A genetically defined insula-brainstem circuit selectively controls motivational vigor
Open accessAbstract
The anterior insular cortex (aIC) plays a critical role in cognitive and motivational control of behavior, but the underlying neural mechanism remains elusive. Here, we show that aIC neurons expressing Fezf2 (aIC Fezf2), which are the pyramidal tract neurons, signal motivational vigor and invigorate need-seeking behavior through projections to the brainstem nucleus tractus solitarii (NTS). aIC Fezf2 neurons and their postsynaptic NTS neurons acquire anticipatory activity through learning, which encodes the perceived value and the vigor of actions to pursue homeostatic needs. Correspondingly, aIC → NTS circuit activity controls vigor, effort, and striatal dopamine release but only if the action is learned and the outcome is needed. Notably, aIC Fezf2 neurons do not represent taste or valence. Moreover, aIC → NTS activity neither drives reinforcement nor influences total consumption. These results pinpoint specific functions of aIC → NTS circuit for selectively controlling motivational vigor and suggest that motivation is subserved, in part, by aIC's top-down regulation of dopamine signaling.
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The aIC can causally regulate motivational vigor via its top-down projections to the NTS.
“A recent study shows that the aIC can causally regulate motivational vigor via its top-down projections to the NTS [7].”
From The Insular Cortex: An Interface Between Sensation, Emotion and Cognition (2024) · cites this paper as [7]
Inhibition or activation of neurons along the aIC-NTS pathway potently suppresses or heightens motivational vigor without affecting food or fluid consumption or valence processing.
“Inhibition or activation of neurons along the aIC-NTS pathway potently suppresses or heightens, respectively, motivational vigor without affecting food or fluid consumption or valence processing, suggesting the specialized function of this insular circuit.”
From The Insular Cortex: An Interface Between Sensation, Emotion and Cognition (2024) · cites this paper as [7]
Activation of the aIC-NTS pathway promotes dopamine release in the nucleus accumbens in a context-dependent manner.
“Activation of the aIC-NTS pathway promotes dopamine release in the nucleus accumbens, a neural indicator of motivational level, in a context-dependent manner (Fig. 3E).”
From The Insular Cortex: An Interface Between Sensation, Emotion and Cognition (2024) · cites this paper as [7]
The insula establishes direct long-range connections with the midbrain and hindbrain, such as the brainstem nucleus of the solitary tract (NTS).
“Notably, the insula establishes direct long-range connections with the midbrain and hindbrain, such as the brainstem nucleus of the solitary tract (NTS), a major first relay for incoming body-to-brain information carried via the vagus nerve [7].”
From The Insular Cortex: An Interface Between Sensation, Emotion and Cognition (2024) · cites this paper as [7]
Activation of the aIC-NTS pathway significantly invigorates need-seeking actions in a need- and learning-dependent manner, in both goal-directed licking and running tasks.
“Activation of the aIC-NTS pathway significantly invigorates need-seeking actions in a need-and learning-dependent manner, in both goal-directed licking and running tasks (Fig. 3B-D).”
From The Insular Cortex: An Interface Between Sensation, Emotion and Cognition (2024) · cites this paper as [7]
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Mutschler, I., Hänggi, J., Frei, M., Lieb, R., Holforth, M. G., Seifritz, E., & Spinelli, S. (2019) · Neurology Psychiatry and Brain Research · doi:10.1016/j.npbr.2019.06.002 · Cited by 12 · see citing works
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The Insular Cortex: An Interface Between Sensation, Emotion and Cognition
Zhang, R., Deng, H., & Xiao, X. (2024) · Neuroscience Bulletin · doi:10.1007/s12264-024-01211-4 · Cited by 158 · see citing works
Self-citationAn insula hierarchical network architecture for active interoceptive inference
Fermin, A. S. R., Friston, K., & Yamawaki, S. (2022) · Royal Society Open Science · doi:10.1098/rsos.220226 · Cited by 101 · see citing works
Mesolimbic dopamine release precedes actively sought aversive stimuli in mice
Yawata, Y., Shikano, Y., Ogasawara, J., Makino, K., Kashima, T., Ihara, K., Yoshimoto, A., Morikawa, S., Yagishita, S., Tanaka, K. F., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-38130-3 · Cited by 24 · see citing works
- Authors
- Deng, H., Xiao, X., Yang, T., Ritola, K., Hantman, A., Li, Y., Huang, Z. J., & Li, B.
- Affiliations
- Cold Spring Harbor Laboratory (US)
- Howard Hughes Medical Institute (US)
- Peking University (CN)
- Duke University (US)
- Corresponding author
- Deng, Hanfei
- Li, Bo
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2021-12
- Volume
- 184
- Issue
- 26
- Pages
- 6344-6360.e18
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC9103523
- OpenAlex
- W4200110365
- Cited by
- 75
- References
- 90
- Citations by year
- 2026: 18 · 2025: 15 · 2024: 16 · 2023: 16 · 2022: 9 · 2021: 1
- FWCI
- 4.84
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 386 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (submittedVersion)
- Funders
- National Institutes of Health (R01MH101214, R01MH108924, R01DA050374, R01NS104944, U19MH114823-01)
- Columbia University
- Chinese Academy of Sciences
- Cold Spring Harbor Laboratory
- Oregon Health and Science University
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Keywords
- anterior insula, nucleus tractus solitarius, pyramidal tract neurons, brainstem projections, anticipatory activity, effort, striatal dopamine release
- MeSH terms
- Insular Cortex, Animals, Behavior, Animal, Brain Stem, Dopamine, Female, Learning, Male, Mice, Inbred C57BL, Motivation, Neural Pathways, Neurons, Nucleus Accumbens, Time Factors, Mice
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 ›
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