How the Brain Works

 The brain communicates through a complex network of pathways involving neurons and neurotransmitters. Here are some key communication pathways in the brain:

NUERONS AND NUEROTRANSMITERS

The brain is made up of a vast network of neurons that transmit vital electrical and chemical signals within the brain and to other body organs influencing how you feel and behave in particular circumstances and to the greater extent determining your personality.

Neurons use both electrical and chemical signals to transmit messages. A neuron is a nerve cell with a long tail-like end called a “dendrite.” When it gets a message, it sends the signal from one end of the tail all the way down to the other end of the cell via electricity. But it can’t send its electrical signal through to its neighbouring neuron. To send that message over, it communicates with its neighbouring neuron by neurotransmitters.

What are neurotransmitters?

Neurotransmitters are chemical messengers that your body can’t function without. Their job is to carry chemical signals (“messages”) from one neuron (nerve cell) to the next target cell. The next target cell can be another nerve cell, a muscle cell or a gland.

Types of neurotransmitters

Scientists know of at least 100 neurotransmitters and suspect there are many others that have yet to be discovered. They can be grouped into types based on their chemical nature. Some of the better-known categories and neurotransmitter examples and their functions include the following:

Amino acids neurotransmitters

Amino acid transmitters provide the majority of excitatory and inhibitory neurotransmission in the nervous system.

Glutamate. This is the most common excitatory neurotransmitter of your nervous system. It’s the most abundant neurotransmitter in your brain.

It plays a key role in cognitive functions like thinking, learning and memory. Imbalances in glutamate levels are associated with Alzheimer’s disease, dementia, Parkinson’s disease, Huntington's chorea, and conscious seizures.

Glutamate and aspartate are products of the Kreb's cycle, and both have excitatory effects in the CNS. They are produced in the mitochondria, transported into the cytoplasm, and packaged into synaptic vesicles. Specific high-affinity enzymes are responsible for packaging glutamate into vesicles.

The actions of glutamate are terminated by high-affinity uptake systems in neurons and glia. Under normal circumstances most uptake is back into the neuron and this glutamate can immediately be pumped into vesicles for subsequent release. When neuronal activity is high, extracellular glutamate concentration exceeds the capacity of neuronal uptake. At this point, uptake systems in glial cells help absorb the excess glutamate. However, glutamate is not permeable to the plasma membrane. To recycle the glutamate taken up into glial cells, an enzymatic reaction catalyzed by glutamine synthase produces glutamine from glutamate. Glutamine is freely permeable to the glial and neuronal plasma membranes and diffuses back into the neuron. The neuronal enzyme glutaminase then metabolizes glutamine into glutamate where it can then be packaged into synaptic vesicles for another round of release.

Gamma-aminobutryic acid (GABA). GABA is the most common inhibitory neurotransmitter of your nervous system, particularly in your brain.

It regulates brain activity to prevent problems in the areas of anxiety, irritability, concentration, sleep, seizures and depression.

GABA is synthesized from glutamate in a reaction catalyzed by glutamic acid decarboxylase. Antibodies to GAD can be used to identify GABAergic neurons. Like the other amino acid transmitters, GABA's actions are terminated by high affinity uptake systems in neurons and glia. Neuronal uptake permits immediate repackaging into vesicles for release. Compared with glutamate, a more elaborate set of reactions is necessary to return GABA to the neuron when it is taken up by glial cells. Some of these enzymes are shared with those for returning released glutamate to neurons. GABA is first converted back into glutamate by the mitochondrial enzyme GABA transaminase using the -COOH group from alpha-ketoglutarate. This pathway is sometimes referred to as the "GABA shunt". The glutamate is then converted to glutamine by the enzyme glutamine synthase and glutamine diffuses back into the neuron. Finally, glutaminase converts glutamine into glutamate, which can again serve as a substrate for GAD, completing the cycle.

