Postnatal Maternal Separation Enhances Tonic GABA Current Of Cortical Layer5Pyramidal Neurons In Juvenile Rats And Promotes Genesis Of GABAergic Neurons In Neocortical Molecular Layer And Sub Ventricular Zone In Adult Rats

OBJECTIVES:In the present study, we investigated PMS’s effects on1) explorative activity and anxiety-related behaviors;2) cell proliferation, differentiation, and survival of new born cells in the brain; and3) the tonic GAB A currents of L5pyramidal neurons in adolescent animals following neonatal PMS exposure, aiming to understand the developmental origin of certain psychiatric disorders and its underlying mechanisms in children.METHODS:Whole litters were randomly assigned to one of three groups:1h maternal separation (MSlh),3h maternal separation (MS3h) and control group from P2until P15. On P31-54, the rats were performed by the tasks including open field test, elevated plus maze test, sucrose preference test, and forced swimming test. Brain slicing, immunofluorescence staining and whole-cell patch clamp were carried out. Ki-67/BrdU and GAD-67/BrdU positively co-labeled cells were counted in the cortical L1, SVZ and DG at40-times magnification. The number of positive cells was normalized to the total numbers of Ki-67or BrdU positive cells respectively in each region. To examine the changes in tonic GAB A current after PMS, we made whole-cell voltage-clamp recordings from L5neocortical pyramidal cells at two postnatal ages:juvenile (P7-10) and mature (P30-35).RESULTS:In the present study, PMS did change explorative activity and anxiety in the open field and elevated plus maze tests. Secondly, PMS could increase the cell proliferation in SVZ, cortical LI and hippocampal DG in the adult brain. Furthermore, PMS could promote the new born cells to differentiate into GABAergic neurons, and PMS adult rats maintained higher ratios of GABAergic neurons among the survive cells newly born within5days post PMS. Finally, PMS could increase the tonic currents at P7-10and P30-35in cortical L5pyramidal cells. PMS also could significantly increase the change in standard deviation compared to the controls,CONCLUSION:Our results suggest that new born GABAergic neurons and the low GABA concentration-activated tonic currents that dominate GABAergic transmission in neocortical pyramidal cells may play key roles in the development of certain psychiatric disorders in children after PMS.