Biology Of The Neuron Flashcards

1
Q

Where are synapses

A

Between the axons (or sometimes dendrites) of one neuron and the dendrites or soma of another

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2
Q

What does the Nernst equation describe

A

The potential at equilibrium of one ion, If the membrane is permeable to only that ion

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3
Q

What is Wc

A

Work to move 1 mole up conc. gradient

RT x log([K+]o/[K+]i)

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4
Q

What is We

what is the equation for We

A

Work to move 1 mole up elec. gradient

zFE

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5
Q

What is the Nernst equation

A

E= RT/zF x ln( [out]/[in])

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6
Q

What does it mean to say an ion is possibly distributed across the membrane

A

The ion distributes itself so that the Nernst potential is approximately equal to the resting potential

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7
Q

What is the Donnan product rule

A

Since ECl- ~ resting membrane potential
And Ek+~ testing membrane potential
If Cl- is passively distributed, Ek=ECl-

thus:
[K+]out . [Cl-]out = [K+]in . [Cl-]in

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8
Q

What equation can be created from the Donnan product rule

A

[K+] out x [Cl-] out= [K+]in x [Cl-]in

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9
Q

True or false

Cl- ions only enter or leave the neuronal cell passively

A

False

Chloride is also extruded by secondary active processes

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10
Q

Describe secondary active processes to extruded chloride from a neuron? (3)

A

KCC2 (1 K+ and 2Cl- pumped out)
NDCBE ( 1H+ and 1 Cl- out, 1Na+ and 1HCO3- in)

The NDCBE is assisted by the Ca/H+ ATPase which pumps 2 H+ in (for NDCBE) in exchange for 1 Ca2+

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11
Q

In which neurons can the NKCC1 be found?

What does this transporter do?

What is its stoichiometry?

A

In developing neurons and adult olfactory receptors neurons

Raises [Cl-]i So that opening of chloride channels at the resting potential instead allows an outward excitatory flow of chloride ions

1Na:1K:2Cl (all pumped in)

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12
Q

How are calcium ions extruded from cells

A

Primary transport: Ca2+ ATPase; Ca2+/H+ ATPase

Secondary: NCX

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13
Q

What is the stoichiometry of NCX

Which other transporter is used to help the NCX

A

1 Ca2+ out; 3Na+ in

The outward K+ gradient produced by the NCKX

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14
Q

What is the [Ca2+]i in most cells

What does this allow

A

Below 100nM

[Ca2+] to be a second messenger

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15
Q

What does the equivalent circuit of the membrane represent

Which law can be used

A

Battery= Nernst potential for that ion
Resistor = conductance of the membrane to that ion
Resistor and capacitor in parallel= membrane

Ohm’s law can be used
I=V/R = g x V

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16
Q

What does the action potential threshold correspond to

A

The point at which inward current carried by sodium just exceeds outward current across the resting membrane

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17
Q

Does the voltage gated delayed rectifier potassium conductance inactivate on a timescale

A

No

While sodium conductance activates transiently on maintain depolarisation and then inactivates, this does not happen for potassium

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18
Q

Give examples of electrically coupled synapses

A

Gap junction channels which allow ions and smaller molecules to pass freely

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19
Q

Give three disadvantages of electrical synapses

A

They require a large presynaptic terminal to deliver sufficient current to depolarise the post synaptic cell

They are almost all bidirectional

Do not offer the flexibility of chemical synapses, which by using different transmitter/receptor systems allow excitatory or inhibitory signals to be transmitted

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20
Q

When our gap junctions usually used

A

When it is necessary to synchronise the activity of large populations of cells, as in the developing embryo within the heart

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21
Q

How much can the concentration of calcium increase

A

In the immediate vicinity of an open calcium channel concentration can increase rapidly by tens or even hundreds of μM

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22
Q

Which proteins induce vesicle fusion with the membrane

A

v-SNARE and t-SNARE

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23
Q

Which vehicle associated protein acts as the calcium sensor

A

Synaptotagmin

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24
Q

Describe the steps of vesicle fusion

A

1) The vehicle must talk at the presynaptic to zone
2) The vehicle is primed by close association between v SNARE and t SNARE
3) The vehicle must fuse with the plasma membrane in a calcium-dependent manner, releasing its contents into the synaptic cleft

