Underlying mechanisms of diverse functions in excitatory and inhibitory synapses

• Applicant: Dr. Melissa Herman
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 504371651

The activity of a neural network is ultimately determined by the strength of synapses releasing excitatory or inhibitory neurotransmitters. In this project, we will examine the mechanisms regulating the number of neurotransmitter-filled packets, synaptic vesicles, released at glutamatergic (excitatory) or GABAergic (inhibitory) synapses in response to a single stimulation. Using a combination of electrophysiology and pharmacology methods in a single neuron, primary culture preparation, we can determine how signaling pathways, such as protein kinase A, regulate the characteristics of synaptic vesicle release in a cell-type specific manner. In addition to examining molecular mechanisms responsible for regulating the number of synaptic vesicles released at excitatory and inhibitory synapses, we will explore whether these mechanisms are universal across species by comparing results in murine neurons to those in human neurons induced from pluripotent stem cells. Finally, we will investigate divergent mechanisms in excitatory and inhibitory synapses initiated by the same signaling pathways that lead to differences in the regulation of neurotransmitter release. To this end, we will use a molecular biology approach to isolate specific synaptic populations. Overall, this project will add to our understanding of the mechanisms used by different types of synapses to regulate the strength of synaptic transmission. Fundamental knowledge about how excitatory and inhibitory synapses regulate their function is key to understanding how balanced activity is maintained in healthy neural networks.

• DFG Programme: Research Grants