Cellular Physiology of the Brain - Neurotransmission

Question 1

What are the three chemical classes of neurotransmitters in the CNS?

Answer 1

Amino acids
Biogenic amines
Peptides

Question 2

Examples of amino acid neurotransmitters in the CNS
Are they excitatory or inhibitory?

Answer 2

Glutamate - excitatory
GABA -inhibitory
Glycine - inhibitory

Question 3

Examples of biogenic amines neurotransmitters in the CNS

Answer 3

• Acetylcholine
• Noradrenaline
• Dopamine
• Serotonin / 5-HT
• Histamine

Question 4

Examples of peptides neurotransmitters in the CNS

Answer 4

• Dynorphin
• Encephanlins
• Somatostatin
• Cholecystokinin
• Neuropeptide Y

Question 5

What is the main excitatory amino acid neurotransmitter?

Answer 5

Glutamate

Question 6

What are the inhibitory amino acid neurotransmitters?

Answer 6

Glycine
GABA

Question 7

Types of glutamate receptors
How do they exert their effects

Answer 7

Ionotropic: contain integral ion channel
- AMPA: permeable to Na + K
- Kainate: permeable to Na + K
- NMDA receptors: permeable to Na, K + Ca
.
Metabotropic: G protein coupled receptors
- mGluR1-7: via IP3/Ca or changes in cAMP

Question 8

Types of ionotropic glutamate receptors
What are they permeable to?

Answer 8

• AMPA: permeable to Na + K
• Kainate: permeable to Na + K
• NMDA receptors: permeable to Na, K + Ca

Question 9

What does glutamate release cause?

Answer 9

• depolarisation on post synaptic cell by acting on ligand gated ion channels
• excitatory postsynaptic potential
• causes APs

Question 10

What do AMPA receptors mediate?

Answer 10

Initial fast depolarisation

Question 11

What do NMDA need to allow ion flow?

Answer 11

Glutamate binding
Cell to be depolarised

Question 12

What do NMDA receptors have an important role in?
How?

Answer 12

Learning + memory
- activation of NMDA receptors > up regulates AMPA receptors
- strong high frequency stimulation casues long term potentiation
- Ca2+ entry through NMDA receptors is important for LTP

Question 13

What is long term potentiation?

Answer 13

Persistent strengthening of synapses leading to long lasting increase in signal transmission between neurones

Question 14

What can cause exictotoxicity?

Answer 14

Too much Ca2+ entry through NMDA receptors
(Too much glutamate)

Question 15

What is the main inhibitory transmitter in the brain?

Answer 15

GABA

Question 16

What is the main inhibitory transmitter in the brainstem + spinal cord?

Answer 16

Glycine

Question 17

How do inhibitory amino acid transmitter work?

Answer 17

• GABA + glycine have integral Cl- channels
• opening of the channels + Cl- influx causes hyperpolarisation
• inhibitory post synaptic potential
• decreased firing of AP

Question 18

What drugs enhance the response to GABA?
What effects do they have?

Answer 18

Barbiturates
Benzodiazepines
Sedative + anxiolytic

Question 19

What is benzodiazepines used to treat?

Answer 19

Anxiety
Insomnia
Epilepsy

Question 20

What are barbiturates not used as much now?

Answer 20

Risk of fatal overdose
Addictive

Question 21

What receptors do ACh act on in the brain?

Answer 21

Nicotinic
Muscarinic

Question 22

What are cholinergic pathways in the CNS involved in?

Answer 22

Arousal
Learning
Memory
Motor control

Question 23

Key dopaminergic pathways in CNS
What are their functions?

Answer 23

• nigrostriatal: motor control
• neocortical + mesolimbic: mood, arousal + reward

Question 24

Degeneration of what pathway causes Parkinson’s disease?

Answer 24

Nigrostriatal

Question 25

Overactivity of what pathway may contribute to schizophrenia?

Answer 25

Mesolimbic

Question 26

Why can amphetamine use cause similar symptoms to schizophrenia?

Answer 26

- Causes release of dopamine - Overactivity of dopamine can contribute to schizophrenia

Question 27

What is the nigrostriatal pathway between? What is its function? What is its clinical significance?

Answer 27

- substantia nigra to striatum - motor control - degeneration causes Parkinson’s disease

Question 28

What is the mesolimbic pathway between? What is its function? What is its clinical significance?

Answer 28

- midbrain to limbic system - mood, arousal, reward - Overactivity can contribute to schizophrenia

Question 29

What is the neocortical pathway between? What is its function?

Answer 29

- midbrain to cerebral cortex - mood, arousal + reward

Question 30

How can Parkinson’s disease be treated?

Answer 30

**co-careldopa** - **levodopa** (dopamine precursor) - converted to dopamine by DOPA decarboxylase - given with **carbidopa**

Question 31

Why do you give carbidopa with L-DOPA in treatment of Parkinson’s disease?

Answer 31

- you want levodopa to be converted to dopamine in the brain not the periphery - high levels in periphery can effect heart, GI + urinary systems - cardbidopa does not cross BBB + **inhibits conversion in periphery**

Question 32

Outline noradrenergenic pathways in CNS

Answer 32

- cell bodies of NA containing neurone within brainstem *locus coeruleus* - diffuse release throughout cortex, hypothalamus + cerebellum - involved in behavioural arousal

Question 33

Where does most noradrenaline come from?

Answer 33

Locus coeruleus in brainstem

Question 34

What is a low level of NA related to?

Answer 34

Depression

Question 35

When are locus coeruleus neurones inactive?

Answer 35

During sleep

Question 36

Functions of serotonin

Answer 36

Sleep/wakefullness Mood

Question 37

What is used for the treatment of depression or anxiety?

Answer 37

Serotonin selective reuptake inhibitors SSRIs

Question 38

Where is serotonin released from?

Answer 38

Raphe nuceli of brainstem

Question 39

What transmitters are involved in pain transmission?

Answer 39

Dynorphin Encephalins