Parasynaptic signalling by fast neurotransmitters: the cerebellar cortex

Classic central synaptic transmission by fast neurotransmitters-glutamate, GABA or glycine-involves liberation from vesicles directly opposite postsynaptic receptors at junctions containing both a presynaptic active zone and a postsynaptic specialisation. Such classic transmission is thought to underlie much of the information transfer and processing in the brain. However, there also exist a substantial number of reports of signalling by the same transmitters outside this classic framework, whereby liberation and/or receptor activation occur beyond synaptic boundaries. We term these processes collectively parasynaptic signalling. Here, we describe the various forms of parasynaptic signalling and the available methods for distinguishing them from synaptic transmission. We then review the numerous reports of parasynaptic signalling in the cerebellar cortex, a structure whose specialised anatomy and synapses have facilitated studies of these mechanisms. We examine more generally the question of how the multiple signalling pathways might avoid interaction and address the possible functions of parasynaptic transmission, which in the cerebellar cortex include the regulation of network activity, glial tropism and the control of synaptic plasticity.