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Review
. 2023 Nov 16:17:1247335.
doi: 10.3389/fncel.2023.1247335. eCollection 2023.

Glial regulation of critical period plasticity

Jacob Starkey  1 , Eric J Horstick  1   2 , Sarah D Ackerman  3
Affiliations
Review

Glial regulation of critical period plasticity

Jacob Starkey et al. Front Cell Neurosci. .

Abstract

Animal behavior, from simple to complex, is dependent on the faithful wiring of neurons into functional neural circuits. Neural circuits undergo dramatic experience-dependent remodeling during brief developmental windows called critical periods. Environmental experience during critical periods of plasticity produces sustained changes to circuit function and behavior. Precocious critical period closure is linked to autism spectrum disorders, whereas extended synaptic remodeling is thought to underlie circuit dysfunction in schizophrenia. Thus, resolving the mechanisms that instruct critical period timing is important to our understanding of neurodevelopmental disorders. Control of critical period timing is modulated by neuron-intrinsic cues, yet recent data suggest that some determinants are derived from neighboring glial cells (astrocytes, microglia, and oligodendrocytes). As glia make up 50% of the human brain, understanding how these diverse cells communicate with neurons and with each other to sculpt neural plasticity, especially during specialized critical periods, is essential to our fundamental understanding of circuit development and maintenance.

Keywords: E/I balance; astrocyte; critical period plasticity; extracellular matrix; microglia; oligodendrocyte; pruning.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Glial modulation of signaling between two neurons regulating critical periods associated plasticity. (A) Representative illustration of various glial cells regulating the signaling between pre- (gray-blue) and post-synaptic (gray-green) neurons. (B) Neuron with the strongest synaptic input creating complement regulating proteins (blue) and releasing C3 proteins (orange) onto weaker inputs, thus signaling to microglia for engulfment and removal. (C) Oligodendrocyte (blue) myelination wrapping the axon of pre-synaptic neurons (gray-blue) and communicating through NgR/Nogo-A signaling. Oligodendrocyte Nogo-A (green) and MAG (magenta) are upregulated through critical period with increased binding to neuronal NgR1/2 (orange/yellow) to solidify projection and decrease plasticity. (D) Oligodendrocyte precursor cell (OPC, cyan) regulating neuronal signaling via phagocytosis of the pre-synaptic axon terminals. (E) Astrocyte modulating the strength of inhibitory signaling between neurons by utilizing GABABR (blue-red) to detect GABA release and upregulate GAT (yellow) channels to uptake GABA, reducing critical period associated inhibitory signaling. (F) Astrocyte (orange) and microglia (magenta) regulating the formation of the perineuronal net in the extracellular matrix (ECM) around the pre-synaptic neuron. IL-33 is released from the astrocyte and neuron, signaling the microglia to break down the ECM and thus, perineuronal net formation. (G) Table describing the processes of glial regulation of critical period progression and closure for microglia (magenta), astrocytes (orange), OPCs (cyan), and oligodendrocytes (blue).
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