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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Animals
  • Biomarkers
  • Brain / cytology*
  • Brain / diagnostic imaging
  • Brain / metabolism*
  • Brain / physiopathology
  • Calcium / metabolism*
  • Cerebrovascular Circulation
  • Cognition Disorders / genetics
  • Cognition Disorders / metabolism
  • Cognition Disorders / psychology
  • Gene Expression
  • Humans
  • Membrane Glycoproteins / genetics*
  • Membrane Glycoproteins / metabolism
  • Mice
  • Mice, Knockout
  • Middle Aged
  • Neurons / metabolism*
  • Protein Transport


  • Biomarkers
  • Membrane Glycoproteins
  • NPTN protein, human
  • Calcium