3. Synapse and Neurotransmitters Flashcards
What are the components of a synapse?
The modern synthesis is that a synapse consists of three components
- Pre ganglionic neurone
- Post ganglionic neurone
- Astrocyte (we don’t really understand the contribution of these and other glial cells)
What are the two types of synapse?
- Electrical
2. Chemical
Which type of synapse is the simplest form of impulse transmission?
Electrical
Which type of synapse is limited in the number of connections it can make?
Electrical
Limited coupling, with high resistance i.e the resistance reduces the signal too much for extensive connections.
Which type of synapse is bi-directional?
Electrical
Which type of synapse is uni-directional?
Chemical
Which type of synapse can be both excitatory and inhibitory?
Chemical
Which type of synapse can only be excitatory only?
Electrical
Which type of synapse exhibits limited convergence?
Electrical
typically just one cell to the next
Which type of synapse exhibits flexibility and adaptation and undergoes both short term and long term changes?
Chemical
Which type of synapse contributes little to complex function or divergence?
Electrical
Which type of synapse has huge potential for integration and convergence?
Chemical
Which type of synapse is important for processes like memory and learning?
Chemical
Which type of synapse is faster?
Electrical
Which type of synapse is important in the developing Brain?
Electrical
Which type of synapse is more common?
Chemical
What are the main differences between electrical and chemical synapses?
- Electrical
– Continuous electrical conduction (fast), important in developing brain)
– Simplest form of transmission
– Limited coupling, with high resistance i.e the resistance reduced the signal
– Bi directional
– Excitatory only
– Little convergence (i.e. typically just one cell to the next)
– Little or no plasticity or modulation over time
– Limited use in complex function or adaptation. - Chemical
– Most common in the nervous system
– Uses a chemical intermediary
– Single action potential pre synaptically can result in a large post synaptic potential
– Excitatory and inhibitory
– Unidirectional
– Huge potential for integration and convergence (many thousands)
– Flexible and adaptable
– Synaptic plasticity
– Long and short term changes
– Important for processes such as memory Diversity of modulators.
What the three structures that make up the anatomy of the synapse?
- Presynaptic terminal
- Post synaptic terminal
- Synaptic cleft.
What can be detected that distinguishes these structures from one another?
Specific proteins can be detected presynaptically (e.g. synaptophysin) or postsynaptically (e.g.PSD-95)
What confers function in transmission and direction of information flow?
Structural specialisation of membranes confers function in transmission and direction of information flow.
Describe the ultrastructure components of the chemical synapse?
Presynaptic vesicles and active zones, coupled with post synaptic receptors.
Detailed: High density of vesicles present at the presynaptic terminal – containing transmitter. Dense clusters of proteins are evident around the synaptic cleft. These correspond to structural specializations related to release of and response to transmitters.
Describe the ultrastructure components of the electrical synapses?
Gap junction channels
What is the agent of transmission in electrical synapses?
Ionic Current
What is the agent of transmission in chemical synapses?
Chemical Neurotransmitters
Which type of synapses have cytoplasmic continuity?
Electrical Synapses
Which type of synapse exhibit synaptic delay?
Chemical Synapses
usually 1-5ms, 0.3ms minimum
List the 3 steps in the lifecycle of the neurotransmitter?
1) Release from presynaptic neuron
2) Binding to receptors (can be presynaptic as well as postsynaptic)
3) Breakdown by enzymes in synaptic cleft (e.g. ACh – acetylcholineaterase) or reuptake by transporters in neurons or glia (e.g. glutamate – excitatory amino acid transporters)
The effect of an action potential is a function of what?
- Quantal Size
- Mean number of quanta released
(QS x MQR)
The effect of an action potential (or any stimulus) is a function of:
What is a quanta in the context of neurotransmitter release?
Q: The quantal size, or amplitude (a single vesicle might be associated with the release of around 5000 molecules of transmitter.). Minimum amount of NT release is the contents of a vesicle.
The mean number of quanta released is a function of what?
M: The mean number of quanta released. This itself is a function of n, the number of available vesicles, and pr, the probability of release.
“Transmitter release is probabilistic”
Describe what is meant by the term probabilistic
The probability of release in an unstimulated neurone is not zero and the release of NT can occur spontaneously. Signals will only increase the possibility.
Is it accurate to say that “an action potential causes transmitter release?”
No.
Keypoint: It is more accurate to say that an action potential transiently increases the probability of transmitter release, than to say an action potential causes transmitter release.
Describe how Ca2+ affects release probability? List the steps involved.
Action Potentials cause transmitter release from the presynaptic terminal
During an action potential Ca2+ concentration at the active zone can rise x1000 fold.
From 100 nM to 100 mM within a few hundred μs. So the following is the sequence of events;
1) An action potential depolarizes the axon terminal.
2) The depolarization opens voltage- gatedCa2+ channels and Ca2+ enters the cell.
