Learning and Memory chapter 11

What is the evidence that the UPS is involved in memory consolidation?

(cp) 1) Behavioral experiences that induce lasting memories increase ubiquitination and proteasome activity; and 2) drugs that block proteasome activity also prevent long-term memory formation.

How did John Guzowski examine the importance of CREB for memory retention?

(cp) He used an antisense to CREB and tested rats at both a short and long retention interval.

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?

(cp) Inhibitory avoidance procedure revealed that rapamycin selectively impaired performance when the retention interval was 24 hours but not when it was only 3 hours.

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?

(cp) 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 were the results and implications from systematically injecting the protein-synthesis inhibitor anisomycin prior to fear conditioning?

(cp) 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 can be said about the contribution of molecule X to memory?

(cp) These results indicate that molecule X contributes to the consolidation of the long-term memory trace but is not required for short-term memory.

Why would one vary the interval separating training and the administration of a protein synthesis inhibitor such as anisomycin?

(cp) 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.

What is the role of BDNF in the autoregulatory loop?

(cp) it is critical to both the first and second waves of protein synthesis.

What are the differences between mTORC1 and mTORC2?

(cp) mTORC1 is sensitive to rapamycin and regulates protein synthesis; mTORC2 is insensitive to rapamycin and regulates actin polymerization.

Describe two sources of evidence that BDNF is important for memory consolidation.

(cp)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.

Which of the following statements is true? - C/EBPβ targets CREB for transcription - C/EBPβ mRNA becomes detectable as soon as CREB is phosphorylated. - BDNF can initiate phosphorylation of CREB - A second wave of protein synthesis is necessary for a memory to last for 7 or more days - CREB targets C/EBPβfor transcription

- BDNF can initiate phosphorylation of CREB - A second wave of protein synthesis is necessary for a memory to last for 7 or more days - CREB targets C/EBPβfor transcription

Which of the following statements is false? - CREB deletion impairs LTM - Blocking CREB translation impairs STM. - C/EBPβ is a transcription factor - antisense against C/EBPβ5 hours but not 24 hours following to avoidance training interferes with long term retention

- Blocking CREB translation impairs STM.

Which of the following statements about memory is false? - CREB deletion impairs LTM. - Blocking CREB translation impairs STM. - CREB overexpression can improve LTM under certain conditions. - Neurons that overexpress CREB do not compete successfully for selection in the neuronal ensemble

- blocking CREB translation impairs STM - Neurons that overexpress CREB do not compete successfully for selection in the neuronal ensemble

The initial round of protein synthesis - depends on genomic signaling - depends of post-translation processes - depends on BDNF->TrkB signaling - depends on both post-translation processes and BDNF signaling - does not depend on post-translation processes

- depends of post-translation processes - depends on BDNF->TrkB signaling - depends on both post-translation processes and BDNF signaling

Inhibiting protein synthesis just prior to avoidance training - impairs memory retention 1 hour following training - impairs memory retention at all retention intervals - impairs retention at all retentions intervals longer than hour - has no effect on memory retention 1 hour following training

- impairs retention at all retentions intervals longer than hour - has no effect on memory retention 1 hour following training

Inhibiting the mTORC1 complex - interferes with actin polymerization - interferes with local protein synthesis - could interfere with consolidation - would have no effect on memory retention

- interferes with local protein synthesis - could interfere with consolidation

which is true about memory consolidation? - memory consolidation depends only on the translation of new proteins - memory consolidation does not require post-translation processes - memory consolidation is over in about 1 hour - memory consolidation can depend on multiple waves of transcription and translation none of the above

- memory consolidation can depend on multiple waves of transcription and translation

If mTOR is inhibited by rapamycin 5 minutes after avoidance conditioning... - memory retention would be impaired at all retention intervals longer than 1 hour - memory retention would be impaired at all retention intervals longer than 1 day - memory retention would not be impaired at any retention interval - memory retention would not be impaired if the retention interval is 1 hour or less.

- memory retention would not be impaired at any retention interval - memory retention would not be impaired if the retention interval is 1 hour or less.

What is the importance of the two distinct peak levels of BDNF expression?

1. one BDNF peak is one hour after training and is important on day 1 and 7 retention intervals 2. the other peak is 12 hours after and that is important for only the 7-day retention test

The TOP protein ______ normally interferes with the initiation of local protein synthesis

4E-BP

If _____ is inhibited BDNF will not be transcribed

C/EBPβ

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 If a molecule is critical for long-term memory, it should also be critical for short-term memory.

False

T/F The decay rate for long-term memories is more rapid than the decay rate for short-term memories

False

T/F A memory may be considered consolidated when it is no longer vulnerable to transcription and translation inhibitors.

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

The mTORC2 complex regulates processes that contribute to the regulation of __________.

actin

T/F Blocking protein synthesis interferes with the formation of short-term memories.

false

T/F Rapamycin administer prior to training interfered with retention 1hour later.

false

T/F The TrkB receptor is activated by the first messenger glutamate.

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

Rapamycin ______ the function of the mTORC1 complex.

inhibits

How might sleep contribute to consolidation.

intrinsic neural processes could activate the rounds of local protein synthesis that use mRNA and proteins from the autoregulatory loop

Why is the rictor KO mouse useful?

it allows researchers to study the contribution of mTORC2 to consolidation

what is the role of C/EBPβ in the autoregulatory loop?

it targets BDNF for transcription

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.

Inhibiting protein synthesis should ______ effect short-term memory.

not

what is the key independent variable manipulated to determine if a molecule is selectively involved in LTP but not STM?

retention interval

What is the retention interval?

the time between the training that establishes the memory and the test used to retrieve it

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.

true

T/F C/EBPβ is a transcription factor.

true

T/F C/EBPβ is critical to the second wave of protein synthesis

true

T/F C/EBPβ is targeted by CREB for transcription

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 Rapamycin administer prior to training interfered with retention 2 and 7 days later.

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

C/EBPβ's primary role in the autoregulatory loop is to target _____ for transcription

BDNF

_____ it is critical to both the first and second waves of protein synthesis.

BDNF