emotions in addition to fear (Diano et al., 2017; Phelps & LeDoux, 2005; Sergerie et al., 2008).”
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“The basolateral amygdala (BLA) is a cortical-like brain region controlling emotional behavior (Duvarci and Pare, 2014; Janak and Tye, 2015).”
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“Keywords: amygdala, moral emotions, shame, emotion recognition, Guilt INTRODUCTION The amygdala is a subcortical nucleus which has been related to a broad variety of functions including facial emotion recognition, social cognition, and reward learning (Adolphs, 2010; Janak and Tye, 2015).”
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“…of negative emotion, drug reward of positive emotion, and pain and fear of aversive behaviors (Baxter and Murray, 2002; Gottfried et al., 2003; Murray, 2007; Etkin et al., 2011; Mahan and Ressler, 2012; Fernando et al., 2013; Janak and Tye, 2015; Cai et al., 2018; Neugebauer et al., 2020).”
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“The BLA is essential for processing stressors (Janak and Tye, 2015); 457 it is activated by the anticipation of a stressor (Cullinan et al.”
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“It was proved that hippocampus and amygdala are associated with emotionality in mice (Janak and Tye 2015).”
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“The amygdala is another crucial limbic system structure associated with emotion and motivation, playing an essential role in processing both fear-inducing and rewarding environmental stimuli [4].”
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“67,68 Considering that the amygdala is part of the limbic system and is implicated in emotional processing and reward learning, 69 it is not surprising that our analyses found involvement of this structure.”
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“This is particularly important, as amygdala has been shown to be involved not only in processing and memory of fearful events but also rewardbased behaviors and encoding valence of stimuli [90,91].”
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“, emotion dysregulation)—a finding that is reported across a range of emotion-related disorders.(10) A similar pattern of reduced FC with shorter sleep has been reported in two separate studies in healthy adults, wherein sleep deprivation or shorter sleep was associated with reduced FC between the amygdala and brain r…”
Barreto-Cordero, L. M., Ríos-Carrillo, J., Roldán-Roldán, G., Rasia‐Filho, A. A., Flores, G., Bringas, M. E., Briones-Aranda, A., & Picazo, O. (2019) · Behavioural Brain Research · doi:10.1016/j.bbr.2019.112355 · Cited by 15
Ex vivo diffusion-weighted MRI tractography of the Göttingen minipig limbic system
Bech, J., Orłowski, D., Glud, A. N., Dyrby, T. B., Sørensen, J. C. H., & Bjarkam, C. R. (2020) · Brain Structure and Function · doi:10.1007/s00429-020-02058-x · Cited by 16
Zheng, L. J., Li, L., Zhong, J., Zhang, Z., Ye, Y. B., Zhang, X. Y., Wang, Y. F., Zhang, H., Liu, Y., Lu, G., et al. (2020) · Brain Imaging and Behavior · doi:10.1007/s11682-019-00223-3 · Cited by 15
Pan, H., Zhang, W., Liao, C.-Z., He, Y., Xiao, Z.-M., Qin, X., Liu, W.-Z., Wang, N., Zou, J., Liu, X., et al. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.00299 · Cited by 15
“Amygdala, a diamondshaped region located deep inside the temporal lobe, is critically engaged in encoding external information with distinct valence (Janak and Tye, 2015).”
BackgroundThe Amygdala – A Hub of the Social Auditory Brain
Wenstrup, J. J., Ghasemahmad, Z., Hazlett, E., & Shanbhag, S. J. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-809324-5.24194-1 · Cited by 16
Fujita, T., Aoki, N., Mori, C., Fujita, E., Matsushima, T., Homma, K. J., & Yamaguchi, S. (2020) · Scientific Reports · doi:10.1038/s41598-020-78247-9 · Cited by 17
Parcellation of the human amygdala using recurrence quantification analysis
Bielski, K., Adamus, S., Kolada, E., Rączaszek‐Leonardi, J., & Szatkowska, I. (2020) · NeuroImage · doi:10.1016/j.neuroimage.2020.117644 · Cited by 17
Restructuring of amygdala subregion apportion across adolescence
Campbell, C. E., Mezher, A. F., Eckel, S. P., Tyszka, J. M., Pauli, W. M., Nagel, B. J., & Herting, M. M. (2020) · Developmental Cognitive Neuroscience · doi:10.1016/j.dcn.2020.100883 · Cited by 16
“Building on previous research (Rollins and King, 2000; Baxter and Murray, 2002; Herting et al., 2014; Wierenga et al., 2014; Janak and Tye, 2015; Tyszka and Pauli, 2016; Herting et al., 2018; Wierenga et al., 2018), we then examined how age, sex, and pubertal status were associated with subregion volumes as well as th…”
MethodPeng, L., Liu, X., Yang, Y., Guo, Q., & Zhong, T. (2021) · Neurochemical Research · doi:10.1007/s11064-021-03368-0 · Cited by 15
Ueda, S., Hosokawa, M., Arikawa, K., Takahashi, K., Fujiwara, M., Kakita, M., Fukada, T., Koyama, H., Horigane, S., Itoi, K., et al. (2021) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2021.741895 · Cited by 17
Song, C., Zhang, W., Wang, X., Zhang, J.-Y., Tian, X., Yin, X., & Pan, B. (2017) · Molecular Brain · doi:10.1186/s13041-016-0283-6 · Cited by 17
“It has been known for decades that the stress coping system is evolutionally conservative in brain across species ranging from rodents to primates and to humans [2].”
