What are neurotransmitters?

Introduction

In the late 1880s and the early 1900s, Santiago Ramón y Cajal and Charles Sherrington, respectively, demonstrated that there is a gap separating one neuron (nerve cells that transmit and store information) from another, which Sherrington called the synapse. Their work was extended by Otto Loewi, who proved in 1920 that neurons send messages across the synaptic gap using chemicals. By the 1950s, the principle that neurons communicate with one another through chemicals was well established, stimulating both a search for new neurotransmitters and new drugs for psychiatric and other medicinal uses.

The early view was that a presynaptic (sending) neuron discharges only one kind of neurotransmitter across the synaptic cleft to a postsynaptic (receiving) neuron. However, later researchers found that not only are multiple neurotransmitters released in most synapses, but neurotransmitters can be discharged from nonsynaptic neuronal membranes and postsynaptic neurons can send chemical messages to presynaptic cells. Furthermore, the idea that thoughts, feelings, and behavior can be reduced to specific neuronal chemicals is overly simplistic. Neurotransmitter effects depend on a combination of the type of neurotransmitter, what kind of receptor (a transmitter-activated protein molecule) picks up the neurotransmitter, and where in the nervous system the chemicals are released. For example, drug addiction has been linked with high amounts of dopamine at D2 receptors in the mesolimbic system.

Although what is known about neurotransmitters is complex and somewhat hard to grasp, there are three general principles that clarify matters. First, neurotransmitters can be distinguished from one another by the thoughts, feelings, and behaviors with which they are most prominently associated. Second, neurotransmitters can be classified into a handful of categories based on their chemical structure. Third, most neurotransmitters tend to have either an excitatory (activating) or inhibitory (deactivating) effect on affected cells.

Small Molecule Neurotransmitters

The first neurotransmitter discovered was
acetylcholine. Acetylcholine is the primary neurotransmitter for stimulating muscles (atropine and botulism block its effects) and conveying information in the parasympathetic nervous system. In the central nervous system, acetylcholine promotes rapid eye movement (REM) sleep and is critical for learning: Foods high in choline—a precursor of acetylcholine—boost learning; low acetylcholine levels inhibit learning, such as in Alzheimer’s disease.

Several small molecule transmitters are amines (substances containing NH2, an amino group). Four amines tend to have arousing effects.
Dopamine is essential for experiencing pleasure and has been implicated in almost any kind of addiction. Low levels of dopamine are associated with depression, restless leg disorder, and Parkinson’s disorder; very high levels are associated with schizophrenia and impulsiveness.
Epinephrine and norepinephrine are related: Norepinephrine plays a primary role in arousal, vigilance, active emotions, and emotional memories. Stimulant drugs, such as amphetamines, activate norepinephrine pathways. Most norepinephrine receptors accept epinephrine, which is the primary neurotransmitter in the sympathetic nervous system. Histamine conducts itching sensations, and its release by mast cells causes the red flaring typical in allergic reactions. Unlike the other amines, higher levels of serotonin tend to induce a calming effect, reducing impulsivity and decreasing appetite. Low levels are linked with depression (selective serotonin reuptake inhibitors, or SSRIs, form a category of antidepressants that increase serotonin), increased aggression (including suicide), and sudden infant death syndrome. Many hallucinogenic drugs (for example, lysergic acid diethylamine, or LSD, and 3,4-methylenedioxy-N-methylamphetamine, known as MDMA or Ecstasy) appear to work by interacting with serotonin.

The three most prevalent neurotransmitters are amino acids (substances containing amino and carboxyl groups). Almost all synaptic excitation requiresglutamate; almost all synaptic inhibition necessitates gamma-aminobutyric acid (GABA) in the brain or glycine in the spinal cord and lower brain areas. Glutamate is essential for learning; however, an overrelease can precipitate amnesia and neuronal death. Too much glutamate is also implicated in diseases of white matter (loss of myelin), such as multiple sclerosis; not enough glutamate is associated with schizophrenia. GABA has a sedative effect on the nervous system: Benzodiazepines, barbiturates, and alcohol bind on GABA receptors. Lack of GABA and glycine overactivates the nervous system and can induce disorders such as epilepsy (GABA deficits) and lockjaw (glycine deficits).

Peptides

The largest group of neurotransmitters—several dozen—are peptides (amino acid chains). Two peptides have a complementary effect: Substance P is the main carrier of pain; beta endorphins decrease pain. Beta endorphins and enkephalins belong to a family of opiate chemicals produced by the brain that typically increase pleasure but may inhibit learning.

Neuropetides play a role in many basic drives, including drinking (vasopressin), eating (neuropeptide Y), and sexuality (oxytocin).
Oxytocin, the hormone that is involved in uterine contractions and lactation, also serves as the bonding neurotransmitter. Higher levels of oxytocin stimulate and help to maintain pair bonding, parenting, and other prosocial behaviors.

Lipids, Nucleotides, and Gases

The brain not only produces opioids but also cannabis-like lipids called endocannabinoids. One of these chemicals, anandamide, helps to regulate the release of several small molecule transmitters. Endocannabinoids appear to interact with opioids to produce pleasurable effects, and, as with the opioids, overrelease may interfere with learning.

Adenosine, a nucleotide involved in sleep production, is also released by the nervous system’s other main cell type: glia. Caffeine has excitatory effects because it blocks adenosine receptors.

Two water-soluble gases, nitric acid and carbon monoxide, are neurotransmitters that can be released from any neuronal area, unlike all other neurotransmitters. Both neurotransmitters modulate the activity of other neurotransmitters and play a role in metabolic processes. Nitric oxide also dilates blood vessels: Erectile dysfunction drugs enhance the activity of nitric oxide.

Bibliography

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