Cortical Control of Affective Networks
Open accessAbstract
Transcranial magnetic stimulation and deep brain stimulation have emerged as therapeutic modalities for treatment refractory depression; however, little remains known regarding the circuitry that mediates the therapeutic effect of these approaches. Here we show that direct optogenetic stimulation of prefrontal cortex (PFC) descending projection neurons in mice engineered to express Chr2 in layer V pyramidal neurons (Thy1–Chr2 mice) models an antidepressant-like effect in mice subjected to a forced-swim test. Furthermore, we show that this PFC stimulation induces a long-lasting suppression of anxiety-like behavior (but not conditioned social avoidance) in socially stressed Thy1–Chr2 mice: an effect that is observed >10 d after the last stimulation. Finally, we use optogenetic stimulation and multicircuit recording techniques concurrently in Thy1–Chr2 mice to demonstrate that activation of cortical projection neurons entrains neural oscillatory activity and drives synchrony across limbic brain areas that regulate affect. Importantly, these neural oscillatory changes directly correlate with the temporally precise activation and suppression of limbic unit activity. Together, our findings show that the direct activation of cortical projection systems is sufficient to modulate activity across networks underlying affective regulation. They also suggest that optogenetic stimulation of cortical projection systems may serve as a viable therapeutic strategy for treating affective disorders.
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Optical stimulation of layer V pyramidal neurons in the PFC expressing channelrhodopsin-2 was sufficient to produce an antidepressant-like response in the forced swim test and suppress anxiety-like behavior in the elevated plus maze for over 10 days after the last optical stimulation session.
“Dzirasa et al. demonstrated that optical stimulation of layer V pyramidal neurons in the PFC expressing channelrhodopsin-2 was sufficient to produce an antidepressant-like response in the forced swim test and suppress anxiety-like behavior in the elevated plus maze for over 10 days after the last optical stimulation session (180).”
From Psychedelics and Other Psychoplastogens for Treating Mental Illness. (2021) · cites this paper as [180]
PLc tends to promote active coping, while ILc promotes passive coping.
“where these regions have been discriminated, regardless of the model, PLc tends to promote active coping [226,227] whilst ILc appears to have the opposite effect, promoting passive coping [228].”
From Prefrontal cortex and depression (2022) · cites this paper as [227]
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- Authors
- Kumar, S., Black, S. J., Hultman, R., Szabo, S. T., DeMaio, K. D., Du, J., Katz, B. M., Feng, G., Covington, H. E., & Dzirasa, K.
- Affiliations
- Duke Medical Center (US)
- Duke University (US)
- McGovern Institute for Brain Research (US)
- ORCID
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2013-01-16
- Volume
- 33
- Issue
- 3
- Pages
- 1116-1129
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC3711588
- OpenAlex
- W2002599599
- Cited by
- 110
- References
- 47
- Citations by year
- 2026: 2 · 2025: 7 · 2024: 7 · 2023: 12 · 2022: 7 · 2021: 14 · 2020: 10 · 2019: 8 · 2018: 8 · 2017: 4 · 2016: 4 · 2015: 9 · 2014: 9 · 2013: 9
- FWCI
- 7.60
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
- Funders
- National Institute of Mental Health (RC1MH088434, R37MH073853, P50MH060451)
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Neurology › Transcranial Magnetic Stimulation Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- optogenetic stimulation, prefrontal cortex, cortical projection neurons, emotion regulation, anxiety-like behavior, social stress, forced swim test, neural oscillations, mood disorders, antidepressant effects, treatment-resistant depression
- MeSH terms
- Affect, Animals, Anxiety, Behavior, Animal, Cerebral Cortex, Male, Nerve Net, Neurons, Mice
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