NRSC4032 - Chapter 11: Memory Consolidation
What were the results and implications from systematically injecting the protein-synthesis inhibitor anisomycin prior to fear conditioning?
The drug had no effect at the 1-hour retention interval but impaired retention at the longer 6- and 24-hour tests. These results are consistent with the idea that a short-term memory trace can be formed that does not depend on protein synthesis, whereas a long-term memory trace requires new proteins.
What is the retention interval?
The time between the training experience that establishes the memory and the test used to retrieve the memory.
What can be said about the contribution of molecule X to memory?
These results indicate that molecule X contributes to the consolidation of the long-term memory trace but is not required for short-term memory.
(T/F) The mTORC2 complex regulates protein synthesis but the mTORC1 complex regulates actin polymerization.
false
Inhibiting protein synthesis just prior to avoidance training
impairs retention at all intervals longer than an hour, but has no effect on memory retention an hour after training
Rapamycin ______ the function of the mTORC1 complex.
inhibits
Inhibiting the mTORC1 complex
interferes with local protein synthesis and could interfere with consolidation
Describe two sources of evidence that BDNF is important for memory consolidation.
1) BDNF protein levels are increased in the hippocampus by contextual fear conditioning and place learning and in the BLA by fear conditioning. 2) Interfering with BDNF function by either the BDNF scavenger TrkB-IgG or the TrkB receptor antagonist K252a impaired the development of long-term memory.
What is the evidence that the UPS is involved in memory consolidation?
1) Behavioral experiences that induce lasting memories increase ubiquitination and proteasome activity 2) drugs that block proteasome activity also prevent long-term memory formation.
(T/F) A memory may be considered consolidated when it is no longer vulnerable to transcription and translation inhibitors.
true
(T/F) A second wave of protein synthesis is necessary for a memory to last for 7 or more days
true
(T/F) BDNF can initiate phosphorylation of CREB
true
(T/F) C/EBPβ is a transcription factor
true
(T/F) C/EBPβ is targeted by CREB for transcription
true
(T/F) CREB deletion impairs LTM.
true
(T/F) CREB overexpression can improve LTM under certain conditions.
true
(T/F) Disrupting either the mTORC1 or the mTORC2 complex will impair the development of long-term memory but have no influence on the formation of short-term memory.
true
(T/F) If the first wave of BDNF protein synthesis is blocked retention at both the 1- and 7-day interval will be impaired.
true
(T/F) Short-term memories are more vulnerable to disruption than long-term memories.
true
(T/F) That rapamycin administers just before training interfered with retention 2 and 7 days later indicates that the mTOR pathway is critically for at least two ways of protein synthesis.
true
(T/F) The BDNF-TrkB pathway is critical to two waves of protein synthesis.
true
(T/F) The TOP protein 4E-BP normally interferes with the initiation of local protein synthesis
true
(T/F) The mTORC2 complex regulates actin polymerization but the mTORC1 complex regulates protein synthesis
true
(T/F) The second wave of protein synthesis depends on genomic signaling initiated by the BDNF-TrkB pathway.
true
(T/F) To determine the role of a molecule in memory consolidation the experiment should use at least two retention intervals.
true
(T/F) memory consolidation can depend on multiple waves of transcription and translation
true
How did John Guzowski examine the importance of CREB for memory retention?
He used an antisense to CREB and tested rats at both a short and long retention interval.
Why what is the role of C/EBPβ in the autoregulatory loop?
It targets BNDF for transcription.
(T/F) Neurons that overexpress CREB do not compete successfully for selection in the neuronal ensemble
false
(T/F) Rapamycin administer prior to training interfered with retention 1hour later.
false
The mTORC2 complex regulates processes that contribute to the regulation of __________.
actin
(T/F) The TrkB receptor is activated by the first messenger glutamate.
false
(T/F) The decay rate for long-term memories is more rapid than the decay rate for short-term memories
false
The TOP protein ______ normally interferes with the initiation of local protein synthesis
4E-BP
_____ it is critical to both the first and second waves of protein synthesis.
BDNF
If _____ is inhibited BDNF will not be transcribed
C/EBPβ
How might sleep contribute to consolidation.
During sleep intrinsic neural processes might reactive the additional rounds of local proteins synthesis that use the mRNA and proteins provided by the autoregulatory loop.
What is the evidence that proteins translated in response to the mTORC1 signaling are important for the consolidation of long-term memory but not for producing a short-term memory?
Inhibitory avoidance procedure revealed that rapamycin selectively impaired performance when the retention interval was 24 hours but not when it was only 3 hours.
Why is the rictor KO mouse useful?
It allows researchers to study the contribution of mTORC2 to consolidation.
Anisomycin administered just prior to training prevents retention at 2, 7, and 9-day intervals but If administered just a few minutes following training only impairs retention at the 7 and 9- day intervals. What does this collection of findings imply?
It implies that there is an initial wave of protein synthesis initiated almost immediately by the training and a second wave that is initiate some time later. It also indicates that the second wave depends on proteins synthesize by the first wave.
What is the importance of the two distinct peak levels of BDNF expression?
One peak of BDNF occurs 1 hour after training and is critical for fear response memory on 1-day and 7-day retention intervals. The second occurs 12 hours later and supports the memory on the 7-day retention test.
Why would one vary the interval separating training and the administration of a protein synthesis inhibitor such as anisomycin?
This would be done to be sure that the effect was selective for proteins synthesized in response to the memory-inducing behavioral experience and not just a nonselective effect of blocking protein synthesis.
(T/F) Alberini's laboratory found that inhibiting protein synthesis (with anisomycin) a few minutes after training did not interfere with retention 2 days after training but did prevent retention 7 and 9 days later 9.
false
(T/F) Blocking CREB translation impairs STM.
false
(T/F) Blocking protein synthesis interferes with the formation of short-term memories.
false
(T/F) C/EBPβ is critical to the first wave of protein synthesis
false
(T/F) C/EBPβ is targeted by CaMKII for transcription
false
(T/F) C/EBPβ targets CREB for transcription
false
(T/F) If a molecule is critical for long-term memory, it should also be critical for short-term memory.
false
When trying to assess the effect of a gene or drug on short-term memory, the retention interval is __________.
four hours or less
The idea that a behavioral experience can generate the transcription of new genetic material is called the __________.
genomic signaling hypothesis
The mTORC1 complex regulates __________.
local protein synthesis
The de novo protein synthesis hypothesis states that
long-term memory depends on behavior initiating the synthesis of new protein.
What are the differences between mTORC1 and mTORC2?
mTORC1 is sensitive to rapamycin and regulates protein synthesis; mTORC2 is insensitive to rapamycin and regulates actin polymerization.
If mTOR is inhibited by rapamycin 5 minutes after avoidance conditioning
memory retention would not be impaired at any retention interval
Inhibiting protein synthesis should ______ effect short-term memory.
not
The initial round of protein synthesis depends on
post-translational processes, BDNF -> TrkB signaling,
What is the key independent variable manipulated to determine if a molecule is selectively involved in LTM but not STM?
retention interval