Critical periods and resilience to stress depend on SATB2

As kids and juveniles, all of us were able to accumulate extensive knowledge within incredible short periods of time, knowledge that accompanies us throughout life and determines our path of life. In order to process such a flood of information kid brains are especially sensitive for environmental stimuli during defined developmental periods. In such phases, known as critical periods, brains are also particularly sensitive to stress. It is well-demonstrated that exposure to toxic stress during puerile and juvenile years exerts livelong negative effects on cognition and increases risk for neuropsychiatric disorders in adulthood. In our project, we aim to study molecular and cellular processes underlying the critical period for learning in the hippocampus, a brain structure that plays a central role for processing of environmental stimuli. In particular, we will test whether the three- dimensional folding of DNA undergoes modifications within the cell nucleus of hippocampal nerve cells during the critical period. The three-dimensional structure of DNA exerts a strong influence on how genetic information is utilized within the cell nucleus. Appropriate deployment of genes forms the basis for the correct functioning of each and every nerve cell and consequently for all higher functions of our brains. We will also investigate whether the 3D-folding of DNA, once it is established during the critical period, remains stable later on in life. By this novel form of epigenetic memory mechanism juvenile experiences might influence adult function of the hippocampus as well as its sensitivity to stress. In our experiments we will employ transgenic mice in which the protein SATB2 is genetically deleted either prior to or after the critical period. In previous work we already were able to demonstrate that SATB2 determines the 3D-structure of DNA and regulates expression of a large number of genes. If successful, our project will contribute to our understanding at molecular level of why our experiences as kids and juveniles have lifelong impact on us. Such knowledge might subsequently be applied to provide support to kids with learning difficulties and to lower risks for psychiatric diseases such as schizophrenia in adults.