The DOI matches its Crossref record; 27 of the 27 references it cites were found in a registry or an index.
Excitatory transmission from the amygdala to nucleus accumbens facilitates reward seeking
Open accessAbstract
The basolateral amygdala (BLA) has a crucial role in emotional learning irrespective of valence. The BLA projection to the nucleus accumbens (NAc) is thought to modulate cue-triggered motivated behaviours, but our understanding of the interaction between these two brain regions has been limited by the inability to manipulate neural-circuit elements of this pathway selectively during behaviour. To circumvent this limitation, we used in vivo optogenetic stimulation or inhibition of glutamatergic fibres from the BLA to the NAc, coupled with intracranial pharmacology and ex vivo electrophysiology. Here we show that optical stimulation of the pathway from the BLA to the NAc in mice reinforces behavioural responding to earn additional optical stimulation of these synaptic inputs. Optical stimulation of these glutamatergic fibres required intra-NAc dopamine D1-type receptor signalling, but not D2-type receptor signalling. Brief optical inhibition of fibres from the BLA to the NAc reduced cue-evoked intake of sucrose, demonstrating an important role of this specific pathway in controlling naturally occurring reward-related behaviour. Moreover, although optical stimulation of glutamatergic fibres from the medial prefrontal cortex to the NAc also elicited reliable excitatory synaptic responses, optical self-stimulation behaviour was not observed by activation of this pathway. These data indicate that whereas the BLA is important for processing both positive and negative affect, the glutamatergic pathway from the BLA to the NAc, in conjunction with dopamine signalling in the NAc, promotes motivated behavioural responding. Thus, optogenetic manipulation of anatomically distinct synaptic inputs to the NAc reveals functionally distinct properties of these inputs in controlling reward-seeking behaviours.
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In the citing paper
“This work has, for instance, proposed that BLA PNs innervating the NAc and vHPC primarily encode information with positive and negative valence, respectively (17,20,22,23).”
From Chronic Stress Remodels Synapses in an Amygdala Circuit-Specific Manner (2019) · cites this paper as [23]
Experimental — accuracy not yet measuredIn the citing paper
“Thus circuits associated with motivated action (Stuber et al., 2011) may be strengthened before top-down projections to these regions have matured with experience and age (Casey, 2015).”
From Beyond simple models of adolescence to an integrated circuit-based account: A commentary (2016) · cites this paper as Stuber et al., 2011
In the citing paper
“The amygdala is important in learning the emotional significance of cues in the environment, and can facilitate ventral striatal activity through its direct inputs, leading to motivated action (Stuber et al., 2011).”
From Beyond simple models of adolescence to an integrated circuit-based account: A commentary (2016) · cites this paper as Stuber et al., 2011
In the citing paper
“Recent optogenetic studies have shown that photostimulating BLA PNs targeting the vHPC increases anxiety-like behavior and reduces social interaction, whereas photosilencing this pathway has the opposite effects, and, conversely, stimulating NAc-targeting BLA PNs promotes reward-seeking (20,22,23,39).”
From Chronic Stress Remodels Synapses in an Amygdala Circuit-Specific Manner (2019) · cites this paper as [23]
In the citing paper
“Recent optogenetic studies have shown that photostimulating BLA PNs targeting the vHPC increases anxiety-like behavior and reduces social interaction, whereas photosilencing this pathway has the opposite effects, and, conversely, stimulating NAc-targeting BLA PNs promotes reward-seeking (20,22,23,39).”
From Chronic Stress Remodels Synapses in an Amygdala Circuit-Specific Manner (2019) · cites this paper as [23]
In the citing paper
“Recent optogenetic studies have shown that photostimulating BLA PNs targeting the vHPC increases anxiety-like behavior and reduces social interaction, whereas photosilencing this pathway has the opposite effects, and, conversely, stimulating NAc-targeting BLA PNs promotes reward-seeking (20,22,23,39).”
