Chapter 5: Synaptic Transmission Flashcards
Goes with Action potential so study that too!
Overall Process
What is the overall process of synaptic transmission?
- Nuerotransmitter releases across synaptic cleft
- Bind to receptors on the post -synaptic side on the dendrites & soma
- When it binds, a ligand- gated ion channel will either open or close
- EPSPs and IPSPs constantly go into the cell or neuron and then it will be summed to see if we can initiate an action potential once again!
Chemical —> Electrical —-> Chemical
A Brief History
Compare and describe the differences between the reticular theory and the neuron doctrine in the sense of electrical and chemical transmission…
**Reticular Theory (Golgi)
*** Flow of signals was purely electrical and there was a continuos flow
Neuron Doctrine (Cajal)
* ****Current would flow out into the extracellular spce
* A chemical signal (neurotransmitter) is relseased by the cell sending the signal to the (presynaptic cell)
* Does something to the cell recieveing the signal.
Both were right :)
A Brief History
What are synapses and does it have to be between two neurons?
Synapses is the functional connection between two cells and it can be between 2 neurons or even between a neuron and a muscle cell.
A Brief History
In what way does the information flow?
Unidirectional. It goes from pre synaptic to post synaptic.
There are exceptions to this but for now this is okay.
A Brief History
Describe the Loewi Experiement
Gave us the first evidence of pure synaptic chemical transmission.
* He put two frogs hearts into seperate solutions but the first still had the vagus nerve attached. He used a tube to connect both solutions with the hearts in it.
* The heart rate of heart one slowed and then as the solution was transferred to heart 2, the heart rate also slowed.
Electrical Synapses
Describe electrical synapses
- Electrical synapses allows direct transfer of ionic current from one cell to the next.
- Occurs at the neuronal gap junctions which are found in several brain regions.
- There are connexons on both pre-synapctic and post-synapctic sides and they bring the cells very close in contact.
Electrical Synapses
What are gap junctions channels made up of?
- Formed by 2 connexons
- A connexon is formed by 6 connexins
Electrical Synapses
What exactly do gap junctions do?
* They allow the flow of ions from cytoplasm of one cell to cytoplasm of another cell
* Allows bi-directional flow of ionic current
* Very Fast transmission
Ex. flies are really fast b/c of this.
Chemical Synapses
Describe the pre-synaptic & post-synaptic sides
Presynaptic Side
* Axon terminal
* Neurotransmitter vesicles & secretory glands
* Active zones: sites of neurotransmitter release
**Postsynaptic Side
* **Post Synaptic Denstiy: Contains Neurotransmitter receptors
Chemical Synapses
How wide is a synaptic cleft?
20-50 nm wide
Chemical Synapses
Compare electrical vs. chemical synapses
Electrical
* Gap junctions connect cytoplasm of pre & postsynaptic cell
* Bidirectional
*** Ionic current flows through gap junctions channnels that bridge pre and post synaptic cells **
* If post synaptic cells is depolarized then it causes an action potential
Chemical
* Neurons seperated by synaptic cleft
* No current crosses from pre to post
* **Action Potential leads to release of chemical transmitter that diffuses across synaptic cleft **
* Transmitter interacts with receptors on postsynaptic cell»_space;> depolarization or hyperpolarization.
Chemical Synapses
You are recording from a pre-and post synaptic neuron. You measure a post-synaptic potential (PSP) in the presynaptic neuron and almost instantly see an PSP in the post-synaptic neuron . This is an example of a chemical synapse.
T/F
False
Has to be an electrical synapse because a chemical synapse isn’t that fast.
Properties of Chemical Synapses
What are the types of CNS synapses?
- Axodendritic: Axon to dendrite
- Axospinous: Axon to dentritic spine
- Axosomatic: Axon to axon
- Axoaxonic: Axon to Axon <— can cause more or less neurotransmitters to be released b/c nerve terminals of neurons are touching each other.
Properties of Chemical Synapses
What are autoreceptors and what are their purpose?
Autoreceptors are presynaptic receptors sensitive to neurotransmitter released by the presynaptic terminal.
* **located outside active zone and far from post synaptic density so if a neurotransmitter gets close to it then there is too many being released. **
* When too many neurotransmitters are released, they inhibit it and functions as a safety valve (negative feedback) by informing neuroterminal to stop releasing neurotransmitters.
