Lecture 13, The Synapse Flashcards
The Synapse
transmission of an action potential ends when it reaches the end of the axon (axon terminal)
synapse: an anatomically defined junction between two neurons, at which the electrical activity of the presynaptic neuron influences the electrical activity of the postsynaptic neuron
- includes:
◦ components of the presynaptic neuron
◦ components of the postsynaptic neuron
◦ the extracellular space between the two neurons
hundreds to thousands of presynaptic neurons can affect a single postsynaptic neuron
* convergence
a single presynaptic neuron can affect several postsynaptic neurons
* divergence
Chemical vs Electrical Synapses
chemical synapses: neurotransmitters stored in synaptic vesicles are released into the synaptic cleft, and bind to receptors on the postsynaptic neuron
- signal transmission occurs via neurotransmitters
electrical synapses: consist of gap junctions that allow electrical current to directly pass from the presynaptic cell to the postsynaptic cell
- signal transmission occurs via current
-> gap junctions connect one cell to another (form hole so that information can flow between 1 cell to another without having to go through or touch extracellular fluid)
Chemical Synapse
analogous to the neuromuscular junction, except the postsynaptic cell is a neuron
- the postsynaptic density is the analog for the motor end plate
- contains a high density of membrane receptor proteins
- 10 to 20 mm of extracellular space
- prevents direct propagation of the action potential from the presynaptic neuron to the postsynaptic neuron
- instead, neurotransmitters need to be released and cross the cleft, in order for the signal to be transmitted
more than one type of neurotransmitter can be released from the presynaptic axon at a given time
- cotransmitters bind to different receptors on the postsynaptic cell
chemical synapses are much more prevalent than electrical synapses
Neurotransmitter Release
signal transmission at the synapse is similar to the NMJ
step 1: action potential reaches the axon terminal
- the axon terminal depolarizes
step 2: voltage-gated Ca2+ channels open
- the depolarization of the axon terminal stimulates the opening of Ca2+ ion channels
step 3: Ca2+ enters the axon terminal
- flows into the cell down its concentration gradient
step 4: Ca2+ binds to synaptic vesicles containing neurotransmitters, causing them to bind with the membrane
- exocytosis of the neurotransmitter into the cleft
step 5: the neurotransmitter diffuses across the synaptic cleft
- binds to receptors on the postsynaptic cell (on the postsynaptic density)
step 6: neurotransmitter is removed from the synaptic cleft, and returned to the presynaptic cell
Neurotransmitter Release (SNARE proteins and Synaptotagmin)
at rest, synaptic vesicles in the active zone are loosely anchored near the synaptic terminal membrane by
SNARE proteins
when an action potential reaches the synaptic end bulb, Ca2+ floods into the cell
- synaptotagmins are a family of proteins that are also associated with the synaptic vesicles
- Ca2+ interacts synaptotagmins, which cause a conformational change in the SNARE proteins
- this change pulls the vesicle towards the membrane, and initiates fusion of the vesicle membrane with the plasma membrane of the neuron (synaptic terminal membrane)
depending on the synapse and the cell, partial or full fusion may occur
- full fusion: The vesicle membrane completely fuses and becomes part of the synaptic terminal membrane
- partial fusion: only one segment of the vesicle fuses with the synaptic terminal membrane, creating a pore for the contents to be secreted
◦ after secretion, the vesicle reseals and remains
within the cell
◦ “kiss-and-run fusion”
Postsynaptic Activation
ionotropic receptors are linked to ion channels
- activation of the receptors directly causes the opening of an associated ion channel
metabotropic receptors are linked to G proteins and/or secondary messengers, that initiate a signal transduction pathway to open/close an ion channel
- activation of the receptors indirectly causes the opening of an associated ion channel
in either case, there is a slight synaptic delay
* delay between the arrival of the presynaptic signal and the initiation of the action potential in the postsynaptic cell
* due to the sequence of events involved
* the change in membrane potential is dependent on the conformational change in the receptor, and the transmission of that signal to an ion channel
* delay is ~0.2 msec
Neurotransmitter Clearance
after the signal has been transmitted to the postsynaptic cells, neurotransmitters are removed from the synaptic cleft in a variety of ways:
- active transport back into the presynaptic cell to be reused
◦ neurotransmitter reuptake
- are transported into nearby glial cells and degraded
- diffusion out of the cleft
- conversion into an inactive form via enzymes
◦ sometimes occurs as a step prior to
neurotransmitter reuptake
some drugs are used to inhibit the reuptake of certain neurotransmitters
- selective serotonin reuptake inhibitors (SSRIs)
- serotonin is a neurotransmitter that plays a key role in mood; the “feel good hormone”
- SSRI Function: keeps serotonin in the synaptic cleft for longer, to initiate a prolonged response from the postsynaptic cell
- treatment for depression, anxiety, and OCD
Excitatory Synapses and Inhibitory Synapses
synapses can either be excitatory or inhibitory – key difference is the effect of the neurotransmitter on the postsynaptic cell
- excitatory synapses – increased activity of the presynaptic neuron brings the postsynaptic neuron closer to threshold potential
◦ promotes the initiation of an action potential in
the postsynaptic neuron
◦ presynaptic neuron provides a depolarizing
stimulus
* inhibitory synapses – increased activity of the presynaptic neuron brings the postsynaptic neuron father from threshold potential
◦ inhibits the initiation of an action potential in the
postsynaptic neuron
◦ presynaptic neuron provides a repolarizing or
hyperpolarizing stimulus, or inhibits
depolarization
because one neuron can have interactions with several to thousand presynaptic neurons, the level of excitability of that neuron depends on:
* the number of synapses active at a given time
* the proportion of active synapses that are excitatory or inhibitory
what happens at excitatory and inhibitory chemical synapses?
