Impaired bidirectional communication between interneurons and oligodendrocyte precursor cells affects social cognitive behavior

Fang, Li‐Pao; Zhao, Na; Caudal, Laura C.; Chang, Hsin-Fang; Zhao, Renping; Lin, Ching-Hsin; Hainz, Nadine; Meier, Carola; Bettler, Bernhard; Huang, Wenhui; Scheller, Anja; Kirchhoff, Frank; Bai, Xianshu

doi:10.1038/s41467-022-29020-1

Cited by 44 publications

(58 citation statements)

References 68 publications

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“…Tamoxifen was administrated at p7 and 8 (Fig. 2I), inducing tdT expression in about 80 % of OPCs at p14 (Fang et al, 2022). Again, we observed a small population (about 3 %) of Pα pos tdT pos cells expressing no Olig2 (Fig.…”

Section: Resultsmentioning

confidence: 99%

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Brain injuries and complex motor learning suppress Olig2 in a subpopulation of oligodendrocyte precursor cells

Fang

Liu

Meyer

et al. 2022

Preprint

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Oligodendrocyte precursor cells (OPCs) are uniformly distributed in the mammalian brain, however their function is rather heterogeneous in respect to their origin, location, receptor/channel expression and age. The basic helix-loop-helix transcription factor Olig2 is expressed in all OPCs as a pivotal determinant of their differentiation. Here, we identified a subset (2-26%) of OPCs lacking Olig2 in various brain regions including cortex, corpus callosum, CA1 and dentate gyrus. These Olig2 negative (Olig2neg) OPCs were enriched in the juvenile brain and decreased subsequently with age, being rarely detectable in the adult brain. However, the loss of this population was not due to apoptosis or microglia-dependent phagocytosis. Unlike Olig2pos OPCs, these subset cells could not be labelled for the mitotic marker Ki67. And, accordingly, BrdU was incorporated only by a three-day long-term labeling but not by a two-hour short pulse, suggesting these cells do not proliferate any more but were derived from proliferating OPCs. The Olig2neg OPCs exhibited a less complex morphology than Olig2pos ones. Olig2neg OPCs preferentially remain in a precursor stage rather than differentiating into highly branched oligodendrocytes. Changing the adjacent brain environment, e.g. by acute injuries or by complex motor learning tasks stimulated the transition of Olig2pos OPCs to Olig2neg cells in the adult. Taken together, our results demonstrate that OPCs transiently suppress Olig2 upon changes of the brain activity.

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Section: Resultsmentioning

confidence: 99%

“…8B). About 90 % OPCs were recombined at the age of 9 weeks (Fang et al, 2022). Analyzed at 3 dpi, all the Pα pos Olig2 neg cells in the ipsilateral side were GFP pos (Fig.…”

Section: Resultsmentioning

confidence: 99%

Brain injuries and complex motor learning suppress Olig2 in a subpopulation of oligodendrocyte precursor cells

Fang

Liu

Meyer

et al. 2022

Preprint

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“…Oligodendrocyte precursor cells (OPCs) are also indispensable regulators of interneuron populations via GABA signaling and the cytokine tumor necrosis factor-like WEAK inducer of apoptosis (TWEAK) (Fang et al, 2022 ). Ablation of GABA B R in OPCs is associated with an increment in the number of PV+ interneurons in all cortical layers of the adult mouse prefrontal cortex.…”

Section: Interneuron Programmed Cell Deathmentioning

confidence: 99%

“…Ablation of GABA B R in OPCs is associated with an increment in the number of PV+ interneurons in all cortical layers of the adult mouse prefrontal cortex. Surprisingly, this increment in the number of PV neurons does not cause an increment of the PV inhibitory input but an impairment of interneuron activity in the medial prefrontal cortex of OPC-GABA B R conditional KO mice (Fang et al, 2022 ).…”

Section: Interneuron Programmed Cell Deathmentioning

confidence: 99%

Origin, Development, and Synaptogenesis of Cortical Interneurons

Llorca

Deogracias

2022

Front. Neurosci.

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The mammalian cerebral cortex represents one of the most recent and astonishing inventions of nature, responsible of a large diversity of functions that range from sensory processing to high-order cognitive abilities, such as logical reasoning or language. Decades of dedicated study have contributed to our current understanding of this structure, both at structural and functional levels. A key feature of the neocortex is its outstanding richness in cell diversity, composed by multiple types of long-range projecting neurons and locally connecting interneurons. In this review, we will describe the great diversity of interneurons that constitute local neocortical circuits and summarize the mechanisms underlying their development and their assembly into functional networks.

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“…MACS was performed according to the manufacturer's instruction (Miltenyi Biotec) with some modifications as shown previously (Fang et al, 2022). In brief, 4 weeks old mice were perfused with cold Hank's balanced salt solution without Ca 2+ and Mg 2+ (HBSS, H6648, Gibco) and cortices were dissected in ice cold HBSS.…”

Section: Magnetic-associated Cell Sorting (Macs) Of Glial Cellsmentioning

confidence: 99%

Specific detection and deletion of the Sigma-1 receptor in neurons and glial cells for functional characterization in vivo

Liu

Guo

Fang

et al. 2022

Preprint

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The chaperon protein sigma-1 receptor (S1R) has been discovered over forty years ago. Recent pharmacological studies using S1R exogenous ligands demonstrated a promising therapeutical potential of targeting the S1R for several neurological disorders. Although intensive in vitro studies have revealed S1Rs are mainly residing at the membrane of the endoplasmic reticulum (ER), the cell-specific in vivo expression pattern of S1Rs is still unclear, mainly due to the lack of a reliable detection method which also prevented a comprehensive functional analysis. Here, first, we identified a highly specific antibody using S1R knockout (KO) mice and established an immunohistochemical protocol involving a 1% SDS antigen retrieval step. Second, we characterized the S1R expression in the mouse brain and can demonstrate that the S1R is widely expressed: in principal neurons, interneurons, and all glial cell types. Finally, we generated a novel Cre-dependent S1R conditional KO mouse (S1R flox) to study cell type-specific functions of the S1R. As a proof of concept, we successfully ablated S1R expressions in neurons or microglia employing neuronal and microglial Cre-expressing mice, respectively. In summary, we provide powerful tools to cell-specifically detect, delete and functionally characterize S1R in vivo.

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Impaired bidirectional communication between interneurons and oligodendrocyte precursor cells affects social cognitive behavior

Cited by 44 publications

References 68 publications

Brain injuries and complex motor learning suppress Olig2 in a subpopulation of oligodendrocyte precursor cells

Brain injuries and complex motor learning suppress Olig2 in a subpopulation of oligodendrocyte precursor cells

Origin, Development, and Synaptogenesis of Cortical Interneurons

Specific detection and deletion of the Sigma-1 receptor in neurons and glial cells for functional characterization in vivo

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