Lecture 22 : Synapses and Neurotransmission Flashcards
Define a synapse
The point at which electrical signals move from one nerve cell to another. Allows neurons to pass electrical/chemical signals to another neuron or to the target effector cell
Give the general outline for how they work
- The arrival of an action potential at the synaptic terminal will trigger channels in the presynaptic membrane to open and release neurotransmitters into the synaptic cleft
- These neurotransmitters bind to the receptors in the membrane of the dendrites or in the cell body of the postsynaptic neuron.
- The receptors are activated and generate a graded potential in the postsynaptic neuron.
- The postsynaptic potential may be inhibitory or excitatory.
Name the two types of synapses
electrical and chemical
Electrical synapses are also known as…
gap junctions
What makes electrical synapses different to chemical synapses?
There is a direct point of contact between the cytoplasm of two adjacent neurons- pre and postsynaptic neurons
What are the three parts of an electrical synapse?
- presynaptic neuron
- postsynaptic neuron
- connexons
Gap junctions in electrical synapses are formed by connexons in both cell membranes. What is a connexon?
channels/pores which allow the direct passage of ions and small molecules through them. They connect the cytoplasm of the presynaptic and postsynaptic neuron
electrical synapses are hard to control. Why?
very rapid transfer of signals
Where do we find electrical synapses?
non-mammalian and invertebrate
electrical synapses work in both…
directions - bidirectional
Chemical synapses are the most…
common
How do chemical synapses differ to electrical?
The presynaptic and postsynaptic neuron are physically separated by the synaptic cleft.
What are the three parts of a chemical synapse?
presynaptic neuron, postsynaptic neuron, the synaptic cleft.
What crosses the synaptic cleft in the chemical synapses. What is the effect of this?
The presynaptic neuron releases a neurotransmitter which diffuses across the synaptic cleft and bind to receptors on the postsynaptic membrane and chemically stimulates the postsynaptic cell. Takes time to release neurotransmitters and for it to diffuse, so we have synaptic delay
Chemical synapses only work in…
one direction
Where are chemical synapses found?
In the CNS and NMJ
There are three types of synapses in the CNS. Name them
Axo-dendritic
Axo-somatic
Axo-axonal
Axo-dendritic synapse
axon of one neuron synapses with a dendrite of another
Axo-somatic synapse
the axon terminal of one neuron projects onto a cell body of another nerve cell
Axo-axonal synapse
the axon terminal of one neurone projects onto the axon of another neuron
Synapses vary in…
size and shape
Pre-synaptic terminals contain vesicles arranged at…
active zones
The postsynaptic membrane is specialised how?
contains clusters of neurotransmitter receptors and signalling molecules.
What is a neurotransmitter?
a chemical messenger that is released from the pre-synaptic neuron. After release, the neurotransmitter crosses the synaptic cleft and attaches to receptors on the post synaptic neuron, either exciting or inhibiting the postsynaptic neuron
What does the suffix -ergic apply to?
neurons which release neurotransmitters. For example, dopaminergic neuron releases dopamine
Neurotransmitters are released from the presynaptic neurone by exocytosis. Explain the process.
- When the action potential reaches the terminal, there is an influx of sodium ions in the terminal of presynaptic neuron.
- This causes depolarization of the terminal
- Voltage gated calcium channels are activated and calcium ions diffuse into the terminal.
- The influx of calcium ions through VGCC initiates the exocytosis process that leads to neurotransmitter release.
- Calcium interacts with a vesicle bound protein called synaptotagmin. This protein is a calcium sensor and when calcium is present the synaptotagmin interacts with the SNARE proteins.
- Synaptic vesicle membranes fuse with presynaptic membrane. Exocytosis occurs and the neurotransmitters are released.
- The neurotransmitters bind to receptors on the postsynaptic membrane either exciting or inhibiting the neuron.
How are neurotransmitters removed form the synaptic cleft?
