Synaptic Transmission Flashcards
Some of these may be docked already without needed calcium to make them
Vesicles
These are procured by the spontaneous release of the contents of one vesicle
Mini postsynaptic potentials
This depends on internal resistance (ri) and membrane resistance (rm)
Length constant
These are easier to study than CNS synapses
NMJ
SLIDE 27
SLIDE 27
These synapses allow for the coordinate firing of cells or neurons
Electrical synapses
These are similar to CNS synapses
NMJ
There are thousands of these on every neuron
Channels
Synapses that are evolutionarily old and present in many organisms
Electrical synapses
Faster response, ionotropic receptors
Ligand gated
Summation that occurs when many signals come down the same axon quickly
Temporal summation
Synapses between dendrites and dendrites
Dendrodendritic
How can glia enhance presynaptic function?
Create more NT release due to cholesterol from glial cells
These synapses are usually inhibitory
Grays type 2
What types of things can G-proteins activate?
G-protein activated ion channels and second messengers
These can regulate synaptic development by creating silent but structurally normal synapses, enhanced presynaptic functions, and being postsynaptically active (functions)
Glia
What happens to voltage over a distance that can be shown in a formula?
It will dissipate over a distance
What does connexin make up and what does that make up?
Connexin makes up a connexon which makes up a gap junction (a connexon of two cells coming together to form one pore)
These are fast, large, reliable synapses. They release a lot of vesicles (lots of NTs)
NMJ
Usually dendrites cant fire these
APs
What can happen to the downstream steps for some time after the G protein has been inactivated?
They can proceed for some time
What happens after the G protein has activated or inhibited downstream effectors?
It eventually hydrolyzes the GTP and returns to the inactive form, terminating the signaling. It goes back to inactive to wait for the next signal
Comparing miniature and evoked potentials can be used to decide how many of these are released
Vesicles (NTs)
These are not released at the active zone and have a lower time course (50 msec), they generally are released in response to higher Ca levels (granules are parked further back)
Peptide NTs
There are present in all cells as basic amino acids used in protein synthesis, but are loaded into synaptic vesicles by specific vesicular transporters
Glycine and glutamate
When a neuron has two NTs and releases them at the same time, they are in the same vesicle
Co-release
Eventhough activation of GPCRs doesn’t immediately depolarize or hyperpolarize the cell, they can do this by acting through second messenger systems
Modulate signaling
What does ACh cause at negative membrane potentials (voltages)?
Inward current
This depends on diameter and electrical properties of cytoplasm and is constant in a mature neuron
Internal resistance
These are slower acting and are seen with amino acid, amine, and peptide NTs
GPCRs
What do axons often do at NMJs?
Spread out to create lots of surface area
This depends on synaptic activity and how many ion channels are open
Membrane resistance
These activate receptors and mimic the actions of NTs. Examples include nicotine
Agonists
These synapses are common in mammalian CNS, glia, cardiac muscle cells, smooth muscle, epithelial cells, liver cells
Electrical synapses
What are enzymes markers for in cells?
Markers for what NT the cell makes
Is the synapse empty and is it organized?
It is not empty and it is highly organized
Synapses between axons and axons
Axoaxonic
What is contained in a secretory granule (dense-core vesicle)
Protein NTs (they show up darker on EM views of a synapse)
Synaptic vesicles contain a large number of these specific vesicle SNARES
v-SNARES
These are between motor neurons and muscle
Neuromuscular junction (NMJ)
These block receptor activation. Examples are curare and cobra venom
Antagonists
What happens to many NTs in the synapse to terminate signaling (happens to the vast majority of NTs)?
Taken up into the neuron or nearby glial cells (astrocytes)
These types of synapses occur due to symmetrical membrane thickness at synapse
Grays type 2, usually inhibitory
This toxin inc ACh release
Black widow venom
What are synaptic vesicles bound to in the presynaptic cell?
Docking proteins
We want this to be high for a longer length constant
Membrane resistance
These produce opening of VG Ca channels producing large influx of Ca
APs
When a neuron has two NTs and releases them at the same time, they are in two different vesicles
Co-transmission
Only small molecules and ions can move through these
Gap junctions
Why can dendrites with Na, Ca, and K channels synapse further from the axon hillock?
They can generate APs because the depolarizing input is transmitted further. It doesn’t just diffuse, it gets replenished
What does the I/V (current/voltage) curve of a non-voltage dependent channel look like?
It is a straight line (SLIDE 48)
What is the equilibrium potential of Cl?
