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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Circuits associated with motivated action may be strengthened before top-down projections to these regions have matured with experience and age.
“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
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.
“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
BLA projection neurons innervating the nucleus accumbens and ventral hippocampus primarily encode information with positive and negative valence, respectively.
“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]
Photostimulating BLA PNs targeting the vHPC increases anxiety-like behavior and reduces social interaction.
“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]
Photosilencing the BLA→vHPC pathway has effects opposite to photostimulation.
“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]
Stimulating NAc-targeting BLA PNs promotes reward-seeking.
“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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- 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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