Modulating Efr3a Expression In The Brain Affects Parvalbumin Neuron Development And Behaviors In Mice

Pho eighty-five requiring 3（Efr3）is an important auxiliary protein which can keep phosphatidylinositol 4-kinase alpha（PIK4A）on the plasma membrane by forming a complex with a scaffold protein.It plays a key role in the metabolism of phosphoinositide on the plasma membrane.Although Efr3 is highly expressed in the brain,its roles in the brain are unclear.In mammalian cells,Efr3 has two subtypes:pho eighty-five requiring 3a（Efr3a）and pho eighty-five requiring 3b（Efr3b）.We found previously that brain-specific ablation of Efr3a enhanced the brain-derived neurotrophic factor（BDNF）-tyrosine kinase receptor B（TrkB）pathway.To further investigate the roles of Efr3a in the brain,we crossed Ca MKII-cre mice with Efr3a^f/fmice to delete Efr3a specifically in excitatory neurons.Results of western blot analysis showed that excitatory neurons-specific ablation of Efr3a had no effect on the expression of BDNF,TrkB and its downstream molecules such as protein kinase B（PKB/AKT）and mitogen-activated protein kinase（MAPK）in the hippocampus.Immunostaining results showed that specific ablation of Efr3a in excitatory neurons had no effect on the number of parvalbumin（PV）neurons in the hippocampus.Behavioral tests revealed that ablation of Efr3a in excitatory neurons did not affect mouse behaviors（locomotor ability,anxiety-like behaviors,social interaction）.These results indicate that Efr3a in excitatory neurons did not play major roles in the brain.Next,we evaluated the effects of Efr3a overexpress.We found that overexpressing Efr3a reduced the expression of TrkB,p-Akt and p-MAPK,suggesting that the BDNF-TrkB pathway is down regulated.Immunostaining results showed that overexpression of Efr3a affects the number of PV-positive neurons in the hippocampus.Taken together,our data suggest that Efr3a may affect PV neuron development by regulating the BDNF-TrkB pathway which is important for brain functions.However,Efr3a in excitatory neurons has little effect.Future studies are needed to further explore:（1）Whether and how Efr3a inγ-aminobutyric acid（GABA）ergic neurons affect BDNF-TrkB pathway?（2）Whether overexpression of Efr3a will affect mouse behaviors?...