Group Leader

Ingo Greger

AMPA receptor biogenesis, structure and function

Ingo Greger
Group Members
  • Ondrej Cais
  • Xinyao Dou
  • Yaoyao Han
  • Josip Ivica
  • Christina Kick
  • Mikel Perez Rodriguez
  • Aditya Pokharna
  • Nayanika Sengupta
  • Oksana Sintsova

Information transfer and storage in the nervous system occur at synapses, where presynaptic signals in the form of action potential trains are interpreted by postsynaptic receptors. Receptors responding to the ubiquitous neurotransmitter L-glutamate are central to brain function and enable learning and memory processes. AMPA-type receptors form a highly versatile signalling system, comprising around 30 components, which is capable of decoding diverse action potential patterns and enables the storage of information through synaptic plasticity mechanisms.

Our core aim is to understand how AMPA receptor complexes transmit and store information, and we use a variety of approaches to do this. We combine electron cryomicroscopy and patch-clamp electrophysiology to study how the organisation of physiologically relevant receptor complexes enables the decoding of different neuronal activity patterns at model synapses. We also develop small-molecule ligands capable of modulating specific AMPA receptor subtypes, towards the generation of selective therapeutics.

Glutamate receptor complex, labelled GluA1 (core subunit), GluA2 (core subunit), CNIH2 (auxiliary subunit), TARP-gamma8 (auxiliary subunit), a major AMPA receptor assembly
Structure of a predominant AMPA receptor/auxiliary subunit complex (Zhang et al., Nature, 2021).

We build on this information to unravel AMPA receptor operation at synapses. We ask how receptors of different subunit compositions are selectively targeted to and anchored at synapses undergoing learning. To this end, we use a combination of brain slice electrophysiology as well as super-resolution light and electron microscopy approaches.

Confocal microscopy image of pyramidal neurons (left panel); electrophysiology data from these cells exhibiting synaptic potentiation (right panel)
CA1 pyramidal neurons (bioctin filled; left), and recorded synaptic potentiation (STDP LTP) from such cells (right) in mouse hippocampus.

Selected Publications

Structure and organization of AMPA receptor-TARP complexes in the mammalian cerebellumScrutton AM, Sengupta N, Ivica J, Stockwell I, Peak-Chew S, Singh B, Suzuki K, Chang VT, McLaughlin SH, Krieger JM, Aricescu AR, Greger IHScience: (2025)
Structural mobility tunes signalling of the GluA1 AMPA glutamate receptorZhang D, Ivica J, Krieger JM, Ho H, Yamashita K, Stockwell I, Baradaran R, Cais O, Greger IHNature 621(7980): 877-882 (2023)
Gating and modulation of a hetero-octameric AMPA glutamate receptor.Zhang D, Watson JF, Matthews PM, Cais O, Greger IHNature 594(7863): 454-458 (2022)
Architecture of the heteromeric GluA1/2 AMPA receptor in complex with the auxiliary subunit TARP γ8.Herguedas B, Watson JF, Ho H, Cais O, García-Nafría J, Greger IHScience 364(6438): (2019)