neurotransmitters

How neurons communicate

• Early experiments suggested electrical signalling (Luigi Galvani – frog legs).

• Otto Loewi discovered chemical neurotransmission:
  

  • Stimulated the vagus nerve → slowed heart rate

  • Transferred solution to second heart → same effect

  • Discovered acetylcholine (“Vagusstoff”)

➡ Synapses can be electrical, chemical, or both

Electrical synapses

• Found in many systems (frog spinal cord, zebrafish retina, hippocampus).

• Crayfish giant synapse (Furshpan & Potter, 1959).

• Neurons connected by gap junctions (made of connexons).

Functions

• Very fast transmission

• Bidirectional

• Cannot be blocked by toxins

• Synchronises neurons (e.g. breathing control)

• Important for escape responses

Chemical synapses (classic neurotransmission)

• Unidirectional (presynaptic → postsynaptic)

• Slower than electrical signalling

• Use neurotransmitters

Key features

• Neurotransmitters:
  

  • Synthesised in neuron

  • Stored in vesicles

  • Released on demand

  • Bind receptors on postsynaptic membrane

  • Reuptaken and recycled

Types of neurotransmitters

1. Amines

• Dopamine – reward, pleasure, attention

• Noradrenaline – attention

• Serotonin (5-HT) – mood, appetite, sleep

• Histamine – arousal, wakefulness

2. Amino acids

• Glutamate – main excitatory transmitter (CNS)

• GABA – main inhibitory transmitter

• Glycine – inhibitory

3. Neuropeptides

• Examples: endorphins, substance P, neuropeptide Y

• Roles: pain, appetite, stress

• Gene-coded → evolve faster

Neurotransmitter release (quantal release)

• Discovered by Bernard Katz

• Released in discrete packets (quanta) from vesicles

Release mechanism

1. Vesicle docks at active zone

2. SNARE complex forms

3. Ca²⁺ enters presynaptic terminal

4. Ca²⁺ binds synaptotagmin

5. Vesicle fuses → neurotransmitter released

Receptors

Neurotransmitters act as ligands (key-lock model)

1. Ligand-gated ion channels (ionotropic)

• Fast

• Open ion channels directly

• Cause:
  

  • EPSPs (excitatory): Na⁺ / Ca²⁺ influx

  • IPSPs (inhibitory): K⁺ efflux or Cl⁻ influx

2. G-protein coupled receptors (metabotropic)

• Slower

• Activate G-proteins

• Trigger signalling cascades

• Can be excitatory or inhibitory

• Important drug targets

EPSPs vs IPSPs

• EPSP → depolarisation → easier to fire AP

• IPSP → hyperpolarisation → harder to fire AP

• Summation determines if AP occurs

• Balance of excitation/inhibition is critical

⚠ Imbalance → epilepsy

• Treated with drugs like valproate

Agonists & antagonists

• Agonists → activate receptors

• Antagonists → block receptors

• Example:
  

  • Antihistamines treat allergies but cause drowsiness

Termination of neurotransmitter signalling

Neurotransmitters removed by:

1. Diffusion

2. Enzymatic breakdown

3. Reuptake into presynaptic neuron

• Reuptake via transporter proteins

• Neurotransmitters are reused

Context matters

• Same neurotransmitter can have different effects:
  

  • Acetylcholine
    

    • Excitatory at neuromuscular junction

    • Inhibitory in the heart
      ➡ Effect depends on receptor type

Parkinson’s disease

• Loss of dopamine neurons in substantia nigra

• Symptoms: tremor, stiffness, balance loss, depression

• L-DOPA used → converted into dopamine

Depression & SSRIs

• Linked to reduced 5-HT signalling

• SLC6A4 gene codes for 5-HT transporter
  

  • Short allele → higher depression risk

• SSRIs:
  

  • Block 5-HT reuptake

  • Increase serotonin in synapse

  • Take weeks–months to work

Drugs of abuse

• Hijack neurotransmitter systems

• Example:
  

  • Cocaine blocks dopamine transporter (DAT)

  • ↑ dopamine signalling → reward effects

Key summary

• Neurotransmitters are chemical messengers

• Synthesised, stored in vesicles, released by Ca²⁺

• Bind ionotropic or metabotropic receptors

• Mostly reuptaken and recycled

• Imbalances → neurological & psychiatric disease