Molecular mechanisms of activity dependent synapse stabilization mediated by CPG15

• Applicant: Dr. Katrin Michel
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells
• Term: from 2017 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 354475192

The plasticity of neuronal networks is key to processes of learning and memory. During memory formation, a large number of new dendritic spines are formed, but only a few are stabilized and integrate in the existing neuronal network. So far, the detailed molecular mechanisms that underlie the selective stabilization of spines activated during memory consolidation remain unknown. Genes that are regulated by neuronal activity are prime molecular candidates for mediating the effects of neuronal activity on synapse formation and elimination. One such gene is the candidate plasticity-related gene 15 (cpg15), which has been shown to be involved in axonal and dendritic growth and the maturation of excitatory synapses. Besides a developmental delay, adult cpg15 KO mice exhibit reduced ability to adapt the synaptic strength of visual cortex synapses and show poor performance in learning tasks. This suggests that cpg15 is not only important for the correct development of neuronal networks, but also for their activity dependent refinement in adulthood. Our preliminary results reveal that there is reduced PSD95 recruitment to newly formed spines of layer 2/3 pyramidal neurons in the visual cortex when CPG15 is absent. Furthermore, we find in primary neuronal cultures from cpg15 KO mice an increase in the number of dendritic spines that contain GluA1 AMPA receptor subunits but lack PSD95. In this proposal we will address the hypothesis that CPG15 mediates activity dependent synapse stabilization in cooperation with the AMPA receptor proteome by regulating the recruitment of PSD95 at newly formed excitatory synaptic connections. To understand the role of CPG15 in activity dependent synapse stabilization we will investigate the subcellular localization of CPG15 in vivo, its activity dependent translocation, CPG15s pre- and postsynaptic interaction partners at excitatory synapses, and their cooperative role in synapse stabilization and maturation.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professorin Elly Nedivi, Ph.D.