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Removal of Perineuronal Nets in the Medial Prefrontal Cortex Impairs the Acquisition and Reconsolidation of a Cocaine-Induced Conditioned Place Preference Memory
Open accessAbstract
Pyramidal neurons in the medial prefrontal cortex (mPFC) critically contribute to cocaine-seeking behavior in humans and rodents. Activity of these neurons is significantly modulated by GABAergic, parvalbumin-containing, fast-spiking interneurons, the majority of which are enveloped by specialized structures of extracellular matrix called perineuronal nets (PNNs), which are integral to the maintenance of many types of plasticity. Using a conditioned place preference (CPP) procedure, we found that removal of PNNs primarily from the prelimbic region of the mPFC of adult, male, Sprague Dawley rats impaired the acquisition and reconsolidation of a cocaine-induced CPP memory. This impairment was accompanied by a decrease in the number of c-Fos-positive cells surrounded by PNNs. Following removal of PNNs, the frequency of inhibitory currents in mPFC pyramidal neurons was decreased; but following cocaine-induced CPP, both frequency and amplitude of inhibitory currents were decreased. Our findings suggest that cocaine-induced plasticity is impaired by removal of prelimbic mPFC PNNs and that PNNs may be a therapeutic target for disruption of cocaine CPP memories.
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“The mPFC has an integrative role in object, place and time information [114, 115] as well as reward-regulated mechanisms of spatial learning [116, 117].”
From The extracellular matrix and perineuronal nets in memory (2022) · cites this paper as [117]
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“For example, removal of PNNs with ChABC in the mPFC or lateral hypothalamus prior to training for conditioned place preference (CPP) attenuates acquisition of the CPP memory [117, 159], and removal after CPP training also attenuates memory reconsolidation [117].”
From The extracellular matrix and perineuronal nets in memory (2022) · cites this paper as [117]
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“Several studies have demonstrated that removal of PNNs with ChABC alters behavioural responses to drugs.”
From The extracellular matrix and perineuronal nets in memory (2022) · cites this paper as [117]
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“degrading PNNs with Ch--ABC in the mPFC reduced the acquisition and/or maintenance (reconsolidation) of cocaine memory in a conditioned place preference model of addiction in rats (Slaker et al., 2015)”
From Casting a Wide Net: Role of Perineuronal Nets in Neural Plasticity (2016) · cites this paper as Slaker et al., 2015
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“Moreover, the ChABC-induced removal of PNs in the medial prefrontal cortex impaired acquisition and reconsolidation of conditioned place preference memory after its impairment by cocaine (Slaker et al., 2015).”
From Damaged Neocortical Perineuronal Nets Due to Experimental Focal Cerebral Ischemia in Mice, Rats and Sheep (2017) · cites this paper as Slaker et al., 2015
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Metadata
- Authors
- Slaker, M., Churchill, L., Todd, R. P., Blacktop, J. M., Zuloaga, D. G., Raber, J., Darling, R. A., Brown, T. E., & Sorg, B. A.
- Affiliations
- Washington State University Vancouver (US)
- Washington State University (US)
- Oregon Health & Science University (US)
- Oregon National Primate Research Center (US)
- University of Wyoming (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2015-03-11
- Volume
- 35
- Issue
- 10
- Pages
- 4190-4202
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC4355195
- OpenAlex
- W2059869176
- Cited by
- 208
- References
- 64
- Citations by year
- 2026: 12 · 2025: 15 · 2024: 21 · 2023: 13 · 2022: 18 · 2021: 20 · 2020: 32 · 2019: 19 · 2018: 19 · 2017: 18 · 2016: 15 · 2015: 6
- FWCI
- 8.98
- 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
- National Aeronautics and Space Administration (#NNJ12ZSA001N)
- Washington State University
- National Institute on Drug Abuse (DA030647, R21DA030647, DA033404, T32DA007262, R01DA033404)
- National Institute of General Medical Sciences (P30 GM103398-32128, P30GM103398)
- 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 › Memory and Neural Mechanisms
- Keywords
- perineuronal nets, medial prefrontal cortex, prelimbic cortex, cocaine, conditioned place preference, memory reconsolidation, memory acquisition, parvalbumin interneurons, fast-spiking interneurons, pyramidal neurons, c-fos, extracellular matrix, cocaine-seeking behavior, addiction treatment targets
- MeSH terms
- Animals, Association Learning, Brain Injuries, Cocaine, Conditioning, Operant, Extinction, Psychological, Male, Memory Disorders, Nerve Net, Nerve Tissue Proteins, Neuronal Plasticity, Time Factors, Proto-Oncogene Proteins c-fos, Rats, Sprague-Dawley, Prefrontal Cortex, Microscopy, Confocal, Dopamine Uptake Inhibitors, Chondroitin ABC Lyase, Receptors, N-Acetylglucosamine, Plant Lectins, Rats
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