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25
Q

Where would electrodes be placed around the signups of a squid giant axon

A

Stimulating electrode and presynaptic voltage sensor in presynaptic terminal

Post synaptic sensor in post synaptic neuron

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26
Q

Describe the relationship between post synaptic voltage as a function of presynaptic depolarisation

What does this reflect

A

Very steep

The [Ca2+]^4 dependance of vesicle fusion on external calcium

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27
Q

What are the three criteria a substance must have to be accepted as a neurotransmitter

A

1) Must be present within the presynaptic terminal or can be quickly synthesised
2) Must be released in adequate quantity on stimulation
3) Added neurotransmitter must have the same effect as stimulation

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28
Q

Which type of receptor is direct

A

Ionotrophic - is itself an ion channel

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29
Q

What is a Metabotrophic receptor

A

A receptor which achieves its effects that your second messenger cascades

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30
Q

What are the five categories of neurotransmitter found in the CNS

A

Amino acid

Biogenic amine

Purine

Neuropeptide

Gaseotransmitter

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31
Q

What are the major inhibitory transmitters in the brain and spinal cord

A

Brain: GABA

Spinal-cord: glycine

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32
Q

True or false

Bioactive amines act on both the CNS and PNS

A

True

These include ACh, dopamine and serotonin

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33
Q

What category of neurotransmitter do ATP and adenosine fall under

A

They act as transmitters in their own right at a number of non-adrenergic non-cholinergic autonomic synapses, acting at purinergic receptors.

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34
Q

Which class of neurotransmitters were originally regarded as hormones

A

Neuropeptides

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35
Q

Describe gasseous neurotransmitters

A

The role of NO as endothelium derived relaxing factor is now well established, while evidence is building that CO and H2S may act as transmitters also

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36
Q

Ionotrophic receptors are present for which transmitter families?

A

All

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37
Q

Which receptor is particularly prevalent at the neuromuscular junction

What kind of receptor is this

A

Nicotinic Acetyl choline receptor

Ionotrophic

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38
Q

What are the advantages of ionoTropic receptors (2)

A

Allow for rapid response to transmitter

They allow an influx of calcium ions

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39
Q

What are the most important excitatory IonoTropic receptors in the CNS

A

Those which respond to the amino acid transmitter glutamate

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40
Q

What are the two distinct classes of Ionatropic glutamate receptors?

A

NMDA and non-NMDA

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41
Q

What two classes can non NMDA receptors be divided into

How are they named

A

AMPA and kainate receptors

After their most potent synthetic agonist

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42
Q

Do glutamate receptors differ only in their pharmacology

A

No – also in their ionic permeability

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43
Q

Describe the current voltage relationship of an AMPA receptor

How permeable are they to divalent cations

A

Linear and ohmic

Mostly impermeable

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44
Q

Describe the permeability of NMDA receptors

A

Permeable to Na+ and calcium but at negative potentials they are blocked by extracellular magnesium ions trying to enter the channel

When the membrane is depolarised this block is relieved, so that sodium and calcium ions can pass through the channel

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45
Q

How do you Metabotropic receptors work generally

A

They are coupled to a secondary messenger cascade by way of a G protein

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46
Q

Classically, Describe the action of each sub unit of a G protein receptor

What is new

A

GTP- bound α subunit has an action on effector enzyme
βγ subunits remain at membrane

Some cases have been found where the βγ subunits act on the effector instead (often a K+ channel)

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47
Q

Give 2 Familiar examples of a G protein coupled cascade

A

Stimulation or inhibition of the formation by adenylyl cyclase of cAMP, which can act either via PKA or directly on cyclic nucleotide gated channels (Gs is stimulatory and Gi is inhibitory)

Gq is used to form IP3 and DAG via phospholipase C.
IP3 stimulates Ca2+ release
DAG stimulates PKC

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48
Q

Which G protein coupled activation forms arachidonic acid?

How does arachidonic acid act

A

G protein coupled activation of phospholipase A2

As a retrograde messenger, modulating transmitter release from presynaptic terminals

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49
Q

How does nitric oxide act on its effector enzyme

What is the effector enzyme

A

Directly

Soluble guanylyl cyclase

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50
Q

What do RTK and NO receptors sacrifice

A

They lose the versatility of GPCRs (different G proteins can modulate a single effector enzyme in different ways)

Lose 1 or both stages of amplification

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51
Q

Which NT’s are fastest acting?