-65 mV
This is not empty and it contains extracellular matrix proteins which help organize the synapse and enzymes which can break down NTs
Synaptic cleft
Dendrites cant fire APs but they can do this
Add current
This part of the transmitter gated channel is usually closed until ligand binds, or is stabilized in the open state by an agonist
Pore (channel)
these are recycled by endocytosis in multiple ways
Vesicle membranes
Most of these are treated as electrically passive cables
Dendrites
If inhibitory synapses are present between the site of input (on soma or most likely dendrites) and the axon hillock, opening of Cl channels can do this to the depolarization
Shunt or short circuit the depolarization
What do various NTs have that is distinct for them?
Distinct synthetic pathways
These form a continuous channel pore that is open always and connects two cells
Gap junction channels
Discovered chemical synapses in 1921 and the first NT, vagusstoff (ACh)
Loewi
These can vary in structure seen as differences in membrane thickness
Pre and postsynaptic sides
This is synthesized from glutamate by glutamic acid decarboxylase and loaded into vesicles
GABA
What do oval vesicles indicate?
Inhibitory NTs
This part of a neuron integrates many signals acting though multiple receptors
Postsynaptic neuron
What is the next most common way for NTs to be removed behind reuptake?
Degradation by enzymes
This protein is essential for Ca sensing and release won’t occur without it
Synaptotagmin
Opening of Na, K, and Ca channels on special dendrites allows the addition of current which allows the propagation of what
EPSPs
What does binding of the ligand (NT) to the receptor produce in a GPCR?
A conformational change which activates the g protein
What must happen to the NT in the cleft for signaling to stop?
It must be destroyed or removed
We want this to be low for a longer length constant. Fatter axon = lower this
Internal resistance
These types of synapses occur do to asymmetrical membrane thickness at synapse
Grays type 1, usually excitatory
These synapses are usually excitatory
Grays type 1
Summation that occurs when many signals come from different axons
Spatial summation
What type of synapses are most synapses in the brain?
Chemical
These block acetylcholinesterase and thus acetylcholine breakdown. This results I the over stimulation then paralysis. Nerve gas and some insecticides are examples
Organophosphates
There are more than 100 of these
Different NT receptors
How does the G protein stop signaling?
It eventually hydrolyzes the GTP and returns to the inactive form, terminating the signaling. It goes back to inactive to wait for the next signal
Dendrites that have longer length constants are able to do this
Synapse further from the axon hillock
This is the point when the flow of current is reversed (in to out) and thus the voltage changes (negative to positive)
Reversal potential
The process in which multiple inputs are combined within one neuron to determine an output
Synaptic integration
What can the same transmitter produce in different receptors?
Same NT can have different actions depending on the type of receptor (fast at ligand gated but slow at GPCRs)
Studied motor neurons going to mucles
Katz
These create a highly organized matrix presynaptically to be able to be released quickly
VAS (vesicle attachment sites)
Due to gating Na, K, and Ca, these are excitatory and produce excitatory post synaptic potentials (EPSPs)
nicotinic ACh receptors
Step in synaptic transmission that is putting NTs in vesicles or secretory granules in the case of peptides
- loading into vesicles
These proteins form gap junctions
Connexin proteins
Overall structure of these types of receptors are similar
Ligand gated
This has to be active for shunting to occur
Inhibitory synapse
Can single channel spontaneously open?
Yes they can and they can be recorded
The brain performs billions of these ever second
Neural computations
Slower response, metabotropic receptors
GPCRs
What makes cells with gap junctions (electrical signaling) so effective?
The postsynaptic cell requires almost no input to match firing of the presynaptic cell that had to reach an AP
These are large dense-core vesicles which are further from the terminus
Secretory granules
What can blockage of the process of enzyme degrading NTs cause?
Death due to overstimulation
This gives some idea how far away from the axon hillock depolarization can occur and still get an AP
Length constant
How else can NTs get out of the synapse other than destruction or removal?
