Function and developmental origin of a mesocortical inhibitory circuit
Abstract
Midbrain ventral tegmental neurons project to the prefrontal cortex and modulate cognitive functions. Using viral tracing, optogenetics and electrophysiology, we found that mesocortical neurons in the mouse ventrotegmental area provide fast glutamatergic excitation of GABAergic interneurons in the prefrontal cortex and inhibit prefrontal cortical pyramidal neurons in a robust and reliable manner. These mesocortical neurons were derived from a subset of dopaminergic progenitors, which were dependent on prolonged Sonic Hedgehog signaling for their induction. Loss of these progenitors resulted in the loss of the mesocortical inhibitory circuit and an increase in perseverative behavior, whereas mesolimbic and mesostriatal dopaminergic projections, as well as impulsivity and attentional function, were largely spared. Thus, we identified a previously uncharacterized mesocortical circuit contributing to perseverative behaviors and found that the diversity of dopaminergic neurons begins to be established during their progenitor phase.
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Some dopaminergic neurons projecting to the various PFC subdomains are capable of co-releasing glutamate and have an exclusive excitatory effect on the GABAergic interneurons in the various layers of the PFC.
“Of note here is that some of these dopaminergic neurons projecting to the various PFC subdomains are capable of co-releasing glutamate as well and have an exclusive excitatory effect on the GABAergic interneurons in the various layers of the PFC [170–173].”
From Development of prefrontal cortex (2022) · cites this paper as [172]
Various sources of glutamatergic input projections include a subset of (non-)dopaminergic VTA neurons to GABAergic interneurons in the PFC.
“There are various sources of glutamatergic input projections including a subset of (non-)dopaminergic VTA neurons to GABAergic interneurons in the PFC [170–173].”
From Development of prefrontal cortex (2022) · cites this paper as [172]
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- Authors
- Kabanova, A., Pabst, M., Lorkowski, M., Braganza, O., Boehlen, A., Nikbakht, N., Pothmann, L., Vaswani, A. R., Musgrove, R., Di Monte, D. A., Sauvage, M., Beck, H., & Blaess, S.
- Affiliations
- University of Bonn (DE)
- Ruhr University Bochum (DE)
- German Center for Neurodegenerative Diseases (DE)
- Corresponding author
- Blaess, Sandra
- ORCID
- Venue
- Nature Neuroscience
- Published
- 2015-05-11
- Volume
- 18
- Issue
- 6
- Pages
- 872-882
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- OpenAlex
- W1625270370
- Cited by
- 61
- References
- 65
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 5 · 2023: 9 · 2022: 4 · 2021: 5 · 2020: 6 · 2019: 7 · 2018: 8 · 2017: 4 · 2016: 4 · 2015: 3
- FWCI
- 2.94
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- DZNE Pub (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- 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 › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- ventral tegmental area, prefrontal cortex, GABAergic interneurons, glutamatergic excitation, Sonic hedgehog signaling, perseveration, dopaminergic neuron development, cognitive function
- MeSH terms
- Animals, Attention, Behavior, Animal, Cognition, Conditioning, Operant, gamma-Aminobutyric Acid, Glutamates, Interneurons, Nerve Net, Neurons, Reward, Prefrontal Cortex, Ventral Tegmental Area, Pyramidal Cells, Mice, Dopaminergic Neurons, Optogenetics
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