Neurochemical basis of LTP Flashcards
LTP is dependent on the release of the excitatory neurotransmitter _______. This binds to 2 receptors:
- AMPA and NMDA
These are BOTH seen in the same _______.
The immediate response you get from stimulating a glutamtergic neuron is from ______ receptors. When glutamate binds, NA+ ions enter the cell and the post-synaptic neuron is _______. If it crosses the threshold, it triggers an _____ potential. This is known as a fast ______ post-synaptic ________ (EPSPs). This spreads across the neuron.
The ______ receptors are co-localised in these neurons. When Glu binds it allows _____ ions in. This triggers a number of proceses related to learning.
glutamate
synpases
AMPA
depolarised
action
excitatory
potential
NMDA
Ca+
An Intracellular cascade occurs with the binding of Glu to AMPA and NMDA - what is the ultimate result of this cascade?
Ulimately leads to upregulation of AMPA receptors to allow more Glu to bind - for the same amount of Glu there is more opportunity for it to bind - makes membrane more sensitive (increasing effeciveness of membrane)
NMDA receptors have 2 properties that underlie their involvement in synaptic plasticity.
- Stimulation from pre-synaptic neuron allows _____ into the neuron. This triggers _______ inside neuron that leads to increased _______ of post-synaptic neuron (increased no. of ______ receptors which increases _____ influx)
- In order for Ca+ ions to enter:
- Glu needs to bind to NMDA receptor (______-gated) AND
- the post-synaptic neuron must be _______ (by Glu binding to AMPA receptors initiatlly - must be on the SAME ______, but not the same synapse). This is ______-gated, and it removed Mg ion blocking the channel.
Two ____-fold ______ system which is responsible for the ________ and ________ of the NMDA-mediated synaptic plasticity.
Ca+
cascade
sensitivity
AMPA
Na+
ligand
depolarised
neuron
voltage
two
gating
specificity
associativity
In this diagram, synaptic plasticity is not occuring.
This is because the reactions are very ______. There is Glu which stimulates _____ receptors and leads to _______. This in turn, is one part of activating the _____ receptors (_____-gated). However, you also need Glu (____-gated). There is Glu at the area you are proving with HFS, but not in the part of the cell without stimulation.
localised
AMPA
depolarisation
NMDA
voltage
ligand
In contrast to specificity, describe how associativity occurs in LTP
See diagram
Changes in synaptic strength and memory traces
The stages that convert initial learning into long-term memory are:
- generating ______ change
- _______ changes
- _______ changes
- Maintaining changes
synaptic
stabilising
consolidating
Generating the synaptic change
The rapid, initial changes are called post-translational because…
This must mean there are….
they use existing proteins in neurons and do not require synthesis of new proteins (which requires synthesis from RNA)
extra receptors held in the cell. Indeed, there is a consecutive trafficking and recycling of receptors to create these synaptic changes.
Receptors are ______. The recipe for this is in the ____.
The post-translational changes that occur are _______, unless other intracellular processes are activated to ______ the changes.
Eg: interferring with stablisation - memory trace is lost - such as concussion - leads to forgetting what happened in the accident
proteins
DNA
transient
stablise
GENERATING MEMORY TRACE - INITAL STRENGTHENING
Describe the cascade that is triggered by Ca+ ions for the up-regulation of AMPA receptors that is responsible for short-lived potentiation
–> can be achieved by weak HFS
See diagrams 1
See diagrams 1
GENERATING MEMORY TRACE - INITAL STRENGTHENING
Describe the cascade that is triggered by Ca+ ions for the up-regulation of AMPA receptors that is responsible for short-lived potentiation
–> can be achieved by weak HFS
See diagrams 2
See diagrams 2
STABLISATION
Describe the cascade that is triggered by Ca+ ions for the up-regulation of AMPA receptors that is responsible for short-lived potentiation
–> can be achieved by weak HFS
See diagrams 3
See diagrams 3
STABLISATION
Describe the cascade that is triggered by Ca+ ions for the up-regulation of AMPA receptors that is responsible for short-lived potentiation
–> can be achieved by weak HFS
See diagrams 4
See diagrams 4
CONSOLIDATION
Long-lasting potentiation (hours) is achieved by strong HFS, or HFS using ______ _______ frequency. This requires _________ processes (where new proteins are ________). It is known that drugs (azithromycin) that block protein synthesis after strong HFS can prevent long-lasting _______ (BUT have no effect on _____-term potentiation)
theta burst
translational
synthesised
potentiation
short
CONSOLIDATION
Calcium ions can also trigger the process to create new AMPA receptor protein. Describe this mechanism part 1.
Local translation - in the dendritic spine
–> even if you cut the dendrite from soma this process will still occur (so some of the machinery is there in the dendritic spine)
CONSOLIDATION
Calcium ions can also trigger the process to create new AMPA receptor protein. Describe this mechanism part 2.
Actual transcription.
Ca+ can activate the process for the DNA to transcribe new mRNA.
This can then be translated to make new AMPA receptor protein
Finally, in the last stage, the dendritic spine has to _____, so a process triggered by ______, causes a protein called _____ to synthesise more actin for the cytoskeleton.
This is important, as it needs more ______ _____ to increase the dendrite’s sensitivity, and more internal space to store extra _____ receptors.
CONSOLIDATION
After this, no further ______ is possible. This is related to the gradations of LTP previously discussed. There is a _____-dependency of HFS, where more and more HFS leads to increased _______ of the neurons. This is because you are potentiating more and more synapses. However, eventually it reaches _______ and there would have to be growth of new dendrites for further plasticity.
So, according to this theory, synapses are either _____ or ________ (rigger this whole process to strengthen them).
grow
BDNF
Arc
surface area
AMPA
plasticity
dose
sensitivity
saturation
weak
potentiated
Overview
See diagram