List them from fastest to slowest

A

1) Amino acid and amine transmitters acting on ionotrophic receptors
2) Amino acid and amine transmitters acting on metabotropic receptors
3) neuromodulatory effects
4) peptides
3) neurotropic growth factors are slowest of all

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52
Q

Describe current stimulation in a sensory receptor

What does this result in

A

Stimulation evokes a receptor current whose amplitude changes in a graded manner according to the stimulus strength

A graded receptor potential

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53
Q

What does a graded receptor potential result in

What are exceptions to this

A

Depolarisation of the site of impulse initiation, which is specialised to vary its rate of spike firing according to the magnitude of the depolarising current

Retinal photoreceptors, which hyperpolarised in light

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54
Q

Sensory receptors can be divided into which two broad categories

A

Long and short receptors

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55
Q

What do long sensory receptors do

What about short

A

Send afferent axons to the CNS and fire action potentials

They don’t have an axon, which immediately synapse with a second order cell for conduction to the CNS

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56
Q

Do short receptors have axons

A

No

They generate a graded potential instead of firing spikes

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57
Q

Short receptors generate a graded potential instead of firing spikes. What does this mean for transmitter release

A

There are graded changes in transmitter release at the synapse and therefore a graded generator potential in the second order cell, modulating the rate of spike firing

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58
Q

What do the accessory structures on receptors do

A

Filter the incident stimulus before the sensory terminal is stimulated

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59
Q

What do accessory structures on sensory receptors modify (4)

A

Sensitivity
Selectivity
Time course
Response

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60
Q

How is the magnitude of the stimulus normally encoded in long receptors

Eg

A

As the frequency of AP firing

Eg Cutaneous sensory receptors

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61
Q

True or false

Sensory receptors usually adapt

A

True

This leads to diminution of firing frequency with time

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62
Q

Name a quintessential long receptor

A

Cutaneous mechanoreceptor

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63
Q

Special senses are generally supplied by what kind of receptor

What is the exception

A

Short receptor

Olfactory which send axons directly to the olfactory bulb

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64
Q

Are mechanoreceptors direct or indirect?

What do they involve? Is this always true?

A

Direct

They involve the opening of stretch sensitive channels coupled to the cytoskeleton
- for hearing, they are coupled to more specialised structures

65
Q

What do stretch receptor channels allow passage of

What is the result

A

Small cations

Depolarisation of the receptor

66
Q

What kind of receptor channel is used in salt receptors

A

Direct

For Salty receptors in the tongue the stimulus is itself a permeant ion

67
Q

What do indirect receptors use

Eg

A

A secondary messenger cascade

Retinal photoreceptors; taste and smell receptors

68
Q

What are sensory indirect receptors similar to

What is the advantage of this

A

Metabotrophic synaptic transmission,

This offers the advantage of amplification, flexibility, and selectivity

69
Q

How are α-motor neurons within the spinal cord different to neurons at the NMJ

A

At the NMJ a single end plate terminal generates a sufficiently large EPP to reach threshold

An α- motor neurone in the spinal cord receives thousands of synaptic terminals

70
Q

Give an example of α-motor neurons within the spinal cord

A

Spindle Group IA fibres which mediate the monosynaptic spinal stretch reflex

71
Q

What does each of the thousands of afferent terminals to the α-motor neurons within the spinal cord generate

What does this mean

A

Only a small excitatory post synaptic potential (EPSP) of a few hundred μV

Many afferent fibres must be excited to fire the α-motor neurons within the spinal cord

72
Q

What is the reversal potential of α-motor neurons within the spinal cord

What does this suggest? Is this inference always true?

What happens if you instead excite Group IA afferents from the antagonist muscle?

A

0mV

This Glutamate-gated channel is permeant to both Na+ and K+

No In some cases glutamate guarded channels in the CNS also allow Ca2+ to enter

They inhibit the α motor neurons of the agonist, via inhibitory interneurons which release glycine

73
Q

Briefly describe the experiment to find the reversal potential of α-motor neurons within the spinal cord

A

If you inject a steady current into a spinal motor neuron to perturb its membrane potential and then stimulate the Group IA afferents, the EPSP changes sign at a potential around 0mV

74
Q

The IPSP in an α-motor neurons within the spinal cord reverses at what voltage?

