Control of Long-Term Plasticity by Glutamate Transporters

Summary & key facts

This paper reviews evidence that a group of proteins called excitatory amino acid transporters, or EAATs, control how the brain's main excitatory chemical, glutamate, moves at synapses. By shaping how much glutamate reaches receptors and how far it spreads, EAATs can change whether connections between nerve cells get stronger or weaker after activity. The authors suggest that changes in EAAT levels with experience could make some synapses more or less likely to undergo long-term change, and that EAATs may act like gates that help the brain choose which inputs lead to learning-related changes. These ideas are based on experimental studies and some informed speculation, not clinical proof.

Key facts:

• Long-term plasticity means lasting changes in the strength of connections between nerve cells, and it is a core process for learning and memory.
• EAATs are proteins that take glutamate out of the space between nerve cells. This uptake controls how much glutamate reaches nearby receptors and how far glutamate spreads.
• Because EAATs change the timing and spread of glutamate signals, they can influence whether synapses become stronger (potentiation) or weaker (depression) after certain activity patterns.
• Experimental studies summarized in the paper show that changing EAAT activity can alter both the direction and size of long-term synaptic changes.
• The authors suggest that EAAT levels themselves can be changed by experience, which would make some synapses more sensitive to specific timing or frequency patterns of activity.
• The paper proposes that EAATs help 'gate' which inputs are able to induce long-term changes, so the brain can use different learning rules depending on the synapse and behavioral context.
• The review draws on lab studies and proposes ideas about behavior and experience. This means some conclusions are speculative and more experimental work is needed to confirm them.

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.

Topics

Biochemical effects in animals Neuroscience and Neuropharmacology Research Photochromic and Fluorescence Chemistry

Categories

Cellular and Molecular Neuroscience Life Sciences Neuroscience

Tags

AMPA receptor Biochemistry Biology Computer science Excitatory amino-acid transporter Excitatory postsynaptic potential Glutamate receptor Inhibitory postsynaptic potential Long-term depression Neuroplasticity Neuroscience Physics Plasticity Psychology Quantum mechanics Receptor Synaptic plasticity Term (time) Thermodynamics