Lecture 4: Neuronal signalling in the context of CNS disorders

What are the two main components of membrane potential?

Chemical driving force (ion concentration gradients) and electrical driving force (charge difference across the membrane)

What is secondary active transport?

Uses the free energy of an existing electrochemical gradient (not direct ATP hydrolysis) to move another ion/molecule against its gradient

What is the resting membrane potential (Vm) of a neuron?

About -70 mV

What is depolarization?

When Vm becomes less negative (e.g., -40 mV) due to Na⁺ or Ca²⁺ influx, increasing excitability

What is hyperpolarization?

When Vm becomes more negative (e.g., -90 mV) due to K⁺ efflux, decreasing excitability

What is an action potential?

A rapid change in membrane potential with depolarization followed by repolarization when a neuron is stimulated

What are the phases of an action potential (0-4)?

0. Membrane is polarized, with a potential of around -70 mV, Na+ and K+ channels are closed

1. Rapid influx of Na+ through voltage-gated sodium channels (Nav) causes the membrane potential to rise sharply, overshooting 0 mV

2. K+ channels open, allowing K+ to exit the cell, which begins to restore the negative membrane potential

3. The membrane potential temporarily becomes more negative than the resting potential due to continued K+ efflux

4. The membrane stabilizes back to resting potential as ion channels reset

What is the role of acetylcholine (ACh)?

Involved in muscle activation and autonomic functions; excitatory at nicotinic receptors, inhibitory at muscarinic receptors

What is the primary excitatory neurotransmitter in the brain?

Glutamate - important for synaptic plasticity and cognitive functions

What is the main inhibitory neurotransmitter in the CNS?

GABA (Gamma-aminobutyric acid) - crucial for reducing neuronal excitability

Where is noradrenaline synthesized?

In the adrenal medulla and postganglionic sympathetic neurons

What diseases are associated with reduced noradrenaline?

Depression, poor memory, lack of energy, poor concentration, and low motivation

What conditions are associated with increased noradrenaline?

High blood pressure, increased heart rate, anxiety, stress, irritability, and insomnia

Where is dopamine synthesized?

In specific neurons and in the adrenal medulla

What diseases are associated with reduced dopamine?

Parkinson’s disease, ADHD, depression, and schizophrenia

What are the key symptoms of Parkinson’s disease?

Tremor, slow movement, stiff and inflexible muscles

Where is serotonin produced?

In the midbrain and hypothalamus

What is serotonin deficiency associated with?

Mood disorders - especially depression

What are diseases and symptoms associated with serotonin dysfunction?

Depression, confusion, agitation, headaches, ↑BP & temperature, N/V, diarrhoea, tremor, muscle control loss, shivering, sweating, high fever

Where is ACh synthesized in the brain?

In certain midbrain neurons

What happens when acetylcholinesterase (AChE) is inhibited by neurotoxins?

Excess ACh at neuromuscular junctions → muscular paralysis

What diseases are associated with low acetylcholine levels?

Alzheimer’s disease, Parkinson’s disease, and Myasthenia gravis (autoimmune)

What is Alzheimer’s disease (AD)?

A progressive neurological disorder characterized by memory loss and other intellectual impairments that interfere with daily life

What causes many of the symptoms in Alzheimer’s disease?

A cholinergic deficit in the central nervous system

How does Donepezil work in Alzheimer’s disease?

It inhibits the breakdown of acetylcholine (ACh) and compensates for the deficiency of ACh in the brain

Why is acetylcholine important in Alzheimer’s disease?

Acetylcholine is a key neurotransmitter, and its loss contributes to memory and cognitive decline in AD