Left-right asymmetry of the hippocampal synapses with differential subunit allocation of glutamate receptors

Abstract

Left-right asymmetry of the brain has been studied mostly through psychological examination and functional imaging in primates, leaving its molecular and synaptic aspects largely unaddressed. Here, we show that hippocampal CA1 pyramidal cell synapses differ in size, shape, and glutamate receptor expression depending on the laterality of presynaptic origin. CA1 synapses receiving neuronal input from the right CA3 pyramidal cells are larger and have more perforated PSD and a GluR1 expression level twice as high as those receiving input from the left CA3. The synaptic density of GluR1 increases as the size of a synapse increases, whereas that of NR2B decreases because of the relatively constant NR2B expression in CA1 regardless of synapse size. Densities of other major glutamate receptor subunits show no correlation with synapse size, thus resulting in higher net expression in synapses having right input. Our study demonstrates universal left-right asymmetry of hippocampal synapses with a fundamental relationship between synaptic area and the expression of glutamate receptor subunits.

Hippocampal Structure, Metabolism, and Inflammatory Response after a 6-Week Intense Aerobic Exercise in Healthy Young Adults: A Controlled Trial

“…Kawakami et al 37 observed an asymmetric synaptic distribution of N-methyl-D-aspartate receptor between the left and right adult mouse hippocampus. Shinohara et al 38 reported that hippocampal CA1 synapses, which receive neuronal input from the right CA3 pyramidal cells are larger and have markedly higher expression level from glutamate receptor GluR1 than those which receive input from the left CA3. Thus, we can only speculate that this lateralized molecular pattern might have contributed to our findings.…”

Functional MRI of long-term potentiation: imaging network plasticity

“…Although some reports start to show an intriguing bilateral asymmetry in rat hippocampus [88][89][90][91], little is known about its functional relevance. Two commissural systems connect the hippocampus, the CA3 contralateral projection to CA1, CA2 and CA3, and the contralateral DG projection mainly formed by hilar mossy cells (MCs).…”

Smaller Dentate Gyrus and CA2 and CA3 Volumes Are Associated with Kynurenine Metabolites in Collegiate Football Athletes

“…25,30 Intriguingly, our observation of left lateralized volume differences is also consistent with work in animals and tissue culture experiments on NMDA receptor subunits. NMDA receptors that contain NR2B subunits are more densely expressed in the left hippocampus than in the right, 31,32 and NMDA-mediated excitotoxicity is dependent on NMDA receptors containing NR2B subunits. 33 Therefore, the left hippocampus may be more susceptible to excitotoxicity-induced injury.…”