From Chronic Stress Remodels Synapses in an Amygdala Circuit-Specific Manner (2019) · cites this paper as [23]
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Citations
Cites
Predictive reward signal of dopamine neurons
Schultz, W. (1998) · Journal of Neurophysiology · doi:10.1152/jn.1998.80.1.1 · Cited by 4,564
The Emotional Brain, Fear, and the Amygdala
LeDoux, J. (2003) · Cellular and Molecular Neurobiology · doi:10.1023/a:1025048802629 · Cited by 1,818
Neuronal signalling of fear memory
Maren, S., & Quirk, G. J. (2004) · Nature Reviews Neuroscience · doi:10.1038/nrn1535 · Cited by 1,428
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
Self-citationPhasic Firing in Dopaminergic Neurons Is Sufficient for Behavioral Conditioning
Tsai, H.-C., Zhang, F., Adamantidis, A., Stuber, G. D., Bonci, A., de Lecea, L., & Deisseroth, K. (2009) · Science · doi:10.1126/science.1168878 · Cited by 1,266
Self-citationSubsecond dopamine release promotes cocaine seeking
Phillips, P. E. M., Stuber, G. D., Heien, M. L. A. V., Wightman, R. M., & Carelli, R. M. (2003) · Nature · doi:10.1038/nature01476 · Cited by 1,113
Self-citationMolecular and Cellular Approaches for Diversifying and Extending Optogenetics
Gradinaru, V., Zhang, F., Ramakrishnan, C., Mattis, J., Prakash, R., Diester, I., Goshen, I., Thompson, K. R., & Deisseroth, K. A. (2010) · Cell · doi:10.1016/j.cell.2010.02.037 · Cited by 1,040
Self-citationAravanis, A. M., Wang, L., Zhang, F., Meltzer, L. A., Mogri, M., Schneider, M. B., & Deisseroth, K. A. (2007) · Journal of Neural Engineering · doi:10.1088/1741-2560/4/3/s02 · Cited by 960
Self-citationThe primate amygdala represents the positive and negative value of visual stimuli during learning
Paton, J. J., Belova, M. A., Morrison, S. E., & Salzman, C. D. (2006) · Nature · doi:10.1038/nature04490 · Cited by 917
McFarland, K., Lapish, C. C., & Kalivas, P. W. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-08-03531.2003 · Cited by 884
Channelrhodopsin-2 and optical control of excitable cells
Zhang, F., Wang, L., Boyden, E. S., & Deisseroth, K. A. (2006) · Nature Methods · doi:10.1038/nmeth936 · Cited by 683
Self-citationUnmanageable motivation in addiction: a pathology in prefrontal-accumbens glutamate transmission
Kalivas, P. W., Volkow, N., & Seamans, J. (2005) · Neuron · doi:10.1016/j.neuron.2005.02.005 · Cited by 657
Involvement of the amygdala in stimulus-reward associations: interaction with the ventral striatum
Cador, M., Robbins, T. W., & Everitt, B. J. (1989) · Neuroscience · doi:10.1016/0306-4522(89)90354-0 · Cited by 652
Parallel incentive processing: an integrated view of amygdala function
Balleine, B. W., & Killcross, S. (2006) · Trends in Neurosciences · doi:10.1016/j.tins.2006.03.002 · Cited by 622
Midbrain Dopamine Neurons Signal Preference for Advance Information about Upcoming Rewards
Bromberg-Martin, E. S., & Hikosaka, O. (2009) · Neuron · doi:10.1016/j.neuron.2009.06.009 · Cited by 548
Ambroggi, F., Ishikawa, A., Fields, H. L., & Nicola, S. M. (2008) · Neuron · doi:10.1016/j.neuron.2008.07.004 · Cited by 523
Di Ciano, P., Cardinal, R. N., Cowell, R. A., Little, S. J., & Everitt, B. J. (2001) · The Journal of Neuroscience · doi:10.1523/jneurosci.21-23-09471.2001 · Cited by 354
Ciano, P. D., & Everitt, B. J. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.1581-04.2004 · Cited by 333
Reward-Predictive Cues Enhance Excitatory Synaptic Strength onto Midbrain Dopamine Neurons
Stuber, G. D., Klanker, M., de Ridder, B., Bowers, M. S., Joosten, R. N. J. M. A., Feenstra, M. G. P., & Bonci, A. (2008) · Science · doi:10.1126/science.1160873 · Cited by 319
Self-citationRapid strengthening of thalamo-amygdala synapses mediates cue–reward learning
Tye, K. M., Stuber, G. D., de Ridder, B., Bonci, A., & Janak, P. H. (2008) · Nature · doi:10.1038/nature06963 · Cited by 216
