AMPA receptor biogenesis, structure and function
Information transfer in the nervous system occurs at synapses, where presynaptic signals are interpreted by postsynaptic receptors. We study this process with a focus on AMPA-type glutamate receptors.
AMPA-Rs are glutamate-gated cation channel tetramers. They are the prime mediators of excitatory neurotransmission and are regulators of synaptic plasticity, which underlies higher-order cognitive processes. Our ultimate aim is to understand how AMPA-R signalling contributes to learning at synapses at various levels of complexity.
First, we study fundamental mechanisms underlying AMPA-R signalling with a specific focus on receptor biogenesis and allosteric modulation by interacting proteins. This aspect includes structural approaches such as X-ray crystallography, electron cryo-microscopy (cryo-EM), complemented by simulations of receptor dynamics and high-resolution electrophysiological recordings.
Secondly, we build on this information to unravel AMPA-R operation at synapses. We ask how AMPA-Rs of different subunit compositions are selectively targeted to and anchored at potentiated synapses, and how structural dynamics of AMPA-R tetramers contribute to functional and structural synaptic plasticity. Towards this aim we utilize a combination of brain slice electrophysiology and super-resolution light microscopy approaches.