Prefrontal cortical regulation of brainwide circuit dynamics and reward-related behavior
Open accessAbstract
A way to modulate reward-seeking: Which brain regions are causally involved in reward-related behavior? Ferenczi et al. combined focal, cell type-specific, optogenetic manipulations with brain imaging, behavioral testing, and in vivo electrophysiology (see the Perspective by Robbins). Stimulation of midbrain dopamine neurons increased activity in a brain region called the striatum and was correlated with reward-seeking across individual animals. However, elevated excitability of an area called the medial prefrontal cortex reduced both striatal responses to the stimulation of dopamine neurons and the behavioral drive to seek the stimulation of dopamine neurons. Finally, modulating the excitability of medial prefrontal cortex pyramidal neurons drove changes in neural circuit synchrony, as well as corresponding anhedonic behavior. These observations resemble imaging and clinical phenotypes observed in human depression, addiction, and schizophrenia. Science , this issue p. 10.1126/science.aac9698 ; see also p. 10.1126/science.aad9698
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Optogenetic stimulation of ILc reduced the BOLD response to optogenetic-induced dopamine stimulation and blocked DA-stimulation-induced place preference.
“Moreover, optogenetic stimulation of ILc reduced the BOLD response to optogenetic-induced dopamine stimulation and blocked DA-stimulation-induced place preference [62].”
From Prefrontal cortex and depression (2022) · cites this paper as [62]
The Results section, “Elevated mPFC excitability suppresses striatal responses to dopamine” (page unavailable), reports that optogenetic mPFC activation suppressed the striatal BOLD response to dopamine-neuron stimulation and eliminated the stimulation-associated place preference while activation was on. The cited passage identifies the stimulated region as mPFC, not specifically ILc, so the claim’s anatomical specificity is not established by our copy. (LLM, conf=0.84)
Experimental — accuracy not yet measuredFrontal cortical areas play a key role in top-down modulation of striatal response to dopaminergic stimuli.
“Recent studies using optogenetic stimulation found that also frontal cortical areas play a key role in top-down modulation of striatal response to dopaminergic stimuli (Ferenczi et al. 2016).”
From Dysfunctional Autism Risk Genes Cause Circuit-Specific Connectivity Deficits With Distinct Developmental Trajectories (2018) · cites this paper as Ferenczi et al. 2016
Increased mPFC excitability leads to reductions in striatal BOLD response to midbrain dopaminergic stimulation and in reward-seeking behavior.
“Furthermore, increased excitability of the mPFC, as shown in depression, led to reductions of BOLD signal in response to stimulation of midbrain dopaminergic neurons in the striatum and of reward-seeking behavior as measured with the sucrose preference test and social interaction test (Ferenczi et al., 2016).”
From Circuit Mechanisms of Reward, Anhedonia, and Depression (2019) · cites this paper as Ferenczi et al., 2016
Optogenetic stimulation of midbrain dopaminergic neurons leads to ipsilateral BOLD increases in dorsal and ventral striatum.
“The optogenetic stimulation of dopaminergic neurons in the midbrain led to ipsilateral increases of the blood oxygenation level dependent (BOLD) signal in the dorsal and VS.”
From Circuit Mechanisms of Reward, Anhedonia, and Depression (2019) · cites this paper as Ferenczi et al., 2016
Blue light inducing dopaminergic stimulation is self-administered by rodents, indicating rewarding effect.
“On a behavioral level, blue light, inducing dopaminergic stimulation, was self-administered by the rodents as an expression of its rewarding effect.”
