The infralimbic cortex bidirectionally modulates mesolimbic dopamine neuron activity via distinct neural pathways
Open accessAbstract
The ventral tegmental area (VTA) has been implicated in a number of psychiatric disorders, including schizophrenia, depression, and bipolar disorder. One major regulator of the mesolimbic dopaminergic system is the medial prefrontal cortex (mPFC), which makes direct and indirect connections to the hippocampus and amygdala, as well as directly to the VTA. The mPFC is comprised of two subregions: the infralimbic and prelimbic cortices (ilPFC and plPFC). However, the specific roles of these subregions in regulating VTA dopamine activity have remained unclear. In this study, we aim to clarify this role and to examine the divergent neuranatomical circuits by which the mPFC regulates VTA activity. Using in vivo extracellular recordings in rats, we tested the effects of pharmacological activation (with NMDA) and inactivation (with TTX) of the ilPFC and plPFC on dopamine neuron activity, and tested the roles of the ventral subiculum (vSub) and basolateral amygdala in this process. We found that the ilPFC exerts a bidirectional control of VTA dopamine neurons, which are differentially modulated through the vSub and the basolateral amygdala. Specifically, activation or inactivation of the ilPFC attenuated or activated dopamine neuron population activity, respectively. Furthermore, dopamine activation depended on the ventral hippocampus and inactivation on the amygdala. In contrast, only inactivation of the plPFC altered dopamine neuron activity. These data indicate that the mPFC has the ability to uniquely fine-tune dopaminergic activity in the VTA. Furthermore, the data presented here suggest that the ilPFC may have a role in the pathophysiology of psychiatric disorders.
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The mPFC is one of the main regulators of the mesolimbic-dopamine network and makes direct and indirect connections to the amygdala and hippocampus.
“one of the main regulator of mesolimbic-dopamine network is the mPFC that makes direct and indirect connections to the amygdala and hippocampus”
From The Functional Role of Dreaming in Emotional Processes (2019) · cites this paper as Patton et al., 2013
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“It is worth noting that one of the main regulator of mesolimbic-dopamine network is the mPFC that makes direct and indirect connections to the amygdala and hippocampus (Patton et al., 2013).”
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- Authors
- Patton, M. H., Bizup, B. T., & Grace, A. A.
- Affiliations
- University of Pittsburgh (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2013-10-23
- Volume
- 33
- Issue
- 43
- Pages
- 16865-16873
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC3807020
- OpenAlex
- W2020867780
- Cited by
- 94
- References
- 61
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 5 · 2023: 2 · 2022: 8 · 2021: 9 · 2020: 9 · 2019: 9 · 2018: 9 · 2017: 6 · 2016: 9 · 2015: 10 · 2014: 5 · 2013: 1
- FWCI
- 4.09
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Eli Lilly and Company
- Pfizer
- H. Lundbeck A/S
- National Institutes of Health (2r01mh057440-26a1, 5r01mh101180-05)
- National Institute of Mental Health (R01-MH101180, MH-57440, R01-MH057440, R37MH057440)
- 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 › Neural and Behavioral Psychology Studies
- Keywords
- infralimbic cortex, prelimbic cortex, mesolimbic dopamine system, ventral tegmental area, ventral subiculum, basolateral amygdala, ventral hippocampus, medial prefrontal cortex, bidirectional modulation, mental illness
- MeSH terms
- Action Potentials, Amygdala, Animals, Hippocampus, Male, Nerve Net, Tetrodotoxin, N-Methylaspartate, Rats, Sprague-Dawley, Prefrontal Cortex, Ventral Tegmental Area, Excitatory Amino Acid Agonists, Sodium Channel Blockers, Rats, Dopaminergic Neurons
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