Phospholipase C I33 is Required for Climbing Fiber Synapse Elimination in Aldolase C-positive Compartments of the Developing Mouse Cerebellum

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 -P7 to -P11 (early phase of CF elimination) and from -P12 to -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 I33 (PLCI33) and I34 (PLCI34) are expressed complementarily in PCs of aldolase C (Aldoc)-positive (+) and Aldoc-negative (-) cerebellar compartments, respectively. PLCI34 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 PLCI33 and Aldoc in CF synapse elimination are unknown. Here, we investigated CF innervation of PCs in AldoctdTomato knock-in mice that underwent lentivirus-mediated knockdown (KD) of PLCI33 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 PLCI33-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 PLCI33 is required for the late phase of CF elimination in Aldoc (+) PCs. This article is part of a Special Issue entitled: In Memoriam: Masao Ito?A Visionary Neuroscientist with a Passion for the Cerebellum. ? 2020 IBRO. Published by Elsevier Ltd. All rights reserved.

Automated summary

Research indicates that the expression levels of phospholipase C I33 (PLC I33) can impact the extent of climbing fiber (CF) innervation in Purkinje cells in the cerebellum of mice, consequently affecting the elimination of CF synapses.