Synapse-type-specific plasticity in local circuits

•Induction and expression of long-term plasticity is specific to synapse type.•Synaptic dynamics is also connection-type specific.•The presynaptic NMDAR is a prime example of a determinant of synapse-type-specific plasticity.•Synapse-type-specific plasticity has implications for microcircuit function in health and disease.•The resulting increase in complexity makes local circuits more powerful, but also harder to study.

Neuroscientists spent decades debating whether synaptic plasticity was presynaptically or postsynaptically expressed. It was eventually concluded that plasticity depends on many factors, including cell type. More recently, it has become increasingly clear that plasticity is regulated at an even finer grained level; it is specific to the synapse type, a concept we denote synapse-type-specific plasticity (STSP). Here, we review recent developments in the field of STSP, discussing both long-term and short-term variants and with particular emphasis on neocortical function. As there are dozens of neocortical cell types, there is a multiplicity of forms of STSP, the vast majority of which have never been explored. We argue that to understand the brain and synaptic diseases, we have to grapple with STSP.