Potential mechanism of radiation-induced persistent learning and memory deficit. Schematic presentation of long-term effects of ionising radiation on the brain combining all presented data from 1.0 Gy-exposed hippocampus is shown. Microglia and astrocytes regulate neuronal activity by influencing cytokines (TNFα) or neurotrophic factors. This results in changes in the receptor profile of G protein coupled receptors (GPCR’s) and AMPA and NMDA receptors which are important for steady state signal transmission from neuron to neuron. In turn, this affects long-term potentiation/long-term depression (LTP/LTD) and leads to alterations in synaptic morphology (actin reorganisation via Rac1-Cofilin-pathway, changes in synaptic scaffold proteins such as PSD-95/MAP-2) and synaptic plasticity (CREB pathway). Phosphorylated CREB (CREB-P) regulates the expression of miR-132 and immediate early genes such as c-Fos, Arc and Crem affecting both synaptic morphology and adult neurogenesis. The connecting arrows are based on the literature mentioned in the discussion; genetic, chemical or pharmacological manipulations have to be performed to ascertain these links in detail.