Neurotransmitters and

Neuronal Tracts
Irene Carmelle S. Tan, MD, DSBPP
 • Defined by meeting three criteria:
1. The substance must be stored in the presynaptic
neuron.
2. It must be released with depolarization of the
presynaptic neuron induced by the influx of Ca2+.
3. The substance must bind with a specific receptor
on the postsynaptic neuron.
Neurotransmitters • Neurotransmitters differ from hormones by their close
physical proximity of the release to the receptor
• Three basic categories:
1. The classic neurotransmitters
2. Neuropeptides
3. Unconventional neurotransmitters
 • Glutamate
• It is the major workhorse of the brain
• Makes up more than half of the excitatory
Classic neurons.
• Do not cross the blood brain barrier.
Neurotransmitter: • Synthesized in the brain from glucose and
Amino Acids other precursors.
• Glial cells assist in the reuptake,
degradation, and resupply of glutamate for
neurons.
 • GABA and Glycine
• GABA is the major inhibitory transmitter in
the brain and is used by approximately 25%
of the cortical neurons.
• Glycine is the other inhibitory amino acid,
Classic but is less common.
Neurotransmitter: • GABA puts the brakes on the brain: not
Amino Acids enough GABA and one can have seizures.
• GABA interneuron quiets an overactive
neuron.
• Increasing GABAergic activity has been used
to treat insomnia, pain, and anxiety, and to
assist in the management of mania.
 • Two principle classes of monoamines:
• Catecholamines (DA, NE, and epinephrine)
• Indoleamines (serotonin and melatonin)
• All the monoamines are inactivated and degraded when
taken back by the neuron. (Clinicians often refer to this as
Classic the reuptake pump, but neuroscientists call this the
Neurotransmitter: transporter, e.g., the DA transporter.)

Monoamine • The class of enzymes in the terminal that degrades the

neurotransmitters is the monoamine oxidases (MAOs).
• Consequently, MAO inhibitors cause an increase in
catecholamines (e.g., DA, NE, and serotonin), by limiting
the degradation process, with well-known benefits for
depression and anxiety.
 • Dopamine
• DA neurons constitute approximately half a million of
the cells in the brain
• Substantia nigra located in the ventral midbrain has
primary projections to the caudate and putamen
(collectively called the striatum).
Classic • This pathway is called the nigrostriatal system or
Neurotransmitter: mesostriatal system.
• As part of the basal ganglia this pathway is integral to
Monoamine voluntary movement.
• Parkinson's disease is the result of a loss of DA
neurons in the substantia nigra.
• The extrapyramidal side effects due to antipsychotic
medications can induce parkinsonian symptoms by
blockade of these neurons.
 • Dopamine
• The cells of the ventral tegmental area, also
in the ventral midbrain, project to the
nucleus accumbens, prefrontal cortex,
amygdala, and hippocampus.
Classic
• These innervations, called the
Neurotransmitter: mesolimbocortical DA system, are
Monoamine particularly dense in primates.
• Subdivided to 2 branches:
• mesolimbic (nucleus accumbens,
amygdala, and hippocampus)
• mesocortical (prefrontal cortex)
 • Dopamine
• The short tracts in the arcuate nucleus of
the hypothalamus called the
tuberoinfundibular DA system release DA
Classic into the portal veins of the pituitary gland.
• The synthesis and release of prolactin in the
Neurotransmitter: anterior pituitary is inhibited by this DA.
Monoamine • Any process that interrupts the action of DA
on the prolactin-producing cells will lead to
hyperprolactinemia.
• Antipsychotic medications that block the DA
receptor can cause an increase in prolactin
 • Dopamine
• In summary there are 4 tracts:
1. Nigrostriatal tract – controls
movement (parkinsonian symptoms)
2. Mesolimbic tract – projects to the
Classic limbic system (positive symptoms in
Neurotransmitter: schizophrenia)
Monoamine 3. Mesocortical tract – projects to the
prefrontal area (negative symptoms in
schizophrenia)
4. Tuberoinfundibular tract – controls
prolactin (hyperprolactinemia with the
use of antipsychotic)
 • Norepinephrine
• Noradrenergic neurons - contain an additional
enzyme in their terminals that converts DA to
NE.
• Approximately 50% of the NE neurons are
Classic located in the locus coeruleus.
Neurotransmitter: • Project to virtually every area of the brain and
spinal cord.
Monoamine • Noradrenergic neurons are important in
handling danger (Sympathetic nervous system)
• NE is cleared from the synaptic cleft by a
reuptake transporter that is also capable of
taking up DA.
 • Serotonin (5-hydroxytryptamine)
• Synthesized from tryptophan that must be
obtained in the diet (grains, meats, and dairy
products are good sources of tryptophan).
• Levels of serotonin in the brain can be lowered
Classic significantly with insufficient dietary tryptophan.
Neurotransmitter: • In the pineal gland there are two additional
enzymes that convert serotonin to melatonin,
Indoleamines the other indoleamine.
• Cell bodies are relatively few and reside in the
raphe nuclei in the brain stem.
• As with NE, the serotonin neurons project to
virtually all areas of the brain.
 • Histamine
• Released from mast cells as part of an
allergic reaction in the peripheral tissue
• In the brain, it is involved in arousal and
Classic attention.
• Most of the cell bodies start in the
Neurotransmitter: tuberomammilary nucleus of the posterior
Indoleamines hypothalamus
• When animals are alert, the histamine
neurons are active.
• Histamine neurons are quiet when animals
are sleeping.
 • Acetylcholine
• Only small molecule transmitter that is not an
amino acid or directly derived from one.
• Not a monoamine, but is often grouped with
Classic these neurotransmitters due to similar size and
distribution.
Neurotransmitter:
• Plays a prominent role in the peripheral ANS
Indoleamines and is the neurotransmitter at the
neuromuscular junction.
• Projections to the hippocampus that are
involved with learning and memory and are
disrupted in Alzheimer's disease.
 • The neuropeptides are small chains of amino acids,
which are considerably larger than the classic
neurotransmitters.
• Initially, the peptide is a large propeptide precursor,
which is cleaved into an active neuropeptide as it is
moved from the Golgi apparatus
• Not recycled by the neuron, but are rather broken
Neuropeptides down by degradative enzymes (peptidases) on the
receptor membrane.
• Examples:
• adrenocorticotropic hormone (ACTH),
luteinizing hormone, somatostatin, and
vasopressin
• endorphins and enkephalins
 • Gas: Nitric Oxide
• Most commonly associated with erectile
dysfunction,
• Formed in glutamate neurons when arginine is
converted into citrulline and NO.
• Diffuse (without obstruction) out of the
Unconventional originating cell, through the extracellular
Neurotransmitters medium and into any neighboring cell that it
meets.
• Converts guanosine triphosphate (GTP) into
cyclic guanosine monophosphate (GMP) that
acts as a second messenger.
• Send a message to the neighboring cells that
signals an increase in activity
 • Endocannabinoids
• Main active compound of marijuana is
tetrahydrocannabinol (THC), which binds to the
cannabinoid receptor and causes the well-known
euphoria, calm, distorted cognition, and munchies
• The cannabinoid receptor 1 (CB 1) is widely expressed
throughout the brain on presynaptic terminals.
• calming effect of marijuana.
Unconventional • activating or blocking the CB1 receptor for
Neurotransmitters therapeutic reasons such as pain, anxiety, and
nausea are being pursued vigorously.
• Potential for a weight loss treatment
• Rimonabant - selective blocker (antagonist) of
the CB1 receptor - facilitate weight loss
• The cannabinoid receptor 2 (CB 2) implicated in
depressing the immune system