What happens if you inject Cl- ions?

What does this suggest

A

-80mV

This reversal potential is made less negative

Inhibition is due to an elevation in Cl- conductance

75
Q

How can inhibition be achieved in the CNS

A

By either elevated Cl- or K+ conductance via the central inhibitory transmitter, GABA

76
Q

True or false

If EPSPs and IPSPs are simultaneously, the underlying synaptic conductance changes summate linearly

A

False

They summate nonlinearly, each drawing the membrane potential towards its own reversal potential

77
Q

Where does a cortical pyramid cell receive synapses

A

Soma
Dendritic shaft
Dendritic spines

78
Q

How can synapses be sub divided

How do their vesicles change

A

Type 1 - excitatory (round vesicles)

Type 2 - inhibitory (flat vesicle)

79
Q

How does a signal propagate along a dendrite

Do all dendrites have the same properties

What does this mean

A

Passively

No they change and can be divided into passive cable segments - they are smaller further from the body (so conduction is lower and so are space and time constant)

Any stimulation closer to the body is more likely to elicit a response because there is a rapid decay in small dendrites

80
Q

Are voltage gated conductance present in dendrites

What does this do

A

Yes is many dendrites there is conductance of both Na+ and Ca2+

This serves to boost the decaying passively conducted dendritic signal

81
Q

Which part of the neuron has the lowest threshold

Why is this

A

Axon hillock

The AP is initiated here

82
Q

How can it be demonstrated that the axon hillock has the lowest threshold for action potentials

A

Recording intracellular voltage from a single pyramidal cell in a the cortical slice with 2 Patch pipettes simultaneously

Irrespective of whether you stimulate through the dendritic pipette, the somatic pipette or via synapses to the apical dendrite, the action potential is always recorded first at the soma

83
Q

When demonstrating that the axon hillock has the lowest threshold for action potentials, do you use a voltage or current clamp?

A

Current clamp so that the voltage can vary Freely

84
Q

True or false

Once the action potential has been initiated, it actively propagates back into the dendritic tree

A

True

85
Q

The extent to which a given synapse can influence the potential axon hillock depends on what

A

How far away it is from the cell body along the dendritic tree

86
Q

Will synaptic current be more strongly attenuated when they flow along small dendrites or large dendrites

Why

A

They are more strongly attenuated when they flow along small dendrites

The space constant of an unmyelinated nerve varies with the square root of its diameter

87
Q

How does the decay of an action potential differ from small dendrites to large ones

A

In small dendrites there is a rapid decay and potential but the decay becomes more gradual in larger dendrites closer to the cell body

88
Q

How does the time to peak of the potential change from small to large dendrites

A

Becomes slower as the synaptic current has to charge a progressively larger and larger fraction of the cells capacitance

89
Q

Overall how do synaptic potentials change as they are conducted towards cell body

A

They become smaller and slower as they are conducted decrementally towards cell body

90
Q

When 2 excitatory synapses are activated together, their ability to stimulate the axon hillock depends on what?

What does this mean

A

How close together they are in time and space

If the time constant of the cell is short, then the two stimuli will need to be close together in time. If two inputs are widely separated on the dendritic tree, then the space constant must be long if the summed current is to reach threshold

91
Q

When 2 excitatory synapses are activated together, their ability to stimulate the axon hillock depends on how close together they are in time and space.
What does this mean if the time constant of the cell is short?

What about if two inputs are widely separated on the dendritic tree?

A

The two stimuli will need to be close together in time

The space constant must be long if the summed current is to reach threshold

92
Q

Describe the algebra of synapses

A

If 2 excitatory synapses are stimulated simultaneously on neighbouring dendrites then their depolarising currents add together

If instead an inhibitory input is activated on the neighbouring dendrite, and the current will subtract, drawing the axon hillock further from firing threshold

For shunting inhibition, you divide

93
Q

What is shunting inhibition

A

If the inhibitory synapse is located closer to the cell body on the same dendrite then much of the excitatory current leaves before it can ever influence the cell body

94
Q

Is overt hyper polarisation required for shunting inhibition

A

No

Instead simply Less excitatory current is available and would otherwise have been the case

95
Q

How are excitedly and inhibitory inputs usually located on the dendrite

Why

A

Excitatory - further out
Inhibitory - closer to the soma

Bc this allows shunting inhibition

96
Q

Opening which channels can reduce the height of the action potential in the presynaptic terminal