3) Calcium entry triggers exocytosis of synaptic vesicle contents.
4) Neurotransmitter diffuses across the synaptic cleft and binds with receptors on the postsynaptic cell.
5) Neurotransmitter binding initiates a response in the postsynaptic cell.
Is diffusion of neurotransmitters fast or slow?
Slow
What are the possible fates of neurotransmitters?
1) Neurotransmitters can be returned to axon terminal for reuse or transported into glial cells
2) Enzymes inactivate neurotransmitters
3) Neurotransmitters can diffuse out of the synaptic cleft
What are the two ways in which neurotransmitters can be classified?
Functionally
Chemically (By Molecule Type)
What different functional classes of neurones?
Excitatory neurotransmitters cause membrane depolarization and make the neuron more excitable (excitatory post synaptic potentials, EPSPs).
Inhibitory neurotransmitters cause membrane hyperpolarization and make the neuron less excitable (inhibitory post synaptic potentials, IPSPs)
What are the different chemical classes of neurones?
- Acetylcholine
- Amines (derived from amino acids)
- Amino acids
- Purines
- Gases
- Peptides
- Lipids
(An Always Alert Patient Get Particularly Lonesome)
Name the Amino Acid neurotransmitters? State whether each is excitatory or inhibitory.
Glutamate is the primary excitatory transmitter in the brain. Aspartate is also excitatory.
Gamma aminobutyric acid (GABA) is the main inhibitory transmitter in the brain, while glycine serves this role in the spinal cord
Where is GABA the main inhibitory neurotransmitter?
Brain
Where is glycine the main inhibitory neurotransmitter?
Spinal Cord
Name the (mono) amine neurotransmitters/subgroups?
- Catecholamines (adrenaline, noradrenalin, dopamine etc.)
- Serotonin (5-HT)
- Histamine
From what are amine neurotransmitters derived?
All derived from single chain amino acids
Catecholamines = Tyrosine
Serotonin = Tryptophan
Histamine = Histadine
What are the properties of neuropeptides?
Many neuropeptides can act as both neurohormones and neurotransmitters.
These are often released with other transmitters. (cotransmission)
Give an example of a neuropeptide?
Opiods such as morphine. (Pain Pathways + Gut Motility)
Name the Purine group of neurotransmitters?
Adenosine
AMP
ATP
How do the purines act as neurotransmitters? Give an example of an adenosine receptor antagonist.
Adenosine acts on presynaptic receptors to INHIBIT transmitter release. Caffeine is an antagonist of adenosine receptors.
Name a member of the Gases group of neurotransmitters?
Nitric Oxide (Synthesised by Nitric Oxide Synthase of NOS and breaks down with seconds)
How does Nitric Acid act as a neurotransmitter?
When acting as a neurotransmitter, Nitric Acid does not bind to surface receptors, but diffuses freely into the target cell, where it binds to proteins
Give an example of a lipid neurotransmitter?
Eicosanoid Paracrines
How do eicosanoid paracrines act as a neurotransmitter?
Bind cannabinoid receptors, which are named for their binding of the exogenous ligand THC
What is Acetylcholine and Where is Acetylcholine released?
Acetylcholine is a single molecule released by peripheral motor neurons, (i.e. at neuromuscular junctions), and the main transmitter in autonomic ganglia.
What determines whether a neurotransmitter is excitatory or inhibitory?
The nature of the receptor to which it binds
What are the possible effects of a neurotransmitter binding to its receptor?
A transmitter binding to its receptor initiates an electrical response (ion channel/ionotropic) or a second messenger-signaling pathway (G-protein/metabotropic)
What allows neurotransmitters to illicate different responses in different cells?
One neurotransmitter has multiple receptors, allowing different cells to respond in different ways to the same stimulus
What precedes the release of neurotransmitter from its receptor?
Transmitters are released from their receptors when the concentration of transmitter in the cleft drops
What is the effect of transmitter uptake/breakdown on neurotransmission?
Transmitter uptake or breakdown acts as a break on neurotransmission
How can the effect of an action potential be altered?
By pharmacological, physiological or pathological processes.
Describe how the Nicotinic Ach Receptor acts as an excitatory receptor?
An Excitatory Receptor → Nicotinic ACh • Ionotropic receptor • Ligand-gated ion channel • Ion channel is permeable to sodium and potassium ions. • When activated, sodium entry exceeds potassium exit, resulting in depolarization • Broad distribution • Skeletal muscle • Autonomic nervous system • CNS
Describe how the Muscarinic Ach Receptor acts as an excitatory receptor?
An Excitatory receptor – Muscarinic ACh
• Metabotropic receptor
• G-protein coupled receptor
• 5 subtypes (M1-M5)
• Tissue response depends on receptor subtype
-Smooth muscle contraction
-Slowing of heart rate
-EPSPs in the CNS
-Increased intracellular calcium
• Because of the complexity of the second messenger signalling, some muscarinic receptor activation may be inhibitory (M4 receptor)
Describe how GABAa acts as an inhibitory receptor?
