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
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
3
Q
What is Wc
A
Work to move 1 mole up conc. gradient
RT x log([K+]o/[K+]i)
4
Q
What is We
what is the equation for We
A
Work to move 1 mole up elec. gradient
zFE
5
Q
What is the Nernst equation
A
E= RT/zF x ln( [out]/[in])
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
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
8
Q
What equation can be created from the Donnan product rule
A
[K+] out x [Cl-] out= [K+]in x [Cl-]in
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
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+
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)
12
Q
How are calcium ions extruded from cells
A
Primary transport: Ca2+ ATPase; Ca2+/H+ ATPase
Secondary: NCX
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
14
Q
What is the [Ca2+]i in most cells
What does this allow
A
Below 100nM
[Ca2+] to be a second messenger
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
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
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
18
Q
Give examples of electrically coupled synapses
A
Gap junction channels which allow ions and smaller molecules to pass freely
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
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
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
22
Q
Which proteins induce vesicle fusion with the membrane
A
v-SNARE and t-SNARE
23
Q
Which vehicle associated protein acts as the calcium sensor
A
Synaptotagmin
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
25
Where would electrodes be placed around the signups of a squid giant axon
Stimulating electrode and presynaptic voltage sensor in presynaptic terminal
Post synaptic sensor in post synaptic neuron
26
Describe the relationship between post synaptic voltage as a function of presynaptic depolarisation
What does this reflect
Very steep
The [Ca2+]^4 dependance of vesicle fusion on external calcium
27
What are the three criteria a substance must have to be accepted as a neurotransmitter
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
28
Which type of receptor is direct
Ionotrophic - is itself an ion channel
29
What is a Metabotrophic receptor
A receptor which achieves its effects that your second messenger cascades
30
What are the five categories of neurotransmitter found in the CNS
Amino acid
Biogenic amine
Purine
Neuropeptide
Gaseotransmitter
31
What are the major inhibitory transmitters in the brain and spinal cord
Brain: GABA
Spinal-cord: glycine
32
True or false
Bioactive amines act on both the CNS and PNS
True
| These include ACh, dopamine and serotonin
33
What category of neurotransmitter do ATP and adenosine fall under
They act as transmitters in their own right at a number of non-adrenergic non-cholinergic autonomic synapses, acting at purinergic receptors.
34
Which class of neurotransmitters were originally regarded as hormones
Neuropeptides
35
Describe gasseous neurotransmitters
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
36
Ionotrophic receptors are present for which transmitter families?
All
37
Which receptor is particularly prevalent at the neuromuscular junction
What kind of receptor is this
Nicotinic Acetyl choline receptor
Ionotrophic
38
What are the advantages of ionoTropic receptors (2)
Allow for rapid response to transmitter
They allow an influx of calcium ions
39
What are the most important excitatory IonoTropic receptors in the CNS
Those which respond to the amino acid transmitter glutamate
40
What are the two distinct classes of Ionatropic glutamate receptors?
NMDA and non-NMDA
41
What two classes can non NMDA receptors be divided into
How are they named
AMPA and kainate receptors
After their most potent synthetic agonist
42
Do glutamate receptors differ only in their pharmacology
No – also in their ionic permeability
43
Describe the current voltage relationship of an AMPA receptor
How permeable are they to divalent cations
Linear and ohmic
Mostly impermeable
44
Describe the permeability of NMDA receptors
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
45
How do you Metabotropic receptors work generally
They are coupled to a secondary messenger cascade by way of a G protein
46
Classically, Describe the action of each sub unit of a G protein receptor
What is new
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)
47
Give 2 Familiar examples of a G protein coupled cascade
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
48
Which G protein coupled activation forms arachidonic acid?
How does arachidonic acid act
G protein coupled activation of phospholipase A2
As a retrograde messenger, modulating transmitter release from presynaptic terminals
49
How does nitric oxide act on its effector enzyme
What is the effector enzyme
Directly
Soluble guanylyl cyclase
50
What do RTK and NO receptors sacrifice
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
51
Which NT’s are fastest acting?
| List them from fastest to slowest
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
52
Describe current stimulation in a sensory receptor
What does this result in
Stimulation evokes a receptor current whose amplitude changes in a graded manner according to the stimulus strength
A graded receptor potential
53
What does a graded receptor potential result in
What are exceptions to this
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
54
Sensory receptors can be divided into which two broad categories
Long and short receptors
55
What do long sensory receptors do
What about short
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
56
Do short receptors have axons
No
They generate a graded potential instead of firing spikes
57
Short receptors generate a graded potential instead of firing spikes. What does this mean for transmitter release
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
58
What do the accessory structures on receptors do
Filter the incident stimulus before the sensory terminal is stimulated
59
What do accessory structures on sensory receptors modify (4)
Sensitivity
Selectivity
Time course
Response
60
How is the magnitude of the stimulus normally encoded in long receptors
Eg
As the frequency of AP firing
Eg Cutaneous sensory receptors
61
True or false
| Sensory receptors usually adapt
True
| This leads to diminution of firing frequency with time
62
Name a quintessential long receptor
Cutaneous mechanoreceptor
63
Special senses are generally supplied by what kind of receptor
What is the exception
Short receptor
Olfactory which send axons directly to the olfactory bulb
64
Are mechanoreceptors direct or indirect?
