LTD

Question 1

What is a hebbian synapse and what is some evidence for it

Answer 1

coordinated activity of a presynapse and a postsynapse strengthen the synaptic connections between them.

london taxi drivers have an enlarged hippocampus, did they have a large one to begin with or did their job make it grow.

Question 2

what is one of the first areas of neurodegeneration in alzhiemers

Answer 2

hippocampus

Question 3

what is the simple circuitry in the hippocampus

Answer 3

the input comes from the entorhinal cortex.
then to the dentate gyrus.
then to the CA3 mossy fibres.
then to the CA1 schaffer collaterals.
then the output to the fornix and subiculum.

Question 4

how is long term potentiation induced in the hippocampal circuit

Answer 4

the CA3 cells were activated with a high frequency stimulus which resembles the human theta rhythm, and this produces a long lasting potentiation of the synapse.
a recording electrode is put on CA1 and the stimulation electrode is put on CA3.
the EPSP recorded in CA1 will increase in amplitude by 50% when high frequency stimulation is applied to CA3.

Question 5

why is long term potentiation input specific

and cooperativity

Answer 5

a neuron receiving two separate inputs will only show increased EPSPs in the synapses connected to the one input receiving high frequency stimulation.
both LTP and LTD are input specific.

you dont need a high frequency stimulation of the synapse to trigger LTP, instead you can depolarise both the pre and post synaptic neurons at the same time.
stimulating the CA3 and CA1 neurons at the same time will cause the synapse to undergo LTP.

Question 6

how can LTP explain how associative learning works

Answer 6

two pathways converging on the same target can both be strengthened if they fire together, one of the pathways may be weak.
a neuron for the conditioned stimulus and a neuron for the unconditioned stimulus are stimulated at the same time to strengthen them.

Question 7

how can LTP occur

Answer 7

it could happen due to presynaptic changes, proteins in the presynapse could change and affect the release rate of the synapse.

or when the post synapse is hyperpolarised the NMDA glutamate receptors is blocked by Mg, so even if glutamate binds nothing will happen.
NDMA receptors need to be indirectly preactivated by a separate depolarising input, which will cause the removal of the Mg.
the LTP will be caused by the depolarisation of both the post and pre synapse.

Question 8

what happens when NMDA receptors are activated

difference between AMPA and NMDA

Answer 8

Ca enters the post synapse and causes depolarisation

AMPA acts to depolarsie the post synapse.
NMDA only depolarises the post synapse a little.

Question 9

why is it good to use high frequency stimulation for LTP

Answer 9

it causes a much stronger depolarisaion of the postsynaptic membrane
this is because of the summation of the EPSPs and there is enough depolarisation to remove the Mg from the NMDA receptors.

Question 10

what is early LTP vs late

Answer 10

the early part does not require protein synthesis and the late part does.
LTP induction is what happens early on and LTP expression with protein synthesis is what happens later on.

Question 11

what happens with LTP if you block protein synthesis

Answer 11

the amplitude of the EPSP goes back to the normal level.

Question 12

what are some examples of early LTP:

CamKII

Answer 12

the Ca entry to the post synapse activates calmodulin kinase II (CamKII). This takes up to 5% of the post synapses protein content.
It has multiple catalytic subunits and autophosphorylates itself.
the catalytic subunit is covered by the regulatory subunit and when it is activated by Ca and calmodulin, the catalytic subunit becomes free and it can autophosphorylate itself. this will stabalise its conformation in the open form.
CamKII can go onto phosphorylate other things and increase the AMPA currents.

Question 13

PKC and its KO.

KO vs inhibitors as an experimental technique

Answer 13

if there is a PKC KO then the embryos die early in development.

inhibitors are not usually 100% specific and so can bind to and affect other protiens,
KO have an affect on how the embryo develops and it will affect all the PKC pathways and the results will be showing indirect effects.

Question 14

what is AMPAfication and why does it happen

Answer 14

the delivery of readily made AMPA receptors to the synapse which occur due to early LTP.

Question 15

what happens during late LTP and how long does it take

CRE and PKA

Answer 15

long term storage needs protein synthesis, it takes one hour after LTP initiation.
CRE is a DNA sequence that regulates transcription, when it has CREB2 bound there is no transcription, when it has CREB1 bound and is phosphorylated there is transcription activation.
During LTP CREB2 is swapped for CREB1 .

the ca entry during phosphorylation will activate a CAMP pathway and activate PKA.
PKA migrates to the nucleus and will trigger gene expression.

Question 16

how is LTP linked to memory

water maze and drugs

Answer 16

inhibiting LTP inhibits some memory formation.
Morris water maze, mice go around the maze and find a hidden platform for them to stand on, once the mouse has found it it will memorise the position and can find it again.
mutations in CamKII, NMDA receptors and the CAMP pathway all affect how well the mouse can learn where the platform is.
drugs to enhance memory (nootropics) can also enhance LTP.

Question 17

is LTP sufficient for memory and what does this have to do with LTD

Answer 17

LTP is not sufficient for memory, it is only necessary for some memory formation.
LTP is related to LTD, which can be a related form of plasticity.

Question 18

what is LTD and where does it happen

what are the two types

hebbian or non hebbian

Answer 18

a decrease in the EPSP amplitude, long lasting reduction in synaptic efficacy.
it happens in the cerebellum and hippocampus.

there is depotentiation which is removal of LTP by triggering LTD.
or there is LTD de novo where there is no previous LTP and LTD is activated.

it can be both, and doesn’t always need pre synaptic activity.

