The review presents the mechanisms of participation of ions (Na+, K+, and Ca2+) in the processes of synaptic plasticity in the postsynaptic neuron during long-term potentiation and long-term depression. It is assumed that the main participants are AMPA and NMDA receptors, voltage-dependent Na+, K+, Ca2+ channels, Ca2+ and Na+-activated K+ channels, ATP-sensitive K+ channels, and Ca2+ channels of the endoplasmic reticulum. The review provides their molecular characteristics and discusses their role in long-term potentiation and long-term depression. The significance of changes in the intracellular ratio [Na+]i/[K+]i and Ca2+-dependent mechanism are considered for the first time from the signal formation to the level of gene expression. We believe that additional research is needed to identify a subset of neuronal genes whose differential expression contributes to synaptic plasticity, which is implemented with the participation of [Na+]i/[K+]i-sensitive Ca2+-independent “excitation–transcription coupling” mechanism.