Postsynaptic signaling networks: cellular cogwheels underlying long-term plasticity

Abstract

Learning depends on positive or negative changes in synaptic transmission that are synapse-specific and sustained. Synaptic signals can be directly measured and respond to certain kinds of stimulation by becoming persistently enhanced (long-term potentiation, LTP) or decreased (long-term depression, LTD). Studying LTP and LTD opens a window on to the molecular mechanisms of memory. Although changes in both pre- and postsynaptic strength have been implicated in LTP and LTD, most attention has been focused on changes in postsynaptic glutamate receptor density. This is controlled by intracellular Ca(2+) ions via a network of signaling molecules. Changes in postsynaptic Ca(2+) concentration depend on the coincidence of appropriate synaptic signals, as is found in learning situations. The long-term persistence of LTP and LTD requires gene transcription and translation. It is posited that local translation at the synapse, in a self-sustaining manner, mediates the persistence of long-term changes despite constant turnover of the synaptic components.