TY - JOUR
T1 - Celsr3 is required for Purkinje cell maturation and regulates cerebellar postsynaptic plasticity
AU - Zhou, Qinji
AU - Qin, Jingwen
AU - Liang, Yaying
AU - Zhang, Wei
AU - He, Siyuan
AU - Tissir, Fadel
AU - Qu, Yibo
AU - Zhou, Libing
N1 - Publisher Copyright:
© 2021 The Author(s)
PY - 2021/7/23
Y1 - 2021/7/23
N2 - Atypical cadherin Celsr3 is critical for brain embryonic development, and its role in the postnatal cerebellum remains unknown. Using Celsr3-GFP mice, Celsr3 shows high expression in postnatal Purkinje cells (PCs). Mice with conditional knockout (cKO) of Celsr3 in postnatal PCs exhibit deficit in motor coordination and learning, atrophic PC dendrites, and decreased synapses. Whole-PC recording in cerebellar slices discloses a reduction frequency of mEPSC and defective postsynaptic plasticity (LTP and LTD) in Celsr3 cKO mutants. Wnt5a perfusion enhances LTP formation, which could be occluded by cAMP agonist and diminished by cAMP antagonist in control, but not in Celsr3 cKO or Fzd3 cKO cerebellar slices. Celsr3 cKO resulted in the failure of mGluR1 agonist-induced LTD and paired stimulation-induced PKCα overexpression in PC dendrites, and downregulation of mGluR1 expression compvared to controls. In conclusion, Celsr3 is required for PCs maturation and regulates postsynaptic LTP and LTD through Wnt5a/cAMP and mGluR1/PKCα signaling respectively.
AB - Atypical cadherin Celsr3 is critical for brain embryonic development, and its role in the postnatal cerebellum remains unknown. Using Celsr3-GFP mice, Celsr3 shows high expression in postnatal Purkinje cells (PCs). Mice with conditional knockout (cKO) of Celsr3 in postnatal PCs exhibit deficit in motor coordination and learning, atrophic PC dendrites, and decreased synapses. Whole-PC recording in cerebellar slices discloses a reduction frequency of mEPSC and defective postsynaptic plasticity (LTP and LTD) in Celsr3 cKO mutants. Wnt5a perfusion enhances LTP formation, which could be occluded by cAMP agonist and diminished by cAMP antagonist in control, but not in Celsr3 cKO or Fzd3 cKO cerebellar slices. Celsr3 cKO resulted in the failure of mGluR1 agonist-induced LTD and paired stimulation-induced PKCα overexpression in PC dendrites, and downregulation of mGluR1 expression compvared to controls. In conclusion, Celsr3 is required for PCs maturation and regulates postsynaptic LTP and LTD through Wnt5a/cAMP and mGluR1/PKCα signaling respectively.
KW - Cognitive neuroscience
KW - Developmental neuroscience
UR - http://www.scopus.com/inward/record.url?scp=85109916850&partnerID=8YFLogxK
U2 - 10.1016/j.isci.2021.102812
DO - 10.1016/j.isci.2021.102812
M3 - Article
AN - SCOPUS:85109916850
SN - 2589-0042
VL - 24
JO - iScience
JF - iScience
IS - 7
M1 - 102812
ER -