Simulation model of CA1 pyramidal neurons reveal opposing roles for the Na+/Ca2+ exchange current and Ca2+-activated K+ current during spike-timing dependent synaptic plasticity

PloS One
Damien M O'Halloran

Abstract

Sodium Calcium exchanger (NCX) proteins utilize the electrochemical gradient of Na+ to generate Ca2+ efflux (forward mode) or influx (reverse mode). In mammals, there are three unique NCX encoding genes-NCX1, NCX2, and NCX3, that comprise the SLC8A family, and mRNA from all three exchangers is expressed in hippocampal pyramidal cells. Furthermore, mutant ncx2-/- and ncx3-/- mice have each been shown to exhibit altered long-term potentiation (LTP) in the hippocampal CA1 region due to delayed Ca2+ clearance after depolarization that alters synaptic transmission. In addition to the role of NCX at the synapse of hippocampal subfields required for LTP, the three NCX isoforms have also been shown to localize to the dendrite of hippocampal pyramidal cells. In the case of NCX1, it has been shown to localize throughout the basal and apical dendrite of CA1 neurons where it helps compartmentalize Ca2+ between dendritic shafts and spines. Given the role for NCX and calcium in synaptic plasticity, the capacity of NCX splice-forms to influence backpropagating action potentials has clear consequences for the induction of spike-timing dependent synaptic plasticity (STDP). To explore this, we examined the effect of NCX localization, density, an...Continue Reading

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