Neuronal function and neuropharmacology Flashcards

1
Q

What are the two types of brain cells?

A

Neurones - transmission and integration of information

Glial cells - specialised for mechanical and metabolic support of neurones, and tissue repair

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2
Q

What are the 5 key structural features of neurones?

A

Cell body - nucleus and organelles
Dendrites - around cell body, specialised for receiving and integrating information
Axon - rapid transmission of electrical signals, often surrounded by a myelin sheath
Axon hillock - point where axon leaves cell body, specialised for generation of action potentials
Synapse - chemical transmission of a signal from one neurone to another

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3
Q

What is the membrane potential in neurones?

A

a charge/voltage across the membrane, which is 70mV at rest with the inside of the cell more negative than outside - we say the RESTING POTENTIAL of the neurone is -70mV, a charge which is due to uneven distribution of ions across the membrane

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4
Q

How are signals transmitted in neurones?

A

By changes in the membrane potential

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5
Q

In the dendrites and cell body, how does a change in membrane potential occur?

A

By passive diffusion, in which the signal strength decays over distance

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6
Q

What is meant by excitatory and inhibitory post-synaptic potentials?

A

EPSP - depolarisation caused by changes in membrane conductance e.g. opening of sodium channels
IPSP - hyperpolarisation caused by changes in membrane conductance e.g. opening of chloride channels

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7
Q

What is meant by temporal and spatial summation?

A

TEMPORAL - combining of changes in membrane potential occurring at same time to give a larger membrane potential change
SPATIAL - combining of changes in membrane potential occurring close together spatially to give a larger membrane potential change

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8
Q

How are signals transmitted in axons?

A

By an “all-or-nothing” reversal of the membrane potential called an action potential

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9
Q

What are 4 key features of action potentials?

A

Always the same size
Travel very quickly
Do not decay over distance
Mediated by rapid changes in membrane permeability to sodium and potassium

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10
Q

What is the characteristic pattern of an action potential?

A

Spike lasts around 1msec
3-5msec refractory period during which time the membrane is unresponsive, preventing the signal from travelling backwards

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11
Q

What is conduction velocity along an axon dependent on?

A

Diameter of the axon and amount of myelination (basic conduction speed is 2-5 m/sec, but in larger axons it is ~200m/sec

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12
Q

What happens when the signal reaches the synapse?

A

Neurotransmitters released from the terminal button (presynaptic) and bind to receptors in the postsynaptic membrane
Depending on types of receptors present, this binding can have an excitatory or inhibitory effect

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13
Q

What are the different classes of NTs?

A

Some are always excitatory e.g. glutamate
Some are always inhibitory e.g. GABA - opens chloride channels on postsynaptic membrane so neurone more negative and harder to depolarise
Others can be either depending on the receptor type present e.g. dopamine, noradrenaline, serotonin

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14
Q

On what levels can therapeutic drugs act on neuronal transmission?

A
Membrane potentials (e.g. local anaesthetics)
Neurotransmitter synthesis (e.g. L-Dopa)
Neurotransmitter release (e.g. amantadine)
Neurotransmitter-receptor interactions (anticonvulsants, antipsychotics)
Neurotransmitter clearance (e.g. antidepressants)
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15
Q

Why are inhibitory synapses important?

A

Control spread of excitatory activity, keeping activity “channelled” - epilepsy is the result of different brain circuits being activated all at the same time

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16
Q

What is acetylcholine like as a neurotransmitter?

A

Generally excitatory but depends on receptor
Voluntary movement, behavioural inhibition, memory
We see degeneration of ACh-producing neurones in Alzheimer’s disease

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17
Q

How is dopamine connected to brain disease?

A

Parkinson’s - degeneration of DA-releasing neurones

Schizophrenia - Excess DA

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18
Q

What do we see in Huntington’s disease?

A

Degeneration of GABA cells

19
Q

How do opioids work?

A

Interfere with release of neurotransmitters from presynaptic neurones transmitting pain info - thus we have reduced PERCEIVED pain, although the pain info probably still reaches the brain as actual pain receptors are not directly being influenced

20
Q

What is a drawback of the high degree of specialisation of neurones?

A

Metabolic machinery/capabilities are very limited - susceptible to problems when blood supply interrupted as no capacity to store energy; need continuous replenishment of glucose and oxygen via blood

21
Q

What are oligodendrocytes and schwann cells?

A

Oligodendrocytes - support and insulate axons in CNS by creating myelin sheath
Schwann - support and insulate axons in PNS; cell body wraps around the axon and physically becomes the sheath

22
Q

What are the ionic characteristics of a neuronal membrane at rest?

A

Impermeable to large proteins (-ve) so they remain inside cell
Resting membrane more permeable to potassium than sodium i.e. fewer sodium ions through leak channels
Greater conc of potassium inside, more sodium, chloride and calcium outside (both conc and elec gradient for sodium INTO cell)
Membrane more positive outside
Sodium kept out by sodium/potassium pumps

23
Q

What is meant by the equilibrium potential of potassium?

A

Initially conc gradient means net movement outside - difference in charge across the membrane isnt enough initially to create a gradient
Eventually enough ions have moved out such that the inside of the membrane is significantly negative and electro and chemical gradients balance out –> no further net movement

24
Q

What is meant by signal integration?

