Dynamics of AMPAR proteome across brain regions and in postnatal development

Native AMPA receptors (AMPAR) in the mammalian brain are macromolecular complexes whose functional characteristics vary across brain regions and postnatal development and change in response to neuronal activity. Both, structural and functional properties of the AMPARs are determined by their proteome, the ensemble of their protein building blocks. Here we use high-resolution quantitative mass spectrometry to analyze the entire pool of AMPARs affinity-isolated from distinct brain regions, selected sets of synapses/neurons and from whole brains at distinct stages of postnatal development. These analyses show that the AMPAR proteome is largely dynamic in both space and time: AMPARs exhibited profound region-specificity in their architecture and the constituents building their core and periphery. Likewise, AMPARs (ex)change numerous of their building blocks during postnatal development. These results provide an as yet unique resource for analysis of the individual subunits of native AMPAR complexes and their role in excitatory neurotransmission.