Effects of synaptic adhesion molecules on the survival of adult born granule cells in the dentate gyrus

• Applicant: Professor Dr. Valentin Stein
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells
• Term: from 2013 to 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 240088636

Neurons are born even in adult mammals and provide an additional level of plasticity to the existing neuronal circuitry. The functional integration of these newborn neurons determines the impact of this form of plasticity. Many newborn neurons do not survive the first weeks and only a fraction is fully integrated into the existing neuronal network. The process of network integration and survival is intimately linked to the formation of glutamatergic synapses. Synaptic adhesion molecules have been shown to tightly regulate the formation of synapses. Surprisingly, this class of molecules has not been studied in the context of synapse formation of newborn neurons. We recently demonstrated that the synaptic adhesion molecule SynCAM1 regulates the number of synapses. Confocal microscopy of the dentate gyrus of animals with GFP labeled neurons revealed that the number of GFP expressing neurons is nearly doubled in SynCAM1 overexpressing animals, while SynCAM1 knockout animals showed a strong reduction in the number of GFP positive neurons. Here, we hypothesize that the synaptogenic function of SynCAM1 helps newborn neurons to form excitatory synapses leading to a more reliable functional integration into the existing network and thereby increasing the chance to survive. Using SynCAM1 knockout and overexpressing animals we will now test this hypothesis by determining the number of surviving neurons compared to newly generated neurons. In a second step we plan to compare the morphology and synaptic function of these neurons at different time points to study the time course of the development. Finally, we want to address the question at which time point during maturation of newborn neurons the aided synapse formation is required. This project will increase our understanding of the mechanisms underlying the integration of newborn neurons into the existing neuronal network. In addition it might be of interest for future therapeutic approaches that rely on the replacement of neurons, especially in diseases like Alzheimer or Parkinson.

• DFG Programme: Research Grants