Lecture 8 - synapses & neurotrasmitter Flashcards
What is a synapse?
a junction between 2 neurons allowing signals to pass from one to the other
What is evidence for neurons?
- Golgi stain (Ramon & Cajal, late 1800s)
- Physiological evidence from study of reflexes (Sherrington around 1900)
- Final evidence from electron microscopy (1950s)
Explain how synapses enable flexible processing
A very simple animal: sensory input –> behaviour
More specialisation, flexibility: sensory input –> muscle –> behaviour
Even more flexibility integration: sensory input (multiple) –> motor neuron –> muscle –> behaviour
How are electrical synapses are formed of gap junctions and what does this allow?
- allow current to pass directly between neurons
The membranes of the 2 neurons must be close together as the gap is very small. Gap junction about 1 nanometer big - allows charge & ions to pass through
When 2 neurons are connected by gap junctions, electrical changes in one neuron pass directly to the other
- stimulation of the first neuron (action potential) will lead to a smaller action potential and a smaller hyper-potential in the second neuron. This is because they are electrically connected
Whatever is going on in neurone 1 will be faintly reflected in neuron 2, as they are electrically connected by gap junctions
How do you tell if neurons are connected by gap junctions?
- small molecules like dyes diffuse from one neurone to the other, as they travel through the pore.
- both hyperpolarisation & depolarisation stimuli are passed from one neuron to the other. This is blocked by deleting a connexin gene (shakB2 mutation) - as connexin genes create a gap junction
What are electrical synapses good for?
- fast communication
- synchronising neurons
What is the first evidence of chemical synapses 100 years ago?
Otto Loewi - demonstrated using 2 isolated frog hearts that nerves release a chemical which slows the heartbeat
- Stimulate vagus
- Heart rate slows
- Remove fluid sample
- Add fluid to recipient heart
- Heart rate slows
What is a prototypical chemical synapse?
The post-synaptic cell could be another neuron, or a non-neuronal cell:
- Motor neuron –> skeletal muscle
- Autonomic neuron –> hormonal gland smooth muscle, or heart
Synaptic vesicles found at active zone (very electron-dense) - ready to exocytose
What are the steps in chemical synapse transmission?
- Package neurotransmiiter in vesicles
What are the 2 major categories of vesicle - defined by what they store?
1 type - clear synaptic vesicles - small (40-50nm) - these store small molecule transmitters (e.g. GABA, glutamate & acetylcholine). Filled by transporter proteins at the presynaptic terminal. Recycled by endocytosis.
2 type - dense synaptic vesicle - large (100nm) - peptide neurotransmitter - created & filled by the ER (endoplasmic reticulum)/Golgi secretory apparatus. ‘One & Done’.
What happens after there is an influx of calcium?
vesicle fuses to membrane
What has a larger synapse - chemical or electrical synapses?
Chemical synapse
What do vesicles fuse to?
SNAREs
What does Ca2+ bind to, and what happens after?
when Ca2+ binds to synaptotagmin, a conformational change makes the SNAREs ‘zipper’ together, forcing the vesicle to fuse to the plasma membrane
What are SNAREs the target for?
toxins (Botulinum toxin, tetanus toxin)
- SNAREs also used in other cellular processes
What happens when neurotransmitters bind to postsynaptic?
neurotransmitters affect the postsynaptic neurone by binding to receptors
- Ligand-gated ion channels (ionotropic receptors) –> directly depolarise then hyperpolarise the postsynaptic cell.
- G-protein-coupled receptors (metabotropic receptors) –> more complex effects
Does the neurotransmitter itself enter the postsynaptic cell?
NO
What are different ways of removing neurotransmitters?
- They diffuse away
- They are actively taken up by transporters for recycling (into the presynaptic neuron or glia)
- They are destroyed in the synaptic cleft by enzymes
Describe features of electrical synapses
- electrical signals pass in both directions
- signals are passed directly, can only be attenuated
- fast (<0.3ms)
Describe the features of chemical synapses
- signals pass in one direction
- signals can be radically transformed - presynaptic may inhibit postsynaptic (inverted, amplified, modulated)
- slower (0.3-5ms)
Are both electrical & chemical synapses plastic?
YES
Which type of synapse is more plastic?
chemical synapses
Do both types of synapses allow for summing?
YES - both allow summing up inputs by the post-synaptic neuron
What is the most common type of synapse?
most synapses are chemical synapses
Describe the features of a neuromuscular junction
- fast & reliable neurotransmission
- motor neuron action potentials always cause muscle cell action potentials
- uses the neurotransmitter acetylcholine
What are the parts of the Neuromuscular junction?
- synaptic vesicles
- active zone
- synaptic cleft
- receptors
- junctional fold
- postsynaptic muscle fibre
How does the NMJ achieve such efficient transmission?
one of the largest synapses in the body
Presynaptic:
- large number of active zones
Postsynaptic (motor end-plate)
- contains junctional folds, densely filled with neurotransmitter receptors
Active zones and junctional folds are precisely aligned
How did we figure out than neurotransmitters are released from vesicles?
Bernard Katz - stimulated motor nerve and recorded muscle. He noticed how the evoked responses are all integer multiple ps of a spontaneous potential
What is each peak?
each peak is each quantum (vesicle), which is full of neurotransmitter
Describe varieties of CNS synapses
- the shape of the synapse is adapted to the function - e.g. NMJ have folds that make it sensitive to acetylcholine
- dendrosomatic
- dendrodendritic
