Synaptic Transmission Flashcards
What’s the differnece b/w the type of GABAa + GABAb r? (4)
GABA A =
ionotropic (ligand gated)
GABA B =
metabotropic
(GPCR)
What does the hippocampus have, in terms of GABA neuron density? (2)
Lots of different GABAergic cell types
loads of interneurons in hippo - each are distinct in morphology + pharm
How do we characterise these GABAergic cells? (2)
via their embryonic origin
Diversity and different embryonic developmental
sources
What is feed-forward inhibition? (2)
usually:
1) 2 excitatory cells (eg CA1 + CA3 - connected)
2) AP flows through 1st cell’s axon - exciting next cell through the synapse
in feed-forward:
1) 1st excitatory cell will not target another excitatory cell but instead an inhibitory interneuron
2) 2nd cell is inhibited
What is feed-back (recurrent) inhibition? (2)
so instead of the 2nd cell targeting another/different cell - it feeds back into the original circuit
= switches off the cell
Describe inhibition of inhibition (3)
1)1st AP from excitatory cell targets 1st inhibitory cell/interneuron
2)1st in turn = inhibits 2nd interneuron
3)2nd interneuron cannot act on the excitatory cell ==> inhibition of inhibition
Why do you need inhibition? (1)
To avoid hyperexcitability –> seizures
What is PTZ ands why is it used? (2)
Gaba antagonist = induces seizures
- helps to model hyperexcitability
How can you model hyperexcitability in zebrafish? (3)
put PTZ drug into bath solution => osmosis => see excitatory response in fish via calcium imaging (fluorescence)
GABA chemical structure (1)
C4H6NH2OH
GABAergic synapses do not usually occur on…(1)
dendritic spines
what is GABA made from? (1)
from glutamate - using glutamate decarboxylase (GAD)
How is GABA made + synaptic transmission? - steps (8)
1) TCA cycle
2) Glutamate production
3) Glut –> GABA (GAD)
4) GABA packaged + moves to edge of TM in V’s (VGAT)
5) GABA V’s fuse + release
6) (GABA + GABAAr) or (GABA + GABABr)
7) GAT transports GABA back into synapse - glial or astrocytes
8) TCA cycle
GABAA structure (5)
-pentamer
-2x A1
- 2x B2
-1x gamma2 (or delta)
- most common combination: a1,b2,g2
-binding site b/w a + b subnits
Describe GABAA’s MOA binding to GABA (3)
1) GABA binds to r at a + b binding site
2) opens cl- channels in pore (main inhib molecule)
3) drive of cl- (prevents AP generation)
Why is cl- inhibitory? (3)
look at the equilibrium potential - ECl
see that it is v negative (just shy of EK)
ECl is much more depolarised in juvenile neurons
Different subunits have different localisations - so? (2)
essential for drug targeting
eg alpha6 only found in cerebellum
What is the plus side and what is the minus side in the TM domain? (2)
+ = TM2 and TM3
- = TM2 and TM1
GABAA Agonists + binding site (4)
GABA
Muscimol
Gaboxadol
BS: between alpha + beta subunits
GABAA Antagonists+ binding site (4)
Bicuculline
GABAzine
Picrotoxin
BS: between alpha + gamma subunits
GABAA modulators + binding site(5)
Benzodiazepines (BZD)
Barbiturates
Neurosteroids
Anaesthetics
Alcohol
BS: differing
Why would you use positive allosteric modulators for GABAA? (4)
common for drug target
but if you use antagonise gaba = seizures
so want to bind elsewhere - not where primary ligand binds also
= modulators
BZD - SSRI’s
Why would you use antagonists for GABAA? (3)
for inhibition of GABAergic circuit studies/experiments
= blocks components
but not for recreational use = seizures