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Abstract
This review covers recent developments in the cellular neurophysiology of retrograde
signaling in the mammalian central nervous system. Normally at a chemical synapse
a neurotransmitter is released from the presynaptic element and diffuses to the postsynaptic
element, where it binds to and activates receptors. In retrograde signaling a diffusible
messenger is liberated from the postsynaptic element, and travels "backwards" across
the synaptic cleft, where it activates receptors on the presynaptic cell. Receptors
for retrograde messengers are usually located on or near the presynaptic nerve terminals,
and their activation causes an alteration in synaptic transmitter release. Although
often considered in the context of long-term synaptic plasticity, retrograde messengers
have numerous roles on the short-term regulation of synaptic transmission. The focus
of this review will be on a group of molecules from different chemical classes that
appear to act as retrograde messengers. The evidence supporting their candidacy as
retrograde messengers is considered and evaluated. Endocannabinoids have recently
emerged as one of the most thoroughly investigated, and widely accepted, classes of
retrograde messenger in the brain. The study of the endocannabinoids can therefore
serve as a model for the investigation of other putative messengers, and most attention
is devoted to a discussion of systems that use these new messenger molecules.