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Sci Rep. 2017 Aug 4;7(1):7273. doi: 10.1038/s41598-017-07839-9.

Neuroplastin deletion in glutamatergic neurons impairs selective brain functions and calcium regulation: implication for cognitive deterioration.

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Department of Neurochemistry and Molecular Biology, Leibniz Institute for Neurobiology, Magdeburg, Germany.
Croatian Institute for Brain Research, School of Medicine, University of Zagreb, Zagreb, Croatia.
Department of Systems Physiology; Special Laboratories, Leibniz Institute for Neurobiology, Magdeburg, Germany.
Department of Molecular Biology Techniques, Leibniz Institute for Neurobiology, Magdeburg, Germany.
Neurogenetics, Leibniz Institute for Neurobiology, Magdeburg, Germany.


The cell adhesion molecule neuroplastin (Np) is a novel candidate to influence human intelligence. Np-deficient mice display complex cognitive deficits and reduced levels of Plasma Membrane Ca2+ ATPases (PMCAs), an essential regulator of the intracellular Ca2+ concentration ([iCa2+]) and neuronal activity. We show abundant expression and conserved cellular and molecular features of Np in glutamatergic neurons in human hippocampal-cortical pathways as characterized for the rodent brain. In Nptn lox/loxEmx1Cre mice, glutamatergic neuron-selective Np ablation resulted in behavioral deficits indicating hippocampal, striatal, and sensorimotor dysfunction paralleled by highly altered activities in hippocampal CA1 area, sensorimotor cortex layers I-III/IV, and the striatal sensorimotor domain detected by single-photon emission computed tomography. Altered hippocampal and cortical activities correlated with reduction of distinct PMCA paralogs in Nptn lox/loxEmx1Cre mice and increased [iCa2+] in cultured mutant neurons. Human and rodent Np enhanced the post-transcriptional expression of and co-localized with PMCA paralogs in the plasma membrane of transfected cells. Our results indicate Np as essential for PMCA expression in glutamatergic neurons allowing proper [iCa2+] regulation and normal circuit activity. Neuron-type-specific Np ablation empowers the investigation of circuit-coded learning and memory and identification of causal mechanisms leading to cognitive deterioration.

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