THESIS
2020
1 online resource (xiii, 134 pages) : illustrations (some color)
Abstract
Synaptic plasticity is important for information processing, learning, and memory encoding.
In particular, homeostatic synaptic plasticity is the ability of neurons to produce compensatory
changes at synapses in response to prolonged changes in neuronal activity. This form of synaptic
plasticity enables neural circuits to maintain specificity and stability during learning-related
processes. Astrocytes, as the most abundant glial cells in the central nervous system, actively
regulate synapse formation, functions, and maintenance throughout life, but how they sense
changes in neuronal activity or interact with neurons in regulating plasticity at the circuit level
is largely unknown. Here, I found that astrocyte-secreted interleukin-33 (IL-33) is a critical
regulator of homeostatic synapti...[
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Synaptic plasticity is important for information processing, learning, and memory encoding.
In particular, homeostatic synaptic plasticity is the ability of neurons to produce compensatory
changes at synapses in response to prolonged changes in neuronal activity. This form of synaptic
plasticity enables neural circuits to maintain specificity and stability during learning-related
processes. Astrocytes, as the most abundant glial cells in the central nervous system, actively
regulate synapse formation, functions, and maintenance throughout life, but how they sense
changes in neuronal activity or interact with neurons in regulating plasticity at the circuit level
is largely unknown. Here, I found that astrocyte-secreted interleukin-33 (IL-33) is a critical
regulator of homeostatic synaptic plasticity in the adult hippocampus. The suppression of
neuronal activity in the hippocampal cornu ammonis 1 (CA1) region increased the expression
and secretion of IL-33 by astrocytes. Moreover, in vivo administration of IL-33 promoted
excitatory synapse formation and enhanced synaptic transmission in CA1 hippocampal neurons.
The action of IL-33 at synapses is mediated through its neuronal receptor activation and the
synaptic recruitment of the scaffold protein PSD-95. Furthermore, IL-33 signaling was found
to be required for the neuronal activity blockade-induced increase of hippocampal CA3–CA1
excitatory synapses in vivo, while perturbation of IL-33 signaling results in impaired memory
functions. These results reveal a critical role for IL-33 in astrocyte–neuron signaling, and
provide insights into how astrocytes maintain homeostasis of the adult hippocampal circuitry.
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