A

Cl-

K+

97
Q

What causes primary afferent depolarisation

How does this affect Na+ channels

A

The action potential height will still be decreased even if the chloride Nernst potential is slightly more positive than the resting potential

Partially inactivates sodium channels

98
Q

What does reduced action potential height lead to

Is there another way to do this

A

Reduced opening of voltage gated calcium channels

Ca2+ channels can also be modulated by second messenger systems within the presynaptic terminal

99
Q

How important is timing of inhibition

How does this differ for peptide transmitters

A

Timing must be precise since it must arrive at virtually the same time as the AP

It is more relaxed as they have slow neuromodulatory actions than ionotrophic transmitters

100
Q

What kind of action potential occurs in interneurons

A

None - interneurons are short and therefore do not require APs

101
Q

Which cation receptors are the work horses of the brain

A

AMPA and kainate receptors

102
Q

What is the difference in ion permeability between AMPA and NMDA receptors

A

AMPA - only K+ and Na+

NMDA - Na+ and Ca2+ only

103
Q

Where is the hypothalamus

A

In the paleocortex

104
Q

How many layers does the paleocortex have

A

3 - it is evolutionarily older

105
Q

Which parts of the brain loop through the hypothalamus

A

All

106
Q

What are CA3 / CA1 synapses rich in

A

NMDA receptors

107
Q

Which channel can be blocked to prevent formation of long term memory

A

NMDA receptors

108
Q

What is the sequence once Ca2+ has entered through the NMDA receptor

A

Ca2+ -> AC -> cAMP -> PKA

109
Q

What does PKA do in the post synaptic terminal after Ca2+ has entered through the NMDA channel

Is this long term or medium term

A

PKA phosphorylates AMPA, making it more sensitive (medium term)

Also activates CREB, which increases AMPA receptor expression (long term)

110
Q

What is the turnover rate of AMPA receptors

A

1 day

111
Q

Does Ca2+ only activate kinases after entering through NMDA receptors

How can this be

A

Phosphatases are also activated

Phosphatases are more Ca2+ but their number plateaus earlier than kinases
Therefore phosphatases are more active at low [Ca2+] but at high [Ca2+] amount of kinases can outstrip that of phosphatases

112
Q

If an axon containing just VG Na+ and delayed rectifying K+ conductances is depolariser by injecting a steady current, what is the rate of firing dependant on?

1)What is the rate of firing dependant on if a neuron cell body is depolarised? 2)What does this allow? 3)What does this require?

A

Steeply dependant on the magnitude of the injected current

1)It is a graded function of the injected current. 2)This allows a depolarising input to a sensory receptor or neuron to be encoded as a train of action potentials whose frequency represents the magnitude of the stimulus or synaptic potential. 3) This requires a further conductance to K+ which inactivates on maintained depolarisation

113
Q

How did they discover the A current

Which graphs are relevant

A

Blocked Na+ channel with Tetrodotoxin

Depolarising voltage clamp steps reveal a component of K+ current which inactivates and is abolished at a held depolarisation

This is the A current

Graph of Ik (normal K+ current) and IA (A-current) together and then subtract Ik from Ik+IA

114
Q

What happens to A - current and K+ current following an AP

A

Immediately after, IA remains inactivated at first but IK remains high for a time, holding the membrane at a negative potential

After, IA activates, preventing injected current from raising membrane to threshold. But IA progressively inactivates, allowing them membrane to approach threshold for next AP to fire

115
Q

What is the purpose of the A current

A

To space out the AP in the spike train

116
Q

True or false

Cortical pyramidal cells demonstrate intrinsic bursting when stimulated continuously

A

True

117
Q

When does bursting in Neurons occur

A

When depolarisation activates low threshold Ca2+ channels

118
Q

True or false

Only one kind of Ca2+ channel will exist in a cell

A

False

Neurons contain a number of different voltage gated calcium channels open by depolarisation

119
Q

Which calcium channels contribute to bursting in neurons?

