Prof. Dr. Sebastian Jessberger

 

Main Goals, Keywords

New neurons are continuously generated in two discrete areas of the adult brain – the dentate gyrus of the hippocampus and the subventricular zone of the lateral ventricles. Our group is interested in the underlying biology of adult neurogenesis, including the fate plasticity of adult neural stem cells (NSCs) and the molecular mechanisms governing the neuronal maturation process. Our projects also aim to understand the functional contribution of adult neurogenesis to normal hippocampal function and its role in the epileptic disease process, which is associated with aberrant neurogenesis.

Group Members

1 professor, 2 postdoc, 5 graduate students

Previous, Current and Future Research

The finding that new neurons are continuously born in the adult brain has challenged traditional concepts of brain plasticity. Our efforts are focused on four main aspects of adult neurogenesis (please check also http://www.cell.biol.ethz.ch/research/jessberger/
for details):

• Stem cell division, potency, and early neuronal maturation
  We established a slice culture system of the adult hippocampus that allows both the longitudinal observation of retrovirally-labeled NSCs and visualization of early neuronal migration over several days. We plan to use this system to identify the mode of NSC division and early migration in an ex vivo model, characterizing basic features of stem cell biology that are currently unknown. We are also interested in the fate plasticity and epigenetic specification of NSCs in vivo.
• Integration of newborn neurons
  We have previously found that selective inhibition of cyclin-dependent kinase 5 (cdk5) activity in newborn neurons impeded proper orientation of dendritic processes (Jessberger et al., in prep). Using unbiased gene and microRNA expression arrays we will try to identify additional pathways that are involved in the growth and integration of new neurons.
• Functional relevance of adult neurogenesis
  We will use molecular imaging to analyze the impact on postsynaptic targets following the activation of newborn neurons in the adult brain. Furthermore, we will analyze the functional significance of adult neurogenesis with a variety of behavioral tasks by knocking-down neurogenesis using lentiviral and genetic strategies.
• Involvement of adult neurogenesis in the disease process of epilepsy
  Epileptic activity within the adult brain does not only affect mature neural networks, but also dramatically induces the birth of new granule cells within the dentate area. However, seizure-induced neurogenesis is partially aberrant as newborn neurons are ectopically localized in the hilus and extend extensive basal dendrites. Future experiments aim to identify the molecular mechanisms leading to aberrant neurogenesis and will try to further elucidate the functional significance of seizure-induced neurogenesis.

Techniques and Equipment

Standard protocols in cell and molecular biology. Lenti- and retroviral techniques. Steretotactic intracerebral injections. Primary neural and NSCs cultures. Adult hippocampal slice cultures. Animal facility with the ability to perform retro- and lentiviral injections with subsequent behavioral testing.

Selected Publications

• Jessberger, S., Clark, R.-E., Broadbent, N., Clemenson, G.-D., Consiglio, A., Lie, D.-C., Squire, L.-R., Gage, F.-H. Dentate gyrus-specific knockdown of adult neurogenesis impairs spatial and object recognition memory in adult rats". Learning & Memory, 16, 147-154 (2009).
• Clelland, C.-D., Choi, M., Romberg, C., Clemenson, G.-D., Fragniere, A., Tyers, P., Jessberger, S., Saksida, L.-M., Barker, R.-A., Gage, F.-H., Bussey, T.-J. A functional role for adult hippocampal neurogenesis in spatial pattern separation. Science 325(5937): 210-3 (2009).
• Jessberger, S., Aigner, S., Toni, N., Clemenson, G.-D., Lie, D.-C., Karalay, O., Overall, R., Kempermann, G., Gage, F.-H. "Cdk5 regulates accurate maturation of newborn neurons in the adult hippocampus". PLoS Biology, 11; 6(11): e272 (2008).
  

Funding

Swiss National Science Fondation, NCCR Neural Plasticity and Repair, ETH Zürich

URL

www.cell.biol.ethz.ch/research/jessberger/