Week 4 - topic 3

Question 1

Common neurotransmitters and their general effects on the CNS and PNS

Answer 1

*look up image

Question 2

Amino acid neurotransmitters

Answer 2

In the brain, most synaptic communication is accomplished by two amino acid neurotransmitters:

Glutamate = excitatory effects on cells.
Gamma-aminobutyric acid, or GABA = inhibitory effects on cells

Question 3

Glutamate - production, storage and release

Answer 3

• Synthesised from a precursor amino acid (glutamine) by an enzyme (glutaminase)
• Glutamate is pumped into synaptic vesicles by vesicle glutamate transporters, and released from presynaptic neuron following an action potential

Question 4

Glutamate - receptors

Answer 4

NMDA receptor, (ionotropic – controls calcium ion channel) (Voltage and neurotransmitter dependent ion channel - requires particular neurotransmitter for binding and particular charge to open)
AMPA receptor, (ionotropic – controls sodium ion channel)
Kainate receptor (ionotropic –controls sodium ion channel)
Metabotropic glutamate receptor (metabotropic)

Question 5

Glutamate - Reuptake and deactivation

Answer 5

Glutamate is removed from the synapse by excitatory amino acid transporters (reuptake) and broken down by enzymes (enzymatic deactivation)

If glutamate isn’t removed from the synapse, glutamate excitotoxicity occurs = prolonged overexcitation which damages neurons.

Question 6

GABA - production, storage and release

Answer 6

• It is produced from a precursor (glutamic acid) by the action of an enzyme (GAD)
• GABA is pumped into synaptic vesicles by the vesicle GABA transporter, and released from presynaptic neuron following an action potential
• GABA-secreting neurons have an inhibitory influence to help keep brain stable
• A lack of inhibition might be related to seizure disorders

Question 7

GABA - receptors

Answer 7

• GABAA receptors are ionotropic and control chloride channels (Cl-).
• They have at least five different binding sites, and other ligands (e.g. hormones) bind to these additional sites

Question 8

GABA - Reuptake and deactivation

Answer 8

• GABA is removed from the synapse by proteins that are GABA transporters (reuptake).
• GABA is broken down by an enzyme (enzymatic deactivation)

Question 9

Non-amino acid neurotransmitters

Answer 9

• Although amino acid neurotransmitters like GABA and Glutamate are widespread throughout the brain, other neurotransmitters (i.e. non-amino acid ones) are located in distinct pathways in the brain.
• Furthermore, whereas amino acid neurotransmitters are most concerned with information transmission, non-amino acid neurotransmitters tend have modulating effects.

Question 10

Acetylcholine (ACh) - pathways

Answer 10

ACh functions in both the CNS and PNS
PNS = primary neurotransmitter involved in muscle contraction
CNS = found in specific locations and pathways: 
Dorsolateral pons (REM sleep - dreaming)
Basal forebrain (facilitate perceptual learning)
Medial septum (memory formation)

Question 11

Acetylcholine (ACh) - production, storage and release

Answer 11

• Synthesised from two precursors (choline and acetyl coenzyme A) by an enzyme (ChAT)
• Loaded into vesicles by the vesicle ACh transporters and released from vesicles following an action potential
• Botox prevents the release of ACh when injected into a muscle. Also used to to treat migraines and severe muscle contractions.

Question 12

Acetylcholine (ACh) - receptors

Answer 12

• Ionotropic ACh receptors stimulated by nicotine = nicotinic receptor (found in PNS)
• Metabotropic ACh receptors stimulated by muscarine (found in the mushroom Amanita muscaria) = muscarinic receptor (predominate in CNS)

Question 13

Acetylcholine (ACh) - reuptake and deactivation

Answer 13

• Deactivated by the enzyme acetylcholinesterase (AChE) which is present in the postsynaptic membrane.
• Once broken down, ACh parts (choline) are returned to presynaptic neurons via reuptake via choline transporters.
• > Drugs are used to deactivate AChE.
  e. g. AChE inhibitors used to treat myasthenia gravis (autoimmune, neuromuscular disease that causes weakness in the skeletal muscles)

Question 14

Monoamine neurotransmitters

Answer 14

• Monamines are neurotransmitters produced in cell bodies mainly in the thalamus, hypothalamus, mid brain and brain stem, and whose axons project widely throughout the brain.
• Monoamine neurotransmitters include serotonin, dopamine, histamine norepinephrine, and epinephrine, all of which have wide ranging functions.
• For instance, you have probably heard about serotonin in relation to mood and depression, but it is also involved in digestion.

Question 15

Dopamine (DA)

Answer 15

Produces both EPSPs and IPSPs

Impacts movement, attention, learning, and reinforcing effects of drugs

Question 16

Dopamine (DA) - pathways

Answer 16

Originate from midbrain structures (substantia nigra and ventral tegmental area):

• Nigrostriatal system (movement control)
• Mesolimbic system (reward and reinforcement)
• Mesocortical system (memory and problem solving)

Question 17

Dopamine (DA) - production

Answer 17

• Dopamine is a catecholamine - subclass of monoamines
• Producing catecholamines requires several enzymatic steps:
• > Precursor molecule which is modified slightly step by step to reach final shape
• > enzymatic process, modifications are made by enzyme
• look up image

Question 18

Dopamine (DA) - storage and release

Answer 18

• Vesicle monoamine transporters move dopamine into synaptic vesicles for release into the synapse following an action potential.

