Part 3 : Neurochemistry

Any chemical that are in the brain.
Ex) Myeline, cell membrane, etc.

A chemical molecules that transmits messages between neurons.

Two scientists who won the Nobel prize in 1936 for discovering the first neurotransmitter acetylcholine.

An experiment conducted by Otlo Loewi and Sir Henry Dale which resulted in the second heart’s rate changed due to a substance rather than electricity.
Vagas Stuff and Henry isolated the neurotransmitter that was release within the watered-down buffered solution.

The gap between two neurons which was first named by Henry Dale. It means all different things come in together.

A principle postulated by Henry Dale that one neurons only releases one neurotransmitter. Although this is not perfectly right, this founded the way we name neurotransmitters.

Neurotransmitters are classified by its speed. (There are other possible way to classify as well: functions, chemicals, etc)

1) Amino Acids
2) Monoamines
3) Neuropeptides

Also called point to point or wired neurotransmitters.

4 Major Amino Acids neurotransmitters
1) GABA/Glycine
2)Glutamate/aspactate

Amino Acids are fast! The reason is that their receptors are simple ion-channels.

1) Ion Channel – simple open and closure.
2) Metabolic – requires enzymes to open

Types of Monoamines
1) Serotonin
2) Dopamine
3) Noradrenaline(norepinephrine)
4) Acetylcholine
And etc.

Medium speed / require metabolism / diet

Types of Neuropeptides :
There are about 50 of them including
1) CCK
2) Substance P
3) VIP
4) Oxitocin

Slow speed (could take a day or two) / have to be made in nucleus / require genes and etc. / have to be made in cell body then transported/carried down to where they release

Could be made in brainstem / Very slow. Sensitizing receptors / turning off the activity / also called neuro modulate

90% GABA/Glutamate
5-10% Others

Neurons which only moves around and switch on and off inside the brain.

Neurons which go down and up to the cortex. Whole brain is on and off controlled mostly by projecting neurons.

Type
1) Nitric Oxde
2) Endogenous (meaning naturally occurring)Endocannabinoids (marijuana receptor)
3) Neurosteroids

Other neurotransmitters are discovered due to its atypical activity. They usually diffuse out.

1) Synthesis
2) Storage
3) Release
4) Receptors
5) Removal

Monoamines require food diet (all food in balance) / Serotonin and dopamine are in competition / it can be be taken by supplements

Transmitters need a protection -> vesicles / Each vesicles have a maximum number -> over that number will release a transmitter / We can tell which neurotransmitter it is by looking at its vesicle (via electron microscope)

Amino acids – small / clear
Monoamines – medium / clear
Neuropeptides – big / dark

Action potential arrives through sodium channel -> Vesicles move to the end of the neuron – > Ca++ fuses with negatively charged presynaptic membrane and also negatively charged vesicles -> Triggers the muscles in the proteins at the nerve ending -> Rips out the membrane to release neurotransmitters at the active zone. (between funnel like dark proteins at the end of the terminal)

The site at the terminal where neurotransmitters release.

A a very potent poison from fish which blocks the sodium channel in neurons that causes people not able to break and leads to dead. Too big to get into the brain therefore it makes people to remain conscious.

Axo-dendritic Receptors
Axo-axonic Receptors
Auto Receptors : provides feedbacks so that neurons will know how much has it been released
Glial Cell Receptors :

4-5 subunits (individual proteins) that recognize the neurotransmitters which has regulatory sites.

Also called Second messenger or Seven Membrane Spanning.
Require metabolism
Plastic receptors which means that depending on the amount of flow of the neurotransmitters, the receptors will change its sensitivity. 1) Subsensitivity 2)Supersensitivity

More positive signals will fire Excitatory Postsynaptic Potential. The opposite will result in Inhibitory Postsynaptic Potential.

1) Reuptake : Neurotransmitters will go back in to where it’s released
2) Enzymes :
1. SSIR: Selective Serotonin Reuptake Inhibitor. (Also Prozac, Zola)
2. Block specific Enzyme (emzyme inhibitors)
3) Diffusion : Difusses away from the active zone

Major excitatory neurotransmitter.
– Discovered in seaweed
– Most recent taste “Umani” was based on glutamate
– Interneurons (stay in one place) (there are some projecting glutamate neurons)

AMPA <- Na+ NMDA <- Ca2+ - Found in hippocampus, - Role of releasing neurotransmitters, reforming dendrites. - It also have cellular properties that too much glutamate will kill this receptor. both multiple subunits <- ions can flow in both ionotropic

– Major inhibitory neurotransmitter.

– Receptors have 4-5 subunits that brings in Cl-
— alpha-subunits : modulate so that GABA increases its activity. (there are many different types of alpha-subunits. ex) some childrens don’t have many alpah-subunits and that triggers seizures.
*Related drugs
– CNS depressants ex) Zanax, Valium, alcohol.
*CNS drugs are very addictive.
– Neurosteroids : naturally occurring substance that occur more in women.
— beta-subunits : recognize GABA

1. Excitotoxicity : too much glutamate will kill this cells.
– NMDA antagonist for strokes and head traumas
ex) – Ketamine (special K) : dissociative anesthetics
– Memontime : developed for alzheimer.

2. Plasticity and Learning
When glutamate fuses with Ca2+, it turns on 1) genes, 2) Nitric Oxide (which diffuses glutamate black to the presynaptic membrane and then release again <- increase glutamate activity), and 3) Dendritic changes. - Causes Hebbian Synapse and LIP. - More learning was observed then died early. *Nootropics : A study focused on increasing learning ability. Piracetam : A drug that is effective on learning. This drug cannot be taken a lot of dose. Glutamate Uptake Inhibitor : A drug that was developed for Alzheimer's disease. This causes long them neurotoxicity.

Glutamate
1. alpha-ketoglutamate is created in mitochondria in neuron.
2. It becomes glutamate then it is released.
3. glutamate is taken up to the glial cell
4. It breaks down to glutamine
5. glutamine comes out of the glial cell then be taken up to the neuron.

GABA
1. glutamine becomes GABA then be released by the neuron.
2. GABA is taken by the neuron then breaks down to glutamate.