First Author | Herrera-Molina R | Year | 2017 |
Journal | Sci Rep | Volume | 7 |
Issue | 1 | Pages | 7273 |
PubMed ID | 28779130 | Mgi Jnum | J:256519 |
Mgi Id | MGI:6108706 | Doi | 10.1038/s41598-017-07839-9 |
Citation | Herrera-Molina R, et al. (2017) Neuroplastin deletion in glutamatergic neurons impairs selective brain functions and calcium regulation: implication for cognitive deterioration. Sci Rep 7(1):7273 |
abstractText | 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 Ca(2+) ATPases (PMCAs), an essential regulator of the intracellular Ca(2+) concentration ([iCa(2+)]) 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 [iCa(2+)] 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 [iCa(2+)] 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. |