Activity-dependent recruitment of AMPA receptors to the postsynaptic compartment by facilitated diffusion in the plasma membrane

Abstract

The brain operates by continually transmitting and processing vast amounts of data through complex networks of neurones. This information is transmitted via the release and detection of neurotransmitters at synapses. In the mammalian brain the predominant excitatory neurotransmitter is glutamate that acts at several types of glutamate receptors located at, or near, the postsynaptic density on specialised dendritic protrusions called spines. The ability of neurones to modulate the efficacy of synaptic transmission in response to previous activity at that synapse, termed synaptic plasticity, is fundamental to cognitive processes such as memory and learning. AMPA receptors (AMPARs) are a subclass of glutamate receptor, which mediate nearly all fast excitatory neurotransmission. Synaptic plasticity largely depends on the activity-dependent trafficking of AMPARs into and out of spines. Thus, a major challenge in neuroscience is to better understand how neurotransmitter receptors get to the right synapse at the right time and how their numbers within spines and at the postsynaptic density are maintained and regulated. We recently reported results that offer a mechanistic explanation of how AMPARs can be recruited to spines by synaptic activity. In this addendum we address technical aspects of this work and further discuss the context and implications of our data.