Chapt. 5 - Consolidating LTP: Translation and Transcription Flashcards
(41 cards)
de novo protein synthesis hypothesis
idea that for memories to endure, the learning experience must produce new proteins, proteins that were not present at the time of the learning event
Muller and Pilzeckers
Problem with DNPS hypothesis
didn’t specify what does the building of the needed new proteins are what gets built (because LTP wasn’t discovered yet)
What is the fundamental consolidation event
the construction of an enlarged stable actin cytoskeleton that is linked to the extracellular matric and presynaptic partner.
THEREFORE this requires no new proteins and disagrees with DNPS hypothesis
Evidence that synaptic events that produce enduring LTP initiate _______ and ______ of _______ into new proteins that can be important for synaptic changes to endure
transcription
translation
messenger RNA (mRNA)
The initial generation and stabilization of synaptic basis of LTP depends on what to do what?
While the enduring of LTP involves what to do what?
Generation and Stabilization = post-translation processes that modify and arrange existing proteins
Enduring = if synaptic changes resist the pressure to return to their original potentiated state, inducing stimulus must also initiate translation processes to generate new proteins
Evidence using a protein synthesis inhibitor shows that S-LTP produced by the weak stimulus depends only on ____. While the consolidation of synaptic changes supports that L-LTP requires _____
post translation modifications and rearrangements of pre-existing proteins
requires new proteins
Transcription
process of converting genetic material from DNA to messenger RNA, happens when signaling molecules enter the nucleus and activate transcription factors which are proteins that interact with DNA to produce mRNA
Translation
process by which mRNA is converted to protein (protein synthesis occurs)
mRNA is translated as it passes through a membrane system that surrounds the nucleus but also translation machinery and relevant mRNA are distributed where?
within the dendrite and soma
means possibility they are translated locally from already existing mRNA
New proteins can be derived from ____ or be the result of ______
derived by local translation of mRNAs already present in the dendrite spine region
OR
result from synaptic activity signaling the genome to transcribe new mRNA
L-LTP depends on parallel effects of the LTP inducing stimulus. It initiates both _____ and _____
local translation
genomic signaling cascades
genomic signaling cascades
transcribe new mRNA that can be translated
(synapse to nucleus and soma to nucleus)
Local protein synthesis
mRNA and protein translation machinery (ER and ribosomes) are present locally in the dendritic spine and is all that you need to produce a new protein. FAST AND SPECIFIC. Machinery is activated during synaptic activity or experience
Experiments that provide evidence for local translation/protein synthesis
- invitro - separate dendrites from somas, making it impossible for proteins that have newly synthesized in the soma from a genomic cascade to influence synaptic strength. stimulation delivered to the schaffer collateral fibers (on dendrite part) can produce LTP therefore protein had to of been translated locally in dendrites
- can produce L-LTP on dendrites in both apical and basal region. when emetine (protein synthesis inhibitor) applied to all, prevented L-LTP in both. when applied to one, other place could still produce L-LPT. when applied to soma, did not block in either region –> therefore proteins were translated in the dendrites
mRNAs that are not produced locally can become generate by a genomic signaling cascade that result in ___ of new mRNA because of ____ and ____
transcription
synaptic activity
neuronal depolarization
for genomic signaling cascades, the signaling molecules enter the nucleus to phosphorylate _____ which interact with DNA to produce ____. This results in production of mRNA that gets _____ into a new protein
transcription factors
mRNA
translated
Synapse to nucleus (1 way to signal the nucleus)
synaptic activity initiates a cascade that produce signaling molecules that eventually move to the nucleus to initiate transcription
Soma to nucleus (other way to signal nucleus)
result of action potentials produced by synaptic activity, calcium enters the soma through voltage dependent calcium channels which it can more directly initiate transcription
Which way of signaling to the nucleus is more likely
soma to nucleus because it is faster and more efficient, 15 mins compared to hours
what support present to support that L-LTP depends on transcription
- inhibitors of transcription blocked development of L-LTP but did not interfere with initial development and stabilization
- transcription factor CREB protein was implicated in both synaptic plasticity and long term memory and memory and L-LTP was prevented if no CREB
CREB when activated vs inactivated
called a ______ switch
inactivated = unphosphorylated state and has little effect on gene transcription
activated = phosphorylated and initiates production of mRNAs and transcribe mRNA that are critical for production of long lasting changes in synaptic strength. mRNAs called plasticity products
called a molecular memory switch
Two general models of how signals reach the nucleus/ activate CREB
- synapse to nucleus signaling
- soma to nucleus signaling
synapse to nucleus signaling
stimulate post synaptic site which activates second messenger system –> activate protein kinases –> secondary messenger or kinase move into nucleus where they phosphorylate CREB protein –> transcription is initiated
In synapse to nucleus signaling there are multiple pathways that can phosphorylate CREB
- Protein Kinase A activated by second messenger system cAMP –> PKA move to nucleus to phosphorylate CREB and initiate transcription (without PKA, block L-LTP and reduces genes controlled by CREB)
- Extracellular regulated kinase-mitogen-activated protein kinase (ERK-MAPK) initiated by neurotrophic factors which binds to tyrosine kinase (Trk) receptors, move to nucleus and initiate transcription factors.