Exam 2: Chapter 13: Synapses Flashcards
What increased the copy number in the doogie mouse?
The over expression of the NR2B genes
Greater activity of the NMDA receptor in the doogie mouse lead to:
- Improved learning and memory
- Improved and strengthened synaptic transmission and connection
- Synaptic plasticity
Synaptic transmission is usually what?
Chemical but can also be electrical
Current flows……
From cell to cell with no delay
Each synapse has a different
Functional role
ELECTRICAL synapses transmit signals…..
Instantaneously
When not polarized, what can happen?
The signal can travel in either direction
What kind of specialization are gap junctions and have far apart are the membranes normally? Why is this unique?
They are structural specializations and the membranes are only 3.5 nm apart, unlike the 20-30 nm that normally lies between cells
What are the subunits that make up gap junctions called? What size pore do they create?
Gap junctions are composed of subunits termed connexons that end up creating a 2 nm pore
How many connexin subunits create a connexon?
6
The 2 nm pore that is created by the connexons within gap junctions are large enough to allow for the passage of ?
Most ions
What can chemical synapses do?
Modify and amplify signals
What size synpatic cleft doesn’t allow for electrical transmission?
A 20-30 nm synaptic cleft
What are the 4 main steps involved in the transmission of an electrical signal?
- The electrical signal is first turned into a chemical signal
- The neurotransmitter then travels from the pore to the postsynaptic region
- The neurotransmitter then binds to receptors there and again an electrical or chemical response occurs
- The synaptic vesicles release neurotransmitters into the synaptic cleft
How do active zones appear in a synapse or neuron/cell? Why?
Denser or thicker bc postsynaptic densities have a lot of neurotransmitter receptors and scaffolding proteins
Where are more excitatory synapses found in general? In particular?
- In general on neuronal dendrites
- In particular on dendritic spines
What are dendritic spines like in adults?
They remain plastic in the adult with the size and shape changing in response to external stimuli
In chemical synapses, what two receptors can be present?
Both ionotropic and metabotropic receptors can be present
In chemical synapses, which receptors use second messengers?
Metabotropic receptors
How long do fast ionotropic chemical synapses takes?
0.3-3 ms
What is an advantage to the chemical synapse vs the electrical synapse?
Chemical synapses can be both excitatory and inhibitory, whereas electrical is nearly always excitatory
Which type of synapse is one- way? Which type is two way?
Chemical synapses are one way whereas electrical are two way
Chemical synapses allow for what?
For a signal to be amplified
What are 3 main characteristics of chemical synapses?
They are modifiable, allow for plastic change, and aid in learning and memory
What is the role of synaptic transmission?
It controls the excitability of the post- synaptic cells
What are the 3 main steps involved in the transmission of a chemical signal?
- Arrival of neurotransmitter causes a synaptic potential changing the resting potential on the post- synaptic cell
- Depolarization is excitatory causing an increase in the impulse frequency
- Hyperpolarization is then inhibitory causing the reverse and bringing the membrane back down to its resting potential
Which type of neuron is a good example of the functions of fast synaptic potentials? Why is this?
Synapses onto a spinal motor neuron
Over how many depolarizations are considered to be excitatory postsynaptic potentials (EPSPs)?
10-20 ms
For EPSPs, how much voltage is enough to depolarize the membrane?
Less than 1 mV
With EPSPs, repeated signals can be additive and lead to what?
They can create a summation and if it is high enough it can cause depolarization
For EPSPs, what dictates whether a temporal or spatial summation will occur?
It depends on whether one or several nerves are stimulated
What happens if EPSPs and IPSPs happen at the same time?
They can reduce or cancel each other out
In what ways are IPSPs and EPSPs similar?
For both, hyperpolarization is caused and both can have temporal or spatial summation
Since a cat motor neuron may receive signals from 10K synapses, what must its body do?
It must balance our responses to signals
What is neuronal integration?
