9/ synapses and NTs 2

Question 1

criteria for NT

Answer 1

• be present in pre ST
• released in response to stimulation
• act on post SN
• blocking should prevent transmission

Question 2

how to determine if a molecule acts as a NT experimentally

Answer 2

• is it there? immunostaining
• does cell have proteins to synthasise/store it? immunostaining, in situ hybridisation
• is it released? collect fluid around neurons after firing
• does it affect post SN? test if molecule mimics effect of stimulating post SN
• block neurotransmitter? drugs, knock out

Question 3

types of NTs

Answer 3

• amino acids - glutamate, gaba, glycine
• amines (have amine group attached) - noradrenaline, acetylcholine
• peptides - opioids, endorphins

Question 4

amino acids and amines vs peptides

Answer 4

• aa and amines: small, stored in synaptic vesicles, can bind to ligand gated ion channels or G protein coupled receptors
• peptides: large, stored in secretory granules, ONLY bind to g protein coupled receptors

Question 5

how many types of NT does a neuron typically release?

Answer 5

• 1, but possible to release more

Question 6

co transmitter?

Answer 6

• small molecule
• released by peptide releasing neurons

Question 7

convergence and divergence

Answer 7

• allows flexibility
• diverge: signal amplification, wide variety of effects from single neuron
• converge: receptors dif but activate same system - increase chance of activation

Question 8

glutamate

Answer 8

• most common excitory nt in CNS
• amino acid (found in all neurons)
• 3 ionotropic/ligand gated receptor subtypes based on drugs that act as selective agonists - AMPA, NMDA, kainate - 4 subunits ion channel
• action terminated by selective uptake into pre ST and glia

Question 9

glutamate - AMPA receptors

Answer 9

• mediate fast excitory transmission
• glutamate binding triggers sodium and potassium resulting in EPSP

Question 10

glutamate - NMDA receptors

Answer 10

• co exist w AMPA
• voltage dependent magnesium block - Mg2+ ion literally blocks pore, positive memb inside forces mg out
• so NMDA only open when neurons already depolarised
• NMDA let calcium in, downstream signalling
• function as a coincidence detector - when neuron was activated right after already being activated
• depolarisation of AMPA alone my not be enough for AP

Question 11

glutamate - metabotropic receptors (mGluRs)

Answer 11

• g protein coupled R
• mGluR1, mGluR2
• activate g protein cascade
• slower
• sometimes inhibitory eg eye

Question 12

GABA

Answer 12

• not an amino acid but used to synthasise proteins
• synthesised from glutamate by enzyme glutamic acid decarboxylase
• action terminated by selective uptake into pre SN and glia

Question 13

mechanisms of GABA inhibition, too much/little gaba

Answer 13

• produces IPSPs (inhibitory postsynaptic potential) via GABA gated chloride channels if the memb potential is above chlorides nerst potential
• too much GABA- coma/loss of consciousness
• too little - seizures

Question 14

modulation of GABAa receptors and example drugs

Answer 14

• other chemicals can bind to GABAa, these have no effet w/o GABA binding - allosteric drug
• ethanol - enhances action of channel (more inhibition) in decision centers/motor control areas. in alcoholics, body adapts to decrease number of receptors. withdrawal symptoms can mimic seizures
• benzodiazepines like diazepam - treats anxiety
• barbiturates - sedatives and anti - convulsants
• neurosteroids - metabolites of steroid hormones

Question 15

how does GABA act via GABAb receptors

Answer 15

• GABAb Rs are GPCRs
• act in different ways, such as open K+ channels, close Ca2+ channels (stop depolarisation and vesicle release), trigger other second messengers like cAMP
• often presynaptic or autonihibitory (release GABA to inhibit itself - feedback loop)

Question 16

glycine

Answer 16

• inhibits neurons via glycine gated chloride channel (glycine receptor)
• also binds to NMDA glutamate receptors

Question 17

importance of how excitatory and inhibitory synapses are arranged spatially

Answer 17

• inhibitory synapse can block the propagation of EPSP towards the soma
• GABAa receptors dont always produce an IPSP
• in this case they act by shunting inhibition
• opening chloride conductance decreases memb resistance - current leaks out of memb
• inhib synapses AFTER excitory

Question 18

presynaptic inhibition

Answer 18

• GABA released, inactivation of calcium channels, less calcium enters pre SN, less nt released