Plasticity of neuron-OPC synapses, changes in OPC intrinsic properties and OPC morphology during development of corpus callosum.

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Dokumentart: PhDThesis
Date: 2024-02-22
Language: English
Faculty: 4 Medizinische Fakultät
Department: Medizin
Advisor: Knipper, Marlies (Prof. Dr.)
Day of Oral Examination: 2023-11-20
DDC Classifikation: 500 - Natural sciences and mathematics
570 - Life sciences; biology
590 - Animals (Zoology)
Keywords: Neurowissenschaften , Entwicklung , Synapse , Glia , Corpus callosum
Other Keywords:
Oligodendrocyte Precursor Cell
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Oligodendrocyte precursor cells (OPC) are unique among the glial cells of the CNS due to their synaptic connections with neurons. Those synapses are also formed in white matter where OPC are the major recipients of neuronal inputs driving their proliferation and differentiation into myelinating glia. After the robust wave of myelination in the 2-4 postnatal week OPCs remain in the white matter and retain their connections with neurons. Up to date the properties of those synapses are poorly understood throughout callosal development. In this work we demonstrate, in murine callosal (CC) slices, which components of synaptic strength are altered throughout three distinct stages of callosal development (juvenility, adolescence and adulthood) to offset hyperpolarizing membrane potentials and increasing membrane leakage. We show by which mechanisms synapses transition from short term depression into potentiation and increase in reliability of transmission and signal integration. Moreover, we investigate how those properties are shaped by different patterns of activity. We supplement the electrophysiological results with whole-cell morphological reconstructions to show how the development of myelin and continuous growth of CC shapes the branching of OPC processes. Our electrophysiological results point to similarities in synaptic development between neuronal and neuron-glia synapses while providing the first comprehensive assessment of the properties of OPC synapses within a developmental framework. Our morphological results highlight the remarkable stability of OPC branching pattern, contrasting with the substantial changes in the synaptic input and OPC intrinsic properties.

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