Distinct transmission sites within a synapse for strengthening and homeostasis

At synapses, miniature synaptic transmission forms the basic unit of evoked transmission, thought to use one canonical transmission site. Two general types of synaptic plasticity, associative plasticity to change synaptic weights and homeostatic plasticity to maintain an excitatory balance, are so far thought to be expressed at individual canonical sites in principal neurons of the cortex. Here, we report two separate types of transmission sites, termed silenceable and idle-able, each participating distinctly in evoked or miniature transmission in the mouse visual cortex. Both sites operated with a postsynaptic binary mode with different unitary sizes and mechanisms. During postnatal development, silenceable sites were unsilenced by associative plasticity with α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)-receptor incorporation, increasing evoked transmission. Concurrently, miniature transmission remained constant, where AMPA-receptor state changes balanced unsilencing with increased idling at idle-able sites. Thus, individual cortical spine synapses mediated two parallel, interacting types of transmission, which predominantly contributed to either associative or homeostatic plasticity.