Building a nervous system

Question 1

What do electric synapses do?

Answer 1

Connect heart muscle fibres - vital for cardiac function

More common in NS than previously thought, but role is unclear

They can propagate action potentials through channels that are able to pierce both the synaptic bouton and dendrite, connecting both cells as if they were one cell, so that the AP can pass straight through

Question 2

What do chemical synapses do?

Answer 2

Great majority of synapses in vertebrates

Many types with many roles

Target for neuro-active chemicals

These release neurotransmitters into the synaptic cleft, which then bind to receptors on the post-synaptic membrane

Question 3

How are neuropeptides synthesised?

Answer 3

Synthesised using protein making machinery within the cell body

They can be transported to the synaptic terminal via the cytoskeleton of the axon

Question 4

How are catecholamines synthesised?

Answer 4

They can be synthesised locally, in the synaptic terminal itself

Question 5

How are neurotransmitters packaged?

Answer 5

Axons ‘bite’ off a bit of their synaptic membrane, and use it to package the neurotransmitter into synaptic vesicles.

These vesicles are then held to the pre-synaptic membrane by proteins

Question 6

What triggers the release of neurotransmitters?

Answer 6

Depolarisation - usually because of arrival of action potential

The release of the neurotransmitter is Ca2+ dependent

An AP causes the VgCC to open, allowing calcium to diffuse into the presynaptic membrane

Calcium attaches to the proteins holding the vesicle to pre-synaptic membrane, and triggers them so that they drag the vesicle into the presynaptic membrane, allowing the vesicle to fuse with the membrane, releasing the neurotransmitter into the synaptic cleft.

The neurotransmitter will then attach to the post-synaptic receptors

Question 7

How are neurotransmitters removed from the synaptic cleft?

Answer 7

NT must be removed to clear synapse, so that synapse can continue to respond to incoming action potentials

Some peptides are able to just diffuse out of the synaptic cleft, where they are removed by non-specific peptide degrading processes.

Ach and MAO for example, are broken down via enzymatic degradation. Enzymes attached to the other membranes can break down the neurotransmitter.

Some neurotransmitters can be reuptaken into the synaptic terminal (these re-uptake transporters are alpha-2 receptors), and they can be repackaged and reused.

Fast neurotransmitters such as glutamate and GABA, are taken back into astrocytes (glia), where they break the neurotransmitters up, and then send them back to the synaptic terminal where they can be used again

Question 8

Describe the transmission that occurs at ligand-gated (ionotropic) receptors

What neurotransmitters can bind here?

Answer 8

• Fast, time-dependent transmission
• Signalling molecules that acts as ligands bind to binding sites of ligand-gated receptors, causing the opening of the VgNa channels, allowing depolarisation inside the cell, producing excitatory postsynaptic potentials

NTs = Glutamate (CNS), Ach (NMJ)

Question 9

Describe the inhibition of action potentials at ligand-gated (ionotropic receptors)

What neurotransmitters can bind to these receptors?

Answer 9

• Ligand (In particular GABA) binds to VgCl channels, causing these to open, allowing chloride ions to enter the cell
• For APs to be inhibited, chloride ions must enter a cell, as they are anions and, therefore, increase the negativity inside the cell, leading to more polarisation (hyper polarisation) of the cell, inhibiting the action potential.
• This is then know as an inhibitory postsynaptic potential (ipsp)
• NTs = GABA, glycine

Question 10

Describe metabotropic (modulatory) receptors and their effects

What neurotransmitters can bind to these receptors?

Answer 10

• Slow, non-time dependent effects
• Have a receptor molecule with neurotransmitter binding site, but has no channel within it
• Instead there’s an active site on the inside, which then activates a G protein embedded within the membrane
• Activated G proteins can have multiple functions such as:
  
  • Opening and closing protein channels
  • Producing secondary messengers (intracellular signalling molecules) - These messengers can open and close ion channels, or they can diffuse into the cell where they can trigger other things, such as protein synthesis
• Metabotropic receptors tend to produce diverse, subtle effects, so they don’t depolarise or hyperpolarise a cell, but rather they adjust how the cell responds to its incoming fast synaptic inputs
• NTs = Dopamine, Ach, serotonin, NA

Question 11

What is the main structural difference between ionotropic and metabotropic receptors?

Answer 11

Ionotropic receptors contain ion channels, allowing for the flow of ions in or out of the cell

Metabotropic receptors have a large protein with a binding unit for a neurotransmitter, which then activates a G protein embedded within the cell membrane, and this G protein can then activate ion channels, or release intracellular messengers (secondary messengers)

Question 12

Why do therapeutic drugs have selective effects?

Answer 12

There are many steps in synaptic transmission:

• Production + packaging NT
• Depolarisation and opening of VgCC for Ca2+ entry
• Ca2+ triggers exocytosis of NT
• NT binds to receptors
• Receptors activate + produce postsynaptic effects
• NT removed from cleft and hence receptors
• Receptor action terminate

Drugs can be designed to target any of these steps, so pharmacological manipulation allows for events in a synapse to be altered

There are many different neurotransmitters, and each can act on different types of receptors.

In this way, different neural pathways use different combinations of transmitter and receptor

Drugs that target different types of synapse have selective effects on different pathways

Question 13

What is synaptic plasticity?

