Synaptic Transmission Part II Flashcards
Electrical synapses are similar to gap junctions and there are no delays in signally…However! gap junctions are bidirectional and this is not..?
However, evolution has preferred chemical over electrical synapses.. this prevents infection from viruses, etc from spreading from cell to cell
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At electrical synapses, gap junctions between pre- and postsynaptic membranes permit current to flow passively through intercellular channels (see blowup). This current flow changes the postsynaptic membrane potential, initiating (or in some instances inhibiting) the generation of postsynaptic action potentials
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How are chemical synapses used in the CNS?
one way transmutation
inhibition
summation signaling
delayed signaling (parallel processing use?)
plasticity (alter efficiency - become bigger and better with use)
what is wired transmission?
***usually neurotransmitter…? like ACH and is very fast EPSP!!
wired transmission… can be close on post or far away on post…. go to glial cell or to presynaptic
a one way transmission
What is volume transmission?
what is its onset/effect time?
**usually peptide… ultra slow EPSP
release site some distance from target cell
neuromodulators
range of action is limited by diffusion and inactivating enzymes
slower onset and longer lasting effects!!
How is the cessation of neurotransmitter action in the CNS done?
diffusion
reuptake into the synaptic terminal
reuptake into the glial cells
What is transcellular signaling?
Done in the CNS!
transmitter is made in post synaptic cell but it goes and effects the presynaptic cell and tells it to enhance its transmitter release!!
this is important in induction of long-term potentiation - is a retrograde messenger…
see this in declarative memory system
metabotropic receptors are not…
ion channels!!
what do metabotropic receptors regulate?
how do they exert their actions?
enzymes associated with these receptors can be either unregulated or down regulated!!
A great deal of diversity is possible by paring different receptors with different effector systems!
regulate second messenger cascades!
exert their action through G proteins!
**ligands bind to it!
A G-protein coupled receptor contains…
seven membrane spanning domains
The serine residues in a G protein do what?
the are phosphorylation sites involved with receptor INACTIVATION!!!!
Where does the binding site for the neurotransmitter lie in a G protein coupled receptor?
lies in the cleft in the receptor that is embedded in the lipid bilayer and it is accessible from the extracellular surface
Give an example of metabotropic receptor?
agonist?
effector mechanisms/onset/offset?
muscarinic acetylcholine receptors
agonist: muscarine
effector mechanism associated with specific muscarinic receptor subtypes (slower onset and slower offset than nicotinic receptors!!!)
- *in both the ANS and CNS
- *5 subtypes do diff thing through the same ligand (neurotransmitter - acetylcholine - but have diff reactions - review them on slide!)
Metabotropic receptors can have G protein act on ion channel directly or can create second messengers or even third messengers that do that!
for ex., can activate an enzyme that phosphorylates to open/close an ion channel
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What are some known second messenger systems involved in metabotropic neurotransmission?
adenylyl cyclase (create CAMP - PKA)
phospholipase C - IP3 and DAG - increase CA2+ for PK)
phospholipase A
guanylyl cyclase (cGMP)
Different neurotransmitter-receptor interactions can activate different signal transduction pathways
There are multiple subtypes for the same neurotransmitter that are differentially coupled to the signal transduction systems
These signaling mechanisms can be immediate, short term, long term (gene expression), etc
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A single neurotransmitter can have short and long term effects on ion channel… this often depends on..
the amount of exposure!
a single exposure to NT - short term effects
repeated exposure to NT - long term effects and gene expression!
What is a consequence of multiple receptors for a neurotransmitter?
ex. with cholinergic receptors
The activation of different receptors by ACh can cause opposite effects on resting membrane potential
for ex. nicotinic cholinergic - depolarize (pos)
muscarinic cholinergic- repolarize (neg)
What three diff things can occur when you have activation of multiple receptors by a single transmitter?
opposing
additive
or independent signaling pathways
second messenger responses can be any of these things
Co-transmitter pairs exist between classic amino acid transmitters and peptide transmitters…
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What gets released at low frequency stimulation of presynaptic cells?
only the classic neurotransmitters!
located right at the active zone
**Regulation is based upon low and high frequency depolarization
what gets released during rapid bursts of presynaptic action potentials?
co-release of both peptide transmitters and classical!
peptides are located in the dense core in the back part of the terminal!
**Regulation is based upon low and high frequency depolarization
where does synaptic facilitation occur?
what is it?
synaptic facilitation occurs only at the postsynaptic membrane potential..
the presynaptic action potential is steady and always go to the same amplitude!
It has to do with calcium release!
Synaptic facilitation is a form of short-term plasticity that enhances synaptic transmission for less than a second
Synaptic facilitation is primarily caused by elevations in pre-synaptic calcium
when there is a series of action potentials in the presynaptic cell, the calcium is entering is added to residual calcium left behind!
Amount of calcium influx is directly proportional to the amount of AcH released and the post synaptic response!!
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post tetanic potentiation.. what is it?
what is it caused by?
again, presynaptic action potentials are always constant! here, there is a rapid burst of signaling from presynaptic cell
there is a potentiation that correlates with rapid burst and then after there is posttetanic potentation
even if the presynaptic goes back to low frequency signaling, the post synaptic is at a high amplitude! (last minutes to hours)
CALCIUM CAUSES IT! - because the calcium buffer system is swamped in the presynaptic term, you have high levels remaining, sending out AcH
Post-Tetanic Potentiation (PTP) is a form of synaptic plasticity which is short-lived and results in increased frequency of miniature excitatory postsynaptic potentials (mEPSPs) or currents (EPSCs) with no effect on amplitude in the spontaneous postsynaptic potential
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What are four major regulatory processes for cytoplasmic calcium levels in a nerve terminal?
calcium binding proteins
uptake in to mitochondria
calcium ATP pump
Sodium calcium antiport (ca2+ out, Na2+ in)
**this is what gets overwhelmed in post-tetanic potentiation!!) — basis for long-term potentiation when swampped
what is long term potentiation?
long-term potentiation (LTP) is a persistent strengthening of synapses based on recent patterns of activity
requires tetani!!
calcium comes in, causes gene expression, grows synapses
what is post-tetanic depression (fatigue)?