An inhibitory receptor – GABAa
• Ionotropic receptor
• Ligand-gated ion channel
• Selectively for chloride ions.
• Intracellular [Cl-] is much less than extracellular [Cl-]
• When channel opens, Cl- influx occurs, and membrane hyperpolarises
• Barbituate and benzodiazapene tranquilizers, and anaesthetic agents such as propofol and isoflurane, are positive allosteric modulators of this receptor, i.e. they increase the chloride conductance when GABA binds to the receptor.
Describe how GABAb acts as an inhibiotry receptor?
An inhibitory receptor – GABAb
• Metabotropic receptor
• G-protein coupled receptor
• G-protein signalling leads to activation of potassium channels, which leads to hyperpolarization.
• Effect of GABA binding to GABAB receptor is slower and longer lasting than binding to GABAA receptor.
What is the difference between GABA binding to GABAa rather than GABAb?
Effect of GABA binding to GABAB receptor is slower and longer lasting than binding to GABAA receptor.
How is GABAa different during birth compared to early life and why?
- In developing brain GABAa can act as an excitatory NT.
- Maternal Oxytocin will cause GABAa to become inhibitory during birth, which reduced brain activity, limiting the effect of oxygen deprivation that is likely during birth.
- It will become excitatory once again to allow for brain development.
- GABAbH is always inhibitory.
- It acts slower that GABAa
Name the types of Glutamate receptors?
- AMPA Receptor
- NMDA Receptor
- Metabolic Glutamate Receptors
Are Glutamate receptors excitatory or inhibitory?
Excitatory
But in the eye glutamate is sometimes excitatory sometimes inhibitory
What type of ion channel is the AMPA receptor and to what is it permeable?
Ligand-gated ion channel
Ion channel is permeable to sodium and potassium ions, similar to nicotinic receptors.
What type of ion channel is the NMDA receptor, to what is it permeable, and what ion blocks it?
Cation channel, permeable to sodium, potassium and calcium
Normally blocked by magnesium ion, which is released by depolarization
Requires glutamate and depolarization for activation.
Why is magnesium important in NMDA receptors?
Magnesium only removed if membrane is already depolarized. It allows for the detection of coincidence.
What is the function of most metabotropic Glutamate Receptors?
Multiple types
Most modulate the NMDA receptors (either increasing or decreasing activity, depending on type)
What are the steps involved in the excitation of Glutamate Receptors?
1) Glutamate is released.
2) Net Na+ entry depolarizes the postsynaptic cell.
3) Depolarization ejects Mg2+ and opens channel.
4) Ca2+ enters cytoplasm.
The activity of transmitter receptors is a function of what? What are the implications of this for therapeutics?
Activity of Transmitter receptors is a function of transmitter release and reuptake/breakdown.
There is least specificity in breakdown/reuptake systems. (Pharmacological Importance)
What does the activation of Neurotransmitter Receptors cause?
Graded Potentials
What causes Graded Potentials?
Largely due to sodium influx into the cells
What reverses Graded Potentials?
Opening of potassium channels
In what direction do graded potentials propagate?
Spread out in all directions
What happens to a graded potential as it spreads?
The potential decreases
What is meant by the term ‘summation’ in the context of graded potentials?
“Summation is a linear sum of the changes in membrane potential”
PSPs from different synapses throughout the dentritic tree directly influence each other. This is called summation.
Two PSPs occurring simultaneously at different locations sum by?
spatial summation
Two PSPs occurring at the same point at different times sum by?
Temporal Summation
Two PSPs occurring at different times and at different places in the dendritic tree summate by?
Temporal + Spatial Summation
Where can inhibitory synaptic inputs occur?
Inhibitory synaptic inputs can be presynaptic or postsynaptic.
What causes pre-synaptic inhibition, where does it occur and what is the affect?
- Here, inhibitory neurotransmission acts to counter the depolarization of membrane as the action potential arrives
- Decreased depolarization of the presynaptic membrane leads to decreased release of neurotransmitter.
- Presynaptic inhibition is selective for an individual synaptic connection.
What causes post-synaptic inhibition, where does it occur and what is the affect?
Postsynaptic inhibition is caused by ipsps. an ipsp can summate in time and space with epsps and other ipsp.
In post sympathetic inhibition, all targets are inhibited equally.
What are the targets for therapeutics which interfere with synaptic transmission?
I Drugs (and diseases) can affect synaptic signalling by targeting any of the following:
• Transmitter release (Botulinum toxin)
• Receptor binding (alpha-bungarotoxin)
• Transmitter uptake (SSRI antidepressants)
• Transmitter breakdown (MAOI antidepressants)
• Action potentials (tetrodotoxin, TTX; sodium channel blocker)
