The tetrapartite synapse: Extracellular matrix remodeling contributes to corticoaccumbens plasticity underlying drug addiction
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Synaptic plasticity has long been known to involve three key elements of neuropil, the presynapse, the postsynapse and adjacent glia. Here we review the role of the extracellular matrix in synaptic plasticity as a necessary component forming the tetrapartite synapse. We describe the role of matrix metalloproteinases as enzymes sculpting extracellular proteins and thereby creating an extracellular signaling domain required for synaptic plasticity. Specifically we focus on the role of the tetrapartite synapse in mediating the effects of addictive drugs at cortico-striatal synapses, and conclude that the extracellular signaling domain and its regulation by matrix metalloproteinases is critical for developing and expressing drug seeking behaviors.
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There is a tetrapartite synaptic organization involving ECM, pre/post synaptic sites and astrocytes.
“Astrocytes extend their processes into PNNs localized near the synapse (Brückner et al., 1993; Blümcke et al., 1995), suggesting a tetrapartite synaptic organization involving ECM, pre/post synaptic sites and astrocytes (Dityatev and Rusakov, 2011; Smith et al., 2015) whose synergistic functions remain unexplored.”
From The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders (2018) · cites this paper as Smith et al., 2015
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- Loffek S Schilling O Franzke CW 2011 Series "matrix metalloproteinases in lung health and disease": Biological role of matrix metalloproteinases: a critical balance Eur Respir J 38 191 208 21177845
- Scofield MD Kalivas PW 2014 Astrocytic Dysfunction and Addiction: Consequences of Impaired Glutamate Homeostasis Neuroscientist PMC4913887 24496610
- Stefanik MT 2013b Optogenetic inhibition of cocaine seeking in rats Addiction biology 18 50 3 22823160 PMC3578202
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Cited by
Sorted by citations
Scofield, M. D., Heinsbroek, J. A., Gipson, C. D., Kupchik, Y. M., Spencer, S., Smith, A. C. W., Roberts-Wolfe, D., & Kalivas, P. W. (2016) · Pharmacological Reviews · doi:10.1124/pr.116.012484 · Cited by 598 · see citing works
Self-citationCasting a Wide Net: Role of Perineuronal Nets in Neural Plasticity
Sorg, B. A., Berretta, S., Blacktop, J. M., Fawcett, J. W., Kitagawa, H., Kwok, J. C. F., & Miquel, M. (2016) · The Journal of Neuroscience · doi:10.1523/jneurosci.2351-16.2016 · Cited by 454 · see citing works
Adult neurogenesis, glia, and the extracellular matrix
Cope, E. C., & Gould, E. (2019) · Cell Stem Cell · doi:10.1016/j.stem.2019.03.023 · Cited by 236 · see citing works
MMPs in learning and memory and neuropsychiatric disorders
Beroun, A., Mitra, S., Michaluk, P., Pijet, B., Stefaniuk, M., & Kaczmarek, L. (2019) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-019-03180-8 · Cited by 207 · see citing works
The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders
Wen, T. H., Binder, D. K., Ethell, I. M., & Razak, K. A. (2018) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2018.00270 · Cited by 170 · see citing works
Namba, M. D., Leyrer-Jackson, J. M., Nagy, E. K., Olive, M. F., & Neisewander, J. L. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.650785 · Cited by 76 · see citing works
Astrocyte-specific transcriptome responses to chronic ethanol consumption
Erickson, E. K., Farris, S. P., Blednov, Y. A., Mayfield, R. D., & Harris, R. A. (2018) · The Pharmacogenomics Journal · doi:10.1038/s41397-017-0012-2 · Cited by 56 · see citing works
Incubation of depression: ECM assembly and parvalbumin interneurons after stress
Spijker, S., Koskinen, M.-K., & Riga, D. (2020) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2020.07.015 · Cited by 55 · see citing works
Peripheral immune-derived matrix metalloproteinase promotes stress susceptibility
Russo, S., Cathomas, F., Lin, H.-Y., Chan, K., Li, L., Durand-de Cuttoli, R., Parise, L., Aubry, A., Muhareb, S., Desland, F., et al. (2023) · doi:10.21203/rs.3.rs-1647827/v1 · Cited by 189 · see citing works
- Authors
- Smith, A. C. W., Scofield, M. D., & Kalivas, P. W.
- Affiliations
- Medical University of South Carolina (US)
- Corresponding author
- Kalivas, Peter W.
- Venue
- Brain Research
- Publisher
- Elsevier BV
- Published
- 2015-12
- Volume
- 1628
- Issue
- Pt A
- Pages
- 29-39
- ISSN
- 0006-8993 (ISSN-L)
- PMC
- PMC4589426
- OpenAlex
- W1989897544
- Cited by
- 71
- References
- 94
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 3 · 2023: 6 · 2022: 3 · 2021: 7 · 2020: 6 · 2019: 7 · 2018: 16 · 2017: 7 · 2016: 8 · 2015: 2
- FWCI
- 1.33
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Brain Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- USPHS (DA03906, DA12513, DA007288, DA15369)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- extracellular matrix remodeling, synaptic plasticity, matrix metalloproteinases, corticostriatal synapses, drug addiction, drug-seeking behavior, glia
- MeSH terms
- Animals, Extracellular Matrix, Humans, Neuronal Plasticity, Synapses, Substance-Related Disorders
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