What are neurotransmitters and their role in brain function?

Neurotransmitters: Chemical Messengers of the Nervous System

Neurotransmitters are chemical messengers that transmit signals between neurons across synapses, enabling all brain functions including movement, emotion, cognition, and pain perception. 1

Core Neurotransmitter Categories and Functions

Excitatory and Inhibitory Systems

• Glutamate serves as the primary excitatory neurotransmitter in the brain, essential for learning, memory processes, and excitatory postsynaptic potentials that drive neuronal firing 1
• GABA (gamma-aminobutyric acid) functions as the major inhibitory neurotransmitter, counterbalancing glutamate's excitatory effects to maintain normal brain function 2
• The balance between glutamate and GABA is critical—disruption leads to conditions like epilepsy and seizures 3

Monoamine Neurotransmitters

• Dopamine controls reward processing, motor control, and motivation, with dysregulation causing Parkinson's disease (deficiency) and addiction (excess) 1
• Serotonin (5-HT) regulates mood, sleep cycles, and pain modulation through descending pain inhibitory pathways 1, 4
• Norepinephrine (noradrenaline) is the main mechanism for controlling visceral pain through reuptake inhibition and descending modulation 1, 4
• Epinephrine (adrenaline) mediates the "fight-or-flight" response and sympathetic nervous system activation 1

Other Critical Neurotransmitters

• Acetylcholine is the primary neurotransmitter at neuromuscular junctions and plays essential roles in memory, learning, and autonomic functions—its deficiency is associated with Alzheimer's disease and myasthenia gravis 1, 3
• Substance P transmits pain signals and inflammatory responses in the dorsal horn of the spinal cord 1, 4
• Opioid peptides (endorphins, enkephalins, dynorphins) bind to opioid receptors in the dorsal horn to naturally modulate pain transmission 1, 4

Mechanism of Action

Basic Transmission Process

• Neurotransmitters are released from neuronal endings through exocytosis, diffuse rapidly across the synaptic cleft (the gap between neurons), and bind to receptor proteins embedded in the postsynaptic neuron's membrane 5
• Ionotropic receptors, such as NMDA receptors for glutamate, mediate fast synaptic transmission by directly opening ion channels 1
• After binding, neurotransmitters are either broken down by enzymes or taken back up into the presynaptic neuron for reuse 2

Neurobiological Basis of Disorders

• Childhood psychiatric disorders are associated with abnormalities in neurotransmitters and structural or functional abnormalities of specific brain regions, caused by environmental factors, genetic factors, or their combination 6
• Stimulant medications for ADHD work by binding to dopamine transporters in the striatum, increasing synaptic dopamine to enhance executive control processes in the prefrontal cortex 6
• Following traumatic brain injury, indiscriminate neurotransmitter release and unchecked ionic fluxes occur, with excess excitatory neurotransmitter binding leading to neuronal depolarization and energy crisis 6

Clinical Therapeutic Applications

Medication Targets

• Many medications target neurotransmitter systems: selective serotonin reuptake inhibitors (SSRIs) for depression, dopamine precursors for Parkinson's disease, and GABAergic drugs for anxiety and epilepsy 1
• SNRIs (serotonin-norepinephrine reuptake inhibitors) are effective for pain control by enhancing natural pain inhibition pathways through both serotonin and norepinephrine systems 1, 4
• Stimulants increase norepinephrine and dopamine in the synaptic cleft, though compensatory mechanisms after oral absorption remain unclear 6

Detection and Monitoring

• Advanced neuroimaging techniques like PET scanning can visualize neurotransmitter receptor binding in various neurological and psychiatric conditions 1
• PET scans have demonstrated that untreated adults with ADHD show 8.1% lower cerebral glucose metabolism than controls, with greatest differences in the superior prefrontal cortex 6

Common Clinical Pitfalls

• Do not assume single neurotransmitter dysfunction in complex disorders—most neurological conditions involve dysregulation of multiple neurotransmitter systems simultaneously 7
• When prescribing medications that affect neurotransmitters, recognize that the brain may develop compensatory mechanisms over time, potentially requiring dose adjustments 6
• Neurotransmitter imbalances following brain injury create vulnerability to subsequent injury through energy crisis and impaired mitochondrial function 6