Glutamate: Brain's Major Excitatory Neurotransmitter (Vocabulary)

A collection of vocabulary-style flashcards capturing key terms and their definitions from the glutamate-focused lecture notes. Each card pairs a term with its concise definition to aid exam preparation.

Glutamate

Dominant excitatory neurotransmitter in the CNS; drives fast excitatory signaling, learning, memory, and is energetically costly for neurons.

Glutamatergic synapse

Synapse where glutamate is released and mediates most fast excitatory transmission; accounts for a large portion of synapses in the brain.

Glutamate–glutamine cycle

Neuron–astrocyte cooperation: glutamate released, taken up by astrocytes, converted to glutamine, transferred back to neurons, and converted again to glutamate.

Vesicular glutamate transporter (VGLUT)

Transporters (VGLUT1-3) that load glutamate into synaptic vesicles using the proton gradient generated by V-ATPase.

EAATs (excitatory amino acid transporters)

High-affinity plasma membrane transporters that clear glutamate from the synaptic cleft; clearance is energy-dependent via Na+/K+-ATPase activity.

System N transporters (SN1/SN2)

Astrocytic transporters that export glutamine from astrocytes; Na+-coupled and can reverse under certain Na gradients.

System A transporters (SAT1/SAT2)

Neuronal transporters that import glutamine into neurons for conversion back to glutamate.

Glutamine synthetase (GS)

Astrocyte enzyme that converts glutamate + NH3 + ATP into glutamine; aids in detoxifying glutamate and nitrogen handling.

Phosphate-activated glutaminase (PAG)

Mitochondrial enzyme that converts glutamine to glutamate (and NH3) in presynaptic terminals, feeding the neurotransmitter pool.

Glutamine

Amino acid produced from glutamate in astrocytes; shuttled back to neurons to regenerate glutamate via the glutamate–glutamine cycle.

α-ketoglutarate (α-KG)

TCA cycle intermediate; carbon backbone for glutamate synthesis via transamination.

Transamination

Transfer of an amino group to α-ketoglutarate (often via AST/GOT or BCATs) to form glutamate.

Branched-chain amino acids (BCAAs)

Leucine, isoleucine, valine; donate amino groups to brain nitrogen balance, supporting glutamate synthesis.

Glutamate decarboxylase (GAD)

Enzyme that converts glutamate to GABA, the main inhibitory neurotransmitter in the brain.

GABA

Main inhibitory neurotransmitter in the CNS; produced from glutamate by GAD in GABAergic neurons.

Glutathione (GSH)

Tripeptide (glutamate–cysteine–glycine) and major antioxidant in the brain; protects against oxidative stress.

AMPA receptor

Ionotropic glutamate receptor mediating fast excitatory transmission; subunits GluA1–4; Ca2+ permeability depends on GluA2 editing.

NMDA receptor

Ionotropic receptor acting as a coincidence detector; Ca2+-permeable; Mg2+ block at rest; requires glutamate + glycine and depolarization for activation.

Kainate receptor

Ionotropic receptor (GluK1–GluK5) with slower kinetics; modulates synaptic transmission and presynaptic release.

Glycine (NMDA co-agonist)

Co-agonist required with glutamate to activate NMDA receptors; glycine or D-serine binds the GluN1 subunit.

Q/R editing

RNA editing at the GluA2 subunit (ADAR2) converting glutamine (Q) to arginine (R) in the M2 pore loop, reducing Ca2+ permeability.

ADAR2

RNA editing enzyme that converts adenosine to inosine; edits GluA2 at the Q/R site, affecting Ca2+ permeability.

ZnT3 (Zinc transporter 3)

Zinc transporter that loads zinc into synaptic vesicles; vesicular zinc can be co-released with glutamate in some synapses.

Vesicular zinc

Zinc stored in synaptic vesicles and co-released with glutamate; modulates NMDA and other receptors and plasticity.

Zinc modulation of NMDA receptors

Zinc can potentiate NMDA receptors at low concentrations but inhibit them at higher levels; balances excitation and protection vs toxicity.

Aspartate

Amino acid that selectively activates NMDA receptors; release is calcium-dependent and not typically vesicularly loaded like glutamate.

Postsynaptic density (PSD)

Protein-dense specialization under the postsynaptic membrane; anchors receptors, coordinates signaling, and integrates synaptic response.

PSD-95

Major scaffolding MAGUK protein; anchors NMDA receptors and other signaling proteins; links receptors to actin and synaptic signaling.

Neuroligin–neurexin

Trans-synaptic adhesion complex anchoring pre- and postsynaptic zones and aligning release sites with receptors.

Long-Term Potentiation (LTP)

Persistent increase in synaptic strength; involves NMDA Ca2+ influx, CaMKII signaling, and AMPA receptor trafficking to the membrane.

Long-Term Depression (LTD)

Persistent decrease in synaptic strength; often driven by phosphatases and AMPA receptor internalization during low-frequency stimulation.

Hippocampus trisynaptic circuit

Canonical hippocampal circuit: perforant path to dentate gyrus, mossy fibers to CA3, Schaffer collaterals to CA1, with direct entorhinal-to-CA1 input.

NMDA receptor Mg2+ block

Voltage-dependent block by Mg2+ that is relieved by depolarization, enabling NMDA receptor activation during coincident activity.

Silent synapse

A synapse that contains NMDA receptors but lacks functional AMPA receptors; unsilenced by LTP via AMPA recruitment.

Group I metabotropic glutamate receptors (mGluR1/5)

Gq-coupled receptors that activate PLC → IP3 + DAG, increasing intracellular Ca2+ and PKC, enhancing excitability and plasticity.

Group II/III metabotropic glutamate receptors (mGluR2/3, mGluR4/6/7/8)

Gi/o-coupled receptors that inhibit adenylyl cyclase and decrease cAMP; typically presynaptic autoreceptors that reduce glutamate release and protect against excitotoxicity.

Autoimmune glutamate receptor encephalitis

Disorders where autoantibodies target glutamate receptors (NMDA, AMPA, mGluR1), causing seizures and cognitive/psychiatric symptoms but often reversible with immunotherapy.