Christoph Anacker, Ph.D.
Psychological stress is a major risk factor for the pathogenesis of psychiatric disorders, especially anxiety and depression. However, the neurobiological mechanisms by which stress changes the brain to cause differences in mood and behavior remain elusive.
To investigate these mechanisms at the molecular and cellular level, our lab combines neural circuit approaches with molecular techniques in transgenic mice, including in vivo calcium imaging, optogenetics, chemogenetics, next generation sequencing, and epigenetic analyses. Combining these techniques allows us to investigate the effects of stress and antidepressant treatments from molecules to cells, from cells to circuits, and from circuits to behavior. We are particularly interested in understanding how stress that is experienced early on in life can cause epigenetic changes in the brain that in turn exert long lasting effects on gene expression, and ultimately on the functional development of brain circuits involved in mood and anxiety-like behavior.
We recently found that the dentate gyrus region of the ventral hippocampus contains a specific population of ‘stress-responsive’ neurons that can cause anxiety-like behavior in mice. These stress-responsive cells can be silenced by adult hippocampal neurogenesis, which in turn causes resilience to the effects of chronic stress by inhibiting the ventral dentate gyrus (Anacker et al., 2018). We are now interested in understanding how early life experiences affect the development of these stress-responsive cells in the hippocampus and how these cells are modulated by effective antidepressant treatment. As part of this research, we are also using transgenic mice together with early life stress and adult stress paradigms to explore how ‘gene x environment’ interactions contribute to differences in the development of the hippocampus and of the wider neural circuitry underlying anxiety and depression, as well as to differences in antidepressant treatment responses.
Ultimately, our goal is to determine the neurodevelopmental mechanisms that contribute to individual differences in stress susceptibility and resilience, with the goal to find new strategies to treat or prevent psychiatric disorders in humans.
- MSc, 2008 Neuroscience, Max Planck Institute
- PhD, 2011 Neuroscience, King's College, University of London (United Kingdom)
- Fellowship: 2013 MCGill Univ
- Fellowship: 2018 Columbia University
- Stress Susceptibility and Resilience
- Early life Development
- Neural Circuits
- Molecular Mechanisms
1. Anacker C.*, Luna V., Stevens G., Millette A., Shores R., Jimenez JC., Chen B., Hen R, Adult hippocampal neurogenesis confers stress resilience by inhibiting ventral dentate gyrus activity; Nature 2018; Jul,559(7712):98-102
2. Anacker C., and Hen R, Adult hippocampal neurogenesis and cognitive flexibility - linking memory and mood; Nature Reviews Neuroscience 2017; Jun;18(6):335-346
3. Anacker C., Scholz J., O’Donnell KJ., Allemang-Grand R., Diorio J., Bagot RC., Nestler E., Hen R., Lerch JP., Meaney MJ., Neuroanatomic differences associated with stress susceptibility and resilience; Biological Psychiatry 2016; May 15;79(10):840-9.
4. Anacker C., O’Donnell KJ., Meaney MJ., Early Life Adversity and the Epigenetic Programming of Hypothalamic-Pituitary-Adrenal Function; Dialogues in Clin Neuroscience
5. Anacker C., Cattaneo A., Musaelyan K., Zunszain PA., Horowitz M., Molteni R., Luoni A., Calabrese F., Tansey K., Gennarelli M., Thuret S., Price J., Uher R., Riva MA., Pariante CM.; Role for the kinase SGK1 in stress, depression, and glucocorticoid effects on hippocampal neurogenesis, Proc Natl Acad Sci U S A 2013 May 21;110(21):8708-13