Majority of studies on synaptic and cognitive functions have been focusing on the critical role of calcium ion and its channels in such functions.Other divalent cations such as Zinc and Magnesium are essential for proper functioning of many tissues and organs including the central nervous system.Few studies,however,have tried to investigate the potential role of channels involved in divalent cations homeostasis(other than calcium ion homeostasis)in synaptic and cognitive functions.Here,we show that knock down of a divalent cation channel in cultured hippocampal neurons reduced the density of structural and functional synapses without affecting neuronal cell survival and/or their dendritic complexity.In intact animals,hippocampal knock down of the di-ion channel reduced synaptic density and plasticity in the hippocampus and impaired learning and memory abilities.Molecularly,we found significant reduction in the expression of BDNF mRNA,but not NGF.Culture media supplied with low concentrations of BDNF proteins rescued the reductions in synaptic density following knock down of the ion channel.Interestingly,we also found that the protein expression of this di-ion channel was significantly reduced in the hippocampus of aging rats,APP/PS1 mice(a mouse model of Alzheimers disease),and in hippocampal postmortem samples from human subjects with Alzheimers disease.Our results demonstrate for the first time an important role for a divalent-cation-channel(other than the classical calcium ion channels)in controlling synaptic and cognitive functions probably via BDNF dependent mechanisms.Results also suggest that reductions in the expression of this channel might contribute to the cognitive impairments associated with normal aging and/or with Alzheimers disease.