The Tripartite Synapse III.

Glial Cell

I. Presynaptic Neuron A. Astrocyte

Nerve Ending Releases Transmitter

reuptake
Myhea
S

reuptake
eli th
n

blockade
Glutamate
uptake by transporter
+ (GFAP)
Illustration by: Kendra Scouten

Na
Glial
Glutamate Growth Fibrillary
Factors Acidic
Kainate
Transmitter Receptor Protect Glucose Protein
a marker of
Nourish glia activation
Modulate
AMPA Receptor Neurosteroid
Na+ Biosynthesis
Mg++
II. Post Synaptic B.
PSD NMDA Receptor Micro-Glia
Neuron with
Glutamate ↑ Ca++
Receptors
CaMKII
Bz
Second Receptor
Messengers GABA receptor
Ca++
Golgi release synapse formation
Kinases

Cl- sprouting

Transcription
Transcription Factors
Factors
ea s .
Mitochondria

mRNA
ll d l v
th

C.
ce viva

DNA
r

Oligo-
su

Endoplasmic
Reticulum dendrocyte
Endoplasmic
Reticulum
for new myelin
Peptides
Protein
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.