Biological bases of human musicality
Perrone‐Capano, C., Volpicelli, F., & di Porzio, U. (2017) · Reviews in the Neurosciences · doi:10.1515/revneuro-2016-0046 · Cited by 17
Gioia, D. A., Alexander, N., & McCool, B. A. (2017) · Frontiers in Neuroscience · doi:10.3389/fnins.2017.00424 · Cited by 16
“The neural circuitry controlling anxiety-like behavior is well-conserved across mammalian species (Janak and Tye, 2015).”
BackgroundZhu, H., Zhou, Y., Liu, Z., Chen, X., Li, Y., Liu, X., & Ma, L. (2017) · The International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyx104 · Cited by 17
“The amygdala plays an essential part in processing both fearful and rewarding environmental stimuli (Janak and Tye, 2015).”
BackgroundMeixner, F., Montag, C., & Herbert, C. (2019) · Frontiers in Psychology · doi:10.3389/fpsyg.2019.00068 · Cited by 16
“It has been hypothesized that the amygdala, an OXTR-dense area of the brain, plays an important role in the processing of emotional and social information and in the development of autism spectrum disorders (Baron-Cohen et al., 2000; Janak and Tye, 2015; Herrington et al., 2016).”
BackgroundContextual Fear Memory Retrieval Is Vulnerable to Hippocampal Noise
Iwasaki, S., & Ikegaya, Y. (2020) · Cerebral Cortex · doi:10.1093/cercor/bhaa257 · Cited by 16
Language Comprehension and Emotion
Berkum, J. J. A. V. (2019) · Oxford University Press eBooks · doi:10.1093/oxfordhb/9780190672027.013.29 · Cited by 19
GluA1 in central amygdala increases pain but inhibits opioid withdrawal-induced aversion
Cai, Y.-Q., Hou, Y.-Y., & Pan, Z. Z. (2020) · Molecular Pain · doi:10.1177/1744806920911543 · Cited by 15
“Within CeA, two distinct inputs have been identified: while the input from the parabrachial nucleus (PBN) relays peripheral pain signals,(8,35,36) the input from BLA carries modulatory signals from corticolimbic structures after evaluating and decision-making processes of emotional events.(9,11) Importantly, both the…”
BackgroundRecent advances in understanding neural correlates of anxiety disorders in children and adolescents
Zugman, A., Winkler, A. M., & Pine, D. S. (2021) · Current Opinion in Psychiatry · doi:10.1097/yco.0000000000000743 · Cited by 15
Sex-specific divergent maturational trajectories in the postnatal rat basolateral amygdala
Guily, P., Lassalle, O., Chavis, P., & Manzoni, O. J. (2022) · iScience · doi:10.1016/j.isci.2022.103815 · Cited by 15
“Its role in the processing of fearful and rewarding stimuli, as well as emotional memory, is now well established (Bocchio et al., 2017; Janak & Tye, 2015; Phelps, 2004).”
BackgroundNamkung, H., Thomas, K. L., Hall, J., & Sawa, A. (2021) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2021.12.025 · Cited by 17
Sculpting Astrocyte Diversity through Circuits and Transcription
Cheng, Y.-T., Woo, J., & Deneen, B. (2022) · The Neuroscientist · doi:10.1177/10738584221082620 · Cited by 15
“Amygdala nuclei are divided into two main subregions, the basolateral amygdala (BLA) and the central amygdala (CeA) (Ehrlich and others 2009; Janak and Tye 2015).”