Self-citationWright, C. I., & Groenewegen, H. J. (1995) · The Journal of Comparative Neurology · doi:10.1002/cne.903610304 · Cited by 194
Shabel, S. J., & Janak, P. H. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0905580106 · Cited by 194
Shiflett, M. W., & Balleine, B. W. (2010) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2010.07439.x · Cited by 170
Floresco, S., Yang, C. R., Phillips, A. G., & Blaha, C. D. (1998) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.1998.00133.x · Cited by 163
Setlow, B., Holland, P. C., & Gallagher, M. (2002) · Behavioral Neuroscience · doi:10.1037//0735-7044.116.2.267 · Cited by 160
Setlow, B., Holland, P. C., & Gallagher, M. (2002) · Behavioral Neuroscience · doi:10.1037/0735-7044.116.2.267 · Cited by 160
Jones, J. L., Day, J. J., Aragona, B. J., Wheeler, R. A., Wightman, R. M., & Carelli, R. M. (2009) · Biological Psychiatry · doi:10.1016/j.biopsych.2009.11.006 · Cited by 118
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Sorted by citations
From circuits to behaviour in the amygdala
Janak, P. H., & Tye, K. M. (2015) · Nature · doi:10.1038/nature14188 · Cited by 2,011
Self-citationThe brain reward circuitry in mood disorders
Russo, S. J., & Nestler, E. J. (2013) · Nature Reviews Neuroscience · doi:10.1038/nrn3381 · Cited by 1,870
Neuronal circuits for fear and anxiety
Tovote, P., Fadok, J. P., & Lüthi, A. (2015) · Nature Reviews Neuroscience · doi:10.1038/nrn3945 · Cited by 1,786
Optogenetics: 10 years of microbial opsins in neuroscience
Deisseroth, K. A. (2015) · Nature Neuroscience · doi:10.1038/nn.4091 · Cited by 1,335
Self-citationThe neurobiology of anhedonia and other reward-related deficits
Der-Avakian, A., & Markou, A. (2012) · Trends in Neurosciences · doi:10.1016/j.tins.2011.11.005 · Cited by 1,130
Metadata
- Authors
- Stuber, G. D., Sparta, D. R., Stamatakis, A. M., van Leeuwen, W. A., Hardjoprajitno, J. E., Cho, S., Tye, K. M., Kempadoo, K. A., Zhang, F., Deisseroth, K., & Bonci, A.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- University of California, San Francisco (US)
- Stanford University (US)
- National Institute on Drug Abuse (US)
- Corresponding author
- Stuber, Garret D.
- ORCID
- Venue
- Nature
- Published
- 2011-06-29
- Volume
- 475
- Issue
- 7356
- Pages
- 377-380
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC3775282
- OpenAlex
- W2069090835
- Cited by
- 878
- References
- 26
- Citations by year
- 2026: 32 · 2025: 46 · 2024: 54 · 2023: 40 · 2022: 46 · 2021: 64 · 2020: 50 · 2019: 51 · 2018: 65 · 2017: 81 · 2016: 67 · 2015: 80 · 2014: 53 · 2013: 78 · 2012: 53
- FWCI
- 26.40
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- UNC Libraries
- Funders
- National Alliance for Research on Schizophrenia and Depression
- Foundation of Hope for Research and Treatment of Mental Illness
- University of North Carolina at Chapel Hill
- University of California, San Francisco
- National Institute on Alcohol Abuse and Alcoholism (F32AA018610)
- National Institute on Drug Abuse (R01DA032750, DA029325, R21DA029325)
- National Institute of Diabetes and Digestive and Kidney Diseases (DP2DK102256)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- basolateral amygdala, nucleus accumbens, glutamatergic projections, reward seeking, dopamine D1 receptor, dopamine D2 receptor, optogenetic manipulation, sucrose intake, self-stimulation, medial prefrontal cortex, emotional learning, motivated behavior, aversive behavior
- MeSH terms
- Channelrhodopsins, Amygdala, Animals, Cues, Dopamine, Drinking, Light, Male, Mice, Inbred C57BL, Nerve Fibers, Neural Pathways, Neurons, Nucleus Accumbens, Photic Stimulation, Reward, Sucrose, Behavior, Addictive, Receptors, Dopamine D1, Patch-Clamp Techniques, Glutamic Acid, Excitatory Postsynaptic Potentials, Mice
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