Two different types:
* Terminal (located on the nerve terminal)
* Somatodendritic (located on soma or dendrites)
Properties of Chemical Synapses
Compare and contrast Gray’s type 1 to Gray’s type 2
Gray’s type 1: Asymmetrical ; usually excitatory
Gray’s type 2: Symmetrical; usually inhibitory
Properties of Chemical Synapses
What are archetypal synapse: Nueromuscular Junctions (NMJ)
- Chemical synapses exist between motor neurons of the spinal cord and skeletal muscle - the NMJ
- Established the principles of synaptic transmission
- One of the largest synapses in the body
- Not all synaptic junctions exists in the CNS**
The Process of Chemical Synaptic Transmission
Give a brief overview of Chemical Synaptic Transmission
- Neurotransmitter/peptide synthesis
- Packaging into synaptic vesicles
- Vesicles fusions
- Neurotransmitter release into synaptic cleft
- Binding to post synaptic receptors
- Biochemical/electrical response elicited in postsynaptic cell
- Removal of neurotransmiter from synaptic cleft
Neurotransmitters
What is the classical criteria to determine whether a chemical is a neurotransmitter?
- The substance must be present in the presynaptic terminal
- The substance must be released in response to presynaptic depolarization and the release must be calcium-dependent.
- Specific receptors for the substance must be present on the postsynaptic cell.
Neurotransmitters: Synthesis & Storage
What must neurotransmitters be in order to be ready for release?
Synthesized and readied.
* Nuerons have many neurotransmitters that are abundant.
* Each neuron contains specialized enzymes required to synthesize the NT in the nerve terminal.
Neurotransmitters: Synthesis & Storage
What are vesicular transporters?
**They are in the vesicular membrane and concentrate NTs into synaptic vesicles **
* Small, clear-core vesicles
* Packing into synapctic vesicles protects NT from breakdown by enzymes in presynaptic terminal.
Neuropeptides: Synthesis & Storage
What are neuropeptides?
Synthesized in the ER, split in the Golgi, and bud off into a secretory granule.
* Large, dense-core vesicles
* Precursor proteins ar broken down by enzymes during shipment to axon terminals - peptide is “liberated”
* No replenished very quickly
Neuropeptides: Synthesis & Storage
Neurotransmitters vs. Neuropeptides
- NP Release: Greater depolarization needed
- Vesicle Size: Small clear vs large dense core vesicles.
Neurotransmitters: Release
What is Ca2+ mediated exocytosis and how does it work?
- When a wave of depolarizatio reaches the axon terminal»>voltage -gated Ca2+ channels open.
- Neurotransmitter release is depended on the influx of calcium into pre- synaptic terminal to allow synaptic vesicles or secretory granules to fuse to pre-synaptic membrane and release their contents into the synaptic cleft.
* Ca2+ sensitive proteins causes the vesicles to fuse with the cell membrane, releasing neurotransmitters
Neurotransmitters: Release
What are SNARE Proteins and what do they do?
SNARE Proteins bring two membranes close together.
* Synaptobrevin in synaptic vesicle membrane
* Syntaxin & SNAP -25 in plasma membrane
Neurotransmitters: Release
What is the calcium binding protein?
Synaptotagmin which is located in the vesicle membrane and it the calcium sensor.
* It causes the SNARE proteins to fuse together causing the fusion of the vesicle membrane with the plasma membrane allowing the NTs to be released in the synaptic space.
Neurotransmitters: Release
What is botulism?
It is a bacterial toxin that blocks ACh release at neuromuscular junctions
* Enzymes in the toxin attack SNARE proteins by cleaving or cutting it.
* this is what is used in botox
Neurotransmitters: Release
Describe the process of vesicle recycling?
- During exocytosis, vesicle membranes are added to the cell membrane
- Vesicle membrane is recycled by endocytosis and then fuses with an endosome
* Clathrin protein coats vesicles for recycling
Clathrin plays a role in shaping vesicles in the cytoplasm.
Neurotransmitter Receptors: Ionotropic Receptors
What are ionotropic receptors?
Also called Transmitter-gated ion channels
- They are ion channels that open in response to neurotransmitter binding to them.
- Ions then enter the cell and a postsynpatic potential (PSP) is produced, also called “local potentials” because this is happening near the membrane.