What happens

A

Low threshold T channels

The activate as the membrane is slightly depolarised, contributing to that depolarisation and encouraging spike firing, and then inactivating to terminate the burst

120
Q

When do thalamic relay neurons exhibit bursting

A

When at relatively hyperpolarised potentials, as during slow wave sleep

The hyperpolarised membrane potential allows recovery of T channels from in activation, allowing firing of threshold calcium spikes and bursts of 2–5 action potentials

121
Q

Which current depolarises Thalamic relay neuron to T channel threshold

A

A hyper polarisation activated inward current (Ih)similar to the cardiac pacemaker current which comprises both sodium and potassium ions

122
Q

What happens to T channels at more depolarised potentials

A

T channels Are permanently activated and the relay neuron repeatedly fires single spikes in tonic mode

123
Q

Other than IA and Ih, which channels modulate AP firing

How do these work

A

Calcium activated potassium channels

Open when calcium enters through voltage gated calcium channels and contribute to an outward hyperpolarising potassium current

124
Q

Which channels contribute to spike frequency adaptation

What else do they do

A

Calcium activated K+ channels

Contribute to termination of bursts of action potential firing since each burst is accompanied by a rise in intracellular [calcium]

125
Q

Why does the receptor current in the olfactory receptors cell oscillate

A

Long sensory receptors need to ensure that the receptor remains capable of spanking during prolonged stimulation

Oscillation generates repeated bursts of action potentials and avoids complete spike in activation

126
Q

What is the oscillation of receptor current in olfactory receptors cells believed to arise from

A

Coupled oscillation of calcium and

cAMP

127
Q

Does the monosynaptic spinal stretch reflex consist of just a single muscle spindle afferent and a single α-motor neuron

A

No - it consists of a population of IA afferents and the motor neuron pool supplying the agonist muscle

128
Q

What is divergence in the monosynaptic spinal stretch reflex

A

Each IA afferent will synapse with a number of motor neurons

129
Q

Describe convergence in terms of the monosynaptic spinal stretch reflex

A

Each motor neuron will receive synaptic inputs from a number of IA afferents

130
Q

Why is convergence of excitatory input essential for operation of the monosynaptic spinal stretch reflex

A

The EPSP generated by a single IA afferent is far too small to reach threshold

131
Q

What is the subliminal fringe

What happens if to subliminal fringes overlap

A

The neurons surrounding a excitatory input which do not reach firing threshold but are excited

Responses summate supralinearly and the response will be larger than expected

132
Q

What is occlusion when it comes to synaptic summation

A

If inputs are strong enough individually to stimulate all the neurons receiving input then overlap within the motoneuron pool will result in inclusion: a response which is smaller than the sum of the responses to each stimulus presented independently

(Almost like the opposite of the supralinear summation of subliminal fringes)

133
Q

What are the two distinct ways inhibitory interneurons can be deployed within the spinal-cord

A

Feedforward inhibition

Feedback inhibition

134
Q

Describe the feed forward inhibition of interneurons in the spinal cord

A

The pathway to the antagonist muscle is inhibited when the agonist pathway is stimulated – this inhibits extensor muscles when flexes are stimulated

135
Q

How does feedback inhibition of interneurons work

Eg?

A

The excited cell contacts an inhibitory interneurons via recurrent axon collaterals to inhibit its own firing and that of the synergist

Eg Renshaw cell

136
Q

Give an overview of what happens in the flexor withdrawal reflex

A

Stimulation of cutaneous nociceptors leads to reflex extensor inhibition and flexor stimulation to withdraw the limb from harm

137
Q

What happens in the crossed extensor reflex

A

Stimulation of the contralateral extensor and inhibition of the contralateral flexor muscle provide support for the flexor withdrawal reflex

138
Q

At the frog NMJ, what does repeated stimulation lead to

What happens after repeated tetanic stimulation

What do each reflect

A

Synaptic facilitation of the post synaptic potential, reflecting the progressive build up of Ca2+ within the terminal

Synaptic depression ensues, representing a depletion in the readily available vesicle pool

139
Q

What happens to a post synaptic response after cessation of tetanic stimulation at the NJM once the neuron has recovered from depression

What does this reflect

What is this called

How long does this last

A

Post synaptic response is transiently enhanced, reflecting the actions of Ca2+ on vesicle priming

Post tetanic potentiation

Can last for some minutes after repeated stimulation

140
Q

What is a major mechanism believed to underpin memory

A

Long term potentiation (LTP)