- degradation: enzyme changes the structure of the neurotransmitter so it can no longer be recognised by receptor
- diffusion: the neurotransmitter diffuses away from the receptor
- reuptake: the whole neurotransmitter is actively transported back into the presynaptic axon terminal for reuse
- Enzymatically transformed into inactive substances
Give the four main criteria for neurotransmitters.
- Must be synthesized and stored within the presynaptic neuron
- The transmitter must be released by the presynaptic neuron in response to presynaptic depolarization by action potential – release should depend upon calcium ions
- Must be a specific receptor for the substance in the postsynaptic cell to mediate postsynaptic response
- There should be a mechanism for the removal/breakdown of the neurotransmitters
Give the four main categories of neurotransmitter
amines
amino acids
peptides
purines
Give the four types of amine neurotransmitters
histamine
acetylcholine
indoleamines
catecholamines
Give three examples of catecholamine neurotransmitters
noradrenaline
dopamine
adrenaline
Give four examples of amino acid neurotransmitters
glutamate, aspartate, GABA and glycine
Give two examples of peptide neurotransmitters
endorphins
neurokinins
Give two examples of purine neurotransmitters
adenosine
ATP
What is a neurotransmitter receptor/neuroreceptor?
a membrane receptor protein that is activated by a neurotransmitter.
Name the two types of neuroreceptors
- ionotropic receptor
- metabotropic receptor
Describe ionotropic receptors.
ligand gated ion channel – these open up to allow ions like sodium, potassium, calcium and/or chlorine ions to pass through the membrane in response to the binding of a neurotransmitter. The effects can be excitatory (glutamate/aspartate) or inhibitory (GABA/Glycine).
Describe metabotropic receptors
– G protein coupled receptor – GPCR. Neurotransmitter binds to the receptor, activating G proteins, activating second messenger cascade, activating voltage gated ion channels on membrane. These receptors can remain open from seconds to minutes.
What is a neuromuscular junction?
a chemical synapse between a motor neuron and a muscle fibre – skeletal, smooth or cardiac. It allows the motor neuron to transmit a signal to the muscle fibre, causing muscle contraction
Disease of the NMJ can cause…
muscle weakness through mechanisms which can effect presynaptic, synaptic and postsynaptic portions of the NMJ.
Name three main diseases that involve the NMJ
= MG - myasthenia gravis, Botulism, Lambert-Eaton syndrome
What are three parts of the NMJ?
presynaptic = nerve terminal, postsynaptic = motor endplate, synaptic cleft- area between nerve terminal and motor endplate
What is the motor endplate?
The motor endplate is the thickened portion of the muscle plasma membrane that is folded to form depressions called junctional folds. The terminal nerve ending fit into these folds
Junctional folds of the motor endplate are covered in what type of receptor? Describe them - how do they work?
The junctional folds have nicotinic ACh receptors concentrated at the top.
The receptors are ACh gated ion channels - the binding of acetylcholine to these receptors opens channels and allows sodium ions to diffuse into the muscle membrane so the endplate potential changes and an AP is transmitted to muscle membrane
How is acetylcholine synthesised?
- ACh is synthesized in the pre-synaptic terminal from choline and acetyl-CoA by the enzyme choline acetyltransferase, ChAT.
- ACh goes through a series of modifications before packaged into vesicles
How is acetylcholine released from NMJ?
- action potential travels down axon and causes the voltage gated calcium channels to open, resulting in an influx of calcium ions into the presynaptic nerve terminal.
- This causes the vesicles to move towards the nerve terminal membrane and fuse with it.
- Exocytosis of Ach into the synaptic cleft
- ACh bind to receptors and trigger the opening of Ach gated ion channels that allow the influx of sodium ions into the muscle. The membrane potential of the postsynaptic membrane changes from -90mV to -45mV. This decrease in the membrane potential is called endplate potential.
- In the NMJ, endplate potential is strong enough to propagate action potential over the skeletal muscle membrane which ultimately results in muscle contraction.
