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We would like to thank Dr. Maike Paramor for comments on the protocol, Kimberley Evans for comments on the protocol and assistance with the graphics, Dr Omar de Faria Jr for assistance with the figures, and our following funders: the European Research Council (ERC: the European Union's Horizon 2020 research and innovation programme grant agreement No 771411; R.T.K.); the Wellcome (Studentship award 102160/Z/13/Z; Y.K.); the Fonds de recherche du Québec-Santé (a scholarship, Y.K.); The Cambridge Commonwealth European & International Trust (a scholarship, Y.K.); and the Lister Institute of Preventive Medicine (a research prize, R.T.K.). The funders had no role in decision to publish or preparation of the manuscript. Publisher Copyright: © 2021 The Author(s) ; Single-cell electrophysiological recordings combined with dye loading and immunohistochemistry provide unparalleled single-cell resolution of cell physiology, morphology, location, and protein expression. When correlated with bulk RNA sequencing, these data can define cell identity and function. Here, we describe a protocol to prepare acute brain slices from embryonic and postnatal mice for whole-cell patch clamp, dye loading and post-hoc immunohistochemistry, and cell isolation for bulk RNA sequencing. While we focus on oligodendrocyte precursor cells, this protocol is applicable to other brain cells. For complete details on the use and execution of this protocol, please refer to Spitzer et al. (2019). ; Peer reviewed

Publisher's version (útgefin grein) ; Plasticity in the central nervous system (CNS) allows for responses to changing environmental signals. While the majority of studies on brain plasticity focus on neuronal synapses, myelin plasticity has now begun to emerge as a potential modulator of neuronal networks. Oligodendrocytes (OLs) produce myelin, which provides fast signal transmission, allows for synchronization of neuronal inputs, and helps to maintain neuronal function. Thus, myelination is also thought to be involved in learning. OLs differentiate from oligodendrocyte precursor cells (OPCs), which are distributed throughout the adult brain, and myelination continues into late adulthood. This process is orchestrated by numerous cellular and molecular signals, such as axonal diameter, growth factors, extracellular signaling molecules, and neuronal activity. However, the relative importance of, and cooperation between, these signaling pathways is currently unknown. In this review, we focus on the current knowledge about myelin plasticity in the CNS. We discuss new insights into the link between this type of plasticity, learning and behavior, as well as mechanistic aspects of myelin formation that may underlie myelin plasticity, highlighting OPC diversity in the CNS. ; This work was supported by the European Research Council (ERC) under the European Union's Horizon 2020 Research and Innovation Programme (Grant Agreement No. 771411; RK, GB, and KE); a Wellcome Studentship (102160/Z/13/Z; YK), the Fonds de recherche du Québec-Santé, a scholarship (YK); the Cambridge Commonwealth European and International Trust, a scholarship (YK); and the Lister Institute, a Research Prize (RK). ; Peer Reviewed

Oligodendrocyte progenitor cells (OPCs), which differentiate into myelinating oligodendrocytes during central nervous system (CNS) development, are the main proliferative cells in the adult brain. OPCs are conventionally considered a homogeneous population, particularly with respect to their electrophysiological properties, but this has been debated. We show, by using single-cell electrophysiological recordings, that OPCs start out as a homogeneous population, but become functionally heterogeneous, varying both within and between brain regions and with age. These electrophysiological changes in OPCs correlate with the differentiation potential of OPCs; thus, they may underlie the differentiational differences in OPCs between regions and likewise differentiation failure with age. ; We acknowledge the support of the Wellcome - MRC Cambridge Stem Cell Institute core facility managers, in particular for this work Dr Maike Paramor and Miss Victoria Murray with RNA sequencing, and all staff members of the University Biomedical Services (UBS). This project has received funding from: the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (grant agreement No 771411; R.T.K, K.A.E); the Wellcome Trust, a Research Career Development Fellowship (R.T.K. and K.A.E. 091543/Z/10/Z) and a Studentship (102160/Z/13/Z; Y.K); The Paul G Allen Frontiers Group, Allen Distinguished Investigator Award (12076, R.T.K., D.K.V.); The Medical Research Council, a studentship (S.O.S.); The Gates Foundation, a Gates Scholarship (S.S.), The Biotechnology and Biological Sciences Research Council, a studentship (S.A.); Homerton College Cambridge, a Junior Research Fellowship (D.K.V); The UK MS Society, a Cambridge Myelin Repair Centre grant (50; R.T.K, O.D.F.); The Fonds de recherche du Québec-Santé, a scholarship (Y.K.); The Cambridge Commonwealth European & International Trust, a scholarship (Y.K.); and the Lister Institute, a Research Prize (R.T.K., K.A.E, SOS).