Diffuse away
The amplitude of this is a multiple of mini amplitudes produced by the release of each vesicle
The amplitude of an EPSP
Step in synaptic transmission that creates the NT. Each has own enzymes needed for synthesis. Some neurons make multiple and release together or separately
- synthesis of NTs
This side of the chem synapse has densities which contain receptors and associated proteins
Postsynaptic side
What can happen to receptors that are exposed to NTs for too long
They become desensitized, the NTs need to be removed or destroyed to maintain normal synaptic function
SLIDE 29
SLIDE 29
Much of what we know about synapses first was learned at these
NMJ
Most of these are composed of 4-5 subunits, change conformation after the ligand binds, and the channel opens within microseconds
Transmitter gated channels
These are often present at synapses and participate in regulation of signaling
Astrocytes
Studied CNS synapses
Eccles
These go all the way to the end of the axon while these dont
To end = synaptic vesicles
Not to end = secretory granules
This interacts with a specific vSNARE and synaptic vesicle fusion and release occurs rapidly by exocytosis (0.2msec)
Calcium
Single or multiple ones of these can be present at synapses
Active zones
These are also known as metabotropic receptors
GPCRs
Discovered electrical synapses in 1959
Furshpan and Potter
The axon hillock must be depolarized to threshold to generate this
AP
These are located on the membrane at the presynaptic terminus to interact with v-SNARES
t-SNARES
This is the number of NT molecules in a vesicle (usually several thousand)
Quantum
These are present in every cell
Amino acids
These two interact to dock the vesicle to the presynaptic membrane
v-SNARES and t-SNARES
Astrocytes release these in response to NTs to modulate the synapse
Gliotransmitters
What do round vesicles indicate?
Excitatory NTs
This side of the chemical synapse has active zones with docked vesicles and secretory granules (large dense-core vesicles) which are further from the terminus
Presynaptic side
What do folds do at the NMJ?
Inc the surface area to inc how many vesicles there can be (more NTs)
There are a finite number of these per vesicle referred to as the quantum
NTs
These are presynaptic and often G-protein-linked receptors, and give feedback to the neuron releasing the NT
Autoreceptors
Shunting the depolarization through Cl channels opening is a way of doing this
Regulating synaptic transmission by reducing excitement (EPSP)
These are used to tell us what other ions the channel may be permeable to
Reversal potentials
The model receptor for ligand gated receptors
Nicotinic ACh receptors
These are needed in cells with vital functions and cells with needed synchronized firing
Gap junctions
Does every cell only make one NT?
No, some neurons can make multiple NTs
This toxin blocks NT release
Botulinum toxin
Synapses between axons and dendrites
Axodendritic, axospinous
These allow for cells to fire at the same rate
Gap junctions
What does Ca interact with to release NTs?
tSNARES
6 steps of synaptic transmission
- synthesis of NTs
- loading into vesicles
- release of vesicles
- NT binding to postsynaptic receptors
- electrical response
- removal or destruction of NT
What is the length constant?
The value at which depolarization is 37% of its original value
The only amino acid NT not also used for protein synthesis
GABA
What are dendrites that are able to generate APs (add current not fire an AP) called (they contain Na, K, and Ca channels)
Excitable dendrites
Modulation through GPCRs by second messengers can alter this and potentially change this
Alter synaptic transmission and potentially change signaling over along time
In the CNS, this could be as little as one vesicle, 0.1 mV, which makes sense bc integration is needed for computational functions of a neuron
Quantal analysis of EPSPs
Step in synaptic transmission that involves a response through gate channels or biochem response through GPCRs
- electrical response
These channels aren’t as selective as VG channels, they are selective for cations or anions
Transmitter gated channels
The number of channels that open depend on the quantity of these being released
NTs
These are synthesized at axon terminals and loaded into vesicles there by specific vesicular transporters
Amine NTs
These are bidirectional, making the cells electronically coupled, and allowing fast communication
Gap junctions
There is a reserve pool of these away from the synapse incase they are needed
Vesicles
What does ACh cause at positive membrane potentials (voltages)?
Outward current
The use of drugs to study of effect neurotransmission. Has lead to the identification of the molecular details of many of these steps
Neuropharmacology
How are vesicles docked?
Within specific, defined structures
Discovered and named the synapse in 1897
Sherrington
These are synthesized in the soma like other proteins and transported in secretory granules via the fast axonal transport mechanism
Peptide NTs
These have a presynaptic and postsynaptic side with a 20-50 nm cleft
Chemical synapses
These are the largest NTs
Peptide NTs
These channels gate Na, K, Ca
ACh receptors
SLIDE 67
SLIDE 67
200 vesicles are rebased by an AP, resulting in a -40 mV depolarization that needs to work every time here (it is fast and reliable)
NMJ
SLIDE 22
SLIDE 22
What does the I/V (current/voltage) curve of a voltage dependent channel look like?
It has a curve followed by a straight line (SLIDE 48)
What does a G protein do once it has been activated?
Activates or inhibits downstream effectors
These are inhibitory and thus open Cl channels and produce inhibitory post synaptic potentials (IPSPs)
Glycine and GABA