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Glutamatergic Synapse
Glutamate: the major excitatory neurotransmitter at almost all synapses
Neuronal migration • Excitability • Plasticity • Long-term potentiation (LTP) • Long-term depression (LTD) Synaptic cleft Presynaptic terminals Postsynaptic axons Glutamate Synaptic vesicles
ionotropic glutamate receptors (iGluRs) voltage sensitive Glutamate receptors Postsynaptic axons metabotropic glutamate receptors (mGluRs) ligand sensitive
ionotropic glutamate receptors (iGluRs) AMPA Kainate (KA) NMDA GluN1/GluN2A GluN1/GluN2B KA1, KA2, GluR5, GluR6,GluR7 GluA1/GluA2 GluA2/GluA3
Glutamate Na+ AMPA Synapse maturation & Plasticity Postsynaptic axons
Glutamate Na+ Ca2+ NMDA AMPA Depolarization Postsynaptic axons
Glutamate Ca2+ Na+ KA NMDA AMPA Smaller contribution to neuron depolarization than AMPA receptors. Postsynaptic axons
Na+ Ca2+ smaller extent KA NMDA AMPA Fast (<10 ms) Slower (10-100 ms) Synaptic transmission Postsynaptic axons
Glutamate Metabotropic glutamate receptors (mGluRs) Second messengers Gene expression & Protein synthesis Postsynaptic axons
Metabotropic glutamate receptors (mGluRs) Group I mGluRs Group II mGluRs Group III mGluRs mGluR1 mGluR5 mGluR2 mGluR3 mGluR4 mGluR6 mGluR7 mGluR8
Presynaptic terminals mGluR4/6/7/8 mGluR2/3 Glutamate Synaptic cleft mGluR1/5 mGluR4/6/7/8 mGluR2/3 Gi/o Gi/o Gs Gi/o Gi/o Gq Ca2+ DAG IP3 cAMP⬇ PLC PKC Postsynaptic axons
Presynaptic terminals EAAT Glutamine Glia Postsynaptic axons
Glutamatergicsynapse-linked Neurodevelopmental disorders • Autism spectrum disorder • Intellectual disability • Down syndrome • Rett syndrome • Attention-deficit hyperactivity disorder
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