Abstract
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.
Highlights
Information processing at central synapses is governed by two main neural coding strategies: integration and coincidence detection, which rely on the rate- and spike-time coding, respectively
In knock-out mice for either EAAT2 or EAAT type-3 (EAAT3) (Katagiri et al, 2001), glutamatergic transmission is increased, which may lead to enhanced stimulation of NMDARs, precluding the ability of synapses to further potentiate
excitatory amino acid transporters (EAATs) control the extent of glutamate spillover and the access of glutamate to receptors located at the peri- and extrasynaptic sites (Figure 1)
Summary
Information processing at central synapses is governed by two main neural coding strategies: integration and coincidence detection, which rely on the rate- and spike-time coding, respectively (deCharms and Zador, 2000; Brette, 2015). The ability of synapses to undergo long-term changes in synaptic weight have been investigated in vivo and ex vivo using two main types of cell conditioning paradigms: rate-based and spike-timing-based protocols (Malenka and Bear, 2004; Sjöström et al, 2008; Feldman, 2012). The induction of long-term synaptic plasticity at glutamatergic synapses requires the activation of presynaptic and postsynaptic glutamate receptors, situated at synaptic, perisynaptic and extrasynaptic sites (Asztely et al, 1997; Bergles and Jahr, 1997; Bergles et al, 1997; Min et al, 1998; Rusakov and Kullmann, 1998; Lehre and Rusakov, 2002; Zheng et al, 2008; Figure 1). High-affinity membrane glutamate transporters ( named excitatory amino acid transporters, EAATs)
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