What do they involve? Is this always true?
Direct
They involve the opening of stretch sensitive channels coupled to the cytoskeleton
- for hearing, they are coupled to more specialised structures
65
What do stretch receptor channels allow passage of
What is the result
Small cations
Depolarisation of the receptor
66
What kind of receptor channel is used in salt receptors
Direct
For Salty receptors in the tongue the stimulus is itself a permeant ion
67
What do indirect receptors use
Eg
A secondary messenger cascade
Retinal photoreceptors; taste and smell receptors
68
What are sensory indirect receptors similar to
What is the advantage of this
Metabotrophic synaptic transmission,
This offers the advantage of amplification, flexibility, and selectivity
69
How are α-motor neurons within the spinal cord different to neurons at the NMJ
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
Give an example of α-motor neurons within the spinal cord
Spindle Group IA fibres which mediate the monosynaptic spinal stretch reflex
71
What does each of the thousands of afferent terminals to the α-motor neurons within the spinal cord generate
What does this mean
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
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?
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
Briefly describe the experiment to find the reversal potential of α-motor neurons within the spinal cord
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
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
-80mV
This reversal potential is made less negative
Inhibition is due to an elevation in Cl- conductance
75
How can inhibition be achieved in the CNS
By either elevated Cl- or K+ conductance via the central inhibitory transmitter, GABA
76
True or false
If EPSPs and IPSPs are simultaneously, the underlying synaptic conductance changes summate linearly
False
They summate nonlinearly, each drawing the membrane potential towards its own reversal potential
77
Where does a cortical pyramid cell receive synapses
Soma
Dendritic shaft
Dendritic spines
78
How can synapses be sub divided
How do their vesicles change
Type 1 - excitatory (round vesicles)
| Type 2 - inhibitory (flat vesicle)
79
How does a signal propagate along a dendrite
Do all dendrites have the same properties
What does this mean
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
Are voltage gated conductance present in dendrites
What does this do
Yes is many dendrites there is conductance of both Na+ and Ca2+
This serves to boost the decaying passively conducted dendritic signal
81
Which part of the neuron has the lowest threshold
Why is this
Axon hillock
The AP is initiated here
82
How can it be demonstrated that the axon hillock has the lowest threshold for action potentials
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
When demonstrating that the axon hillock has the lowest threshold for action potentials, do you use a voltage or current clamp?
Current clamp so that the voltage can vary Freely
84
True or false
Once the action potential has been initiated, it actively propagates back into the dendritic tree
True
85
The extent to which a given synapse can influence the potential axon hillock depends on what
How far away it is from the cell body along the dendritic tree
86
Will synaptic current be more strongly attenuated when they flow along small dendrites or large dendrites
Why
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
How does the decay of an action potential differ from small dendrites to large ones
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
How does the time to peak of the potential change from small to large dendrites
Becomes slower as the synaptic current has to charge a progressively larger and larger fraction of the cells capacitance
89
Overall how do synaptic potentials change as they are conducted towards cell body
They become smaller and slower as they are conducted decrementally towards cell body
90
When 2 excitatory synapses are activated together, their ability to stimulate the axon hillock depends on what?
What does this mean
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
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?
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
Describe the algebra of synapses
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
What is shunting inhibition
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
Is overt hyper polarisation required for shunting inhibition
No
Instead simply Less excitatory current is available and would otherwise have been the case
95
How are excitedly and inhibitory inputs usually located on the dendrite
Why
Excitatory - further out
Inhibitory - closer to the soma
Bc this allows shunting inhibition
96
Opening which channels can reduce the height of the action potential in the presynaptic terminal
Cl-
| K+
97
What causes primary afferent depolarisation
How does this affect Na+ channels
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
What does reduced action potential height lead to
Is there another way to do this
Reduced opening of voltage gated calcium channels
Ca2+ channels can also be modulated by second messenger systems within the presynaptic terminal
99
How important is timing of inhibition
How does this differ for peptide transmitters
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
What kind of action potential occurs in interneurons
None - interneurons are short and therefore do not require APs
101
Which cation receptors are the work horses of the brain
AMPA and kainate receptors
102
What is the difference in ion permeability between AMPA and NMDA receptors
AMPA - only K+ and Na+
NMDA - Na+ and Ca2+ only
103
Where is the hypothalamus
In the paleocortex
104
How many layers does the paleocortex have
3 - it is evolutionarily older
105
Which parts of the brain loop through the hypothalamus
All
106
What are CA3 / CA1 synapses rich in
NMDA receptors
107
Which channel can be blocked to prevent formation of long term memory
NMDA receptors
108
What is the sequence once Ca2+ has entered through the NMDA receptor
Ca2+ -> AC -> cAMP -> PKA
109
What does PKA do in the post synaptic terminal after Ca2+ has entered through the NMDA channel
Is this long term or medium term
PKA phosphorylates AMPA, making it more sensitive (medium term)
Also activates CREB, which increases AMPA receptor expression (long term)
110
What is the turnover rate of AMPA receptors
1 day
111
Does Ca2+ only activate kinases after entering through NMDA receptors
How can this be
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
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?
