Yunlong Liu, Chi Ren, Guosong Liu, Nashat Abumaria
Department of basic medical research, School of Medicine, Tsinghua University, Beijing, China

Majority of studies on synaptic and cognitive functions have been focusing on the critical role of calcium ion and its channels in such functions. Magnesium ion, the fourth most abundant ion in the body and a cofactor for more than 300 enzymes, is essential for the proper functioning of many tissues and organs including the nervous system. In vitro studies demonstrate that elevation of extracellular magnesium ion ([Mg2+]o) within physiological range increases synaptic density and plasticity [1]. In intact animals, elevation of brain magnesium enhances synaptic plasticity and improves different forms of memories in young and aged rats [2-4]. These data highlight the importance of magnesium ion in synaptic and cognitive functions. Thus, we ought to identify genes, in hippocampal neurons, that are regulated by [Mg2+]o and study their potential implication in synaptic and cognitive functions. We have identified a group of genes belonging to different functional categories: ion channels, protein palmitoylation, protein transport, and mitochondria functions. Interestingly, knock down of one of the identified genes in cultured hippocampal neurons reduced the density of structural and functional synapses without affecting neuronal cell survival and/or dendritic complexity of the neurons. Molecularly, we found significant reduction in the expression of BDNF mRNA following the knock down of the gene in vitro. In intact animals, hippocampal knock down of the identified gene impaired different forms of hippocampus-dependent memory. Our results suggest that an ion channel, presumably involved in magnesium homeostasis, is critical for maintaining normal synapse density, BDNF expression and learning and memory abilities.

  1. Slutsky I et al. Enhancement of synaptic plasticity through chronically reduced Ca2+ flux during uncorrelated activity. Neuron 2004;44(5):835-49.
  2. Slutsky I, Abumaria N et al. Enhancement of learning and memory by elevating brain magnesium. Neuron 2010;65(2):165-77.
  3. Abumaria N et al. Effects of elevation of brain magnesium on fear conditioning, fear extinction, and synaptic plasticity in the infralimbic prefrontal cortex and lateral amygdala. J Neurosci 2011;31(42):14871-81.
  4. Abumaria N et al. Magnesium supplement enhances spatial-context pattern separation and prevents fear overgeneralization. Behav Pharmacol 2013;24(4):255-63.