A

At any one point, the membrane potential is determined by the SUM of all individual depolarising and hyperpolarising events originating nearby (spatial summation)

25
Q

Describe temporal summation in more detail?

A

After an EPSP or IPSP it takes a short time for the mem pot to return to resting level - another IPSP or EPSP occurring at this time will cause additional change in the membrane potential i.e. polarising events close together in time will add together and make an action potential more likely at the axon hillock

26
Q

What is meant by the spiking rate of a neuron?

A

The number of APs propagated per second i.e. the rate of neuronal responding varies relating to the informational code carried by that neuron - some may, for example, have a high spiking rate during speech but not during vision

27
Q

What determines the type of information a neuron responds to?

A

Inputs and outputs, not location in brain

28
Q

What are the 3 different classes of primary afferent axons?

A

A-alpha - extremely fast conduction
A-Beta - slightly less myelinated
A-Delta
C fibres - completely non-myelinated and transmit very slowly

29
Q

When is an action potential triggered?

A

At rest a passive current flows across the axon membrane, opening the voltage-gated sodium channels if the current is strong enough
Sodium enters the cell and the inside of the cell becomes less negative - at -50mV (a change which results from summation at the hillock) the membrane becomes completely permeable and the charge momentarily reverses

30
Q

What is the result of a bigger change in membrane potential?

A

MORE action potential pulses bit they are still all the same size

31
Q

What happens during the repolarising phase?

A

Potassium flows out through voltage-gated potassium channels, and this forces the sodium channels to close, restoring the negative potential

32
Q

What is the “undershoot”?

A

Potassium channels continue operating after repolarisation, making the inside of the cell more negative and thus making it more difficult for depolarisation to occur again straight away/travel backwards

33
Q

Why is there an upper limit to the nerve impulses able to be conducted down an axon per second?

A

The refractory period for most neurons is 1ms, so upper limit of firing rate if ~500-800 impulses per second

34
Q

What is the synthesis of neurotransmitters like in the neurone?

A

Enzymes and precursors for the synthesis are continually transported to axon terminals from the cell body, but actual synthesis occurs at the axon terminal close to the site of release (stored in vesicles until needed)

35
Q

What happens when an action potential invades a presynaptic terminal?

A

Depolarisation of the presynaptic terminal causes opening of voltage-gated calcium channels, allowing an influx of calcium into the terminal
The calcium binds to the synaptic vesicles, causing them to fuse with the presynaptic membrane and transmitter is then released into the synaptic cleft

36
Q

What are the 4 drug types that affect reuptake and breakdown of neurotransmitter?

A

1) Monoamine reuptake inhibitors (tricyclic antidepressants prevent reuptake of serotonin and noradrenaline, fluoxetine prevents reuptake of serotonin)
2) Monoamine oxidase inhibitors (selegiline blocks dopamine breakdown for parkinsons, phenelzine blocks noradrenaline breakdown and serotonin for depression)
3) GABA transaminase inhibitors - prevents breakdown of GABA (anticonvulsants)
4) Amphetamine and cocaine - block dopamine uptake thus increasing levels, amphet also increases DA release and blocks monoamine oxidase

37
Q

What drugs affect NT synthesis and storage?

A

Reserpine - prevents vesicular storage of amine NTs
L-Dopa - precursor for dopamine, increases dopamine conc
Tryptophan - precursor for serotonin, effective in treating some depression

38
Q

What drugs affect NT release into cleft?

A

Botulinum toxin - prevents ACh release at NMJs
Black widow venom - increases then eliminates ACh release at NMJs
Amantidine - may increase dopamine release

39
Q

What drugs affect the membrane potential of the postsynaptic cell?

A

Local anaesthetics - bind to ion channels in membrane and prevent changes in mem pot
Tetrodotoxin - blocks voltage-dependent sodium channels so blocks APs
Batrachotoxin - opens voltage-dependent sodium channels, thus “over-exciting” neurones

40
Q

What drugs act at the postsynaptic receptors?

A

Neuroleptics - anatagonists at dopamine receptors
Anticonvulsants and anxiolytics - barbiturates and benzodiazepines increase GABA receptor function via allosteric binding sites
Curare - antagonist at ACh receptors
Atropine - antagonist at ACh receptors (first pharm treatment for Parkinson’s)
Nicotine and muscarine - agonist at ACh receptors
Bungarotoxin - antagonist at ACh receptors

41
Q

What actually happens when an NT binds to a receptor?

A

Changes the membrane potential, in an excitatory or inhibitory way through the action of sodium or chloride ion channels e.g. ACh gated sodium channels are excitatory

42
Q

What are the 2 amino acid neurotransmitters?

A

Glutamate - acts on excitatory NMDA, and AMPA-type receptors
GABA - Acts on inhibitory A and B-type receptors
These are the two main fast neurotransmitters

43
Q

What are the 3 monoamine neurotransmitters?

A

Dopamine - Acts on excitatory D1 and D5 receptors, and inhibitory D2, D3 and D4 receptors
Noradrenaline - Acts on both excitatory and inhibitory subtypes of alpha and beta receptors
Serotonin - acts on excitatory 5HT-1, 2 and 3 receptors and inhibitory subtypes of 5HT-1 receptors

44
Q

What does acetylcholine act on?

A

Excitatory muscarinic and some nicotinic receptors

Inhibitory subtypes of nicotinic receptors