The axon-spine interface is the sliver of extracellular space between the pre-synaptic and post-synaptic partners at their closest approach to each other. This interface consists of a synaptic and non-synaptic zone. The synaptic zone consists of the widened synaptic cleft and is bordered by vesicles in the presynaptic axonal bouton and a PSD in the dendritic spine. The non-synaptic interface consists of a thinner extracellular space bordered by spine and bouton membranes without specialization. The perimeter of the axon-spine interface is the border from which substances secreted into the synaptic cleft might escape and diffuse to neighboring synapses.