Control of Long-Term Plasticity by Glutamate Transporters

Activity-dependent long-term changes in synaptic strength constitute key elements for learning and memory formation. Long-term plasticity can be induced in vivo and ex vivo by various physiologically relevant activity patterns. Depending on their temporal statistics, such patterns can induce long-lasting changes in the synaptic weight by potentiating or depressing synaptic transmission. At excitatory synapses, glutamate uptake operated by excitatory amino acid transporters (EAATs) has a critical role in regulating the strength and the extent of receptor activation by afferent activity. EAATs tightly control synaptic transmission and glutamate spillover. EAATs activity can, therefore, determine the polarity and magnitude of long-term plasticity by regulating the spatiotemporal profile of the glutamate transients and thus, the glutamate access to pre- and postsynaptic receptors. Here, we summarize compelling evidence that EAATs regulate various forms of long-term synaptic plasticity and the consequences of such regulation for behavioral output. We speculate that experience-dependent plasticity of EAATs levels can determine the sensitivity of synapses to frequency- or time-dependent plasticity paradigms. We propose that EAATs contribute to the gating of relevant inputs eligible to induce long-term plasticity and thereby select the operating learning rules that match the physiological function of the synapse adapted to the behavioral context.