The spatial and temporal summation of EPSPs and IPSPs
How do synapses excite or inhibit a neuron?
By depolarization or hyperpolarization at the site of impulse initiation
What is unique about an axosomatic synapse?
It is a short distance from the site of impulse initiation so there is little decrease in the signal
What is unique about an axodendritic synapse?
It maybe 200um from the axon hillock so it can lose 14-37% of its signal
What do synaptic potentials control?
Neuronal excitability
Where are fast chemical synaptic actions exemplified?
Vertebrae neuromusclar junctions
What is a peripheral synapse?
The neuromuscular junction (motor- end plate)
In a peripheral synapse, how many motor neurons are there per muscle fiber?
1
What does the peripheral synapse function as?
A relay synapse
How does a peripheral synapse work?
Each action potential of the motor neuron initiates a EPSP in the muscle fiber, causing a muscle contraction to take place
How do chemical synapses work?
By releasing and responding to neurotransmitters
What happens in the chemical synapse in the vertebrae neuromuscular junction?
- First Ca2+ enters the presynaptic gated channels
- This signals vesicles to fuse and release ACh into the synaptic cleft
- Neurotransmitter crosses the synaptic cleft and enters the post- synaptic area
- Neurotransmitter binds to specific receptors on post- synaptic surface
- Channel opens enabling ion flow to start resulting an EPSP, which, if large enough, will depolarize the muscle fiber and initiate muscle contraction
What do postsynaptic potentials result from?
Permeability changes that are neurotransmitter- dependent and voltage- independent
What do ligand- gated channels control?
Permeability changes
When do ligand- gated channels open?
They open as a result of binding neurotransmitters, not in response to depolarization
What does an EPSP result from in the vertebrae neuromuscular junction?
A simultaneous increase in the postsynaptic membranes permeability to Na+ and K+
In the vertebrae neuromuscular junction, what contributes to the synaptic current (depolarization)?
All the channels that open in response to neurotransmitters
In the vertebrae neuromuscular junction most of the synaptic current responsible for the ESPS is from where?
Na+
How do EPSPs between neurons and neuromuscular EPSPs compare?
EPSPs between neurons resemble neuromuscular EPSPs but they are smaller
In the vertebrae neuromuscular junction, what is the rise and exponential return of fast EPSPs in the CNS?
Fast EPSPs in the CNS have a rise of 1-2ms and an exponential return of 10-20 ms
How do the mechanism of a neuromuscular synapse and regular CNS excitatory synapse compare?
In a CNS synapse:
- Na+ and K+ are again used, but the neurotransmitter is glutamate - The CNS amplitude is smaller - Less neurotransmitter is released
In a regular CNS synapse, fast IPSPs can result from what?
An increase in permeability to chloride
What is the major mechanism of synaptic inhibition in the CNS?
- Hyperpolarizing results from a an increased permeability to Cl-
- Mechanism is mediated by 2 neurotransmitters, GABA and glycine
Most of the synaptic inhibitory synapses in the brain use what neurotransmitter?
GABA
In the mammalian CNS, what types of synapses are excitatory? Inhibitory?
Type 1 synapses are excitatory and type 2 are inhibitory
Where is acetylcholine synthesized and stored?
In the presynaptic terminal
Availability of choline is a …??
Limiter because it comes from the blood stream. If none is present, synthesis stops
Where is the enzyme choline aceytltransferase made?
It is made in the neuron cell body and is then transported to the presynaptic terminal
What do presynaptic neurons release neurotransmitter molecules in?
Quantal packets (vesicles)
What is required for neurotransmitter release?
Voltage- dependent Ca2+ influx
Depolarization at the presynaptic terminal opens what?
Voltage- gated Ca2+ channels -> Ca2+ enters enabling neurotransmitter release
Vesicular membranes are _____________ to prevent _____________
Vesicular membranes are recycled to prevent depletion
Where are synaptic vesicles cycled in distinct steps?
