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Keywords:

  • brain;
  • Gq-coupled receptor;
  • immunohistochemistry;
  • mouse;
  • phosphoinositide;
  • phospholipase Cβ1

Abstract

Upon activation of receptors coupled to the Gq subclass of G proteins, phospholipase C (PLC)β hydrolyses membrane phospholipid to yield a pair of second messengers, inositol 1,4,5-trisphosphate and 1,2-diacylglycerol. Of four PLCβ isoforms, PLCβ1 is transcribed predominantly in the telencephalon and its gene inactivation in mice impairs metabotropic glutamate receptor- and muscarinic acetylcholine receptor-dependent hippocampal oscillations, endocannabinoid production in the hippocampus and barrel formation in the somatosensory cortex. Here we examined cellular and subcellular distributions of PLCβ1 in adult mouse brains. In the telencephalon, high levels of PLCβ1 were observed in principal neurons, including pyramidal cells in the cortex and hippocampus, granule cells and mossy cells in the dentate gyrus, and medium spiny neurons in the caudate-putamen, whereas most interneurons had low levels of or were negative for PLCβ1 and, instead, expressed PLCβ4. By immunofluorescence, tiny clusters of PLCβ1 were distributed in somatodendritic compartments of principal neurons and positioned close to those of metabotropic glutamate receptor 5, muscarinic acetylcholine receptor M1 and diacylglycerol lipase-α, respectively. Immunoelectron microscopy revealed that PLCβ1 was often associated with the smooth endoplasmic reticulum, cell membrane or postsynaptic density. In particular, it was highly accumulated at the perisynapse of dendritic spines forming asymmetrical synapses. In the cerebellum, PLCβ1 was generally low but was enriched in axons and dendrites of basket cells. These results suggest that PLCβ1 is the key effector in telencephalic principal neurons and cerebellar interneurons. Furthermore, the well-orchestrated molecular arrangement appears to be the anatomical basis for the specificity, efficiency and convergence of the neuronal phosphoinositide signaling system.