Neurotransmitters in the Nervous System

Neurotransmitters

• Glutamate and GABA (Gamma-aminobutyric acid) are neurotransmitters that maintain brain function balance
• Glutamate is excitatory and found in all cells and tissues, while GABA is inhibitory
• Excess glutamate can lead to excitotoxicity, causing cell death
• Glutamate and GABA transmission can be mediated by ionotropic and metabotropic receptors

Glutamate

• Glutamate is an excitatory neurotransmitter
• Glutamate excitotoxicity can occur due to excess glutamate, leading to cell death
• States of hypoxia and ischemia (stroke and TBI) can enhance glutamate's excitatory effects

GABA

• GABA is an inhibitory neurotransmitter
• GABA-A receptors are ionotropic, while GABA-B receptors are metabotropic
• GABA transmission is involved in anxiety, insomnia, and muscle relaxation
• GABA transmission can be enhanced by drugs to treat anxiety and insomnia

Acetylcholine

• Acetylcholine is a neurotransmitter involved in learning, memory, and motor control
• Acetylcholine is a primary rapid transmitter in the brain
• Acetylcholine receptors can be ionotropic (fast) or metabotropic (slow)
• Combined with dopamine, acetylcholine controls motor function, specifically smooth motor function (e.g., handwriting)

Dopamine

• Dopamine is involved in pleasure, addiction, and motor dysfunction
• Dopamine receptors are metabotropic (slow)
• Deterioration of dopamine leads to motor dysfunction and is associated with Parkinson's disease
• Dopamine is involved in motivation, arousal, and reward processing

Norepinephrine (NE)

• Norepinephrine is a neurotransmitter involved in attention, arousal, and motivation
• Norepinephrine receptors are metabotropic (slow)
• Suppression of norepinephrine can lead to sedation (e.g., clonidine)
• Norepinephrine is involved in modulation of pain perception

Serotonin (5-HT)

• Serotonin is a neurotransmitter involved in mood regulation, appetite, and sleep
• Serotonin receptors are metabotropic (with one exception: 5-HT3)
• Increased serotonin levels in the brain can treat depression and anxiety
• Selective serotonin reuptake inhibitors (SSRIs) increase serotonin levels in the brain

Histamine

• Histamine is a neurotransmitter involved in arousal, motivation, and modulation of pain
• Histamine receptors are metabotropic
• Histamine is active during wakefulness and decreased during sleep
• Non-selective histamine antagonists (e.g., diphenhydramine) can cause sleepiness

Peptides

• Peptides are neurotransmitters involved in modulation of behavior states
• Peptides interact across the CNS and PNS
• Peptides are metabotropic

Pain Modulation

• Descending pain modulation involves the use of neurotransmitters norepinephrine and serotonin
• Norepinephrine and serotonin can decrease pain perception
• Glutamate can ascend pain signals to the spinal cord, leading to rapid action to stop painful stimuli
• Pain sensitization can occur due to inflammation, leading to hyperalgesia and allodynia

Myasthenia Gravis

• Myasthenia gravis is an autoimmune disorder that attacks acetylcholine receptors
• The disorder leads to muscle weakness and fatigue, often beginning with facial muscles
• Symptoms can progress to dysphagia, impaired speech, and impaired gait

Lower and Upper Motor Neuron Lesions

• Lower motor neuron lesions affect the brainstem and spinal cord, leading to weakness, muscle atrophy, and hyporeflexia
• Upper motor neuron lesions affect the motor cortex, leading to increased spasticity, hyperreflexia, and weakness

Dysmetria and Dysdiadochokinesia

• Dysmetria is a movement disorder characterized by fluctuations in movement amplitude
• Dysdiadochokinesia is a movement disorder characterized by an inability to conduct rapid alternating movements
• Both disorders are associated with cerebellar dysfunction, which can result from injury, stroke, tumors, or congenital conditions