Differential effect of FHM2 mutation on synaptic plasticity recorded in distinct hippocampal regions

Introduction. Familial hemiplegic migraine 2 (FHM2) is a pathology linked to mutation of the ATP1A2 gene producing loss-of-function of the α2 Na+/K+-ATPase (NKA). W887R/+ knock-in (KI) mice are used to model the FHM2 condition and are characterized by 50% reduced NKA expression in glial cells and reduced rate of K+ and glutamate clearance by astrocytes. These alterations might, in turn, produce synaptic changes in synaptic transmission and plasticity. Memory and learning deficits observed in FHM patients could be ascribed to a possible alteration of hippocampal neuronal plasticity and measuring possible changes of long-term potentiation (LTP) in FHM2 KI mice might provide insights to strengthen this link. Results. Here we have investigated synaptic plasticity in distinct hippocampal regions in FHM2 KI mice. We show that the dentate gyrus LTP of FHM2 mice is abnormally increased in comparison with control animals. Conversely, in the CA1 area KI and WT mice express LTP of similar amplitude. Conclusions. The FHM2 KI mice show region-dependent hippocampal plasticity abnormality, which might underlie some of the memory deficits observed in familial migraine.