Neurotransmitters and the Limbic System

Neurotransmitters

• Neurotransmitters are chemicals that transmit signals across a synapse from one neuron to another 'target' cell.
• Catecholamines are neurotransmitters derived from the amino acid tyrosine.
• Norepinephrine (NE), epinephrine (E), and dopamine are catecholamines.
• Norepinephrine (NE) is the major neurotransmitter in the sympathetic nervous system.
• Epinephrine is more active than norepinephrine on the heart and lungs, and redirects blood flow from skin to skeletal muscles.
• In response to epinephrine, extra glucose is delivered to muscles; the heart and lungs work harder to pump oxygen, and the body prepares to run or defend itself.

Catecholamines

• Catecholamines are derivatives of catechol with an amino group as a side chain.
• Catechol is a dihydroxyphenol with two adjacent hydroxyl groups.
• Norepinephrine, epinephrine, and dopamine are all derived from the amino acid tyrosine.
• These compounds are also known as biogenic amines.

Norepinephrine

• Major transmitter in the sympathetic nervous system, transmitting signals from the spinal cord to ganglia.
• Norepinephrine is released at the postganglionic nerves.
• Stimulation of these nerves is responsible for the "flight or fight" response, including heart rate increase, sweating, and skin and bronchodilation.
• Norepinephrine-containing neurons arise from the locus ceruleus in the brainstem and are distributed across the cortex.

Epinephrine

• Epinephrine is more active than norepinephrine in the sympathetic nervous system, particularly influencing the heart and lungs.
• Redirecting blood flow from skin to skeletal muscle is another significant function.
• Epinephrine stimulates glycogen metabolism in the liver to release glucose.

Dopamine

• Dopamine is a neurotransmitter that plays a key role in voluntary movement control and is also involved in emotional responses and memory.
• Dopamine-containing nerves run in well-defined tracts, one of the most important being the nigrostriatal system, which connects the substantia nigra with basal ganglia.
• Damage to the dopamine-producing pathways can lead to Parkinson's disease.
• Dopamine causes vasodilation.
• Catabolism of dopamine produces homovanillic acid (HVA).

Glutamate

• The most important excitatory neurotransmitter in the central nervous system (CNS).
• Glutamate acts on both ionotropic and metabotropic receptors.
• An example of an ionotropic glutamate receptor is the N-methyl-D-aspartate (NMDA) glutamate receptor.

GABA

• GABA (gamma-aminobutyric acid) is a major inhibitory neurotransmitter in the brain.
• It's synthesized from glutamate.
• GABA acts on two known receptors, GABAA (ionotropic) and GABAB (metabotropic).
• GABAA receptors consist of five subunits from several gene families, resulting in diverse binding properties.
• Psychoactive drugs, like benzodiazepines, enhance GABA's effects by binding to GABAA receptors, increasing the frequency of chloride ion channel opening and hyperpolarizing the membrane.

Serotonin

• Serotonin (5-hydroxytryptamine) is an important neurotransmitter derived from tryptophan.
• Serotoninergic neurons are concentrated in the raphe nuclei of the upper brain stem and project to the cerebral cortex and spinal cord.
• Serotonin is involved in mood regulation, memory processing, sleep control, and is responsive to sensory input.
• Serotonin also affects the peripheral nervous system, controlling gastrointestinal function among other roles.
• Excessive serotonin may cause panic attacks.

Histamine

• Histamine plays roles in pain threshold, sexual arousal, pituitary hormone secretion, and blood pressure control.
• Catabolized to N-methylimidazoleacetic acid or imidazoleacetic acid, via diamine oxidase (DAO), histamine N-methyltransferase (HNMT), and aldehyde dehydrogenase.
• This process requires vitamin B6.

Glycine

• Glycine is an inhibitory neurotransmitter in the spinal cord, with an action comparable to GABA in the brain, resulting in hyperpolarization.
• It is packed in vesicles and released via exocytosis.
• Glycine receptor structure resembles the GABAA receptor, and its primary effect involves opening chloride channels.

Nitric Oxide Gas

• Produced by synaptic terminals that innervate smooth muscle in blood vessels and at the synapses in regions of the brain.
• Also called endothelium-derived relaxing factor (EDRF).
• Causes vasodilation.

Neuropeptides

• Synthesized in neuron bodies like other proteins.
• Undergoes modifications after synthesis, affected by prohormone action, convertases, and carboxypeptidases.
• The processed products (neuropeptides) are transported to the presynaptic region.
• Neuropeptides play diverse roles in regulating pain, pituitary function, digestive reflexes, appetite, and behavioral effects.

Neuromodulators

• Neuromodulators alter the rate of neurotransmitter release from presynaptic neurons or alter the postsynaptic response to neurotransmitters.
• Neuropeptides can be classified as neuromodulators.
• Neuromodulators act by binding to receptors on pre- and postsynaptic membranes and activating cytoplasmic enzymes.