Neurotransmission and neuromodulation Flashcards
What are the two main molecular structures of neurotransmitters?
Amino acid (GABA, Glu, etc.)
Monoamine (DA, 5-HT, NE, …)
In terms of quantitative gene expression for synthesis and packaging , what differentiates neurons releasing aa. NTs and neurons releasing monoamine NTs?
Neurons releasing aa. NTs require only a few genes.
Neurons releasing monoamine NTs require more genes.
Where is VGLUT-1 mostly expressed? VGLUT-2? VGLUT-3?
VGLUT-1: cortex
VGLUT-2: thalamus
VGLUT-3: only expressed in very specific cell types
What is the GABA equivalent of VGLUT and GLT?
VGAT and GAT
True of false: GABA is synthesized from Glu.
True
Why can L-DOPA be used as a treatment against Parkinson’s disease?
Parkinson’s is caused by a loss of dopamine release in the striatal pathway
L-DOPA is the precursor to dopamine -> more L-DOPA = more dopamine (in eq. conditions)
In terms of monoamine synthesis, why could dopamine theoretically be released from 5-HT neurons?
They contain DDC enzymes (dopa decarboxylase), so in the presence of L-DOPA, they could synthesize dopamine + they express VGLUT
How is GABA (aa.) synthesized in neurons? How is adrenaline (monoamine) synthesized in neurons? How is serotonin synthesized?
Glu -> GABA
Tyrosine ->L-DOPA -> Dopamine -> Noradrenaline -> Adrenaline
Tryptophan ->5OH-Tryptophan ->Serotonin // only monoamine that is not synthesized from tyrosine
What do SVs typically expressed on their bilayer membrane? What are the roles of the respective structures?
-Vesicular NT transporters ->fill SV with NTs
-V-ATPase ->proton pump establishing ion gradient necessary for intake of NTs
-Synaptotagmin -> calcium sensor
-Synaptobrevin (VAMP) ->involved in SV fusion
-Rab 3 or 27 -> docking SV closed to Ca++ channel
Why are proton pumps required for the SV to be filled with NTs?
Vesicular transporters rely on H+ gradients (force) to fill SV with NTs
The proton pump fills the SV with H+ (becomes acidic), creating an electrochemical gradient harnessed by the vesicular transporter to import NTs
Why are proton pumps costly in energy?
They depend on ATP (they are ATPases)
What are two functional characteristics of fast synaptic transmission?
Spatially restricted
Temporally controlled
How is the active zone morphologically distinctive from the rest of the plasma membrane?
Electron dense zone
What is the difference between the active zone complex and the SNARE complex?
Both complexes are composed of distinct proteins.
The main role of the active zone complex is to dock SV close to Ca++ channels -> yielding spatial specificity
Which protein in the active zone complex is most tightly linking the SV to the Ca++ channel? What molecule on the SV interacts with that protein?
RIM
Rab3
What happens if KO RIMs (RIM1 and RIM2, only RIM genes in mammals)?
Dramatically impaired exocytosis
To which complex does Munc13 belong? What is its role in exocytosis?
Belongs to the active zone complex, but indirectly interacts with SNARE complex.
Munc13 binds to syntaxin via its MUN domain, relieving the inhibition on Munc18, allowing the latter to form a template for the SNARE complex to properly assemble
*Its role is to prime the SNARE complex (vesicle priming) for fusion ->make SVs “readily releasable” *
How much time elapses between a presynaptic AP and a postsynaptic AP?
0.13 msec
True of false: the exocytosis process in neurotransmission takes longer then the Ca2+-triggered fusion pore opening.
False.
What is the core fusion complex composed of?
Synaptobrevin (VAMP), syntaxin, SNAP-25, Munc18
basically SNARE complex + Munc18
Under which condition does synaptotagmin interact with the SNARE complex?
If calcium is present
What follows KO of Syt1? What follows KO of Syt9?
Abolishment of synchronous and spontaneous release
Abolishment of GABAergic transmission from striatal neurons.
How does synaptotagmin trigger exocytosis?
Binds to SNARE complex, creating a pull and twist motion that forces the vesicular membrane and plasma membrane together
Do neuromodulator agents generate postsynaptic currents?
Not really, they rather affect the capacity of the receptor cell to respond
What are neuropeptides? In what type of neurotransmission are they involved?
Involved in neuromodulation (slow neurotransmission)
Cleaved from precursor proteins (genetic origin), packaged in dense core vesicles,
What is the chemical brain hypothesis?
Neuromodulation would have first helped premetazoan to sense environmental cue
Limited diffusion of neuropeptides would have eventually lead to autocrine amplification of signal
Which would have eventually lead to evolution of protosynapse
Why would have neuropeptides been an efficient way to communication in early multicellular organisms?
No need for synaptic spatial specificity -> only need the right neuropeptides and the right receptors
How are fluorescent NT sensors generated?
Fusion of fluorescent reporter gene to the NT receptor -> binding of NT to receptor generates fluorescence
