PirB regulates asymmetries in hippocampal circuitry.

Hikari Ukai,Noritaka Nitta,Keiko Hirayama,Ryuichi Shigemoto,Michiyo Kasayuki,Ken Wakita,Shihomi Kawashima,Shunichi Sugimoto,Ryohei Oogi,Isao Ito,Kanako Chikamatsu,Shotaro Aino,Tsuneyuki Koga,Toshiyuki Takai,Matthew Julian Case,Aiko Kawahara,Masahiro Miyabe

doi:10.1371/journal.pone.0179377

Abstract

Left–right asymmetry is a fundamental feature of higher-order brain structure; however, the molecular basis of brain asymmetry remains unclear. We recently identified structural and functional asymmetries in mouse hippocampal circuitry that result from the asymmetrical distribution of two distinct populations of pyramidal cell synapses that differ in the density of the NMDA receptor subunit GluRε2 (also known as NR2B, GRIN2B or GluN2B). By examining the synaptic distribution of ε2 subunits, we previously found that β2-microglobulin-deficient mice, which lack cell surface expression of the vast majority of major histocompatibility complex class I (MHCI) proteins, do not exhibit circuit asymmetry. In the present study, we conducted electrophysiological and anatomical analyses on the hippocampal circuitry of mice with a knockout of the paired immunoglobulin-like receptor B (PirB), an MHCI receptor. As in β2-microglobulin-deficient mice, the PirB-deficient hippocampus lacked circuit asymmetries. This finding that MHCI loss-of-function mice and PirB knockout mice have identical phenotypes suggests that MHCI signals that produce hippocampal asymmetries are transduced through PirB. Our results provide evidence for a critical role of the MHCI/PirB signaling system in the generation of asymmetries in hippocampal circuitry.

Highlights

Left–right (L–R) asymmetry in brain structure and function is a central topic in neuroscience, and recent studies have identified possible molecular correlates of such asymmetry in the mouse hippocampus [1,2,3]
Our analysis revealed no significant differences in the input–output relationship between paired immunoglobulin-like receptor B (PirB) KO and wild type (WT) mice
We examined the amplitudes of NMDA EPSCs at CA1 pyramidal neuron synapses in hippocampal slices prepared from PirB KO and ventral hippocampal commissure-transected (VHCT) WT mice

Summary

Introduction

Left–right (L–R) asymmetry in brain structure and function is a central topic in neuroscience, and recent studies have identified possible molecular correlates of such asymmetry in the mouse hippocampus [1,2,3]. While ε2-non-dominant synapses show significant long-term depression (LTD) in response to low-frequency stimulation (1 Hz), ε2-dominant synapses do not [8]. These two populations of synapses are located asymmetrically in hippocampal circuitry, depending on the hemispheric origin of presynaptic inputs (referred to as L–R asymmetry) and on the cell polarity of the postsynaptic neuron (referred to as apical–basal, or A–B, asymmetry; Fig 1, WT)

Methods

Results

Conclusion