Nerve terminals
Several proteins play roles in vesicular __________ and _________
release and recycling
What does synapsin do and when does the attachment release?
Synapsin attaches vesicles to the actin cytoskeleton and the attachment is released when synapsin is phosphorylated
After synpasin attaches the vescile to the actin cytoskeleton and the attachment is released due to phosphorylation of the synapsin, where does the vesicle move?
To the active zone where it will need to be docked
What proteins are required in order for vesicles to be docked? What is the main one?
SNARES-> The main one is VAMP AKA synaptobrevin
The SNARES, or more specifically VAMP AKA synaptobrevin, required for docking of vesicles connect to what? What are 2 other proteins involved in this process?
- t-SNARE syntaxin and SNAP- 25
- Munc18 and complexin
Once the vesicle is docked, what leads to vesicle fusion with the membrane?
Ca2+ on entry binds to synaptotagmin leading to vesicle with the membrane
What protein has a role in vesicular mobilization and recycling?
Rab3
What protein promotes the pinching off of vesicles? How does it do this?
Dynamin promotes pinching off of vesicles via an ATP- dependent pathway
What do SNAREs, such as VAMP AKA synaptobrevin aid in?
Docking of the synaptic vesicles
What protein attaches vesicles to the actin cytoskeleton and releases the attachment when phosphylated?
Synapsin
What does Rab3 aid in?
Vesicular mobilization and recycling
What does the protein dynamin do?
It promotes the pinching off of vesicles via an ATP- dependent pathway
What process is associated with the protein clathrin?
Vesicular endocytosis
Vesicular endocytosis is associated with what?
Protein clathrin
How many general kinds of neurotransmitters are there?
2
What a the two general kinds of neurotransmitters?
Small- molecule neurotransmitters (amines and amino acids) and neuropeptides
What are synpases that have the neurotransmitter acetylcholine called?
Cholinergic synapses
What are synpases that have the neurotransmitter norepinephrine or noradrenline called?
Noradregergic or adrenergic synapses
What neurotransmitters are found in cholinergic synapses and noradregencic/adrenergic synapses, respectively?
Acetylcholine and norepinephrine/ noradrenline
Most of the CNS neurotransmitters are?
Amino acids
How many of the synpases in the CNS are cholinergic? How many are noradrengenic/ adregeneric/ contain norepinephrine?
- Less than 10% are cholinergic
- 1% are noradrengenic/ adregeneric/ contain norepinephrine
Do neurons only have one characteristic neurotransmitter? Can they synthesize more than one kind of neurotransmitter?
No, they can have one or more characteristic neurotransmitters. They can also synthesize more than one kind of neurotransmitter
What are cotransmitters?
What it’s called when a neuron may synthesize more than one kind of neurotransmitter
What are two examples of cotransmitters?
Small- molecules and neuropeptides
Single neurotransmitters may produce what?
Multiple postsynaptic effects
What are the criteria for being a neurotransmitter? (5)
- Must be present in the presynaptic terminal, along with
the means to synthesize it - Released upon presynaptic stimulation
- Mimics the effects of presynaptic stimulation when
present extracellularly - A mechanism for removal exists
- Drug effects may block
Most synapses in the CNS use what kind of neurotransmitter?
Amino acid neurotransmitters
Most fast EPSPs are caused by what neurotransmitter?
Glutamate
Most fast IPSPs are caused by what neurotransmitter?
GABA or glycine
Many CNS neurons also have ________, so they may be _________
Many CNS neurons have peptides, may be a
cotransmitter
What other neurotransmitters are present in a few neurons that connect to large areas and aid in volume transmission?
Biogenic amines like acetylcholine, norepinephrine, dopamine, and serotonin
What kind of modulation do receptors for the bioamines have and how many are there?
-Receptors for the bioamines have slow actions of
modulation
- They have multiple receptors
What affect does acetylcholine have on the skeletal muscle and what affect does it have on the heart muscle?
