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The Brain Soup: Neurotransmitters and Neuromodulators

Some organisms are nothing more than one cell. These tend to be microscopic like bacteria, have short lives and a very restricted repertoire of behaviors. In comparison, multicellular organisms can reach thousands of mets (honey fungus), live virtually forever (lobsters), and pilot space shuttles (humans). To achieve this complexity, they have to overcome one particularly daunting task: coordinating all their cells.

 

Neurotransmitters and neuromodulators

[Source: Nicholas Wright]

 

Multicellular organisms solve this issue by using chemical messengers. For instance, a cell in the periphery of a simple organism might detect the presence of burning heat and promptly release a messenger to inform the remaining cells of the body to start swimming in the opposite direction. While for simple organisms this might be enough, in more complex species (of which we probably rank first) the scale of intercellular communication needed is so vast that one organ has evolved to do just this: the brain.

 

The way the brain works though, is still roughly the same. An array of hundreds of specialised chemical messengers (neurotransmitters) communicate crucial information to be processed in the central nervous system, which then decides a course of action that is launched via chemical commands to the relevant organs. This soup of highly coordinated chemical ingredients contained in our brain is also what, ultimately, enables our rich psychological experiences. In this series of articles I will analyze the main neurotransmitters of our brain with the aim of better understanding our behavior and minds.

 

The basic ingredients: GABA and glutamate

 

GABA and glutamate

GABA and Glutamate are the basic “zeroes” and “ones” of the brain language, playing a dynamic role in inhibiting and exciting, respectively, neighboring neurons. This means that they are, in one way or another, involved in every function of the brain. [Source: UAB Magazine]

 

GABA and Glutamate activity has been implicated in consciousness, sleep, anesthesia, mood, anxiety, working memory, schizophrenia, epilepsy, and Parkinson’s, among many others. Think of any aspect of the mind and these two are most likely to be involved: daydreaming, keeping track of points in a game, recalling your childhood pet, etc.

 

The main ingredients: dopamine, serotonin, noradrenaline and acetylcholine

More interesting perhaps are the widespread modulatory neurotransmitters. These compounds change how different structures of the brain process information, rather than constituting messages in themselves. Their greater specificity means we have a better shot at understanding their role on one hand, and convert them to suitable targets for health interventions on the other.

Depiction of the two main pathways of dopamine in the human brain

Depiction of the two main pathways of dopamine in the human brain: one starting in the substantia nigra destined at nuclei that are involved in movement control, and a second one starting in the ventral tegmental areas that have more widespread distribution in the prefrontal cortex. [Source: Faculty of Pasadena]

 

Dopamine

This neurotransmitter is widely known as the rewarding signal of the brain. Initial research showed that animals and humans would repeatedly stimulate brain regions that release dopamine, to the point of starvation and even death (similarly to the effects of drug addiction). This led to the reasoning that the amount of dopamine released in conjunction with an activity determines how much one enjoys it. However, the reality turned out to be a bit more complex, and by the mid-‘90s early proponents of this idea “no longer believed that the amount of pleasure felt is proportional to the amount of dopamine floating around in the brain”.

 

In fact, it seems that dopamine influences how much one wants a specific reward, more than how much one actually ends up enjoying it. Parkinson patients treated with drugs that increase dopamine levels (the neurotransmitter is also involved in controlling motor actions, as well as attention, wakefulness and learning) often report increased urge to partake in gambling, shopping, drug or pornography consumption, notwithstanding feelings of frustration or dissatisfaction associated with these.

Depiction of the broad serotonergic circuit in the human brain

Depiction of the broad serotonergic circuit in the human brain: starting in the Raphe nuclei and projecting to most parts of the brain.

