PirB regulates asymmetries in hippocampal circuitry

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.

Predominant synaptic potentiation and activation in the right central amygdala are independent of bilateral parabrachial activation in the hemilateral trigeminal inflammatory pain model of rats

“… 65 Functional and morphological asymmetry has been reported for various structures in the rodent, fish, and human brain. 66 – 71 Although the functional and cellular mechanisms underlying such asymmetry remains largely undetermined (but see Ukai et al. 67 ), this would imply asymmetric ontogenic mechanisms during network formation in the embryonic stage.…”

“… 66 – 71 Although the functional and cellular mechanisms underlying such asymmetry remains largely undetermined (but see Ukai et al. 67 ), this would imply asymmetric ontogenic mechanisms during network formation in the embryonic stage. 72 Importantly, the present results do not mean that the left CeA does not receive nociceptive information.…”

Molecular and cellular basis of left–right asymmetry in vertebrates

“…A molecular asymmetry detected in the mouse brain is the distribution of the NMDA subtype of glutamate receptor in the hippocampus. 139 , 140 ) The synaptic distribution of the NMDA receptor subunit GluRε2 (NR2B) in the adult hippocampus is thus asymmetric between the left and right hemispheres as well as between the apical and basal dendrites of individual neurons. L-R asymmetry in hippocampal circuits may be required for spatial learning and memory, 141 ) and it is disrupted in the iv / iv mutant mouse, which lacks motile cilia and thus does not develop nodal flow at the LRO, 142 ) suggesting that such asymmetry depends on the action of motile cilia.…”

Enigma of Pyramidal Neurons: Congruence to Molecular, Cellular, Physiological, Cognitive and Psychological Function

“…It has been previously proposed that sophisticated neuronal circuits associated with non-linear properties of dendrites enable cortical neurons to recognize multiple independent patterns and robust sequence memory The morphology of PyrNs concerning the function was the focus of long-term attention in neuroscience. The major studied structural features were dendritic arborization, synaptic connectivity, and axonal network [84,[114][115][116]. Apical and basal segments of the dendritic tree, complemented by the relative orientation of presynaptic and postsynaptic neurons, were carefully studied [5,6,94,[116][117][118][119][120][121][122].…”