Question 19

Dopamine (DA) - receptors

Answer 19

Five Metabotropic types of receptors

D1, D2, D3, D4, and D5

Question 20

Dopamine (DA) - reuptake and deactivation

Answer 20

• Dopamine transporters remove dopamine from the synapse (reuptake)
• Several drugs serve as dopamine agonists: amphetamine, methamphetamine, cocaine, and Ritalin.
• Deactivation of catecholamines is regulated by an enzyme called monoamine oxidase (MAO)

Question 21

Norepinephrine (NE) - pathways

Answer 21

• Norepinephrine is found in both the CNS and PNS
• The most important system originates in the locus coeruleus located in the dorsal pons – related to vigilance
• catecholamine subclass

Question 22

Norepinephrine (NE) - production, storage and release

Answer 22

• very similar process as dopamine, synthesised from the dopamine molecule using a second enzyme

Differences:

• NE is synthesised in the synaptic vesicle
• Most neurons releasing NE release it via axonal varicosities (beadlike swellings of the axonal branches)
• look up image

Question 23

Norepinephrine (NE) - receptors

Answer 23

• Four types of adrenergic receptors (norepinephrine and epinephrine)
• All metabotropic
• Found in neurons in CNS and in various organs of body

Question 24

Norepinephrine (NE) - reuptake and deactivation

Answer 24

• Norepinephrine transporters remove excess norepinephrine from the synapse (reuptake)
• Excess norepinephrine is deactivated by an enzyme called monoamine oxidase, type A.

Question 25

Serotonin (5-HT) - pathways

Answer 25

- Serotonin = regulation of mood, control of eating, sleep (and dreaming), arousal, and pain regulation - Clusters originate in the raphe nuclei of the midbrain, pons, and medulla - > Dorsal raphe project to cerebral cortex + the basal ganglia - > Median raphe project to cerebral cortex + part of the hippocampal formation

Question 26

Serotonin (5-HT) - production, storage and release

Answer 26

- Synthesised from an amino acid - Loaded into synaptic vesicle by vesicle monoamine transporter - Released from axonal varicosities * look up image

Question 27

Serotonin (5-HT) - receptors

Answer 27

- At least nine different types of serotonin receptors (autoreceptors and postsynaptic receptors). - All are metabotropic except one. - the ionotropic receptor is involved in nausea and vomiting and helps with production of IPSP's

Question 28

Serotonin (5-HT) - reuptake and deactivation

Answer 28

- Serotonin transporter removes 5-HT from the synapse (reuptake) - Drugs that inhibit uptake of serotonin play important role in treatment of depression (e.g. Prozac) - 5-HT can be deactivated by monoamine oxidase (enzymatic deactivation).

Question 29

Histamine

Answer 29

- Found in only one place in the brain: the tuberomammillary nucleus (TMN), located in the posterior hypothalamus - Histamine plays important role in wakefulness - Drugs that block histamine receptors (antihistamines) cause drowsiness

Question 30

Histamine - production, storage and release

Answer 30

- Produced from an amino acid precursor by the action of an enzyme - Stored in vesicles and released following an action potential

Question 31

Histamine - receptors

Answer 31

- CNS contains H1, H2, H3, and H4 receptors | - Antihistamines act as antagonists at histamine receptors

Question 32

Peptides - production, storage and release

Answer 32

Produced from large polypeptide precursor molecules that are broken into smaller neurotransmitter molecules by special enzymes. • Synthesis of peptides occurs in the soma • Vesicles containing the peptides are delivered from the soma to terminal buttons by axoplasmic transport

Question 33

Peptides - production, storage and release part 2

Answer 33

Many terminal buttons have two types of synaptic vesicles (e.g. one with a peptide and one with a monamine, or acetylcholine) = co - release. • Peptides regulate sensitivity of presynaptic or postsynaptic receptors to the neurotransmitter

Question 34

Peptides - production, storage and release part 3

Answer 34

Peptides are released from all parts of the terminal button • Some molecules go to the synaptic cleft - others go to receptors on other cells nearby Several types of peptides • Most peptides are neuromodulators • Some peptides are neurotransmitters (e.g. endogenous opioids)

Question 35

Peptides - receptors

Answer 35

• Several neural systems activated when opioid receptors are stimulated • Analgesia (pain relief) • Inhibition of defensive responses such as fleeing and hiding • Reinforcement (can lead to opioid abuse) • Direct agonists = Heroin • Direct antagonists = Naloxone (drug that blocks opiate receptors which can treat opioid overdose)

Question 36

Peptides - deactivation

Answer 36

Peptides are deactivated by enzymes but there is no | reuptake process

Question 37

Lipids

Answer 37

- non-soluble in water - Substances derived from lipids (fat like molecules) can transmit messages within or between cells - Endocannabinoids – natural ligands for the receptors that THC also activates (active ingredient in marijuana). - > Anandamide

Question 38

Lipids - production, storage and release

Answer 38

- Lipid neurotransmitters like anandamide appear to be synthesized on demand. - They are not stored in vesicles, only produced and released when needed

Question 39

Lipids - receptors

Answer 39

- Two types of cannabinoid receptors, CB1 and CB2 - Both are metabotropic - Found on terminal buttons of glutamatergic, GABAergic, acetylcholinergic, noradrenergic, dopaminergic, and serotonergic neurons > regulate neurotransmitter release - > THC exerts analgesic effects by stimulating CB1 receptors in the PNS - > Paracetamol also acts on these receptors

Question 40

Lipids - deactivation

Answer 40

- Anandamide is deactivated by the enzyme FAAH - Because the enzyme is inside the neuron, the anandamide is transported back into the cell for deactivation via anandamide transporters