Describes the reduction in sensitivity of a synapse’s response (excitatory or inhibitory) to incoming signals following a tetanus. This is generally caused by a reduction of the amount of neuro-transmitters on hand at the synaptic terminal
what are axosomatic synapses?
synapse on the cell body
what are axodendritic synapses?
synapse on dendrite itself or spines of the dendrites (aka shaft or spine)
what are axo-axonic synapses?
terminal of neuron
what is presynaptic inhibition?
where does the inhibitory neuron touch the presynaptic neuron?
what is the effect of the inhibitory neuron on the presynaptic neuron?
results in what?
Inhibitory neuron contacts the terminal of a second presynaptic neuron
Release of neurotransmitter by the inhibitory neuron depresses the calcium current, thereby reducing the amount of neurotransmitter released by the presynaptic cell
This results in a depression of the postsynaptic potential (PSP)
**look at diagrams for this/charts!
AN EXAMPLE OF HOW PRESYNAPTIC INHIBITION CAN BE USED IN THE BRAIN
A modulatory neuron synapses on one collateral of the presynaptic neuron and can selectively inhibit one postsynaptic target
used a lot in parallel circuitry
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presynaptic facilitation….
a facilitating neuron contacts the presynaptic neuron where?
release of neurotransmitter by the facilitating neuron causes what effect in the presynaptic neuron?
results in what in the postsynaptic cell?
A facilitating neuron contacts the terminal of a second presynaptic neuron
Release of neurotransmitter by the facilitating neuron depresses the potassium current in the presynaptic cell, thereby prolonging the action potential and increasing the calcium influx
This results in an increased PSP in the postsynaptic cell
**look at diagram for this/charts!
sequence of events in presynaptic facilitation… (6)
result?
(1) release of serotonin by facilitating neuron
(2) increase of cAMP activates protein kinase
(3) activation of a protein that phosphorylates potassium channels (closes/inactivates it)
(4) these channels usually repolarize the membrane following an action potential
(5) prolonged depolarization results in greater influx of calcium
(6) which leads to greater exocytosis of neurotransmitter
Result: greater response in the motor neuron
but starts in the CNS…?
Synaptic integration.. great example is the hippocampal neuron (dendritic tree) because it has lots of receptors all over it for thousands of axons
There is not a one to one relationship in the CNS!! this is a key difference from the NMJ
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General principles:
1) active inputs contribute proportionally to their synaptic strength
2) cell bodies sum inputs and scale nonlinearly
3) if above threshold, cell fires
4) cell outputs its activity to other neurons
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what is the length constant?
measure of how far a potential travels along a “cylinder” before decaying to 37% of its original peak amplitude
dendrites are not… ?
what is their diameter?
why is this important?
Not myelinated!!
have a small diameter
aka they passively propagate signals!
how far the dendrite is from the cell body contributes to its “weight” - farther away it is, less effect it will have!
What is temporal summation?
Occurs when a second stimulus of the same intensity is applied to a muscle before the completion of the relaxation period of the first stimulus
single cell
what is EPSP-IPSP cancellation
cancellation
neurons have to fire AT THE SAME TIME!
have to be close enough
what is spatial summation?
two diff neurons
close enough to summate
Temporal summation occurs when a single pre-synaptic neuron fires many times in succession, causing the post-synaptic neuron to reach its threshold and fire. Spatial summation occurs when excitatory potentials from many different pre-synaptic neurons cause the post-synaptic neuron to reach its threshold and fire
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comparison of Quantal release at the NMJ and Synapses in the CNS….
NMJ 150-200 quanta released Synaptic potential of about 70 mV Suprathreshold SAFETY FACTOR guarantees the muscle fiber reaches threshold
CNS SYNAPSES
Most presynaptic neurons produce postsynaptic (PSP) potentials of 0.5 mV
Some will be inhibitory
Multiple simultaneous inputs needed to generate an action potential
Drugs acting at a receptor can affect the number of neurotransmitter receptors by decreasing the rate of receptor synthesis.
For ex., can give an agonist that binds to receipts so it down regulates (desensitization)
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Drugs can increase the rate of synthesis of neurotransmitter receptors resulting in an increased sensitivity to neurotransmission
basically, give an antagonist, which causes 50% of the receptors NOT to be bound, so neuron decides to make more (up regulate)
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Therapeutic effects vs. side effects…
3 different possibilities for their relationship between toxic and beneficial - list them - look at diagram too!
(1) Mediated by same receptor-effector mechanism
(2) Mediated by identical receptors but in different tissues or by different effector pathways
(3) Mediated by different types of receptors
Chloropromazine…antipsychotic that binds to both dopamine (wanted effect) and adrenergic receptors (side effects)
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The similarity in the shape of dopamine and chlorpromazine permits this drug to function as a dopamine receptor antagonist.
but poor selectivity - so why you see huge list of side effects from interaction with various receptors and uptake pumps!!!
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cross over binding problem with dopamine receptors also in basal ganglia of motor system for chloropromazine
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