Synaptic transmission and plasticity require AMPA receptor anchoring via its N-terminal domain

Neurons send signals via electrical impulses that are transmitted between cells by small molecules known as neurotransmitters. The information is passed from neuron to neuron at specialized points of contact termed synapses. On release of neurotransmitters from the first neuron, the molecules attach to ‘docking stations’ called receptors on the next neuron, referred to as the postsynaptic cell. One of these receptors, the AMPA receptor, transmits signals by binding to a neurotransmitter called glutamate. Previous research has shown that in order to bind glutamate effectively, these receptors need to be trapped and anchored at the correct location at the synapse. This trapping mechanism controls the number of receptors present, which strengthens the synapse, and ultimately mediates learning and memory. However, it is still not clear how AMPA receptor trapping is achieved. To investigate this question, Watson et al. examined how AMPA receptors (and mutant forms of the receptor) affect the communication between neurons using brain slices from mice. The experiments show that an external segment of the AMPA receptor called the N-terminal domain (or NTD for short) is a key element for receptor anchoring at the postsynapse. The AMPA receptor is made out of four different subunits; when the NTD portion was removed from one specific subunit, fewer receptors were anchored correctly at the postsynapse. When the NTD was removed from another subunit, it completely prevented the synapse from learning. Therefore, the NTD brings about subunit-selective anchoring of the AMPA receptor, which affects the ability of the synapse to transmit signals. Important next steps would be to identify the proteins that interact with the NTD and how this specific anchoring affects the strength of the synapse. Another key step will be to understand what mechanisms control the number of AMPA receptors at synapses, to ultimately enable learning.