141
Q

Which neurons can be used as an example of a long-term potentiation

How can LTP be demonstrated here

A

Synapses from the Schaffer collaterals and commissural fibres which provide spatially segregated inputs to the pyramidal cells of the CA1 area of the hippocampus

To extracellular electrodes are used to stimulate non-overlapping a set of synaptic inputs to the apical dendrites of CA1 pyramidal cells. The current intensity is deliberately adjusted it to evoke either a weak post synaptic response, which is insufficient to fire a spike, or a strong one which is normally reaches spike threshold

142
Q

What are the results of the experiments on pyramidal cells of the area CA1 in hippocampus

A

A repetitive tetanic stimulus to the weak set of synaptic inputs evokes only a transient post tetanic potentiation in the amplitude of the EPSP invoked by test stimuli to these inputs

A tetanic simulation to the strong set of synaptic inputs alone has no affect on the EPSP invoked by weak inputs, although it results in homosynaptic potentiation of the EPSP to the strong inputs

However if both weak and strong are tetanically stimulated together then the EPSPs evokes by both inputs persistently increase, corresponding to associative long term potentiation

143
Q

Which law does potentiation obey

Describe this law

A

Hebb’s law

When an axon cell A is near enough to excite cell B, or repeatedly or consistently takes part in firing it, some growth process or metabolic change takes place in one or both cells such that A’s efficiency as one of the cells firing B is increased

144
Q

How can the Hebbian nature of LTP at synapses in CA1 be demonstrated

What does this show

A

By voltage clamping the target pyramidal cell

Only when the postsynaptic cell is allowed to depolarise during pre-synaptic stimulation does long-term potentiation take place (Mg2+ must move away from NMDAr and AMPAr density increases to increases excitability)

145
Q

What is LTP believed to result from at CA1

Is it always like this?

A

VG relief of the Mg2+ block at NMDA receptors, opened by the release of glutamate, allowing Ca2+ to enter the cell, acting on kinases you achieve long term changes in synaptic excitability by changing postsynaptic AMPAr density

No, some synapses undergo LTP via Ca2+ entry through AMPA channels and opening of VG Ca2+ channels

146
Q

Name retrograde agents in LTP and describe their action

A

NO and arachidonic acid

Modulate presynaptic transmitter release by diffusing backwards

147
Q

What does maintenance of LTP require

A

A persistent increase in kinase activity following gene transcription and protein synthesis

148
Q

Where are excitatory inputs often located in many central neurons?

What do these do

A

On dendritic spines

Both chemically and electrically isolate the postsynaptic machinery from events elsewhere within the cell

149
Q

How do dendritic spines isolate the post synaptic machinery from the cell

A

They have a high neck resistance which attenuates excitatory current flowing into the dendrite

150
Q

How are dendritic spines involved in learning and memory

A

Immature small spines undergo cytoskeletal changes upon potentiation which lead to rapid spine enlargement followed by enlargement of the postsynaptic density upon consolidation

151
Q

What does the enlarged postsynaptic density of dendritic spines provide

A

Extra docking sites for AMPAr which diffuse into the spine and can be tethered to PSD-95 by Stargazin following its phosphorylation by CamKII

The fusion of AMPA receptor containing vesicles then replenishes this extra synaptic supply

152
Q

What does CamKII phosphorylate

A

AMPAr

153
Q

What is CamKII

A

Ca2+/calmodulin-dependent protein kinase II

It phosphorylates AMPAr in LTP

154
Q

What underpins LTP in the CA3 area of the hippocampus

A

Does not require special properties of the NMDAr

LTP takes place presynaptically, involving activation of Adenylyl cyclase and PKA subsequent to Ca2+ entry via R type Ca2+ channels

155
Q

When can long term depression occur in CA1 pyramidal cells

A

If they are stimulated at low frequencies which fail to make the target cells fire

156
Q

How can LTD be initiated (2)

A

1) directly antagonising LTP by activation of phosphatases following Ca2+ entry through NMDAr channels which is too modest to evoke LTP.
2) initiated by Metabotrophic glutamate receptors acting via PKC

157
Q

Which LTD is important in motor learning in the cerebellum

A

mGlutR-dependant LTD

158
Q

Does mGlutR-dependant LTD reverse LTP

A

It does NOT directly reverse LTP

159
Q

Which type of LTD is a widespread feature of synapses in the neocortex

A

NMDAr -dependant LTD