BackgroundUzuneser, T. C., Szkudlarek, H. J., Jones, M., Nashed, M. G., Clement, T., Wang, H., Ojima, I., Rushlow, W. J., & Laviolette, S. R. (2022) · Cerebral Cortex · doi:10.1093/cercor/bhac220 · Cited by 15
Contingent Amygdala Inputs Trigger Heterosynaptic LTP at Hippocampus-To-Accumbens Synapses
Yu, J. J., Sesack, S. R., Huang, Y. H., Schlüter, O. M., Grace, A. A., & Dong, Y. (2022) · Journal of Neuroscience · doi:10.1523/jneurosci.0838-22.2022 · Cited by 15
Yuan, S., Luo, X., Chen, X., Wang, M., Hu, Y., Zhou, Y., Ning, Y., & Zhang, B. (2022) · Journal of Affective Disorders · doi:10.1016/j.jad.2022.09.125 · Cited by 15
The role of astrocytes in behaviors related to emotion and motivation
Shigetomi, E., & Koizumi, S. (2022) · Neuroscience Research · doi:10.1016/j.neures.2022.09.015 · Cited by 16
Excessive Crying, Behavior Problems, and Amygdala Volume: A Study From Infancy to Adolescence
Sammallahti, S., Serdarević, F., & Tiemeier, H. W. (2023) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1016/j.jaac.2023.01.014 · Cited by 15
Bach, E. C., Ewin, S. E., Heaney, C. F., Carlson, H. N., Ortelli, O. A., Almonte, A. G., Chappell, A. M., Raab‐Graham, K. F., & Weiner, J. L. (2023) · European Journal of Neuroscience · doi:10.1111/ejn.15944 · Cited by 17
“…and hippocampus are integral to the aetiology of AUD and comorbid anxiety/stressor-related disorders (Carlson & Weiner, 2021; Gilpin & Weiner, 2017; Janak & Tye, 2015), and recent preclinical evidence strongly suggests that this direct excitatory connection between the BLA and vHC may contribute…”
BackgroundZhang, X., Lai, H., Li, Q., Yang, X., Pan, N., He, M., Kemp, G. J., Wang, S., & Gong, Q. (2023) · Cerebral Cortex · doi:10.1093/cercor/bhad231 · Cited by 16
Goettel, M., Fuertig, R., Mack, S. R., Just, S., Sharma, V., Wunder, A., & den Boer, J. A. (2023) · CNS Drugs · doi:10.1007/s40263-023-01042-3 · Cited by 15
“The amygdala plays a central role in emotional control as a critical component of the brain circuitry that processes emotional stimuli (both fearful and rewarding), for instance, the expression of fear and aggression, and the retrieval of emotional and fear-related memories [31, 34–36].”
BackgroundA pharynx-to-brain axis controls pharyngeal inflammation–induced anxiety
Zhao, W., Zhang, K., Dong, W., Tang, H.-D., Sun, J., Huang, J.-Y., Wan, G., Guan, R., Guo, X., Cheng, P., et al. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2312136121 · Cited by 18
Kong, F., Xu, Z., Yang, G., Jia, Q., Mo, F., Jing, L., Luo, J., Jin, H., & Cai, X. (2024) · Cyborg and Bionic Systems · doi:10.34133/cbsystems.0125 · Cited by 16
“BLA is a vital brain region associated with emotions, receiving projections from areas such as the cortex and hippocampus, integrating and transmitting information to downstream brain regions [46].”
BackgroundRuffini, G., Castaldo, F., Lopez-Sola, E., Sanchez-Todo, R., & Vohryzek, J. (2024) · Entropy · doi:10.3390/e26110953 · Cited by 20
Khoo, S. Y., LeCocq, M. R., Deyab, G., & Chaudhri, N. (2019) · Neuropsychopharmacology · doi:10.1038/s41386-019-0335-6 · Cited by 15
Neurophysiological evidence for early modulation of amygdala activity by emotional reappraisal
Guex, R., Hofstetter, C., Domínguez‐Borràs, J., Méndez‐Bértolo, C., Virginie Sterpenich, A., Spinelli, L., Seeck, M., & Vuilleumier, P. O. (2019) · Biological Psychology · doi:10.1016/j.biopsycho.2019.05.006 · Cited by 15
Günther, V., Hußlack, A., Weil, A.-S., Bujanow, A., Henkelmann, J., Kersting, A., Quirin, M., Hoffmann, K., Egloff, B., Lobsien, D., et al. (2020) · NeuroImage: Clinical · doi:10.1016/j.nicl.2020.102441 · Cited by 17
“conscious processing stages, particularly in the amygdala (LeDoux, 1995, 1996; Janak and Tye, 2015).”
Carlson, H. N., & Weiner, J. L. (2020) · International review of neurobiology · doi:10.1016/bs.irn.2020.09.006 · Cited by 16
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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