Neurotransmitter Receptors: Ionotropic Receptors
What are the two kinds of PSPs produced?
**Excitatory Postsynaptic Potential (EPSP)
*** A positive charged ion enter the cell and causes depolarization of the membrane which makes it more likely to fire an action potential.
Ex. glutamate
Inhibitory Postsynaptic Potential (IPSP)
* A negative charged ion enters the cell and causes hyperpolarization which decreses the chances to fire an AP.
Ex. GABA
Neurotransmitter Receptors: Ionotropic Receptors
Can there be more than one input on a single neuron?
Yes! There can be thousands of inputs on a single neuron and then these inputs are summed and if the sum reached the threshold then an AP results
* None of the PSPs are sufficient to depolarize the cell by themselves.
Neurotransmitter Receptors: Ionotropic Receptors
Describe EPSPs detailed
- Na+ inward current flow causes the membrane depolarization, more likely to fire AP.
Neurotransmitter Receptors: Ionotropic Receptors
Describe IPSPs Detailed
Cl- inward current flow causes the membrane hyperpolarization; less likely to fire an action potential.
Neurotransmitter Receptors: G- Protein Coupled Receptors (GPCRs)
What are the two types of receptors
G-protein Coupled Receptors & Ionotropic Receptors
Neurotransmitter Receptors: G- Protein Coupled Receptors (GPCRs)
What are G-protein coupled receptors?
Also known as metabotropic receptors
They are inserted in the plasma membrane and when NTs bind to them, they act in two ways:
1. They can directly inhibit or activate and ion channel located near it.
2.** They can stimulate or inhibit effector enzymes in the cell membrane that synthesizes or break down second messenger moleucles. **
Neurotransmitter Receptors: G- Protein Coupled Receptors (GPCRs)
Describe more about these second messengers
- **The first messengers are the NTs. *
***They will bind to the first receptors.
**The second messengers are molecules inside the cell produced by effector enzymes that activate protein kinases. **
* Causes phosphorylation of substrate proteins
* Ex. (cAMP)
Neurotransmitter: Degradation & Recovery
how does neurotransmitters stop signal transmission?
They must be REMOVED from the synaptic cleft ;0
1. Diffusion of transmitter molecules away from the synapse.
2. Reuptake via transporters: Neurotransmitter re-enters presynaptic axon terminal or that of neighboring astrocyte.
3. Enzymatic Destruction: inside nerve terminal or in the synaptic cleft. Ex. AChE
Neurotransmitter: Degradation & Recovery
What are some of the transporters that blocks the re-uptake of Serotonin?
- SSRIs
- MDMA
- Cocaine
Neurotransmitter: Degradation & Recovery
What are agonists & antagonists
Agonists: mimic the actions of naturally occuring neurtotransmitters
Antagonists: Inhibitors of neurotransmitter receptors
Taking it all in
What is synpatic integration?
Synaptic integration is the process by which multiple synpatic potentials combine within one postsynaptic neuron.
* Most CNS neurons recieve thousands of synaptic inputs.
Taking it all in
What is EPSP summation and what are the two type?
Integration: EPSPs added together to produce significant postsynaptic depolarization.
* Spatial summation: EPSPs generated simultaneously at different sites
* Temporal summation: EPSPs generated at same synapse in rapid succession.
Taking it all in
Describe Dendritic Cable Properties
- Signal is not regenerated in dendrites (spreads passively)
- Membrane depolarization falls off exponentially with increasing distance along the cable
- Dendrite can be viewed as a straight cable
Taking it all in
Describe Inhibition
- Not all synapses are excitatory
- Action of inhibitory synapses:** take membrane potential away from action potential threshold. **
- Exerts powerful control over neuron output.
Taking it all in
Describe Shunting Inhibition
This is when a synapse inhibits current flow to the axon hillock.
* The depolarizing current is inhibited by inhibitory synpases such as GABA or glycine.
* Knocks down effect of excitatory ion and prevents AP from happening.
* Located on soma and near axon hillock
Taking it all in
Describe Modulation
Many synpases have GPCRs that are not directly associated with an ion channel.
* Therefore activiation of these receptors do not produce EPSPs or IPSPs.
* Instead, it modifies the efficacy of EPSPs generated by other synapses which allows the effects to last longer than the prescence of NT on receptor.