Acetylcholine (ACh) is excitatory on skeletal muscle and is inhibitory in heart muscle
What are the different kinds of post- synaptic receptors involved in skeletal and heart muscle? How are they identified?
One is ligand-gated and the other is G protein- coupled. They are identified by their pharmacology
How is the ACh receptor on skeletal vs the Ach receptor on the heart muscle activated and blocked?
-The ACh receptor on skeletal muscle is activated by
nicotine and is blocked by curare
-The ACh receptor on heart muscle is stimulated by
muscarine and is blocked by atropine
Enzymes and reuptake aid in whaat process?
Termination of neurotransmitter action
Neurotransmitters are only active for a _________ period of time. In just a few milliseconds you have what?
- SHORT
- Release, diffusion, and receptor binding
After receptor activation, what must happen to the neurotransmitter molecules?
They must be cleared from the synaptic cleft
How are neurotransmitters removed from the synaptic cleft?
Enzyme digestion or reuptake mechanisms
What is an example of how neurotransmitters removed from the synaptic cleft? (A)
- Acetylcholine (ACh) is digested by acetylcholinesterase AChE in the synaptic cleft.
- After break down choline is taken back up by the presynaptic terminal
What is an example of how neurotransmitters removed from the synaptic cleft? (NE)
-Norepinephrine is simply taken back up by the
presynaptic terminal
In what ways do peptide neurotransmitters differ from small molecule neurotransmitters?
They differ in synthesis, release, and termination
How long are peptide neurotransmitters normally?
Chains of amino acids 3-55 peptides long
Where are peptide neurotransmitters synthesized? Where are they then transported to and how are they transported?
Synthesized in the cell body and transported to the axon
terminal
- They transported as propeptides in vesicles
How peptide neurotransmitters removed from the synaptic cleft?
Cleared by nonspecific peptidases, can be depleted
The release of peptide neurotransmitters is
Ca2+ dependent
What two kinds of channels/ receptors can be used for fast ionotropic actions?
Ligand- gated channels and g- coupled receptors
What kind of effects do ionotropic receptors have?
They have direct effects
How do ionotropic receptors work?
-The neurotransmitter binds to the active site of the
receptor, which is a ligand-gated channel
-The channel opens allowing ions to enter or exit
What kind of receptor is an example of a ligand- gated channel?
acetylcholine receptors are ligand-gated channels that function as ionotropic receptors with nicotinic acetylcholine receptors causing excitation at the neuromuscular junction
How many subunits does a nicotinic ACh receptor have?
5 subunits with 2 α’s
How many domains does each subunit that makes up the nicotinic ACh receptor have? What are they?
- Each subunit has 4 domains
- M2 domain faces the interior and makes up the channel
- The 2 α’s have an ACh binding site
When 2 ACh molecules are bound in the binding sites of the 2 α’s in the nicotinic ACh receptor, what happens?
The receptor undergoes a conformational change so Na⁺ and K ⁺ can now pass through, but it only remains open for 1 ms
What experiment showed the 4 features of a ligand- gated channel?
The patch- clamp experiment
What 4 features of a ligand- gated channel did the patch- clamp experiment reveal?
- Opening of a ligand-gated channel is all-or-none
- If the concentration of neurotransmitter is high enough, the channel will open
- All the currents from open channels are summated and
make up the synaptic current - The net ionic current through the channel is it’s portion of the synaptic current
What do G- coupled receptors do?
They initiate signal transduction
A GPCR isn’t an ion channel, but rather a part of the
7- TM superfamily
Ligands bind to _________ ______________ and __________ ____________ control G- protein binding
-Ligands bind to the extracellular domains
-Cytoplasmic domains (TM5,6,7 and 4) control G-protein
binding
In the G- protein coupled receptor cascade metabotropic receptors act via what? Which one is the best known?
- Metabotropic receptors act via second messengers
- The best known is cAMP
What are the 5 main steps involved in initiating the G- protein coupled receptor cascade?
