AMPA-type glutamate receptors (AMPARs) mediate fast excitatory neurotransmission throughout the brain, and are central to various forms of synaptic plasticity that underlies learning. AMPARs are highly versatile complexes as in addition to four core subunits (GluA1-4), an array of auxiliary subunits exist.  Core and auxiliary subunits assemble in various stoichiometries, and in a brain-region specific fashion, rendering the AMPAR response uniquely versatile, tuned to the needs of a given circuitry. Moreover, selective AMPAR complexes are recruited to potentiate a synapse during long-term potentiation (LTP).

Recent cryo-EM structural data, combined with functional studies, have started to shed light on the arrangement of both, core and auxiliary subunits. Hence, despite tremendous com-plexity, unique to the AMPA-type glutamate receptor, organizing principles are beginning to emerge. In this talk I will discuss our current understanding of AMPAR organization. I will also discuss recent structural insights into the unique conformational dynamics of GluA1, a receptor which selectively contributes to hippocampal LTP, and its unexpected deviation from the well-studied GluA2-containing AMPARs.

References:

1. Greger et al., Neuron 94:713, 2017 [Review]

2. Herguedas et al., Science 364:eaav9011, 2019

3. Zhang et al., Nature 594:454, 2021

4. Herguedas et al., Nat. Commun 13:734, 2022

5. Zhang et al., Nature 621:877-882, 2023

Biography

Ingo Greger obtained his PhD in 1998 from the University of Oxford (UK), where he investigated mechanisms of gene expression in Nick Proudfoot’s lab, using yeast as a model system. In 1999 he moved to Ed Ziff’s lab at the NYU School of Medicine & HHMI (USA), where he started his work on AMPA receptors, investigating their biogenesis and trafficking mechanisms from the endoplasmic reticulum. Back in the UK, he continued his work on glutamate receptors whilst a Royal Society fellow at the MRC LMB in Cambridge, from 2003-2006. At the LMB he added structural and patch-clamp electrophysiology approaches to his studies of glutamate receptors.

He is currently a senior MRC investigator at the LMB. His lab investigates AMPA receptor operation at various levels of complexity, using a combination of structural, functional and imaging approaches. His ultimate aim is to understand AMPAR receptor operation at the atomic level, and how glutamate receptor regulation at synapses contributes to learning.

IPHYS contact person: Viktor Kuchtiak, viktor.kuchtiak@fgu.cas.cz