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
How did they discover the A current
Which graphs are relevant
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
What happens to A - current and K+ current following an AP
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
What is the purpose of the A current
To space out the AP in the spike train
116
True or false
| Cortical pyramidal cells demonstrate intrinsic bursting when stimulated continuously
True
117
When does bursting in Neurons occur
When depolarisation activates low threshold Ca2+ channels
118
True or false
| Only one kind of Ca2+ channel will exist in a cell
False
| Neurons contain a number of different voltage gated calcium channels open by depolarisation
119
Which calcium channels contribute to bursting in neurons?
What happens
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
When do thalamic relay neurons exhibit bursting
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
Which current depolarises Thalamic relay neuron to T channel threshold
A hyper polarisation activated inward current (Ih)similar to the cardiac pacemaker current which comprises both sodium and potassium ions
122
What happens to T channels at more depolarised potentials
T channels Are permanently activated and the relay neuron repeatedly fires single spikes in tonic mode
123
Other than IA and Ih, which channels modulate AP firing
How do these work
Calcium activated potassium channels
Open when calcium enters through voltage gated calcium channels and contribute to an outward hyperpolarising potassium current
124
Which channels contribute to spike frequency adaptation
What else do they do
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
Why does the receptor current in the olfactory receptors cell oscillate
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
What is the oscillation of receptor current in olfactory receptors cells believed to arise from
Coupled oscillation of calcium and
| cAMP
127
Does the monosynaptic spinal stretch reflex consist of just a single muscle spindle afferent and a single α-motor neuron
No - it consists of a population of IA afferents and the motor neuron pool supplying the agonist muscle
128
What is divergence in the monosynaptic spinal stretch reflex
Each IA afferent will synapse with a number of motor neurons
129
Describe convergence in terms of the monosynaptic spinal stretch reflex
Each motor neuron will receive synaptic inputs from a number of IA afferents
130
Why is convergence of excitatory input essential for operation of the monosynaptic spinal stretch reflex
The EPSP generated by a single IA afferent is far too small to reach threshold
131
What is the subliminal fringe
What happens if to subliminal fringes overlap
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
What is occlusion when it comes to synaptic summation
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
What are the two distinct ways inhibitory interneurons can be deployed within the spinal-cord
Feedforward inhibition
Feedback inhibition
134
Describe the feed forward inhibition of interneurons in the spinal cord
The pathway to the antagonist muscle is inhibited when the agonist pathway is stimulated – this inhibits extensor muscles when flexes are stimulated
135
How does feedback inhibition of interneurons work
Eg?
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
Give an overview of what happens in the flexor withdrawal reflex
Stimulation of cutaneous nociceptors leads to reflex extensor inhibition and flexor stimulation to withdraw the limb from harm
137
What happens in the crossed extensor reflex
Stimulation of the contralateral extensor and inhibition of the contralateral flexor muscle provide support for the flexor withdrawal reflex
138
At the frog NMJ, what does repeated stimulation lead to
What happens after repeated tetanic stimulation
What do each reflect
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
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
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
What is a major mechanism believed to underpin memory
Long term potentiation (LTP)
141
Which neurons can be used as an example of a long-term potentiation
How can LTP be demonstrated here
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
What are the results of the experiments on pyramidal cells of the area CA1 in hippocampus
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
Which law does potentiation obey
Describe this law
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
How can the Hebbian nature of LTP at synapses in CA1 be demonstrated
What does this show
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
What is LTP believed to result from at CA1
Is it always like this?
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
Name retrograde agents in LTP and describe their action
NO and arachidonic acid
Modulate presynaptic transmitter release by diffusing backwards
147
What does maintenance of LTP require
A persistent increase in kinase activity following gene transcription and protein synthesis
148
Where are excitatory inputs often located in many central neurons?
What do these do
On dendritic spines
Both chemically and electrically isolate the postsynaptic machinery from events elsewhere within the cell
149
How do dendritic spines isolate the post synaptic machinery from the cell
They have a high neck resistance which attenuates excitatory current flowing into the dendrite
150
How are dendritic spines involved in learning and memory
Immature small spines undergo cytoskeletal changes upon potentiation which lead to rapid spine enlargement followed by enlargement of the postsynaptic density upon consolidation
151
What does the enlarged postsynaptic density of dendritic spines provide
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
What does CamKII phosphorylate
AMPAr
153
What is CamKII
Ca2+/calmodulin-dependent protein kinase II
It phosphorylates AMPAr in LTP
154
What underpins LTP in the CA3 area of the hippocampus
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
When can long term depression occur in CA1 pyramidal cells
If they are stimulated at low frequencies which fail to make the target cells fire
156
How can LTD be initiated (2)
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
Which LTD is important in motor learning in the cerebellum
mGlutR-dependant LTD
158
Does mGlutR-dependant LTD reverse LTP
It does NOT directly reverse LTP
159
Which type of LTD is a widespread feature of synapses in the neocortex
NMDAr -dependant LTD
