Control of extracellular glutamate by transporters in the CNS

Glutamate, the primary excitatory neurotransmitter in the brain, must be rapidly cleared from the extracellular space to prevent excitotoxicity and maintain precise synaptic signaling. This work examined how high‑affinity, Na⁺‑dependent glutamate transporters regulate extracellular glutamate levels in hippocampal tissue. Experiments in rodent brain slices showed that ambient glutamate is maintained at ~25 nM, below the activation threshold of most receptors, and that transporter activity is essential for sustaining these low levels. Additional analyses revealed that ambient glutamate is uniformly low throughout the neuropil, indicating that dense, widespread transporter expression prevents tonic activation of both synaptic and extrasynaptic receptors.