Ingo Greger

AMPA receptor biogenesis, structure and function

ig@mrc-lmb.cam.ac.uk

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 at various levels of complexity.

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, using a two-fold approach.

First, we study fundamental mechanisms underlying AMPA-R signalling with a specific focus on receptor biogenesis (subunit assembly) and allosteric modulation by novel ligands and interacting proteins. This aspect includes structural approaches such as X-ray crystallography, cryo-electron 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, super-resolution microscopy of live and fixed specimens and RNA-sequencing.

Postdoc position available (closing date 21/9/16).

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Selected Papers

Group Members

  • Ondrej Cais
  • Beatriz Herguedas
  • Sui Hin (Hinze) Ho
  • Bishal Singh
  • Jake Watson
  • Alexandra Pinggera
  • Matti Pronker