Structure and organisation of AMPA receptor-TARP complexes in the mammalian cerebellum

AMPA receptors (AMPARs) are multimodal transducers of glutamatergic signals throughout the brain. Their diversity is exemplified in the cerebellum, the brain structure integrating sensorimotor information. At afferent synapses, AMPARs mediate high-frequency excitation, while in Bergmann glia (BG) they support slow calcium transients that modulate synaptic transmission. This spectrum arises from different combinations of core subunits (GluA1-4), auxiliary proteins, and post-transcriptional modifications. Here, using mass-spectrometry, cryo-EM, and electrophysiology, we characterize major cerebellar AMPARs: low calcium-permeable GluA2/A4 heteromers with four TARP subunits, mainly neuronal in origin, and BG-specific calcium-permeable GluA1/A4 heteromers containing only two Type-2 TARPs. Moreover, GluA4 receptors consistently exhibit compact N-terminal domains that promote synaptic delivery. Our study defines the organisational principles of native AMPAR complexes in the mammalian cerebellum and reveals how different receptor subtypes support cell-type specific functions.