Answer 13

Surviving nerve cells recircuited/rewired (undergo adaptive changes) to have new functions, resulting in the strengthening or weakening of synaptic connections

Question 14

Describe LTP and what happens when a single synapse is activated, and when a group of synapses are activated

Answer 14

• Long-term potentiation
  
  • LTP is important for learning, as it’s the basis for laying down memories
• Effects fast-excitatory synapses
• Strengthens effective synapses
• Weakens useless synapese
• This allows it to create a more effective neural circuit

If a single synapse activates on its own:

• Produces tiny depolarisation, not very effective
• The more often this happens, the weaker the synapse becomes and it loses its machinery, so will eventually stop being used

If a group of synapses are activated:

• Activate all at the same time, as they’re all taking part in a single circuit, so are driven by the same processes
• Their inputs summate - they join together to strongly depolarise the cell
• These synapses become stronger, as the post synaptic cell sends messages back letting the LTP know that that was an effective synapse
• These synapses then gain machinery to make transmitters, release transmitters and gain more receptors, so that the next action potential is stronger
• The singular synapse does not receive more support, so becomes weaker

Question 15

What are the specific conditions under which a synapse potentiates?

Answer 15

Synaptic bouton releases glutamate just before postsynaptic cell strongly depolarises (not always glutamate though)

This is important for the LTP, as glutamate helps neural communication, memory formation, learning and regulation

A synapse potentiates, or strengthens its connections, primarily under conditions of high-frequency, synchronous stimulation and coincident activity in both pre- and postsynaptic neurons. This typically involves delivering brief, high-frequency trains of electrical stimulation to the synapse. Additionally, pairing weak synaptic inputs with action potentials in the postsynaptic cell can also induce potentiation.

Question 16

How do metabotropic receptors enhance LTP?

Answer 16

• Some secondary messengers produced by activation of metatrobic receptors can enhance LTP.
• Activation of some metabotropic receptors increase input strength and hence depolarisation

Question 17

What is convergence?

Answer 17

Many different excitatory or inhibitory inputs synapse onto one neurone

Question 18

Describe synaptic integration

Answer 18

Nerve cells have multiple inputs that can be excitatory or inhibitory

Excitatory inputs will result in small depolarisation of the cell by the synapse

If Inhibitory inputs fire, there will be a dip in the membrane potential as it will become transiently hyperpolarised

Graded (electrotonic) potentials generated by synapses can summate, resulting in a larger depolarisation

So for a cell to fire an action potential, several excitatory inputs must fire at once in a period when there aren’t many active inhibitory inputs

Question 19

Describe presynaptic inhibition

Answer 19

This is when an inhibitory input is contacting the presynaptic bouton of an excitatory input.

If both inputs fire at the same time, the effect of the excitatory input is cancelled out by the inhibitory input

If the inhibitory input fires on its own, it will have no effect on the cell as it’s not in direct contact with the cell, and if another excitatory input fires that this inhibitory one is not in contact with, the inhibitory input will also have no effect on that input.

Presynaptic receptors can be targeted selectively by therapeutic drugs

Question 20

What is divergence?

Answer 20

Each cortical cell gives input to 100s of other cells, allows one neurone to communicate with many other neurones in a network

In diverging nerve pathways, a single neuron’s signal splits to activate multiple other neurons. This allows a single impulse to affect several destinations simultaneously, enabling coordinated responses like controlling different fingers in a hand. Divergence is a key feature of neuronal networks, allowing one neuron to influence many others, amplifying signals and coordinating activity.

Question 21

Explain what determines if and when an action potential is produced by the post-synaptic cell

Answer 21

Summation of electrotonic potentials must exceed threshold value to generate action potential

Question 22

What do nerve cell circuits use frequency for? Use vision as an example

Answer 22

Encode stimulus strength

AP firing frequency is directly proportional to stimulus strength.

For example, if you were to increase brightness of a patch in the retina, frequency of APs would greatly increase

Question 23

Using vision as a model, how do nerve cell circuits get triggered?

Answer 23

By salient changes (salience = detecting, filtering and determining importance of external and interoceptive stimuli)

Salient features are important within the image, but completely homogeneous brightness or darkness is not.

They only capture information when the image changes

The cortical circuitry identifies the characteristics of contrast boundaries, and this will determine whether there is an excitatory or an inhibitory response

Question 24

What are the key characteristics of specific pathways?

Answer 24

• Have precise (e.g. topographic) connections
• Fast synapses (use ionotropic receptors)
• Time-dependent signals (pattern of AP firing matters)
• Highly selective responses (cells respond to specific events)
• Information-rich signals (carry precise information)

Question 25

How is the primary visual pathway an example of a specific pathway?

Answer 25

- Inputs arise from retina - Form very localised and precise connections

Question 26

Describe the modulatory inputs that control the primary visual pathway

Answer 26

- Modulatory inputs arise primarily from brainstem - Form widespread, sparse connections

Question 27

How do modulatory pathway effects change when somebody falls asleep and then stays sleeping?

Answer 27

When you’re falling asleep, the brainstem withdraws modulatory inputs To stay asleep, thalamic cells become insensitive to retinal input The thalamic cells ignore signals from the retina, and instead fire spontaneous action potentials, so that all thalamic cells are synchronised. Thalamic cells change their state without modulatory inputs

Question 28

What does modulation control?

Answer 28

How neurones respond to specific inputs, without altering the information being processed. This is why many therapeutic drugs are targeted towards this type of synapse.

Question 29

What do modulatory pathways depend on?

Answer 29

Signals that have: - Diffuse, imprecise connections - Slow, persistent synapses (metabotropic receptors used) - Non-time-dependent, information-poor signals - Activity linked to: - Changed from sleep to waking - Changes in level of concentration and attention - Mental state

Question 30

What does serotonin do in the visual cortex?

Answer 30

Maintains pattern of firing when you’re not really using your visual cortex that much, but firing is much weaker meaning there are fewer APs.

Question 31

What does acetylcholine do in the visual cortex?

Answer 31

Increases APs being generated, frequency response increases. This is when your visual cortex is in more intense use, and concentration levels have greatly increased. Therefore, increased activity of cholinergic modulatory input **increases responses to inputs from the retina.** Greater concentration = Greater activity of cholinergic inputs