[Source: Faculty of Pasadena]

 

Serotonin

This brain neurotransmitter plays a major role in regulating mood and anxiety. The therapeutic effects of drugs that increase serotonin levels in patients with depression and anxiety disorders suggest that there is an underlying imbalance within the serotonin system in these conditions. Similarly, research shows that genetic debilities in serotonin signaling increase one’s vulnerability to the effects of stressful life events such as unemployment, disabling injuries, or being involved in abusive relationships.

 

Less known outside of the academia is the role of serotonin in aggressive behavior. Innumerous early animal and human studies identified a strong link between lower levels of serotonin in the brain and higher aggressivity. A real life example of this phenomenon is given by chronic Ecstasy (MDMA) consumption. Exposure to this drug leads to the death of serotonin neurons in the brain, which subsequently enables the aggressive tendencies that are often observed in users as soon as the “high” wears off.

 

At the turn of the century, the link between serotonin and aggression was acclaimed by a prominent researcher as “perhaps the most reliable finding in the history of psychiatry.” Later research eventually came to question the simplicity of this finding, and it is now apparent that serotonin plays many diverse and subtle roles in regulating not only mood, anxiety, and aggression, but also sexual behavior, appetite and cognition.

 

Depiction of the broad serotonergic circuit in the human brain

Depiction of the main noradrenergic circuits in the human brain: projecting from the locus coeruleus to the brain cortex, as well as cerebellum and down to the spinal medulla.

[Source: Faculty of Pasadena]

 

Noradrenaline

Also known as norepinephrine. It is the “turbocharger” of the brain. During moments of stress, a minuscule nucleus of a few thousand neurons fires this molecule through the entire brain. Depending on where it is detected, noradrenaline enhances sensorial information processing, attention, memory function, reaction timings, and flexible decision-making. Simultaneously, noradrenaline is released peripherally, where it activates the body parts that are absolutely crucial for action (e.g., heart, lungs, and muscle tissue) and shuts down the remaining others (e.g., digestive and immunity systems). Together, these processes comprise the classic “adrenaline rush” that is characterised by heightened awareness, strength, and stamina.

 

While this reaction is perfectly healthy and adaptive under short periods of time (it can even facilitate romantic attraction), it poses serious health and mental risks if sustained for longer periods. Chronic stress disorders may result. Also problematic are the cases in which it is elicited way too easily, such as in panic disorders.

 

Depiction of the main cholinergic projections in the human brain

Depiction of the main cholinergic projections in the human brain: starting in the pontine nuclei, two pathways can be distinguished, one located more deeply in the cortex and the other near its surface.

[Source: Faculty of Pasadena]

 

Acetylcholine

The first neurotransmitter to be discovered is, interestingly, also the reason why nicotine is so addictive and nerve gas so deadly. It is released by motor neurons to activate our muscles and regulate organ tissues like the lungs and heart (nerve gas works by stopping the degradation of acetylcholine, which in turn keeps the heart continuously constricted).

 

In the brain, this ingredient modulates arousal, the waking-sleeping cycle, attention, reinforcement, and memory. An unfortunate showcase of the last function is given in Alzheimer’s disease, where the deterioration of the acetylcholine system is in part responsible for the memory impairments that follow it. The effects of the neurotransmitter are also evidenced by nicotine, as its chemical similarity easily tricks the brain into enacting them.

 

Summary

In short, here are the main roles of the six neurotransmitters we covered:

  • GABA: inhibitory signal of the brain
  • Glutamate: excitatory signal of the brain
  • Dopamine: motivation and movement
  • Serotonin: mood, anxiety and aggression
  • Noradrenaline: arousal, attention and reaction times
  • Acetylcholine: arousal, sleep and memory

 

If you would like to keep learning about the ingredients of the brain and how they all come together to create our unique experiences, read the second part of this series. We will be discussing how neurotransmitters interact, as well as the role of receptors, enzymes and glial cells.

 

Credit

Ricardo Oliveira is a neuroscientist passionate about research and science divulgation, based in Portugal.

 

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Ricardo Oliveira
Ricardo Oliveira

Author