Molecular signals of plasticity at the tetrapartite synapse
Open accessAbstract
The emergence of astroglia as an important participant of the synaptic machinery has led to the 'tripartite synapse' hypothesis. Recent findings suggest that synaptic signaling also involves the surrounding extracellular matrix (ECM). The ECM can incorporate and store molecular traces of both neuronal and glial activities. It can also modulate function of local receptors or ion channels and send diffuse molecular signals using products of its use-dependent proteolytic cleavage. Recent experimental findings implicate the ECM in mechanisms of synaptic plasticity and glial remodeling, thus lending support to the 'tetrapartite synapse' concept. This inclusive view might help to understand better the mechanisms underlying signal integration and novel forms of long-term homeostatic regulation in the brain.
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In adulthood, mature PNNs regulate synaptic functions representing the fourth element of the 'tetrapartite' synapse.
“In adulthood, mature PNNs regulate synaptic functions representing the fourth element of what has been termed the ‘tetrapartite' synapse.85, 86”
From Aggrecan and chondroitin-6-sulfate abnormalities in schizophrenia and bipolar disorder: a postmortem study on the amygdala (2015) · cites this paper as [86]
Regulation of synaptic connectivity involves at least four main cellular/molecular components: the presynaptic neuron, postsynaptic neuron, glia, and the ECM, which together make up the tetrapartite synapse.
“Regulation of synaptic connectivity involves at least four main cellular/molecular components: the presynaptic neuron, postsynaptic neuron, glia, and the ECM, which together make up the “tetrapartite synapse” (Dityatev and Rusakov, 2011).”
From Adult neurogenesis, glia, and the extracellular matrix (2019) · cites this paper as Dityatev and Rusakov, 2011
The ECM aids in the communication between neurons and glial cells by incorporating their secreted signaling molecules into the extracellular space where they interact with other ECM molecules and/or cell surface receptors.
“The ECM aids in the communication between neurons and glial cells by incorporating their secreted signaling molecules into the extracellular space where they interact with other ECM molecules and/or cell surface receptors (Dityatev and Rusakov, 2011).”
From Adult neurogenesis, glia, and the extracellular matrix (2019) · cites this paper as Dityatev and Rusakov, 2011
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Shaping Synapses by the Neural Extracellular Matrix
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“…to the synapses may influence transmission in functional arrangements as tripartite or tetrapartite (including the extracellular matrix between the pre- and the postsynaptic elements) synaptic units in the human Me (Araque et al., 1999; Halassa and Haydon, 2010; Dityatev and Rusakov, 2011).”
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- Authors
- Dityatev, A., & Rusakov, D. A.
- Affiliations
- Italian Institute of Technology (IT)
- National Hospital for Neurology and Neurosurgery (GB)
- Corresponding author
- Dityatev, Alexander
- Venue
- Current Opinion in Neurobiology
- Publisher
- Elsevier BV
- Published
- 2011-04
- Volume
- 21
- Issue
- 2
- Pages
- 353-359
- ISSN
- 0959-4388 (ISSN-L)
- PMC
- PMC3368316
- OpenAlex
- W2088446288
- Cited by
- 267
- References
- 86
- Citations by year
- 2026: 17 · 2025: 17 · 2024: 20 · 2023: 23 · 2022: 14 · 2021: 22 · 2020: 16 · 2019: 17 · 2018: 21 · 2017: 17 · 2016: 22 · 2015: 16 · 2014: 17 · 2013: 11 · 2012: 15
- FWCI
- 1.37
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Current Opinion in Neurobiology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Wellcome Trust
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- synaptic plasticity, astroglia, extracellular matrix, synaptic signaling, proteolytic cleavage, signal integration, homeostatic regulation
- MeSH terms
- Animals, Astrocytes, Brain, Extracellular Matrix, Humans, Neuronal Plasticity, Neurons, Synapses, Signal Transduction
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