Modulation of the slow afterhyperpolarization by heterotrimeric G-protein and small GTPases in hippocampal neurons.

• Applicant: Dr. Anne Boehlen
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells
• Term: from 2010 to 2011
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 185962144

Acetylcholine and glutamate, through metabotropic receptors, play a crucial role in generating network oscillations, neuronal plasticity and in learning and memory in the hippocampus. An important target for their neuromodulatory actions is the slow calcium-activated potassium current (sIAHP) that shapes the firing pattern of cortical neurons. Neurotransmitter such as acetylcholine and glutamate suppress this current, and thereby enhance neuronal excitability. However, the signalling mechanisms mediating this effect are still largely unknown. This proposal aims to identify the G-proteins that mediate the cholinergic and glutamatergic modulation of sIAHP. We have previously demonstrated a role for G-alpha(q), and preliminary results suggest the involvement of a small G-protein of the Rho family. Our first aim is to validate the function of RhoA and other small G-proteins in the cholinergic and glutamatergic inhibition of sIAHP in hippocampal neurons. We will use an electrophysiological approach to determine whether G-alpha(q) and RhoA act in a common signalling pathway. We have shown that G-alpha(q) mediates only part of sIAHP inhibition by acetylcholine and glutamate, suggesting the existence of a parallel signalling pathway. Our second aim is to verify the role of G-alpha(12)/(13) proteins in this pathway by analysing mouse mutants lacking G-alpha(12)/(13). Finally, our third aim is to analyse the involvement of different G-proteins in the generation of hippocampal gamma network oscillations. This study may reveal novel functions for small GTPases and G-alpha(12)/(13) in neuronal signalling. This will increase our understanding of the molecular mechanisms used by acetylcholine and glutamate to activate distinct signalling pathways and regulate complex behavioural and cognitive processes.

• DFG Programme: Research Fellowships
• International Connection: United Kingdom
• Host: Privatdozentin Dr. Paola Pedarzani