Question 19

what does LTD often require and what is it evoked by

Answer 19

often evoked by low frequency stimulation, and requires NMDA receptors and ca influx to activate serine/threonine phosphatases.
often involves glutamate but can also use 5HT, endocannabinoids which are released post synaptically to inhibit pre synaptic ntm release.

Question 20

what do purkinje cells look like

where does the cerebellum get its input and what are the connections like

Answer 20

they have many synapses and a dense dendritic tree.

they get info from mossy fibres and climbing fibres,
climbing fibres have many synapses with one purkinje cell and this causes a massive purkinje cell depolarisation due to summation.
parallell fibres make one weak synapse with each purkinje cell.

Question 21

what happens if you stimulate both the climbing fibre and the parallel fibre at the same time

Albus marr model

Answer 21

you will see a reduction in the synapse between the parallel fibre and the purkinje cell due to LTD.

climbing fibre input indicates a motor error and weakens the parallel fibre to purkinje cell synapse.

Question 22

what is the pathway of circuitry in the cerebellum for LTD

Answer 22

the climbing fibre releases glutamate onto the purkinje cells AMPA receptors
this leads to depolarisation which will activate ca channels.

glutamate is released from the parallel fibre onto the purkinje cell G protein receptors, this will activate phospholipase C and produce DAG which stimulates PKC.
PKC phosphorylates AMPA receptors but in a different way to that in LTP, this leads to a reduction in AMPA receptors caused by endocytosis.

Question 23

what synapses are used in the hippocampal LTD

Answer 23

uses the same synapses as the LTP (dentate gyrus) but they are stimulated with a low frequency stimulation which triggers the LTD.

Question 24

are LTP and LTD ca dependant

Answer 24

yes they both are

Question 25

what affect does the degree of NMDA activation have on the LTP or LTD

Answer 25

the degree of NMDA receptor activation dictates whether LTP or LTD is induced.
the receptors are activated much less for LTD and so the increase in ca is much smaller.

a small increase in ca stimulates more phosphatase action and reduces the AMPA receptor efficacy.
a large increase in ca activates more kinases which increase AMPA efficacy.

Question 26

what does high/low frequency stimulation cause and how

Answer 26

high causes ca >5um and increased protein kinase activation and this will cause LTP.
low causes ca <1um and increased phosphatase activation and this will cause LTD.

Question 27

channelrhodopsin and halorhodopsin

what can halo be used to treat

Answer 27

channelrhodopsin opens when a blue light is shone on it, it lets Na and K into the cell and depolarises it.

halorhodopsin opens and hyperpolarises the membrane and opens in response to green/yellow light, it moves Cl into the cell.
it can be used to treat seizures caused by overactivity in the brain because it stops depolarisation, it is very non specific.

Question 28

how can light be used to change the shape of molecules and what will this do

Answer 28

small organic compounds contain a double bond and is in trans configuration
when you shine a light on it it changes to cis configuration.
this compound can be injected into the brain and in trans configuration it will block a channel and in cis it will not.
or it can work inside the membrane as it can enter cells using TRPV1 or P2XR and block certain channels in trans form from the inside.
so when light is shone on it it will start spiking.

Question 29

what is photocontrol of receptors

Answer 29

substitute part of one of the small organic compounds (that changes configuration in response to light) for a ligand that is complementary to a receptor.
in one configuration the ligand will activate the channel and in the other it will not activate the channel.
this can be done to GABA receptors to stop the over activation of the brain by activating GABA.

Question 30

does glutamate do depol or hyperpol

Answer 30

both

Question 31

what is retinitis pigmentosa and how is it treated

what has to be stimulated if the optic nerve is damaged or didnt develop

Answer 31

it looks like youre seeing down a tunnel, the visual field gets smaller and smaller until you go blind and it is caused by the death of photoreceptors.

it can be treated using an artificial retina, by light activating electrodes or channelrhodopsin and halorhodopsin.
electrodes dont survive for a very long time, the tissue surrounding the electrode will die after a year.

visual cortex.

Question 32

what part of the eye is exposed to the electrodes

Answer 32

the ganglion cells

the electrode will be activated by light, the photoreceptors and bipolar cells are not stimulated by the electrode.

Question 33

what are the two major classes of ganglion cells and what are their receptive fields like

what kinds of light do they respond to and are they selective in any way

Answer 33

parvocellular and magnocellular.
they have a centre surround organisation of the receptive field, when the centre of the field is stimulated it will cause spikes, and if the surround is stimulated it will cause no spikes.
they can respond to light of different colors and some have direction selectivity.

Question 34

what can be used to stimulate deeper layers

mice with photoreceptors remains

Answer 34

light can be used to stimulate bipolar cells or photoreceptors.

mice with a mutation causing retinal degredation were used, some of the damaged photoreceptors were able to form synapses with bipolar cells.
halorhodospin was expressed in the photoreceptors remains and this allowed them to be able to activate ganglion cells, this is because the photoreceptors need to hyperpolarise to be active.
it will work for both on and off cells but the off cells will spike when the yellow light is off.
this is how to restore the lost function of photoreceptors.

Question 35

what will increasing the diameter of light do to the photoreceptors with halo

Answer 35

it will give no response because there is only activation when light is shone in the centre.

Question 36

where can channelrhodospin and halorhodopsin be expressed in the on and off cells

Answer 36

chennelrho in the on cells.
halo in the off cells.
this can be done instead of using photoreceptor remains.