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Optogenetic dissection of medial prefrontal cortex circuitry

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Riga, Danai, Matos, Mariana R., Glas, Annet, Smit, August B., Spijker, Sabine, Van den Oever, Michel C.·2014·Frontiers in Systems Neuroscience

DOI 10.3389/fnsys.2014.00230PMC PMC4260491

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Abstract

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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Figure 1 Optogenetic evidence for the involvement of the mPFC in depressive-like behavior and anxiety. Yellow flash: photoinhibition; blue flash: photoactivation; ↑ = pro-depressive/anxiogenic effects; ↓ = antidepressant/anxiolytic effects. 1Covington et al. (2010): photoactivation increased sucrose preference and restored social interaction in defeat-susceptible mice. 2Kumar et al. (2013): photoactivation layer V pyramidal cells decreased immobility FST in naïve animals. 3Kumar et al. (2013): photoactivation layer V pyramidal cells increased time in open arms EPM test in defeated animals. 4Warden et al. (2012): photoactivation of mPFC-LHb projection promoted immobility FST in naïve animals. 5Warden et al. (2012): photoactivation of mPFC-DRN projection decreased immobility FST in naïve animals. 6Challis et al. (2014): photoactivation of vmPFC-DRN projection reduced social interaction in naïve animals. 7Challis et al. (2014): photoinhibition of vmPFC-DRN projection prevented social withdrawal in defeated animals. 8Vialou et al. (2014): photoactivation of dmPFC-Nac projection prevented social withdrawal. 9Vialou et al. (2014): photoactivation of dmPFC-BLA projection increased time in open arms EPM test. 10Chaudhury et al. (2013): photoinhibition of VTA-mPFC DA projection reduced social interaction in sub-threshold defeat animals. 11Friedman et al. (2014): photoactivation of VTA-mPFC DA projection restored social interaction in defeat-susceptible mice. 12Gunaydin et al. (2014): photoactivation of VTA-mPFC DA projection evoked anxiety-like behavior and place avoidance in naïve mice. dmPFC: dorsal medial prefrontal cortex; vmPFC: ventral medial prefrontal cortex; NAcc: nucleus accumbens core; NAcsh: nucleus accumbens shell; LHb: lateral habenula; DRN: dorsal raphe nucleus; BLA: basolateral amygdala; VTA: ventral tegmental area.CC BY · PubMed Central

Figure 2 Optogenetic evidence for the involvement of the mPFC in addictive behavior. Yellow flash: photoinhibition; blue flash: photoactivation. ↑ = enhanced drug taking/seeking; ↓ = reduced drug taking/seeking. Optogenetic manipulations indicate that the circuitry that regulates drug taking (when the drug is available) differs from the circuitry that mediates drug seeking (in absence of the drug). (A) Manipulation of drug taking. 1Chen et al. (2013): photoactivation PLC diminished compulsive cocaine taking in aversion resistant rats. 2Chen et al. (2013) and Martín-García et al. (2014): photoinhibition PLC evoked compulsive cocaine taking in aversion sensitive rats and resumption of cocaine intake in rats with history of high-frequency self-administration. 3Seif et al. (2013): photoinhibition of dmPFC-NAcc projection reduced alcohol intake paired with aversive stimulus. (B) Manipulation of drug seeking. 4Stefanik et al. (2013) and Martín-García et al. (2014): photoinhibition dmPFC attenuated cocaine seeking. 5Stefanik and Kalivas (2013): photoinhibition of BLA-dmPFC projection reduced reinstatement of cocaine seeking. 6Van den Oever et al. (2013): photoactivation vmPFC facilitated extinction of remote, but not recent, cocaine memory. 7Van den Oever et al. (2013): photoinhibition vmPFC impaired recall of recent cocaine memory, but prevented extinction of remote cocaine memory. 8Ma et al. (2014): photoactivation (1 Hz) evoked LTD in vmPFC-NAcsh projection reversed cocaine-induced synaptic adaptation and enhanced subsequent cocaine seeking. 9Pascoli et al. (2012): photoactivation (1 Hz) of vmPFC-NAcsh projection reversed cocaine-induced synaptic adaptation and locomotor sensitization. 10Pascoli et al. (2014): photoactivation (13 Hz) of vmPFC-NAcsh projection reversed cocaine-induced synaptic adaptation and abolished cocaine seeking. 11Ma et al. (2014): photoactivation (1 Hz) evoked LTD in dmPFC-NAcc projection reversed cocaine-induced synaptic adaptation and decreased subsequent cocaine seeking. 12Stefanik et al. (2013): photoinhibition of PLC-NAc core projection attenuated cocaine-primed reinstatement of cocaine seeking.CC BY · PubMed Central

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Authors: Riga, D., Matos, M. R., Glas, A., Smit, A. B., Spijker, S., & Van den Oever, M. C.
Affiliations: Amsterdam Neuroscience (NL)
Corresponding author: Van den Oever, Michel C.
ORCID: Riga, Danai
Matos, Mariana R.
Glas, Annet
Smit, August B.
Spijker, Sabine
Van den Oever, Michel C.
Venue: Frontiers in Systems Neuroscience
Publisher: Frontiers Media SA
Published: 2014-12-09
Volume: 8
Pages: 230-230
ISSN: 1662-5137 (ISSN-L)
DOI: 10.3389/fnsys.2014.00230
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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Optogenetic dissection of medial prefrontal cortex circuitry

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