PMID- 32360594
OWN - NLM
STAT- MEDLINE
DCOM- 20210514
LR  - 20220531
IS  - 1873-7544 (Electronic)
IS  - 0306-4522 (Linking)
VI  - 462
DP  - 2021 May 10
TI  - Phospholipase C beta3 is Required for Climbing Fiber Synapse Elimination in Aldolase 
      C-positive Compartments of the Developing Mouse Cerebellum.
PG  - 36-43
LID - S0306-4522(20)30268-2 [pii]
LID - 10.1016/j.neuroscience.2020.04.035 [doi]
AB  - In the cerebellum of neonatal mice, multiple climbing fibers (CFs) form 
      excitatory synapses on each Purkinje cell (PC). Only one CF is strengthened in 
      each PC from postnatal day 3 (P3) to P7, whereas the other weaker CFs are 
      eliminated progressively from  approximately P7 to  approximately P11 (early phase of CF elimination) and 
      from  approximately P12 to  approximately P17 (late phase of CF elimination). Type 1 metabotropic glutamate 
      receptor (mGluR1) triggers a canonical pathway in PCs for the late phase of CF 
      elimination. Among downstream signaling molecules of mGluR1, phospholipase C beta3 
      (PLCbeta3) and beta4 (PLCbeta4) are expressed complementarily in PCs of aldolase C 
      (Aldoc)-positive (+) and Aldoc-negative (-) cerebellar compartments, 
      respectively. PLCbeta4 is reported to mediate the late phase of CF elimination in 
      the anterior half of the cerebellar vermis which corresponds to the Aldoc (-) 
      region. However, roles of PLCbeta3 and Aldoc in CF synapse elimination are unknown. 
      Here, we investigated CF innervation of PCs in Aldoc-tdTomato knock-in mice that 
      underwent lentivirus-mediated knockdown (KD) of PLCbeta3 in PCs during postnatal 
      development. By recording CF-mediated excitatory postsynaptic currents from PCs 
      and immunostaining CF synaptic terminals, we found that significantly higher 
      percentage of PCs with PLCbeta3-KD remained multiply innervated by CFs in Aldoc (+) 
      compartments after P12, which was accompanied by impaired elimination of somatic 
      CF synapses and reduced dendritic CF translocation. In contrast, deletion of 
      Aldoc had no effect on CF synapse elimination. These results suggest that PLCbeta3 
      is required for the late phase of CF elimination in Aldoc (+) PCs.
CI  - Copyright (c) 2020 IBRO. Published by Elsevier Ltd. All rights reserved.
FAU - Rai, Yurie
AU  - Rai Y
AD  - Depertment of Neurophysiology, Graduate School of Medicine, The University of 
      Tokyo, Tokyo 113-0033, Japan.
FAU - Watanabe, Takaki
AU  - Watanabe T
AD  - Depertment of Neurophysiology, Graduate School of Medicine, The University of 
      Tokyo, Tokyo 113-0033, Japan; International Research Center for Neurointelligence 
      (IRCN), The University of Tokyo Institutes for Advanced Study (UTIAS), The 
      University of Tokyo, Tokyo 113-0033, Japan.
FAU - Matsuyama, Kyoko
AU  - Matsuyama K
AD  - Depertment of Neurophysiology, Graduate School of Medicine, The University of 
      Tokyo, Tokyo 113-0033, Japan.
FAU - Sakimura, Kenji
AU  - Sakimura K
AD  - Department of Cellular Neurobiology, Brain Research Institute, Niigata 
      University, Niigata 951-8585, Japan.
FAU - Uesaka, Naofumi
AU  - Uesaka N
AD  - Depertment of Neurophysiology, Graduate School of Medicine, The University of 
      Tokyo, Tokyo 113-0033, Japan; International Research Center for Neurointelligence 
      (IRCN), The University of Tokyo Institutes for Advanced Study (UTIAS), The 
      University of Tokyo, Tokyo 113-0033, Japan.
FAU - Kano, Masanobu
AU  - Kano M
AD  - Depertment of Neurophysiology, Graduate School of Medicine, The University of 
      Tokyo, Tokyo 113-0033, Japan; International Research Center for Neurointelligence 
      (IRCN), The University of Tokyo Institutes for Advanced Study (UTIAS), The 
      University of Tokyo, Tokyo 113-0033, Japan. Electronic address: 
      mkano-tky@m.u-tokyo.ac.jp.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200429
PL  - United States
TA  - Neuroscience
JT  - Neuroscience
JID - 7605074
RN  - EC 3.1.4.11 (Phospholipase C beta)
RN  - EC 3.1.4.11 (Plcb3 protein, mouse)
RN  - EC 4.1.2.13 (Fructose-Bisphosphate Aldolase)
SB  - IM
MH  - Animals
MH  - Cerebellum
MH  - *Fructose-Bisphosphate Aldolase
MH  - Mice
MH  - *Nerve Fibers
MH  - Phospholipase C beta
MH  - Purkinje Cells
MH  - Synapses
OTO - NOTNLM
OT  - PLCbeta3
OT  - Purkinje cell
OT  - aldolase C
OT  - climbing fiber
OT  - mouse
OT  - synapse elimination
EDAT- 2020/05/04 06:00
MHDA- 2021/05/15 06:00
CRDT- 2020/05/04 06:00
PHST- 2020/01/29 00:00 [received]
PHST- 2020/04/15 00:00 [revised]
PHST- 2020/04/21 00:00 [accepted]
PHST- 2020/05/04 06:00 [pubmed]
PHST- 2021/05/15 06:00 [medline]
PHST- 2020/05/04 06:00 [entrez]
AID - S0306-4522(20)30268-2 [pii]
AID - 10.1016/j.neuroscience.2020.04.035 [doi]
PST - ppublish
SO  - Neuroscience. 2021 May 10;462:36-43. doi: 10.1016/j.neuroscience.2020.04.035. 
      Epub 2020 Apr 29.