Glycine. Glycine is the primary neurotransmitter of many inhibitory interneurons in the spinal cord and brainstem, including the ventral horn and motor cranial nerve nuclei, dorsal horn and trigeminal nuclei, and auditory and vestibular systems; it also mediates inhibitory effects of some amacrine cells and Golgi cells of the cerebellum. Glycine also has an essential role in intermediate metabolism; for example, it is the precursor to the one-carbon pool of folic acid intermediates that are fundamental to many synthetic reactions (Benarroch, 2011). As a neurotransmitter, glycine both stimulates and inhibits cells in the brain and central nervous system, affecting cognition, mood, appetite and digestion, immune function, pain perception, and sleep.

It is also present in lower amounts throughout the nervous system. Glycine is synthesized from serine in the mitochondria (Figure 3). The reaction is catalyzed by the enzyme serine transhydroxymethylase. Like glutamate, high-affinity uptake systems remove glycine from the synaptic cleft, which can then be repackaged into vesicles.

The binding of glycine to its receptor on postsynaptic neurons is blocked by the poison strychnine, thus blocking glycine's inhibitory actions (Figure 3).

The block of inhibition leads to hyperexcitation and typically a patient with strychnine poisoning asphyxiates due to an inability to relax the diaphragm.

Monoamines neurotransmitters

These neurotransmitters play a lot of different roles in your nervous system and especially in your brain. Monoamines neurotransmitters regulate consciousness, cognition, attention and emotion. Many disorders of your nervous system involve abnormalities of monoamine neurotransmitters, and many drugs that people commonly take affect these neurotransmitters.

Serotonin. Serotonin is an inhibitory neurotransmitter. Serotonin helps regulate mood, sleep patterns, sexuality, anxiety, appetite and pain. Diseases associated with serotonin imbalance include seasonal affective disorder, anxiety, depression, fibromyalgia and chronic pain. Medications that regulate serotonin and treat these disorders include selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs).

Histamine. Histamine regulates body functions including wakefulness, feeding behavior and motivation. Histamine plays a role in asthma, bronchospasm, mucosal edema and multiple sclerosis.

Dopamine. Dopamine plays a role in your body’s reward system, which includes feeling pleasure, achieving heightened arousal and learning. Dopamine also helps with focus, concentration, memory, sleep, mood and motivation. Diseases associated with dysfunctions of the dopamine system include Parkinson’s disease, schizophrenia, bipolar disease, restless legs syndrome and attention deficit hyperactivity disorder (ADHD). Many highly addictive drugs (cocaine, methamphetamines, amphetamines) act directly on the dopamine system.

Epinephrine. Epinephrine (also called adrenaline) and norepinephrine (see below) are responsible for your body’s so-called “fight-or-flight response” to fear and stress. These neurotransmitters stimulate your body’s response by increasing your heart rate, breathing, blood pressure, blood sugar and blood flow to your muscles, as well as heighten attention and focus to allow you to act or react to different stressors. Too much epinephrine can lead to high blood pressure, diabetes, heart disease and other health problems. As a drug, epinephrine is used to treat anaphylaxis, asthma attacks, cardiac arrest and severe infections.

Norepinephrine. Norepinephrine (also called noradrenaline) increases blood pressure and heart rate. It’s most widely known for its effects on alertness, arousal, decision-making, attention and focus. Many medications (stimulants and depression medications) aim to increase norepinephrine levels to improve focus or concentration to treat ADHD or to modulate norepinephrine to improve depression symptoms.

Peptide neurotransmitters

Peptides are polymers or chains of amino acids.

Endorphins. Endorphins are your body’s natural pain reliever. They play a role in our perception of pain. Release of endorphins reduces pain, as well as causes “feel good” feelings. Low levels of endorphins may play a role in fibromyalgia and some types of headaches.

Acetylcholine

This excitatory neurotransmitter does a number of functions in your central nervous system (CNS [brain and spinal cord]) and in your peripheral nervous system (nerves that branch from the CNS). Acetylcholine is released by most neurons in your autonomic nervous system regulating heart rate, blood pressure and gut motility. Acetylcholine plays a role in muscle contractions, memory, motivation, sexual desire, sleep and learning. Imbalances in acetylcholine levels are linked with health issues, including Alzheimer’s disease, seizures and muscle spasms.