Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2021 Jun:167:17-29.
doi: 10.1016/j.neures.2020.11.005. Epub 2020 Dec 11.

Glia as sculptors of synaptic plasticity

Laura Sancho  1 , Minerva Contreras  1 , Nicola J Allen  2
Affiliations
Review

Glia as sculptors of synaptic plasticity

Laura Sancho et al. Neurosci Res. 2021 Jun.

Abstract

Glial cells are non-neuronal cells in the nervous system that are crucial for proper brain development and function. Three major classes of glia in the central nervous system (CNS) include astrocytes, microglia and oligodendrocytes. These cells have dynamic morphological and functional properties and constantly surveil neural activity throughout life, sculpting synaptic plasticity. Astrocytes form part of the tripartite synapse with neurons and perform many homeostatic functions essential to proper synaptic function including clearing neurotransmitter and regulating ion balance; they can modify these properties, in addition to additional mechanisms such as gliotransmitter release, to influence short- and long-term plasticity. Microglia, the resident macrophage of the CNS, monitor synaptic activity and can eliminate synapses by phagocytosis or modify synapses by release of cytokines or neurotrophic factors. Oligodendrocytes regulate speed of action potential conduction and efficiency of information exchange through the formation of myelin, having important consequences for the plasticity of neural circuits. A deeper understanding of how glia modulate synaptic and circuit plasticity will further our understanding of the ongoing changes that take place throughout life in the dynamic environment of the CNS.

Keywords: Glia; Learning; Plasticity; Synapse.

PubMed Disclaimer

Conflict of interest statement

Declaration of Competing Interest None.

Figures

Figure 1:
Figure 1:. Astrocytes and short-term synaptic plasticity.
Selected effects of astrocytic regulation of synaptic short-term plasticity. (1) Increase in Ca2+ leads to astrocytic glutamate release interacting with group I mGluRs on neuronal presynaptic membranes. (2) Synaptic release of dopamine increases Ca2+ in astrocytes via astrocytic D1 receptors, and leads to the release of ATP/adenosine, which causes temporary depression of excitatory synaptic transmission. (3) Astrocytic Ca2+ increase via GABAB receptor activation leads to glutamate and ATP release. Glutamate initially increases synaptic potentiation and is followed by ATP/adenosine induced depression. (4) Astrocytic K+ uptake by astrocytes regulates K+ availability in the synaptic cleft and accumulation of K+ leads to AMPAR desensitization.
Figure 2:
Figure 2:. Astrocytes and long-term synaptic plasticity.
Selected effects of astrocytic regulation of synaptic long-term plasticity. (1) D-serine released by astrocytes enhances NMDAR-mediated LTP. Exogenous D-serine can also affect NMDAR-mediated LTD. (2) Activation of astrocytic protease activated receptor 1 (PAR1) leads to a rise in intracellular Ca2+, releasing glutamate from astrocytes which then binds to neuronal NMDARs. (3) ATP enhances synaptic strength by activating neuronal postsynaptic P2X purinergic receptors. (4) AQP-4 regulates brain-derived neurotrophic factor (BDNF)- dependent LTP. (5) GLT-1 glutamate uptake regulates expression of spike timing-dependent plasticity (STDP), both potentiation and depression. (6) CB1R-mediated astrocyte activation leads to the depression of excitatory synapses through A1 adenosine receptors. (7) Astrocyte-secreted Hevin, by linking neurexin-1α and NL1 is necessary for proper expression of ocular dominance plasticity during the visual critical period.
Figure 3:
Figure 3:. The role of microglia in synaptic plasticity.
Selected pathways of microglial involvement in synaptic plasticity. (1) Activation of the purinergic P2Y12 receptor or inhibition of the β-adrenergic receptor on microglia promotes ocular dominance plasticity (ODP) after monocular deprivation. (2) Release of TNFα from microglia can lead to the exocytosis of AMPARs and endocytosis of GABAA receptors at the postsynaptic membrane. (3) Secretion of BDNF from microglia can promote synaptic plasticity and motor learning. (4) The classical complement cascade, in which soluble C1q initiates the pathway, with microglial-secreted C3 binding to C3 receptors on microglia. This leads to synapse elimination and facilitates memory erasure. (5) CX3CL1 derived from neurons can bind to microglial CX3CR1 to initiate synaptic elimination and promote barrel cortex plasticity after whisker lesioning. (6) TREM2 on microglia is involved in the phagocytosis of synapses.
Figure 4.
Figure 4.. Oligodendrocytes, myelin plasticity, and neuronal plasticity.
(1) Neuronal activity including, but not limited to, action potential firing, motor task training, and optogenetic stimulation (left to right) can induce changes in myelination such as (2) proliferation of new OPCs, (3) maturation of OPCs into myelinating oligodendrocytes, (4) formation of new sheaths or thickening of existing sheaths, and (5) changes to the internode segments or nodes.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Abel T et al. (2013) ‘Sleep, plasticity and memory from molecules to whole-brain networks’, Current Biology. Elsevier, 23(17), pp. R774–R788. - PMC - PubMed
    1. Adamsky A et al. (2018) ‘Astrocytic Activation Generates De Novo Neuronal Potentiation and Memory Enhancement’, Cell. Cell Press, 174(1), pp. 59–71.e14. - PubMed
    1. Agarwal A et al. (2017) ‘Transient Opening of the Mitochondrial Permeability Transition Pore Induces Microdomain Calcium Transients in Astrocyte Processes’, Neuron. Elsevier, 93(3), pp. 587–605.e7. - PMC - PubMed
    1. Agulhon C et al. (2008) ‘What Is the Role of Astrocyte Calcium in Neurophysiology?’, Neuron, 59(6), pp. 932–946. - PMC - PubMed
    1. Alberini CM et al. (2018) ‘Astrocyte glycogen and lactate: New insights into learning and memory mechanisms’, GLIA - PMC - PubMed

LinkOut - more resources