Neurotransmittesr

Question 1

Describe how synapses work briefly

Answer 1

Depolarisation in the terminal opens VGCC and Ca enters the terminal

Vesicles fuse and release neurotransmitter

Neurotransmitter diffuses across the synaptic cleft and binds to receptors on the post-synaptic membrane

Post-synaptic response depends upon the nature of the neurotransmitter and the nature of the receptor (GPCR or LGIC)

Question 2

What are the three types of neurotransmitters and name some neurotransmitters in each class

Answer 2

Amino acids - GABA, glycine, glutamate

Biogenic amines - ACh, NA, dopamine, 5-HT, histamine

Peptides - dynorphin, enkephalins, substance P, somatostatin, cholecystokinin, neuropeptide Y

Question 3

Which is the main excitatory neurotransmitter in the CNS and what are the main inhibitory neurotransmitters in the CNS

Answer 3

Main excitatory neurotransmitter is glutamate

Main inhibitory neurotransmitter for the brain is GABA

Main inhibitory neurotransmitter for the brainstem and spinal cord is glycine

Question 4

What are the types of glutamate receptors

Answer 4

Ionotropic - have intrinsic ion channel permeable to Na, K and Ca

• AMPA receptors - Na/K
• Karinate receptors - Na/K
• NMDA receptors - Na/K and Ca

Metabotropic (mGluR1-7) - GPCRs linked to either changes in IP3 and Ca mobilisation or lead to inhibtion of adenylate cyclase and decreased cAMP

Question 5

Describe the NMDA receptors

Answer 5

NMDA receptors cause depolarisation and increase excitability of the post-synaptic neurone

NMDA receptors require glutamate to bind and the cell to be depolarised to allow ion flow through the channel, otherwise the channel won’t open - silent synapse if only NMDA receptors

Question 6

What role do glutamate receptors have in learning and memory

Answer 6

Glutamate activates NMDA receptors and so can up-regulate AMPA receptors to make synpases in learning and memory pathways stronger

Strong, high frequency stimulation causes long term potentiation with Ca entery through NMDA receptors important for this

Question 7

Why is it harmful if NMDA receptors are activated excessively

Answer 7

Excessive activation of NMDA receptors results in too much Ca entery through NMDA receptors and causes excitotoxicity

This results in too much glutamate and toxicity to neurones

Question 8

How do GABA_A and glycine receptors inhibit transmission

Answer 8

GABA_A and glycine have integral Cl channels and when opened, cause hyperpolarisation and an inhibitory post-synaptic potential which decreases action potential firing

Question 9

What drugs can bind to GABA_A receptors and what do the cause

Answer 9

Barbiturates and benzodiazepines bind to GABA_A and enhance the response to GABA

Barbiturates have anxiolytic and sedative actions but are not used because of risk of dependency, tolerance and risk of fatal overdose. Sometimes used as anti-epileptic

Benzodiazepines have sedative and anxiolytic effects. They are used to treat anxiety, insomnia and epilepsy

Question 10

Where does ACh act as a neurotransmitter and what is its mechanism of action in the CNS

Answer 10

ACh acts at neuromuscular junctions, ganglion synpases in the ANS, post-synaptic ganglionic parasympathetics and as a central neurotransmitter at nicotinic and muscarinic receptors in the brain

Acts by enhancing release of other neurotransmitters

Question 11

Describe the origin of cholinergic neurones, where they project to and what the cholingeric pathways are involved in

Answer 11

Cholinergic neurones originate in the basal forebrain and brainstem and give diffuse projections to many parts of the cortex and hippocampus

Also have local cholinergic interneurones, e.g. in corpus striatum

Cholingeric pathways are involved in arousal, learning, memory and motor control

Question 12

What is degradation of cholingeric neurones associated with

Answer 12

Degradation of cholingeric neurones in the nucleus basalis is associated with Alzheimer’s disease

Give cholinesterase inhibitors given to alleviate symptoms as they enhance the amount of ACh in the synpatic cleft

Question 13

What pathways are found in the dopaminergic pathways and what are the pathways involved in

Answer 13

Nigrostriatal pathway - motor control

Mesocortical and mesolimbic pathways - mood, arousal and reward

Question 14

What is the assocaition between Parkinson’s disease and dopaminergic pathways and what is used to treat Parkinson’s

Answer 14

Parkinson’s is associated with a loss of dopaminergic neurones and loss of substantia nigra input to corpus striatum

Can be treated with levodaopa which is coverted to dopamine by DOPA decarboxylase

Can be treated by carbidopa which inhibits AADC and cannot cross the BBB so it increases the level of L-DOPA in the periphery which can then cross the BBB and can be converted to dopamine in the brain

Question 15

What is the association between Schizophrenia and dopamine pathways

Answer 15

Schizophrenia is assocaited with too much dopamine release

Treated using antipsychotics which antagonise dopamine D2 receptors

Question 16

Describe the noradrenergic pathway in the CNS and where the majority of NA is produced in the CNS

Answer 16

Cell bodies of NA containing neurones are found in the pons and medulla which send out diffuse projections throughout the cortex, hypothalamus, amygdala and cerebellum

Most NA is produced by a group of neurones in the locus coeruleus - activity increases during behavioural arousal and inactivates during sleep

Question 17

What do amphetamines cause the release of within the CNS

Answer 17

Amphetamines cause the release of dopamine and NA producing schizophrenic like behaviour

Also cause increased wakefulness

Question 18

What is serotonins distribution in the CNS and what are the serotonergic pathways invovled in

Answer 18

Serotongeric pathways are invovled in sleep/wakefulness and in mood

5-HT is produced by raphe nuclei and projects widely thoughout - to cerebellum, hippocampus, amygdala, cerebrum, thalamus and hypothalamus,