A computational study of astrocytic glutamate influence on post-synaptic neuronal excitability
Fig 1
Compartmental model of tripartite glutamatergic synapse.
(1) A 10 Hz simulated spike train mimicking in vivo spontaneous activity results in a deterministic release of vesicular glutamate and voltage-dependent potassium (K+) efflux from the presynaptic neuron into the synaptic cleft: (2a) Glutamate (Glu-) activates N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors on the postsynaptic neuron and (2b) Metabotropic glutamate receptors (mGluRs) located on the astrocytic membrane: (3) Glu- is removed from the synaptic cleft compartment by sodium (Na+) dependent excitatory amino-acid transporters (EAATs): (4) Glu- and 3Na+ enters the astrocytic compartment, the former to be either converted to glutamine or α-ketoglutarate, or packaged into vesicles: (5) Activation of the astrocytic mGluRs results in production of inositol 1, 4, 5-trisphosphate (IP3): (6) IP3 opens Ca2+ channels on the endoplasmic reticulum (ER) allowing an efflux of Ca2+ into the cytoplasm in both the soma and perisynaptic process compartments: (7) Ca2+ elevation in the process stimulates the release of glutamate vesicles: (8) Astrocytic released glutamate binds to extrasynaptic glutamate receptors: (9) A slow inward current (SIC) is generated in the post-synaptic compartment: Astrocytic homeostatic (10a) Sodium/Potassium pump (NaK-ATPase) removes Na+ast. and K+syn (10b) Sodium-Calcium exchanger (NCX) exchanges 1Ca2+ for 3Na+ across the membrane.