Neurotransmitters are specialized chemical messengers used by the nervous system to transmit signals across synapses from one neuron to another or from neurons to effector organs such as muscles and glands. They play a central role in coordinating sensory input, motor output, mood regulation, cognition, and autonomic functions.
Neuronal communication typically occurs across a synaptic cleft , where an electrical signal (action potential) in the presynaptic neuron is converted into a chemical signal (neurotransmitter release) that binds to receptors on the postsynaptic neuron to elicit a response.
Classification of Neurotransmitters
Neurotransmitters can be categorized based on:
1. Functional Effect
- Excitatory neurotransmitters: Promote depolarization of the postsynaptic membrane (e.g., glutamate, acetylcholine)
- Inhibitory neurotransmitters: Induce hyperpolarization and suppress action potentials (e.g., GABA, glycine)
- Modulatory neurotransmitters (Neuromodulators): Modulate the strength, duration, or spread of neural signaling (e.g., dopamine, serotonin, histamine)
2. Chemical Structure
- Amino acids: Glutamate, GABA, glycine
- Amines (monoamines): Dopamine, norepinephrine, epinephrine, serotonin, histamine
- Peptides: Substance P, endorphins, enkephalins
- Others: Acetylcholine, purines (e.g., ATP)
Major Neurotransmitters
1. Acetylcholine (ACh)
- Type: Excitatory (mostly)
- Sites of action:
- Neuromuscular junctions (somatic nervous system)
- Autonomic nervous system (preganglionic sympathetic and both pre- and postganglionic parasympathetic neurons)
- Basal forebrain and brainstem (cognitive and memory functions)
Clinical relevance:
- Alzheimer’s disease is associated with degeneration of cholinergic neurons in the CNS.
- Botulinum toxin blocks ACh release, leading to flaccid paralysis.
- Myasthenia gravis is an autoimmune condition that targets ACh receptors at the neuromuscular junction.
2. Norepinephrine (Noradrenaline)
- Type: Primarily excitatory
- Sites of action:
- Postganglionic sympathetic neurons
- Locus coeruleus in the brainstem (regulates alertness, mood, arousal)
Clinical relevance:
- Increased levels are linked to anxiety , hypertension , and stress response .
- Decreased levels are associated with depression and attention deficits .
- Key target in SNRIs and tricyclic antidepressants .
3. Epinephrine (Adrenaline)
- Type: Excitatory
- Source: Primarily secreted by the adrenal medulla (acts as both hormone and neurotransmitter)
- Function: Activates fight-or-flight response ↑ HR, BP, blood glucose
Clinical relevance:
- Used pharmacologically in anaphylaxis and cardiac arrest .
- Overactivity may cause panic symptoms or pheochromocytoma signs.
4. Dopamine
- Type: Both excitatory and inhibitory (modulatory)
- Pathways in CNS:
- Mesolimbic/mesocortical: reward, mood, motivation
- Nigrostriatal: motor control
- Tuberoinfundibular: inhibits prolactin secretion
Clinical relevance:
- Parkinson’s disease: degeneration of dopaminergic neurons in the substantia nigra
- Schizophrenia: associated with excess dopamine in mesolimbic pathway
- Addiction and reward involve increased dopamine activity
5. Gamma-Aminobutyric Acid (GABA)
- Type: Inhibitory
- Main inhibitory neurotransmitter in the CNS
- Action: Opens Cl⁻ channels, causing hyperpolarization and reducing excitability
Clinical relevance:
- Low GABA activity is linked to anxiety , epilepsy , and insomnia
- Benzodiazepines and barbiturates enhance GABAergic activity
6. Glutamate
- Type: Excitatory
- Main excitatory neurotransmitter in the CNS
- Acts on NMDA, AMPA, and kainate receptors
Clinical relevance:
- Plays a role in learning and memory via long-term potentiation (LTP)
- Excess glutamate causes excitotoxicity , seen in stroke and ALS
- NMDA antagonists used in Alzheimer’s disease (e.g., memantine)
7. Glycine
- Type: Inhibitory
- Main inhibitory neurotransmitter in the spinal cord and brainstem
Clinical relevance:
- Inhibitory action enhanced by strychnine antagonism , leading to convulsions
- Works synergistically with GABA
8. Serotonin (5-HT)
- Type: Mostly inhibitory (modulatory)
- Produced in: Raphe nuclei (brainstem)
- Regulates mood , sleep , appetite , pain perception , GI motility
Clinical relevance:
- Low serotonin levels linked to depression , OCD , and anxiety
- Target of SSRIs and SNRIs
- Involved in migraine pathophysiology and GI disorders
9. Histamine
- Type: Excitatory (modulatory)
- Produced by: Hypothalamus (tuberomammillary nucleus) and mast cells
- Regulates wakefulness , arousal , and immune response
Clinical relevance:
- Antihistamines cause sedation by blocking central histamine receptors
- Contributes to symptoms of allergic reactions (itching, swelling)
Neuromodulators vs Neurotransmitters
- Neurotransmitters act locally and quickly, typically within milliseconds, and are confined to the synaptic cleft.
- Neuromodulators (e.g., dopamine, serotonin, neuropeptides):
- Influence broader areas of the CNS
- Operate over longer timescales
- Modify sensitivity or response of neurons to other neurotransmitters
