Neurotransmitters (NT)😊

Neurotransmitters (NT)

• 1st neurotransmitter discovered: 
• Acetylcholine.

Classification

• Class I: Acetylcholine

• Class II: Biogenic amines (e.g., Dopamine, Norepinephrine, Serotonin)

• Class III: Amino acids (e.g., Glutamate, GABA, Glycine)

• Class IV: Gases (e.g., Nitric oxide, Carbon monoxide)

• Mnemonic: AC Ba Aa Ga

• SNc → Substantia Nigra

• Norepinephrine locked in ICU → Locus ceruleus

• ↑↑ Dopamine activity → Madly (Schizophrenia) hunting ()

• ↓↓ GABA → ↓↓ inhibitions → during anxiety () and hunting ()

• Norad → patients becomes anxious ()

• ↓↓ AcH → Alzheimer's, Huntintons (↑↑ in Park)

Condition	NT	Location
Alzheimer's disease	↓↓ Acetyl choline	Nucleus basalis of Meynert
Parkinson's disease	Dopamine ↓↓ ↳ bradykinesia ↑↑ Acetyl choline	Nigrostriatal Mnemonic: Mayil (Meynert) Basil (Basalis) nu Achingum (Acetylcholine) Alzheimersum vannu
Addiction	Dopamine	Nucleus accumbens Mesolimbic Location ↳ Medial Frontal area ↳ Ventral tegmental area
ALS	Glutamate Amy → Glue	Hippocampus, Subthalamic nucleus → Memory A-delta fibres → Fast pain
Huntington's chorea	Dopamine ↑↑ GABA ↓↓ AcH ↓↓	Loss of GABA in striatum
Tetanospasmin ↳ spastic paralysis ↳ Presynaptic	GABA	Inhibits release of GABA
Strychnine ↳ spastic paralysis ↳ Postsynaptic	Glycine Stry → Gly	Inhibits release of glycine.
Mesocortical	ㅤ	Prefrontal cortex ↳ Motivation ↳ Emotional regulation ↳ Decision making ↳ Memory
Tuberoinfundibular	Dopamine	• Hypothalamus • Physiologic inhibition of prolactin

Acetylcholine

ACh release:

• Mediated by SNARE proteins and Ca2+.

SNARE proteins	ㅤ
v-SNARE	Synaptobrevin
t-SNAREs	Syntaxin + SNAP-25

• Mnemonic: Snake kandapo snap (Snap 25, Synaptobrevin) cheyth

• Synaptotagramin 
• Ca2+ sensor

• Botulinum toxin 
• No release of ACh from excitatory neuron
• Flaccid paralysis

• Clostridium tetani
• Toxin: Tetanospasmin
• Protease → cleaves SNARE
• ⛔ GABA and glycine release from Renshaw cells in spinal cord
• Spastic Paralysis (Lockjaw/Trismus)

• Note: Botulinum toxin

Receptors:

Biogenic Amines

Norepinephrine

• Synthesized from Dopamine.

• Location: 
• Norepinephrine
• Lock in ICU (Locus ceruleus) to give NE

• Function:
• Promotes wakefulness
• Widespread brain area activation

Dopamine Pathways

• Receptors: D1, D2, D3, D4, D5

• G-protein-coupled receptors (GPCR).

Serotonin (5-hydroxytryptamine, 5-HT)

Histamine

• Released from:
• Tuberomammillary nucleus in posterior hypothalamus.

• Location & Function:
• Posterior hypothalamus, Pituitary gland, Pineal gland
• Promote wakefulness.



• Enterochromaffin-like cells (ECL): 



• Produce histamine → Act on Parietal cell → increases acid secretion.
• Produce Serotonin → Richest source of serotonin
• Both cause
1. Vasodilatation
2. ↑ vascular permeability
3. Bronchoconstriction

Amino Acids

Glutamate

• Major excitatory neurotransmitter.

• Function:
• Memory
• Hippocampus
• Subthalamic nucleus
• Only excitatory nucleus of basal ganglia.
• Fast pain
• A-delta fibres

• Receptors:
• AMPA receptor: 
• Na+ channel (Depolarization).
• NMDA receptor: 
• Ca2+ channel
• Requires glycine to activate
• Mg2+ channel blocks NMDA receptor physiologically.
• It is removed by depolarisation from AMPA

Clinical Aspect

GABA (Gamma-Aminobutyric Acid)

• Major inhibitory neurotransmitter.
• Note: GABA is inhibitory by enhancing hyperpolarization.

• Location:
• Basal ganglia

• Mechanism of Action:
• Acts in hyperpolarization phase of action potential
• hyperpolarization → interior of cell more negative

• Applied aspect:
• Loss of GABA in striatum
• Huntington's chorea (involuntary movement).
• Tetanospasmin:
• ⛔ release of GABA from inhibitory neuron
• Presynaptic

Glycine

• Function: Both excitatory & inhibitory.

• Location: α motor neuron.

• Mechanism of Action:
• Feedback inhibition/Renshaw cell inhibition

Clinical aspect:

• Strychnine:
• Inhibits release of glycine.
• Post synaptic
• Glycine is an antagonist of strychnine.

• Both cause Spastic paralysis
• (d/t uninhibited stimulation of α motor neurons → sustained contractions)

Gases

Nitric oxide

• Source: Arginine

• Location: Hippocampus.

• Mechanism of Action:
• Requires cGMP for all action.
• ↑ glutamate release from presynaptic neuron.

• Function: Learning and memory

• Mnemonic: Hippopotamus gas release cheyth

Carbon monoxide

• Source: 
• Heme → (Heme oxygenase 2) → CO

• Function:
• Olfaction.
• Pain transmission.
• Learning and memory.