The Tripartite Synapse III. Glial Cell I. Presynaptic Neuron A. Astrocyte Nerve Ending Releases Transmitter reuptake Myelin Sheath reuptake blockade Glutamate uptake by transporter Na+ (GFAP) Glial Glutamate Growth Fibrillary Factors Kainate Acidic Transmitter Receptor Protect Glucose Protein a marker of Nourish glia activation Modulate AMPA Receptor Neurosteroid Illustration by: Kendra Scouten Kendra by: Illustration Na+ Biosynthesis Mg++ II. Post Synaptic B. NMDA Receptor Neuron with PSD Micro-Glia Glutamate ↑ Ca++ Receptors CaMKII Bz Second Messengers Receptor GABA receptor ++ Golgi Ca release Kinases synapse formation - Cl sprouting Transcription Transcription Factors Factors mRNA DNA C. Endoplasmic survival vs. Oligo- cell death Reticulum dendrocyte Mitochondria Endoplasmic Reticulum for new myelin Protein Peptides CRH vs.TRH Synthesis Axon of Neuron II Legend: The Tripartite (three-part) Synapse involves: I) a presynaptic axon of neuron I (orange, top left) releasing transmitters to activate (glutamate) or inhibit (GABA-Bz) activity of the II) post-synaptic neuron (yellow, middle). The third critical component is III) the glial cell (pink, top right), an (A) astrocyte which protects cells by taking up glutamate to prevent overexcitation and secretes growth factors; provides energy via glucose; and modulates receptor (R) function with the generation of neurosteroids (which interact with Bz-GABA receptors and NMDA receptors. Other (B) microglia secrete cytokines and scavenge cellular debris; while (C) oligodendrocytes make the myelin necessary to insulate the axons of neurons to insure good conductivity. The myelin sheath breaks down in Multiple Sclerosis (MS) and now there is evidence of oligodendroglia dysfunction in bipolar illness and failure in late stages of schizophrenia. CaMK-II is the major calcium ion (Ca++) sensor of the neuron involved in up or down regulation of synaptic excitability necessary for short and long term memory. It is decreased in bipolar illness. The neurons (I and II) and glia (III) of parts of the prefrontal cortex appear deficient in number and function. Lithium increases the survival and production (neuro-glia genesis) of both cell types! Abbreviations: Na++, sodium ion; Mg++, magnesium; NMDA, AMPA, and kainate are three types of glutamate receptors in the postsynaptic density (PSD); Ca++, calcium ion; CaMKII, calcium calmodulin kinase-II; GABA, gamma-aminobutyric acid; Bz, benzodiazepine; Cl-, chloride ion; CRH, corticotropin-releasing hormone; TRH, thyrotropin-releasing hormone..