Differential distribution of phospholipase C beta isoforms and diaglycerol kinase-beta in rodents cerebella corroborates the division of unipolar brush cells into two major subtypes

Abstract

Sublineage diversification of specific neural cell classes occurs in complex as well as simply organized regions of the central and peripheral nervous systems; the significance of the phenomenon, however, remains insufficiently understood. The unipolar brush cells (UBCs) are glutamatergic cerebellar interneurons that occur at high density in vestibulocerebellum. As they are classified into subsets that differ in chemical phenotypes, intrinsic properties, and lobular distribution, they represent a valuable neuronal model to study subclass diversification. In this study we show that cerebellar UBCs of adult rats and mice form two subclasses – type I and type II UBCs - defined by somatodendritic expression of calretinin (CR), mGluR1α, phospholipases PLCβ1 and PLCβ4, and diacylglycerol kinase-beta (DGKβ). We demonstrate that PLCβ1 is associated only with the CR+ type I UBCs while PLCβ4 and DGKβ are exclusively present in mGluR1α+ type II UBCs. Notably, all PLCβ4+ UBCs, representing about 2/3 of entire UBC population, also express mGluR1α. Furthermore, our data show that the sum of CR+ type I UBCs and mGluR1α+ type II UBCs accounts for the entire UBC class identified with Tbr2 immunolabeling. The two UBC subtypes also show a very different albeit somehow overlapping topographical distribution as illustrated by detailed cerebellar maps in this study. Our data not only complement and extend the previous knowledge on the diversity and subclass specificity of the chemical phenotypes within the UBC population but provide a new angle to the understanding of the signaling networks in type I and type II UBCs.

ON and OFF Unipolar Brush Cells Transform Multisensory Inputs to the Auditory System

“…To classify ON and OFF UBCs using previous histochemical criteria (Diño et al, 1999; Nunzi et al, 2002; Sekerková et al, 2014), we correlated the ON/OFF subtype with the presence or absence of an mGluR1α - activated current (Schwartz et al, 2012). After identifying the response of each cell by glutamate application, the puff pipette was switched to 200 μM (S)-3,5-DHPG, a selective group I mGluR agonist (Fig 4 A ).…”

“…Thus, UBCs seemed to amplify and prolong multisensory signals from mossy fibers to their target granule cells. However, later immunohistochemical studies revealed two distinct UBC populations: calretinin + UBCs and mGluR1α + UBCs (Nunzi et al, 2002; Diño and Mugnaini, 2008; Sekerková et al, 2014). A recent study characterized intrinsic (nonsynaptic) electrophysiological properties of these subtypes in cerebellum (Kim et al, 2012).…”

Redefining the cerebellar cortex as an assembly of non-uniform Purkinje cell microcircuits

“…They are most numerous in the nodulus (vermal lobules Xa and Xb), ventral uvula (vermal lobule IXd), flocculus, and ventromedial paraflocculus 29 . Additionally, three molecularly distinct UBC subtypes that express either calretinin, metabotropic glutamate receptor 1 α (mGluR1α) or phospholipase Cβ4 (PLCβ4) have been found, each with their own topographical distribution 29–33, see REF 34 for a recent review). As UBCs are located primarily in areas related to vestibular and oculomotor function, this suggests that the operation of the cerebellar cortex is not solely related to regional differences in the pattern of inputs and outputs, and that certain areas may contain distinct cell types to allow different computational processes to aid specific functions.…”

Phospholipase C Beta 1: a Candidate Signature Gene for Proneural Subtype High-Grade Glioma

“…It is expressed predominantly in neurons of the central nervous system and is barely detectable in other tissues or cell types [14–17]. The PLCβ1 protein catalyzes the formation of inositol 1,4,5-trisphosphate and diacylglycerol from phosphatidylinositol 4,5-bisphosphate (PIP2), which plays an important role in the intracellular signal transduction of extracellular signals, such as metabotropic glutamate.…”