Amino acid neurotransmitters

• obtained from diet or synthesized as in other cells
• glutamate and aspartate obtained from Kreb's cycle
• GABA formed by decarboxylation of glutamate by glutamic acid decarboxylase (GAD)
• Glycine derived from glucose via amino acid serine

• Catacholamines contain catachol ring, all three catacholamine neurotransmitters, dopamine, norephinephrine, and epinephrine all derived from single synthetic pathway
• Serotonin, an amine but not a catacholamine derived from amino acid triptophane

• Consist of chains of amino acids, and therefore probably all synthesized in soma where chemical machinery for assembling, some synthesized directly, others cleaved from longer protein chains

Synthesized from choline and acetyl-CoA

Synthesis takes place mainly in terminals of axon

Nitric oxide by product of conversion of amino acid arginine to citrulline, as gas can pass through any membrane and thus cannot be stored

Carbon monoxide split from heme by heme oxygenase, present in hippocampus and olfactory bulb

Neurotransmitters nervous system

Why so many?

The response of a neuron to a neurotransmitter determined by the receptor to which transmitter binds, therefore no obvious functional explanation for why so many needed

• explanation may be evolutionary, brain evolved by random variation and natural selection, mutations in membrane proteins may have yeilded molecules that respond to various chemical substances that nerves happen to release, particular neurotransmitter systems evolved because different chemicals happened to best serve neurons that had specific functions

Examples:

• ACh released by parasympathetic postganglionic neurons, and by all preganglionic neurons of autonomic nervous system
• Norephinephrine released by sympathetic postganglionic neurons
• GABA released by local neurons in cortex and cerebellum
• Peptides often co-localized in GABAergic neurons
• Dopamine used largely by brainstem neurons

• ACh neurotransmitter of all preganglionic autonomic neurons, and postganglionic parasympathetic neurons, ephinephrine neurotransmitter of postganglionic sympathetic neurons
• At least 3 other classical neurotransmitters, dopamine, serotonin, and GABA are involved
• A bewildering variety of co-transmitters, including neuropeptides, ATP, and nitrous oxide

Histoflourescence

Certain compounds flouresce when amines, chatecholamines or serotonin, used to map distribution in the brain

Immunohistochemistry

Inject protein of interest into mammal (often rabbit) thereby induce to make antibodies

Antibodies extracted from rabbit, bound to marker, spread over slice of tissue containing protein of interest, a two step proceedure of making an antibody to the antibody can be used to amplify signal

In situ hybridization

Label messenger RNA containing instructions for the protein of interest, tends to be more reliable than immunohistochemistry