- Upon ligand binding, GDP is released and the G protein breaks apart
- The α subunit binds GTP and activates adenylyl cyclase AC
- AC activation converts ATP to cAMP
- cAMP contributes to phosphorylation of nuclear proteins and receptor proteins via protein kinase
- Phosphorylating a channel allows it to open increasing ion permeability, changing the membrane potential
Some G proteins can activate ion channels __________, without second messenger action, when does this occur? What does ACh cause here and how?
- Directly
- This occurs at cholinergic synapses in cardiac muscle
- ACh causes inhibition here bc muscarinic ACh receptors are present in the heart
Channels can be gated by signals other than ___________ or _________ _______________ _____________
Voltage or direct neurotransmitter binding
What are 2 examples of second- messengers (besides cAMP) that G- protein- coupled receptors act by?
-G protein activates guanylyl cyclase and generates cGMP, leading to the activation of cGMP-dependent protein kinase and phosphorylation of cellular proteins
- Another GPCR mechanism is using membrane lipid
products and Ca²⁺
What are other examples of second- messengers that are part of another pathway?
PIP2 , Phospholipase C, IP3 and DAG
What are G- protein coupled receptors generally used for?
Slow, metabotropic actions
How does IP3 act as a second messenger?
- Ca²⁺ freed from the ER by IP3 can activate protein kinase C and calmodulin CaM
- Producing CaM kinase, that phosphorylates cellular proteins
G protein- coupled receptors mediate what?
Permeability; decrease synaptic potentials and presynaptic inhibition
What occurs with presynaptic inhibition (PSI)?
One axon terminal ends on another axon terminal, decreasing the amount of neurotransmitter at the second terminal
What are learning and memory based on?
Synaptic plasticity
What is posttetanic poteniation?
Extended enhancement of synaptic response
What can happen with synaptic efficiency over time with use?
Synaptic efficiency can change with those changes being long- lasting
Where is long- term potentiation seen?
In the vertebrae hippocampus and cerebral cortex, AKA the learning and memory regions of the brain
What processes is the hippocampus involved in?
Spatial learning and memory formation
What happens when circuits in the hippocampus are strongly stimulated?
The circuits in the hippocampus receive prolonged changes when strongly stimulated, with these changes being associative and pathway specific
What follows intense stimulation in the CA1 region of the hippocampus?
Long-term potentiation (LTP) where long-lasting changes to synaptic transmission is noticed
Long- term potentiation in the brain involve changes in what? What do these changes cause?
- Synapse strength, causing already successful synapses to get even better, pre and post synaptic regiones to be active together, and for LTP to occur
How long can a strong postsynaptic depolarization last in hippocampal slices? In an intact animal?
A strong postsynaptic depolarization can last hours in hippocampal slices and weeks in an intact animal
What two related glutamate receptors allow for hippocampal LTP?
NMDA and AMPA
AMPA receptors have what kind of excitation?
Rapid excitiation
NMDA receptors have what kind of excitation?
Excitatory but they are only active in postsynaptic areas that are already depolarized
Synaptic plasitcity
Synapses change properties with time and activity
How does the NMDA receptor work?
-Ca²⁺ entering through the NMDA channels act as second
messengers
-Activates Ca²⁺/calmodulin-dependent kinase II (CaMKII) and protein kinase C
A major mechanism for lasting change in synaptic
strength comes from what?
Control of the postsynaptic AMPA channels
What do more AMPA channels allow for?
- More AMPA channels means a larger amplitude of synaptic responses
- More potentiation
- LTD
How does the AMPA receptor work?
- Ca²⁺ that enters through NMDA channels results in downstream events causing phosphorylation and expression of new AMPA channels postsynaptically; they are NMDA dependent!!!
Long- term memories can involve changes to what?
The physical structure of neurons
What does LTP need?
New protein synthesis and gene transcription