From Circuit Mechanisms of Reward, Anhedonia, and Depression (2019) · cites this paper as Ferenczi et al., 2016
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Variable-density spiral-in/out functional magnetic resonance imaging
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Self-citationDorsolateral caudate nucleus differentiates cocaine from natural reward-associated contextual cues
Liu, H.-S., Chefer, S., Lu, H., Guillem, K., Rea, W., Kurup, P., Yang, Y., Peoples, L., & Stein, E. A. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1207531110 · Cited by 23 · see citing works
Interleaved spiral‐in/out with application to functional MRI (fMRI)
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Flagged first, then by citations
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Resting-state connectivity biomarkers define neurophysiological subtypes of depression
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Time for united action on depression: a Lancet–World Psychiatric Association Commission
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Integration of optogenetics with complementary methodologies in systems neuroscience
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Self-citationPrefrontal cortex and depression
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Next-generation probes, particles, and proteins for neural interfacing
Rivnay, J., Wang, H., Fenno, L., Deisseroth, K., & Malliaras, G. G. (2017) · Science Advances · doi:10.1126/sciadv.1601649 · Cited by 514 · see citing works
Self-citationAnimal models of major depression: drawbacks and challenges
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Brain circuit dysfunction in post-traumatic stress disorder: from mouse to man
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Circuit Mechanisms of Reward, Anhedonia, and Depression
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An astroglial basis of major depressive disorder? An overview
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Functional heterogeneity in the bed nucleus of the stria terminalis
Gungor, N. Z., & Pare, D. (2016) · Journal of Neuroscience · doi:10.1523/jneurosci.0856-16.2016 · Cited by 214 · see citing works
Association of neural and emotional impacts of reward prediction errors with major depression
Rutledge, R. B., Moutoussis, M., Smittenaar, P., Zeidman, P., Taylor, T., Hrynkiewicz, L., Lam, J., Skandali, N., Siegel, J. Z., Ousdal, O. T., et al. (2017) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2017.1713 · Cited by 209 · see citing works
Borsini, A., Wallis, A. S. J., Zunszain, P., Pariante, C. M., & Kempton, M. J. (2020) · Cognitive, Affective, & Behavioral Neuroscience · doi:10.3758/s13415-020-00804-6 · Cited by 207 · see citing works
Impact of Sleep and Circadian Rhythms on Addiction Vulnerability in Adolescents
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Communication in Neural Circuits: Tools, Opportunities, and Challenges
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Self-citationPan, P. M., Sato, J. R., Salum, G. A., Rohde, L. A., Gadelha, A., Zugman, A., Mari, J., Jackowski, A., Picon, F., Miguel, E. C., et al. (2017) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2017.17040430 · Cited by 156 · see citing works
“Several experiments demonstrate the key role that dopaminergic signaling in ventral striatal areas plays in reward valuation and effort expended toward reward (31, 32).”
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Deep brain stimulation of the medial forebrain bundle: Distinctive responses in resistant depression
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Dopaminergic basis for signaling belief updates, but not surprise, and the link to paranoia
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- Authors
- Ferenczi, E. A., Zalocusky, K. A., Liston, C., Grosenick, L., Warden, M. R., Amatya, D., Katovich, K., Mehta, H., Patenaude, B., Ramakrishnan, C., Kalanithi, P., Etkin, A., Knutson, B., Glover, G. H., & Deisseroth, K.
- Affiliations
- Stanford University (US)
- Weill Cornell Medicine (US)
- Cornell University (US)
- Stanford Medicine (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Ferenczi, Emily A.
- Zalocusky, Kelly A.
- Liston, Conor
- Deisseroth, Karl
- ORCID
- Venue
- Science
- Published
- 2016-01
- Volume
- 351
- Issue
- 6268
- Pages
- aac9698-aac9698
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC4772156
- OpenAlex
- W2210805002
- Cited by
- 535
- References
- 95
- Citations by year
- 2026: 37 · 2025: 34 · 2024: 38 · 2023: 42 · 2022: 54 · 2021: 47 · 2020: 56 · 2019: 46 · 2018: 58 · 2017: 65 · 2016: 56 · 2015: 1
- FWCI
- 28.15
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Defense Advanced Research Projects Agency
- National Institute of Mental Health
- National Institute on Drug Abuse (NIDA)
- NSF
- Simons Foundation
- Gatsby Foundation
- Wiegers Family Fund
- Grosfeld
- Reeves
- Snyder
- Woo
- Albert Yu and Mary Bechman Foundations
- NIDA (1F31MH105151_01)
- NARSAD
- NIH (P41 EB015891, R00 MH097822)
- 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 › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- medial prefrontal cortex, anhedonia, reward-seeking behavior, dopaminergic neurons, striatum, depression, schizophrenia
- MeSH terms
- Animals, Brain Mapping, Corpus Striatum, Depressive Disorder, Dopamine, Female, Magnetic Resonance Imaging, Male, Mesencephalon, Motivation, Nerve Net, Oxygen, Reward, Schizophrenia, Rats, Sprague-Dawley, Prefrontal Cortex, Rats, Inbred LEC, Rats, Dopaminergic Neurons, Anhedonia
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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