at an excitatory chemical synapse, when the neurotransmitter reaches the postsynaptic cell, the response is depolarization
- opening of Na+ and K+ ion channels
- net movement of positive ions into the cell
- the membrane potential becomes less negative
* excitatory postsynaptic potential (EPSP)
◦ a type of graded potential
at an inhibitory chemical synapse, when the neurotransmitter reaches the postsynaptic cell, the response is repolarization, hyperpolarization, or stabilization of the resting potential
- opening of Cl- and/or K+ ion channels
- net movement of negative ions into the cell
- the membrane potential becomes more negative or is stabilized at -70 mV
* inhibitory postsynaptic potential (IPSP)
◦ a type of graded potential
Integration of Graded Potentials
one postsynaptic cell can have synapses with hundreds to thousands of presynaptic neurons
- each active synapse influences postsynaptic membrane potential (EPSPs and IPSPs)
- an action potential is only initiated if threshold potential is met
◦ often requires input from multiple excitatory
synapses (temporal and/or spatial summation)
◦ temporal summation = the signals received are
separated by time
◦ spatial summation = the signals received are
separated by space
remember, graded potentials are decremental; the signal dissipates farther from the synapse
* the greater the distance between the synapse and the axon hillock, the weaker the EPSP/IPSP
Integration of Graded Potential (Spatial Summation)
spatial summation of post-synaptic potentials
- the graded potential elicited by each presynaptic neuron is integrated at the trigger zone of the postsynaptic neuron
- the potentials originate at different sites on cell body, but are integrated in one spot
if the summation of the graded potentials at the trigger zone reaches threshold potential, we will get an action potential
- two criteria need to be met:
◦ reach threshold potential
◦ at the trigger zone
Synaptic Strength ( presynaptic mechanism)/ autoreceptors def)
synaptic strength: the ability of a presynaptic cell to generate a change in postsynaptic membrane potential
- a measure of the “effectiveness ” of a synapse
- depends on presynaptic and postsynaptic mechanisms
presynaptic mechanisms; a neuron does not release the same amount of neurotransmitter every time, due to:
- inadequate Ca2+ regulation → decreased synaptic strength
- influence from another cell or neuron
◦ in this case, cell A releases a signal that binds to
presynaptic receptors on cell B, which influences
neurotransmitter release from cell B
◦ cell A is influencing the strength of the synapse
between cell B and cell C
◦ presynaptic inhibition – cell A decreases the
amount of neurotransmitter released from cell B
◦ presynaptic facilitation – cell A increases the
amount of neurotransmitter released from cell B
- autoreceptors: receptors on the presynaptic cell that sense chemicals or neurotransmitters, and influence synaptic strength
- feedback mechanism, to control how much neurotransmitter the cell releases
Synaptic Strength (postsynaptic mechanisms
postsynaptic mechanisms; a postsynaptic cell may have a variable response to the same stimulus, due to:
- the expression of the receptor on the postsynaptic cell
◦ decreased expression → decreased synaptic
strength
◦ receptor expression refers to the density of
receptors present on the postsynaptic membrane
◦ receptor expression can be modified via
exocytosis and endocytosis
- the sensitivity of the receptor for the neurotransmitter
◦ receptor desensitization: the decreased
responsiveness of a receptor to an agonist
(molecule that the receptor is made for - activate),
due to chronic or repetitive exposure to the
agonist
◦ receptor sensitization: an increase in the
responsiveness of a receptor to an agonist
- inhibition of the receptor
◦ remember curare?
◦ competitive inhibition; blocking of the ACh receptors, so that ACh cannot bind
Drug/Disease-related Modification of Synaptic Transmission
curare at the NMJ - bind to receptor on postsynaptic membrane to block (antagonist) or mimic (agonist) transmitter action
botulinum toxins at the NMJ (C) - block transmitter release
selective serotinin reuptake inhibitors (E) - block transmitter reuptake
- increase transmitter release into clift, inhibitor transmitter synthesis etc.
Modification of Synaptic Transmission
many therapeutic treatments that target the nervous system do so by modifying synaptic mechanisms, and thus altering synaptic strength
Clostridium Tetani is the bacteria responsible for the neurological disorder tetanus
- targets the SNARE proteins in the presynaptic neuron
- impairs the ability for synaptic vesicles to fuse with the synaptic terminal membrane
- no release of neurotransmitters into the synaptic cleft
- tetanus affects neurons that for inhibitory synapses
- symptoms: muscle spasms, increased muscle contractions, and spastic paralysis of muscles
Clostridium Botulinum is the bacteria responsible for the disease botulism (refer to lecture #5)
- botulinum toxins also target SNARE proteins
- while tetanus affects inhibitory synapses, botulism affects excitatory synapses
- symptoms: muscle weakness, reduced muscle contractions, and flaccid paralysis
