What were some ideas about the mechanisms of neurons/the nervous system in the early 1700s?
- spirits running through hollow nerve fibres, conveying impressions to the brain and activating muscles
- mini explosions caused by fermentation upon the mixing of fluid droplets from the nerve ends and blood, activating muscle
- vibrations, light of different energies transferred vibrations to nerves, conveying sensations to the brain
How was experimentation able to reveal problems in these early theories?
- limbs did not increase in volume when muscles are activated
- nerves cut underwater did not result in bubbling ferment
- ligation of nerves did not cause them to accumulate fluid, and it was suspected that fluid of any sort could not move fast enough to explain the speed of nervous system function
What was ‘The Big Thing’ in the early 16th century and how did it relate to nerves?
- Early in the 16th, electricity was a huge focus and every curious individual seemed to be looking into it.
- there was great enthusiasm for applying electrictity to the body
- this had been done in antiquity, but now Leyden jars (like a battery) replaced electric fish
- the question arose as to whether the nervous system might work by electricity
- but how is it contained with nerves?
- coincidently, early suggestions that nerves convey electricity were made on fish that deliver electricity “externally”
Who was the person most associated with proving the link between nerves and electricity?
- Luigi Galvani (1737 -1798) was an Italian Doctor
- Conducted a huge number of experiments in his home in Bologna, demonstrating that nerves convey electricity, and by this signal activate muscles
- For example, a spark jumping from a scalpel tip to a very nearby nerve causes muscle contraction
- previous studies had shown that to make the muscle contract with external electricity, contact with wires was required
- Galvani concluded that the spark must have activated the natural process by which nerves activate muscle
- Aldi (Galvani’s nephew and co-worker) tried unsuccessfully to activate muscle by electrical stimulation of the brain of executed criminals
- He did manage to activate many facial muscles by stimulating the brain in severed heads he received from the guillotine
How can we measure that neurons transmit electrical signals?
With very, very, very small electrodes
What happens when you inject current into a neuron?
- the membrane potential changes
- inserting negative current hyperpolarises the cell: greater negative current, greater change
- add positive current: little depolarisation, bigger current injection –> generate action potential, same size no matter how big, only thing that might change is the number of single stereotyped events
- i.e. above a certain input you generate a very typical, stereotyped potential known as an action potential (always with similar size and shape)
What allows for the presence of a current that can change?
- selective movement of ions across a membrane
- move ions against a concentration gradient: electrogenic
- allows ions to diffuse down the concentration gradient when you open channels that are normally closed
- if you have a selectively permeable membrane it can change the concentration of a particular ion on either side and therefore create a concentration gradient between the two sides of the membrane –> generates an electrical potential
- the key to using this potential to create the nerve impulse is the voltage dependence of the ion channels
- when the sodium channels open, sodium rushes into the cell generating a rise in membrane potential, however this gate only opens for a set (very short) period of time and closes quickly
- when the gate closes, potassium channels open letting potassium out of the cell
How is an action potential drawn down the neuron?
- change in membrane potential at one point stimulates nearby channels to open thus allowing the electrical signal to propagate
- very slow process
- you can walk fast than the slowest nerve cell in the body, while the fast is ~120m/s
- refractory period prevents an action potential from going backwards
What can help make APs faster?
- Schwann cells and oligodendrocytes wrap around nerve cells, insulating them and allowing for the generation of faster APs without increasing axon size
- these cells leave nodes are where the channels are located
- saltatory conduction
Where does convergence and divergence of a signal occur?
- the synapse
- a lot of synapses in invertebrates are electrical
- others are chemical
What must nerve cells be capable of?
- Transmission
- integrating, processing and storing information
What is an electrical synapse?
- formed through gap junctions between presynaptic and postsynaptic neurons
- excitation is the only effect it can have on the post-synaptic cell
- passive transmission: no complex energy-dependent release machinery
- Fast: no long latency due to complex energy-dependent release machinery, diffusion, and post-synaptic receptor activation
- Good for synchronisation of neuronal groups (e.g. respiratory group)
- Typically bi directional, effects depend on recent of concurrent activity
- we have very very small numbers of these, where we need rapid and concurrent synchronisation of neurons
What are chemical synapses?
Presynaptic neuron releases a chemical signal that is detected by neurotransmitter receptors on the postsynaptic neuron membrane
Variety: over 100 neurotransmitters, huge variety of receptors. What effect a transmitter has is determined by what the postsynaptic receptor does/what it actually is, and how this action affects the membrane potential
Energy dependent processes (synthesis release, reuptake)
Slow, due to complex energy-dependant release machinery, diffusion, and post-synaptic receptor activation
A typical neuron will see something between 1000 and 10000 synaptic inputs to each neuron, from thousands of different cells or maybe many from relatively few
Also each neuron, particularly in the central nervous system, might make contact with 10, 100, in some cases 10,000, or even 100,000 different neurons
100 billion neurons give rise to 1000x or even 10000x that many synaptic connections and most are going all the time.
PRO: allows diversity in synaptic transmission/response
CON: slow, expensive in terms of energy
How does a chemical synapse work?
The type of neurotransmitter and the receptor on the postsynaptic membrane determine the result of this communication
(every one of these processes could be an opportunity to adjust how the nervous system works)
- Transmitter is syntehsised and then stored in vesicles
- An action potential invades the presynaptic terminal
- depolarisation of presynaptic terminal causes opening of voltage-gated Ca2+ channels
- Influx of Ca2+ through channels
- Ca2+ causes vesicles to fuse with presynaptic membrane
- transmitter is released into synaptic cleft via exocytosis
- transmitter binds to receptor molecules in postsynaptic membrane (neurotransmitter binding is quite low affinity - needs to be released quite quickly)
- opening or closing of postsynaptic channels
- postsynaptic current causes excitatory or inhibitory potential changes the excitability of the postsynaptic cell
- retrieval of vesicular membrane from plasma membrane
Who discovered the first neurotransmitter?
Loewi - parasympathetic nerves go the heart and slow it down
he stimulated nerve like crazy - ‘vagus stuff’ (acetylcholine) produced in such vast quantities that some of it released into surrounding fluid.
Took this solution and put it into a second heart that wasn’t being electrically stimulated - heart slowed
How is neurotransmitter synthesised?
- there are some neurotransmitters that are synthesised in the terminal (all the enzymes etc are in the terminal)
- some neurotransmitters are peptides which would have had to be made in ER and travelled all the way down the axon via a microtubule pathway to the synaptic terminal
- neurotransmitter vesicles are very complex
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