Why and how is acetylcholine broken down in the synaptic cleft of the NMJ?
- To prevent sustained depolarization and muscle contraction and to allow for repolarization, acetylcholine is metabolised by acetylcholinesterase into its subunits choline and acetate.
- Choline is reused for synthesis of ACh.
What type of neurone produces the neurotransmitter acetylcholine?
- produced by neurons called cholinergic neurons
Acetylcholine acts on which parts of the nervous system? What is its role in the PNS?
- In the PNS it plays a role in skeletal muscle movement as well as regulation of smooth and cardiac muscle.
- It acts on the CNS, ANS and NMJ
Generally, ACh receptors at the NMJ are what type of receptors?
Nicotinic ACh receptors, which are ligand-gated ion channels
Generally, ACh receptors in the CNS and ANS are what type?
muscarinic ACh receptors which are G protein coupled receptors
We call process that enhance ACh function………… and processes that inhibit ACh function are ……………
cholinergic
anticholinergic
Amino acids are the main brain neurotransmitters. Name the two types of neurotransmitters and give an example of amino acid neurotransmitter for each.
excitatory- glutamate and inhibitory- GABA
What is an excitatory neurotransmitter?
generates an electrical signal in the postsynaptic neuron
What is the role of glutamate
- the main excitatory transmitter in the CNS. Activates both ionotropic- ligand gated and metabotropic receptor- G protein coupled receptor.
- Glutamate is important for learning and memory
What is an inhibitory neurotransmitter?
Inhibitory neurotransmitters stop a specific response from other cells in the body- it prevents an excitatory response
GABA is the main inhibitory neurotransmitter in the CNS. What is it’s role?
- it reduces the activity of neurons, leading to increased relaxation, reduced stress, more calm, decreased pain, improved sleep and concentration. It is also involved in immune and endocrine systems and appetite, metabolism, motor control and vision.
- Activates small family of ionotropic and metabotropic receptors
Draw Glutamate and GABA
What is an Excitatory postsynaptic potential, EPSP? What neurotransmitter would produce this?
- Glutamate generates an excitatory postsynaptic potential -EPSP
- This is a synaptic potential that makes a postsynaptic neuron more likely to produce an action potential.
How does an EPSP occur?
- presynaptic cell releases neurotransmitters into the synapse
- some of them bind to receptors on the postsynaptic cell. Many of these receptors are ionotropic receptors and generally allow sodium ions into the cell, generating an excitatory postsynaptic current
What are inhibitory postsynaptic potentials and what neurotransmitter produces them?
- GABA generates an inhibitory postsynaptic potential – IPSP.
- This is a kind of synaptic potential that makes the postsynaptic neuron less likely to generate an action potential
Describe how IPSPs occur.
- Inhibitory presynaptic neurones release neurotransmitters which bind to the postsynaptic receptors, inducing a change in the permeability of the postsynaptic membrane to certain ions- usually allow flow of negative ions into the cell or positive ions out of the cell. - - This allows for a more negative postsynaptic potential to be generate – the membrane potential becomes more negative -hyperpolarisation, which makes depolarisation less likely and no action potential in postsynaptic neuron occurs
EPSPs and IPSPs are graded potentials. Graded potentials decay with…
time and distance
Explain temporal summation.
Graded potentials decay with time and distance. However, if they happen close enough in time, their effects may be additive- temporal summation
Explain spatial summation
Graded potentials decay with time and distance but if they occur near the same part of the neuron their effects may be additive - spatial summation
When multiple EPSPs occur on a single patch of postsynaptic membrane, their combined effect results in…
a greater membrane depolarisation, increasing the likelihood of reach threshold and an action potential being fired
If excitatory and inhibitory potentials of the same size occur at same time and place…
they may cancel each other out and membrane potential may not change.
In most neurons one excitatory event is not enough to reach threshold. An action potential is therefore initiated by…
the combined effects of many excitatory synapses - temporal / spatial summation
