CNS Physiology and Transmission

Question 1

Describe the structure of a neurone

Answer 1

Dendrites - Have a number of receptors to receive input
Neurotransmitter - Determines types of neurone
Cell Body - ‘Factory’, production of proteins, neurotransmitters etc
Axon - Conducts action potential, insulated by myelin sheath

Question 2

What are regions of the brain made up of?

Answer 2

Collections of cells with similar functions

Question 3

What occurs at the synapse?

Answer 3

Neurotransmitter released into synapse (conversion to chemical signal)
Acts on receptors on dendrites of other neurones to carry on signal

Question 4

What is a neuronal circuit?

Answer 4

Made up of a number of different neuronal pathways

Question 5

Describe the motor circuit in the basal ganglia

Answer 5

Dopamine released into striatum from nigrostriatal pathway
Activates GABA neurone which projects onto a glutamate neurone in the thalamus, glutamate neurone projects to cortex
Synapses onto another glutamate neurone which projects to muscle

Question 6

What do CNS treatments often target?

Answer 6

Pathology of symptom rather than disease

Question 7

How are neuronal pathways named?

Answer 7

First part is where cell body begins, second part is where axon terminates

Question 8

What are GABA and glutamate?

Answer 8

Neurotransmitters
Glutamate = Excitatory
GABA = Inhibitory
“On/off” receptors

Question 9

What are the four process involved in neurotransmission?

Answer 9

Synthesis of neurotransmitter
Storage of neurotransmitter
Release into synapse
Inactivation or reuptake

Question 10

Using acetylcholine as an example, describe the four processes of neurotransmission

Answer 10

Synthesised from choline + acetyl CoA by choline acetyltransferase (in excess)
Stored in vesicles in presynaptic terminal
Release stimulated by influx of calcium ions - exocytosis
Inactivated by acetylcholinesterase in synapse, 40-50% of choline transported back into cell to resynthesise

Question 11

How can drugs be developed to target a more specific dopamine pathway?

Answer 11

Dopamine is broken down in the synapse in some pathways and in others it is taken back into the synapse
Enzyme and transporter provide specific drug targets

Question 12

Using acetylcholine as an example, how do auto receptors work?

Answer 12

Control synthesis and release of acetylcholine from acetylcholine in the synapse
ACh that is released activates autoreceptors to dampen further release

Question 13

How are excitatory signals transmitted?

Answer 13

Cause conformational change in postsynaptic receptors to create a sodium ion channel
Influx of sodium ions causes initiation of action potential in postsynaptic neurone

Question 14

How are inhibitory signals transmitted?

Answer 14

Cause conformational change in postsynaptic receptors to create a chloride ion channel
Influx of chloride ions makes neurone more negative so no action potential and no further neurotransmitter release

Question 15

How do neuromuscular junctions cause muscle contraction?

Answer 15

Chemical synapse between neurone and skeletal muscle fibre - ACh neurotransmitter
Ligand-gated ion channels on skeletal muscle cell membrane allow influx of sodium
Voltage increase causes calcium channels to open, resulting in muscle contraction

Question 16

What is Myasthenia Gravis and how is it treated?

Answer 16

Antibodies interfere with ACh receptors at neuromuscular junction causing movement disorders
Commonly seen in facial/eye muscles
Pyridostigmine prevents breakdown of ACh to improve muscle contraction and strength

Question 17

How is dopamine synthesised?

Answer 17

L-tyrosine to L-dopa by tyrosine hydroxylase

L-dopa to Dopamine by dopa decarboxylase

Question 18

What drug is commonly used to increase dopamine transmission and why?

Answer 18

L-dopa

Dopamine cannot cross BBB, L-dopa transported across by LAT1 and converted to dopamine in brain

Question 19

What is the negative to increasing dopamine transmission?

Answer 19

Dopamine in all pathways is increased, leading to side effects

Question 20

When does dopamine have an excitatory function?

Answer 20

Acts on D1 (D1 and D5) receptors

Question 21

When does dopamine have an inhibitory function?

Answer 21

Acts on D2 (D2, D3 and D4) receptors

Question 22

What are the four dopamine pathways and what do they control?

Answer 22

Nigrostriatal Pathway - Motor function
Mesolimbic Pathway - Reward/pleasure pathway
Mesocortical Pathway - Cognition/memory
Tuberoinfundibular Pathway - Prolactin release

Question 23

Which symptom of dopamine pathways is always first to be treated?

Answer 23

Psychosis

Question 24

How is the amount of brain tissue increased?

Answer 24

Sulci (grooves) and gyri (ridges)

Question 25

What are white matter and grey matter? How are the arranged in the CNS?

Answer 25

White matter - Axons and oligodendrocytes Grey matter - Cell bodies and dendrites Brain: White matter surrounded by grey matter, spinal cord is opposite

Question 26

Where are epidurals/lumbar punctures carried out and why?

Answer 26

Lower third of the spine | Contains individual neurones instead of spinal cord, less likely to cause nerve damage

Question 27

Describe the structure of the meninges

Answer 27

Connective tissue Outer layer - Dura mater Middle layer - Arachnoid mater Inner layer - Pia mater

Question 28

What is meningitis and how is it treated?

Answer 28

Bacterial infection resulting in inflammation of the meninges Diagnosed with rash glass test Benzylpenicillin (or cefotaxime if allergic), continue treatment with cefotaxime once hospitalised

Question 29

What is the subarachnoid space?

Answer 29

Between arachnoid mater and pia mater | Contains cerebrospinal fluid to bathe and protect the brain

Question 30

Describe the composition and function of CSF | Where is it produced?

Answer 30

Shock absorber Similar composition to plasma with less protein Choroid plexus structures

Question 31

How much CSF is produced daily and how much remains in the CNS?

Answer 31

400-500ml a day | About 150ml in CNS

Question 32

How is a build up of CSF prevented?

Answer 32

CSF secreted into lateral ventricles from choroid plexus structures Drain through lateral ventricle to third ventricle Then into fourth ventricle through cerebral aqueduct Then from fourth ventricle into spinal column through central canal or into subarachnoid space through foramen of magendie Once CSF reaches top of brain it drains into superior sagittal sinus and into venous blood

Question 33

What could be a cause of a build up of CSF and what could this cause?

Answer 33

Brain tumour pressing on aqueduct | Could result in hydrocephalus

Question 34

Describe the structure of the brain-CSF barrier

Answer 34

Leaky layer of endothelial cells next to layer of ependymal cells locked together MRP and P-gp present in ependymal cells to prevent passage through barrier Tight regulation of ions and fluid

Question 35

Describe the structure of the blood-brain barrier | What can pass through?

Answer 35

Specialised endothelial cells locked together, surrounded by pericytes and astrocytes MRP1, 2, 4 and 5, BCRP and P-gp present in capillary membrane Allows passage of glucose, nucleosides and amino acids Insulin and transferrin can cross barrier through receptor-mediated endocytosis Small, hydrophilic molecules can pass through

Question 36

Give an example of a drug that is not a substrate for P-gp and can enter the brain - state its effect

Answer 36

Promethazine - Causes sedation

Question 37

Give an example of a method of administration for chemotherapy drugs in the brain

Answer 37

Tumour mass removed surgically and wafer containing drug inserted into area Wafer dissolves to release drug into affected area

Question 38

When would intrathecal administration be used?

Answer 38

When drug cannot cross the BBB

Question 39

Give an example of a drug which must NOT be administered intrathecally and what to do in the case of accidental administration

Answer 39

Vincristine - Potent neurotoxin | Aspirate CSF and irrigate with intrathecal infusion of plasma (binds vincristine)