What are the basics of brain chemistry?

Neuroscientist Paul King weighs in via Quora:

This is a challenging question because neurochemistry is so complex. However at a high level, here is what is going on.

There are two main types of chemical signaling in the brain:

fast chemoelectric signaling: neurotransmitters = glutamate, GABA
slower functional modulation: neurotransmitters = dopamine, serotonin, acetylcholine, norepinephrine

Most neurons in the cerebral cortex have receptors for most (or all) of these neurotransmitters, so one can think of each chemical as communicating on a different broadcast channel, with the receiving neuron listening on all channels simultaneously but treating each one differently.

Here are molecular diagrams of the common neurotransmitters:

The fast-acting neurotransmitters (glutamate and GABA) propagate information throughout the brain by electrically activating neurons. 99% of all neurons in the brain release one of these two chemicals. Glutamate is positive (+) and GABA is negative (-). The contents of perception, cognition, and consciousness come about primarily by neurons communicating using these two neurotransmitters. Sedatives, general anesthesia, and anti-seizure drugs work by enhancing GABA, which suppresses brain activity.

The neurotransmitters that get all the attention, especially in psychiatry, are the neuromodulators, but account for less than 1% of neurons: dopamine, serotonin, acetylcholine, norepinephrine. Each neuromodulator has a slightly different role, and is used by multiple parallel systems. For example dopamine controls habit learning and is studied in addiction. Norepinephrine and acetylcholine shape attention but in different ways (norepinephrine for vigilance and acetylcholine for focus, loosely speaking). Serotonin is somewhat of a mystery, but seems to play a role in mood and personal identity. Nicotine activates the acetylcholine receptors. ADHD drugs, cocaine, and amphetamines activate dopamine and norepinephrine. Antidepressants like Prozac and Effexor generally act on serotonin and sometimes norepinephrine.

Whereas the fast-acting neurotransmitters have a direct electrical effect on neurons, the neuromodulators work indirectly by altering chemical pathways inside the cell. Each neuron contains a complex web of internal signaling pathways that control adaptation and learning, and it is these pathways that are affected.

This is just scratching the surface but gives a flavor, and every statement made above has exceptions.

There are other neurotransmitters not mentioned: endorphins, histamine, endocannabinoids (cannabis-like), melotonin, oxytocin, and many others. Inside the cell, there is a whole world of control molecules, many facilitated by ATP or calcium atoms, with names like PKA, CaMKII, MAPK, PLC, PP1, DARPP-32, DAG, PIP2, cAMP, and on and on (over 100 of them). These are large 3D proteins that work like chemical cogs inside the inner signaling machinery of the cell.

To pick just one molecule from this alphabet soup, DARPP-32 plays a central role in addiction. This diagram shows how different addictive drugs affect different neuroreceptors, altering chemical signaling inside the cell which causes the neuron to learn the wrong thing, reinforcing the feedback loop of addiction. DARPP-32 can be seen in the middle. The cell wall is the circle, and neuroreceptors are labeled with VIP, 5HT4, etc. on the circle edge.

A great textbook on neurochemistry is Basic Neurochemistry, now on its 8th edition and weighing in at 1100 pages(!). (http://www.amazon.com/Basic-Neur…)

What are the basics of brain chemistry?