Changing the tune: plasticity and adaptation of retrograde signals

•Retrograde signaling can be modified by a diverse array of intracellular signaling pathways.•Retrograde signals interact with other neurotransmitters to determine reciprocally the impact on synaptic transmission.•The behavioral and/or physiological state of the organism profoundly impacts retrograde signal capacity.•Several nervous system pathologies are associated with robust changes in retrograde signaling.

Retrograde signaling is a fundamental means by which neurons communicate. The acceptance of this statement has required a revision of how we view transmission and storage of information at the synapse. Although there is a substantial body of literature on the diverse molecules that serve as retrograde signals, less is known about how retrograde signal capacity can be modified. Is retrograde signaling plastic? How does this plasticity manifest? Are there behavioral correlates that may bias a neuron towards ‘changing its tune’, retrogradely speaking, of course? Here, we review recent findings that retrograde signaling is a highly labile process that adds additional layers of complexity that must be untangled to understand information processing in the nervous system.