Optogenetic dissection of medial prefrontal cortex circuitry
Open accessAbstract
The medial prefrontal cortex (mPFC) is critically involved in numerous cognitive functions, including attention, inhibitory control, habit formation, working memory and long-term memory. Moreover, through its dense interconnectivity with subcortical regions (e.g., thalamus, striatum, amygdala and hippocampus), the mPFC is thought to exert top-down executive control over the processing of aversive and appetitive stimuli. Because the mPFC has been implicated in the processing of a wide range of cognitive and emotional stimuli, it is thought to function as a central hub in the brain circuitry mediating symptoms of psychiatric disorders. New optogenetics technology enables anatomical and functional dissection of mPFC circuitry with unprecedented spatial and temporal resolution. This provides important novel insights in the contribution of specific neuronal subpopulations and their connectivity to mPFC function in health and disease states. In this review, we present the current knowledge obtained with optogenetic methods concerning mPFC function and dysfunction and integrate this with findings from traditional intervention approaches used to investigate the mPFC circuitry in animal models of cognitive processing and psychiatric disorders.
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The PFC exerts top-down control over a variety of subcortical regions, and recent research has identified a number of circuits originating in the PFC that control behaviors relevant to the treatment of depression, anxiety, and addiction.
“The PFC is known to exert top-down control over a variety of subcortical regions, and recent research has identified a number of circuits originating in the PFC that control behaviors relevant to the treatment of depression, anxiety, and addiction (Figure 3) (56, 173).”
From Psychedelics and Other Psychoplastogens for Treating Mental Illness. (2021) · cites this paper as [56]
Non-selective activation of the mPFC can reverse behavioral deficits in depression models.
“Our findings build upon prior studies showing that non-selective activation of the mPFC can reverse behavioral deficits in depression models [36–39]”
From A nucleus accumbens-projecting prefrontal cortex circuit underlies chronic social stress-induced depression-like behaviors (2026) · cites this paper as [39]
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The Role of the Medial Prefrontal Cortex in the Conditioning and Extinction of Fear
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Medial prefrontal cortex in neurological diseases
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The human BNST: functional role in anxiety and addiction
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Psychedelic-inspired drug discovery using an engineered biosensor
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Psychedelics and Other Psychoplastogens for Treating Mental Illness.
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Direct dorsal hippocampal–prelimbic cortex connections strengthen fear memories
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Revisiting propranolol and PTSD: Memory erasure or extinction enhancement?
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Persistent post-stroke depression in mice following unilateral medial prefrontal cortical stroke
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Scaling Up Cortical Control Inhibits Pain
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Oxytocin normalizes altered circuit connectivity for social rescue of the Cntnap2 knockout mouse
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Mechanisms of fear learning and extinction: synaptic plasticity–fear memory connection
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Cortical astrocytes regulate ethanol consumption and intoxication in mice
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Plasticity in the prefrontal cortex of adult rats
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Synaptic Regulation of a Thalamocortical Circuit Controls Depression-Related Behavior
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Prefrontal cortex to accumbens projections in sleep regulation of reward
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Crocin Reverses Depression-Like Behavior in Parkinson Disease Mice via VTA-mPFC Pathway
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Prefrontal-accumbens opioid plasticity: Implications for relapse and dependence
Hearing, M. C. (2018) · Pharmacological Research · doi:10.1016/j.phrs.2018.11.012 · Cited by 56 · see citing works
Sex differences in the medial prefrontal cortical glutamate system
Knouse, M. C., McGrath, A. G., Deutschmann, A. U., Rich, M. T., Zallar, L. J., Rajadhyaksha, A. M., & Briand, L. A. (2022) · Biology of Sex Differences · doi:10.1186/s13293-022-00468-6 · Cited by 55 · see citing works
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Levodopa treatment and dendritic spine pathology
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Isolation of psychedelic-responsive neurons underlying anxiolytic behavioral states
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Slow to warm up: the role of habituation in social fear.
Avery, S., & Blackford, J. (2016) · Social Cognitive and Affective Neuroscience · doi:10.1093/scan/nsw095 · Cited by 42 · see citing works
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Converging Evidence for Frontopolar Cortex as a Target for Neuromodulation in Addiction Treatment
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Valence processing in the PFC: Reconciling circuit-level and systems-level views
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Cannabinoids: Revealing their complexity and role in central networks of fear and anxiety
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Effects of sarcosine and N, N-dimethylglycine on NMDA receptor-mediated excitatory field potentials
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Dopaminergic Modulation of Prefrontal Cortex Inhibition
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Intracellular microbial rhodopsin-based optogenetics to control metabolism and cell signaling
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Haploinsufficiency of Cyfip2 Causes Lithium‐Responsive Prefrontal Dysfunction
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Peripubertal Stress With Social Support Promotes Resilience in the Face of Aging
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Targeting the Neuronal Activity of Prefrontal Cortex: New Directions for the Therapy of Depression
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AgRP neurons control structure and function of the medial prefrontal cortex
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Translational considerations for the design of untethered nanomaterials in human neural stimulation
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Wihan, J., Grosch, J., Kalinichenko, L. S., Müller, C. P., Winkler, J., & Kohl, Z. (2019) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2019.03.014 · Cited by 19 · see citing works
Opioidergic activation of the descending pain inhibitory system underlies placebo analgesia
Neyama, H., Wu, Y., Nakaya, Y., Kato, S., Shimizu, T., Tahara, T., Shigeta, M., Inoue, M., Miyamichi, K., Matsushita, N., et al. (2025) · Science Advances · doi:10.1126/sciadv.adp8494 · Cited by 19 · see citing works
- Authors
- Riga, D., Matos, M. R., Glas, A., Smit, A. B., Spijker, S., & Van den Oever, M. C.
- Affiliations
- Amsterdam Neuroscience (NL)
- Venue
- Frontiers in Systems Neuroscience
- Publisher
- Frontiers Media SA
- Published
- 2014-12-09
- Volume
- 8
- Pages
- 230-230
- ISSN
- 1662-5137 (ISSN-L)
- PMC
- PMC4260491
- OpenAlex
- W2035346633
- Cited by
- 208
- References
- 203
- Citations by year
- 2026: 5 · 2025: 10 · 2024: 15 · 2023: 16 · 2022: 22 · 2021: 29 · 2020: 22 · 2019: 20 · 2018: 15 · 2017: 19 · 2016: 25 · 2015: 10
- FWCI
- 2.06
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Frontiers in Systems Neuroscience (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- VU Research Portal (publishedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Funders
- ZonMw
- Hersenstichting
- FP7 People: Marie-Curie Actions (607508, FP7-PEOPLE-2013-ITN, FP7-PEOPLE-2013)
- 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
- medial prefrontal cortex, optogenetics, neural circuits, neuronal subpopulations, mental illness, cognitive processes, animal models
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