CNS Signalling

Question 1

Define depolarisation and hyperpolarisation.

Answer 1

• Depolarisation: excitation of neurone (by making membrane potential more positive).
  
  • Depolarisation results in the generation of an action potential.
• Hyperpolarisation: inhibition of neuronal activity (by making membrane potential more negative).

Question 2

What is the difference between signalling within and between neurones?

Answer 2

• Signalling within neurones is primarily electrical.
• Signalling between neurones must be chemical.

Question 3

How is an action potential generated?

Answer 3

• Action potentials are generated through depolarisation of the neuronal membrane, which occurs via the opening of voltage gated ion channels.
• Action potential occurs once the membrane potential is above the threshold potential.
• Action potentials are always excitatory.
  
  • It is the responses they evoke in the post-synaptic cell that can be either excitatory or inhibitory.

Question 4

What is the basic mechanism of neurotransmission?

Answer 4

1. An action potential is generated in the pre-synaptic neurone. This travels down the axon to the nerve terminal (synapse).
2. Arrival of the action potential triggers an influx of calcium ions, which leads to the release of neurotransmitters from vesicles in the neurone.
3. Neurotransmitter diffuses across the synaptic cleft, binding to pre- and post-synaptic receptors.
4. Neurotransmitters activate these receptors (transmitters are always agonists), leading to a response.
5. The response can be electrical (a change in membrane potential following influx/efflux of ions) or biochemical (e.g. via action of second messengers).

Question 5

How do neurons integrate multiple synaptic inputs to make a firing decision?

Answer 5

• Neurons receive 1,000–10,000 synaptic inputs.
• EPSPs (depolarising) and IPSPs (hyperpolarising) sum together to determine the likelihood of the post-synaptic neurone producing an action potential.
• If the combined potential exceeds threshold, an action potential fires.

Question 6

What roles do astrocytes play in brain function?

Answer 6

• Astrocytes are key mediators of neurovascular and neural network activity.
• Maintain brain homeostasis and ion concentration balance.
• Remove excess potassium.
• Participate in neurotransmitter synthesis and metabolism.
• Act as signalling partners, like inexcitable neurons.
• Help form the blood-brain barrier.

Question 7

What do oligodendrocytes do in the CNS?

Answer 7

• Produce myelin sheaths that insulate axons.
• Myelin sheath enables efficient conduction of action potentials down the axon and to the synaptic terminal.
• A single cell can myelinate multiple axons.

Question 8

What is the function of microglia in the brain?

Answer 8

• Microglia account for 10–15% of all cells found within the brain and form an active immune defence.
• Act as macrophages, phagocytose pathogens, debris, and dead cells.
• Proliferate during disease states.
• Can make up ~50% of cells in tumours.
• Activated in response to injury or infection.

Question 9

What is the blood-brain barrier (BBB) and why is it important?

Answer 9

• Dense neurovascular unit formed by endothelial cells, astrocytes, and neurons.
• Physically separates brain tissue from the bloodstream.
• Maintains CNS homeostasis.
• Limits entry of drugs, toxins, and pathogens.

Question 10

What are different types of neurotransmitters and their role?

Answer 10

• Amines (dopamine, noradrenaline, serotonin) – emotion, cognition.
• Cholinergic (acetylcholine) – attention, memory.
• Amino acids (glutamate, GABA, glycine) – excitation and inhibition.
• Peptides (e.g. Substance P, VIP) – modulation.
• Purines (ATP, adenosine) – neuromodulation.

Question 11

What is the role of dopamine in the CNS?

Answer 11

• A monoamine and catecholamine.
• Mainly inhibitory neurotransmitter.
• Involved in motor control (basal ganglia), behaviour, and reward pathway.
• Involved in pathology of Parkinson’s and schizophrenia.
• Acts via GPCRs: D1 to D5. *

Question 12

What are the functions of serotonin (5-HT) in the brain and body?

Answer 12

• Principally inhibitory effects in the brain.
• Also found in non-neuronal cells and peripheral nervous system.
• Regulates sleep, mood, sensory transmission, and appetite.
• Involved in hallucinogenic drug action.
• Acts on both GPCRs and ionotropic receptors (5HT1–7).

Question 13

What is the role of GABA in the CNS?

Answer 13

• Synthesized from glutamate.
• Found in high concentrations in the brain.
• Causes hyperpolarisation via GABA A (ion channel) and GABA B (GPCR).

Question 14

What is the role of glutamate in CNS function?

Answer 14

• Main excitatory neurotransmitter in the brain.
• Crucial for learning, memory, and cognition.
• Most abundant neurotransmitter in the vertebrate nervous system.
• Can activate a wide range of receptors such as AMPA, NMDA receptors (ionotropic) and mGluR (metabotropic).

Question 15

What is the function of acetylcholine in the brain?

Answer 15

• Excitatory neurotransmitter.
• Supports attention, memory, and motivation.
• Acts on nicotinic (ionotropic) and muscarinic (GPCR) receptors.
• Deficient in Alzheimer’s disease; treated with anticholinesterases.

Question 16

What defines an ionotropic receptor?

Answer 16

• Ligand-gated ion channel.
• Opens when a ligand binds to it.
• Allows rapid ion movement (Na⁺, Cl⁻, etc.).
• Built from 4–5 protein subunits, each with 4 transmembrane helices.
• Pore formed by 2nd transmembrane region of each subunit, which is what allows specificity.

Question 17

What defines a metabotropic (GPCR) receptor?

Answer 17

• Has 7 transmembrane alpha helices.
• Ligand binding activates a G-protein.
• G-protein triggers second messenger cascades (e.g., cAMP, IP₃, DAG).
• Leads to slower but amplified intracellular effects.

Question 18

What are the intracellular consequences of GPCR activation?

Answer 18

• Second messengers like cAMP, IP₃, DAG, Ca²⁺ are produced.
• These activate protein kinases or ion channels.
• Can lead to transcription factor activation (e.g., CREB → gene expression).
• Amplifies the original signal.

Question 19

What are common drug targets at the synapse?

Answer 19

• Ion channels (e.g., Na⁺, Ca²⁺).
• Neurotransmitter release mechanisms.
• Receptors (pre- and post-synaptic).
• Enzymes (synthesis or degradation).
• Reuptake transporters.

Question 20

How do ion channel blockers like lidocaine work?

Answer 20

• Block voltage-gated Na⁺ channels.
• Prevent action potential propagation.
• Stops pain transmission—used as local anaesthetic.

Question 21

How do receptor antagonists like haloperidol work?

Answer 21

• Block post-synaptic receptors (e.g., dopamine D2).
• Inhibit neurotransmitter binding.
• Reduce effects of overactive signalling (e.g., in schizophrenia).

Question 22

How is acetylcholine cleared from the synaptic cleft?

Answer 22

• Broken down by acetylcholinesterase.
• Produces choline and acetate.
• Ends the signal quickly.

Question 23

How are most neurotransmitters removed from the synapse?

Answer 23

• Reuptake into presynaptic neuron or glia.
• Via transporter proteins using Na⁺/Cl⁻ gradients.
• Ends signal and recycles neurotransmitter.

Question 24

How do antidepressants affect neurotransmitter levels in the brain?

Answer 24

• Block reuptake transporters.
• Increase neurotransmitter concentration in synaptic cleft.
• Prolong receptor activation.