Investigation of divergent vesicle recycling mechanisms in glutamatergic and GABAergic synapses.

• Applicant: Dr. Melissa Herman
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells
• Term: from 2016 to 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 319489780

The excitation/inhibition balance within neuronal networks is necessary for normal brain function. In part, this balance depends on communication between neurons releasing the major excitatory and inhibitory neurotransmitters: glutamate and gamma-Aminobutyric acid (GABA), respectively. Because the function of synaptic connections underlie the characteristics of neuronal circuits understanding the determinants of synapse properties is crucial. In this project, we will investigate the specific properties of synapses releasing either glutamate or GABA. Both physiological features and roles within networks confer different demands for neurotransmitter release at glutamatergic and GABAergic synapses. As a result, these synapse types may use different mechanisms of synaptic vesicle recycling to meet demands. Indeed, our preliminary data suggest that glutamatergic and GABAergic synapses may employ different methods of membrane retrieval and recycling after synaptic vesicle exocytosis. In this project, we will examine the mechanisms responsible for synaptic vesicle recycling in synapses from glutamatergic and GABAergic neurons using a combination of state of the art techniques. To address this issue, we will use advanced molecular techniques paired with electrophysiology, live-cell presynaptic imaging, and electron microscopy of high-pressure frozen samples. With this combination of techniques, we will examine the molecular and structural mechanisms contributing to differences in glutamatergic and GABAergic synaptic function. Ultimately, we hope to discover unique mechanisms in synaptic vesicle recycling in GABAergic synapses, which allow these synapses to maintain a high demand for neurotransmitter release and contribute to the maintenance of the excitation/inhibition balance in functional networks.

• DFG Programme: Research Grants