Neurotransmission and Acetylcholine: Brain and Medical Insights

Information between neurons: electrical or chemical?

The communication between neurons is chemical. While an action potential travels down the neuron electrically, the signal between neurons across the synapse is chemical via neurotransmitters.

Neurotransmission

Neurotransmission is the process by which a neuron communicates with another cell using chemical signals (neurotransmitters) across a synapse.

Steps of neurotransmission

1. Action potential arrives at presynaptic terminal. 2. Voltage-gated Ca²⁺ channels open. 3. Ca²⁺ influx triggers vesicle fusion and neurotransmitter release (exocytosis). 4. Neurotransmitter diffuses across the cleft. 5. Binds to receptors on postsynaptic membrane. 6. Receptor activation opens ion channels or activates second messengers. 7. Signal terminated by reuptake, enzymatic degradation, or diffusion.

Role of calcium (Ca²⁺) in neurotransmission

Ca²⁺ enters the presynaptic terminal and triggers synaptic vesicle fusion with the presynaptic membrane, causing neurotransmitter release. Without Ca²⁺, exocytosis does not occur.

Synapse

Junction between neurons (or a neuron and another cell) where information passes via neurotransmitters across the synaptic cleft.

Presynaptic

The neuron or terminal sending the signal and releasing neurotransmitter.

Postsynaptic

The neuron or cell receiving the signal and containing receptors for the neurotransmitter.

Synaptic cleft

The small extracellular gap (20-40 nm) between the presynaptic and postsynaptic membranes where neurotransmitters diffuse.

Vesicle

Small membrane-bound sac in the presynaptic terminal storing neurotransmitter molecules until release.

Exocytosis

Process by which vesicles fuse with the presynaptic membrane and release neurotransmitter into the synaptic cleft.

Neurotransmitter

Chemical messenger released by neurons to transmit signals to other cells across synapses.

Receptor

Protein on postsynaptic membrane that binds neurotransmitter and triggers a cellular response.

Ion channel

Protein pore in a cell membrane that allows specific ions to pass, often gated by neurotransmitters or voltage changes.

Reuptake

Process by which neurotransmitter is reabsorbed into the presynaptic neuron via transporter proteins, ending its action.

Enzymatic degradation

Breakdown of neurotransmitter by enzymes into inactive components (e.g., ACh by acetylcholinesterase).

Diffusion

Passive movement of neurotransmitter molecules away from the synaptic cleft to terminate the signal.

Excitation

Neurotransmitter action that increases likelihood of postsynaptic neuron firing an action potential (depolarization).

Inhibition

Neurotransmitter action that decreases likelihood of postsynaptic neuron firing (hyperpolarization).

Divergence

One presynaptic neuron sends signals to multiple postsynaptic neurons (one → many).

Convergence

Multiple presynaptic neurons send signals to a single postsynaptic neuron (many → one).

Otto Loewi's experiment and first neurotransmitter

Otto Loewi showed that stimulating a frog's vagus nerve slowed its heart and that transferring the surrounding fluid to another heart also slowed it. This proved a chemical signal, later identified as acetylcholine (ACh).

Difference between neurotransmitter and hormone

A neurotransmitter acts locally at synapses and rapidly; a hormone travels through the bloodstream to distant targets and acts more slowly and broadly.

Seven main neurotransmitters and characteristics

1. Acetylcholine (ACh)

excitatory; muscle movement, memory.

2. Dopamine

reward, motivation, movement.

Norepinephrine

arousal, alertness, stress response.

4. Serotonin

mood, sleep, appetite.

5. Glutamate

main excitatory transmitter, learning/memory.

6. GABA

main inhibitory transmitter, reduces anxiety/seizures.

7. Histamine

wakefulness, arousal, appetite control.

Area of brain with ACh

Found in basal forebrain and brainstem (nucleus basalis, mesopontine area); projects to cortex and hippocampus.

Where ACh is found outside brain & its function

Found at neuromuscular junctions and autonomic nervous system synapses; triggers muscle contraction, slows heart rate, stimulates digestion, glandular secretion, and smooth muscle activity.

Myasthenia Gravis

Autoimmune disorder where antibodies attack acetylcholine receptors at neuromuscular junctions, causing muscle weakness and fatigue.

Treatment for Myasthenia Gravis

AChE inhibitors (pyridostigmine), immunosuppressants, thymectomy, plasmapheresis, or IVIG to restore neuromuscular function.

Evidence linking ACh to cognitive function

Alzheimer's disease and Myasthenia Gravis show reduced cholinergic activity linked to poorer memory, attention, and executive function; brain ACh levels correlate with cognitive performance.

How medications to slow Alzheimer's work

Most are cholinesterase inhibitors (Donepezil, Galantamine, Rivastigmine) that increase ACh levels; Memantine (NMDA blocker) modulates glutamate to prevent excitotoxicity.