Living Textbook MC 417

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Neurotransmission in the CNS

Anatomy:

There are several nomenclature for the brain's anatomy.  For example, one can base the nomenclature on cutting through the spinal cord, where the directions are superior (dorsal) , anterior (rostral), posterior (caudal) and inferior (ventral).  One can also slice the brain in different directions leading to different views.  A horizontal slice runs through the middle of the brain parallel to the surface, while both sagittal and coronal cut vertically at a ninety degree angle to each other.

The brain is organized into three different sections: forebrain, midbrain and hindbrain.  The forebrain contains the basal ganglia, cortex, limbic system, the thalmus and hypothalmus.  The midbrain is where the dopamine cell bodies are located, while the hindbrain contains the pons, cerebellum and medulla.

Central neurotransmission is similar to peripheral processes for the most part, with the exception of unique neurotransmitters such as GABA and Glutamate and the presence of glia cells.  Transmission is achieved via long hierarchial arrangments of neurons with the end result depending on the nature of transmission (inhibitory versus excitatory).

Chemical Neurotransmission:

Chemical neurotransmission in the CNS occurs via voltage-gated or ligand gated ion channels.  The latter ion channels can be excitatory or inhibitory depending on the neurotransmission.  

Glutamate

Glutamate is the neurotransmitter with the highest concentration in the CNS.  The glutamate synapse is a typical neuron, with the neurotransmitter broken down to glutamine in the glia and its synthesis taking place in the presynaptic neuron.  It is the neurotransmitter for a number of ligand-gated ion channels including NMDA (Calcium and Sodium) and AMPA (mostly Sodium) as well as a few G-protein-coupled receptors.  It is the major excitatory neurotransmitter in the CNS and plays an important role in memory and learning.  Any imbalance can lead to a number of disorders.

GABA

GABA is the major inhibitory neurotransmitter in the CNS.  The GABA synapse is a typical neuron, with the neurotransmitter broken down to glutamine in the glia and its synthesis taking place in the presynaptic neuron.  GABA is the neurotransmitter for two receptors; a ligand-gated ion channel GABAA (a Chloride channel) and a G-protein-coupled receptor, GABAB.  Agents that enhance the action of GABA at the GABAA receptor are used as sedative, hypnotics and anticonvulsive agents.   Imbalance in GABA transmission can lead to a number of disorders.

Dopamine

Dopamine is an important neurotransmitter in the CNS.  The dopaminergic synapse is a typical neuron, with the neurotransmitter broken down by MAO or COMT in the synapse and is synthesized in the presynaptic neuron from Tyrosine.  Dopamine is encapsulated into the presynaptic vesicles via VMAT and is transported back via DAT.  It binds to two families of G-protein-coupled receptors, D1 and D2 families, with the former leading to an increase in cAMP and the latter leading to a decrease in the same secondary messenger.  Imbalance in dopaminergic transmission can lead to a number of disorders.

Serotonin

Serotonin (5-HT) is an important neurotransmitter in both the periphery and the CNS.  The Serotonergic synapse is somewhat similar to the dopaminergic synapse, with the neurotransmitter broken down by MAO only in the synapse and is synthesized in the presynaptic neuron from Tryptophan.  Serotonin is encapsulated into the presynaptic vesicles via VMAT-2 and is transported back via SERT.  There are a number of serotonin receptors, mostly G-protein-coupled, with the exception of 5-HT-3, which is a ligand-gated ion channel .  Serotonin has a number of physiological roles in the CNS and agents affecting its action can be used in a number of disorders.