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Molecular mechanisms regulating the trafficking of calcium-permeable and -impermeable AMPA receptors in synaptic plasticity

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Researchers in the UK examine brain activity

AMPA-type glutamate receptors (AMPARs) mediate fast excitatory transmission in the central nervous system. Scientists have investigated the mechanisms regulating the synaptic expression of calcium-permeable AMPARs.

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In the brain, cells communicate through specialised contact points called synapses. A presynaptic neuron releases a chemical transmitter that binds to receptors located on a postsynaptic cell. In mammalian brains, the main excitatory neurotransmitter is glutamate, and fast excitatory transmission is mediated mostly by the activation of AMPARs. These receptors are protein complexes embedded in the cell outer membrane. Glutamate binding causes the complex to open and allows cations to flow through the membrane. The most common type of AMPARs is calcium-impermeable (CI-AMPARs), while the rarer calcium-permeable AMPARs (CP-AMPARs) also allow calcium to pass. According to researchers from the CP-AMPAR trafficking project, the fact open CP-AMPARs let calcium into a cell is of particular interest because this process is linked to neuronal development, long-term changes in synapse strength or plasticity, and pain perception, for example. However, the molecular mechanisms underlying CP-AMPAR delivery to synapses remain unclear. To investigate this, the researchers focused particular attention on the potential role of recently discovered AMPA auxiliary subunits in this process. They used cerebellar stellate cells to address this issue as they contain both types of AMPARs, the relative expression of each being tightly regulated and compartmentalised at the neuronal surface. The scientists used high-resolution electrophysiology - the recording of electric activity - and fluorescence-based protein imaging to carry out their investigation. Their findings will be presented in a manuscript that will shortly be submitted for review as a full-length scientific paper.

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