Glutamate Signaling
Excitatory neurotransmission via ionotropic and metabotropic glutamate receptors.
Overview
Glutamate is the primary excitatory neurotransmitter in the CNS. It acts on ionotropic receptors (AMPA — fast excitation, NMDA — coincidence detection/plasticity, kainate) and metabotropic receptors (mGluR1-8). NMDA receptors require both glutamate binding and membrane depolarization (Mg²⁺ block relief) and are permeable to Ca²⁺, making them central to synaptic plasticity (LTP/LTD). Glutamate is cleared by astrocyte transporters (EAAT1/2) and recycled via the glutamine-glutamate cycle.
Cellular Location
Excitatory synapses (cortex, hippocampus, throughout CNS)
Clinical Significance
Excitotoxicity (excess glutamate) causes neuronal death in stroke, trauma, and neurodegeneration; NMDA hypofunction implicated in schizophrenia; ketamine (NMDA antagonist) is a rapid antidepressant.