Week 5 Flashcards
What is a retention interval, and what is usually the retention interval for STM
- The time between the experience that established a memory and the test used to retrieve the memory
- 4 hours
What is the typical research design for testing memory formation/consolidation?
A subject is trained on a task and is tested after the retention interval to see if the memory remains - some pharmacological or genetic manipulation is given before or after the training
When is a memory said to be consolidated?
When it is no longer vulnerable to manipulations that interfere with the transcription and translation processes initiated by its memory event
What is typically used to interfere with translation?
Broadscale inhibitors such as anisomycin - inhibit protein synthesis
What does anisomycin infusion prior to training do to memories?
The memory is only present for ~1 hour, but not longer intervals
What does anisomycin infusion immediately after training do to memories?
The memory is available for 2 days after training
What conclusions can be drawn from Alberini’s experiments?
- STM can be established without new proteins
- Memories lasting more than 3 days require a second wave of protein synthesis that occurs the day after training
- The memory is consolidated into the hippocampus after ~2 days
mRNA and translation machinery are present in _____
The dendritic spine region
What is the local protein synthesis hypothesis?
The initial wave of protein synthesis is the result of engaging the molecules that generate local protein synthesis, creating a memory that lasts for about 2 days
mTOR is responsible for _____
Upregulating the translation machinery in the dendritic spine region
What happens when delaying mTOR activation after training?
No effect on LTM, since mTOR is produced very rapidly after the memory-inducing event
The second wave of protein synthesis can only occur if _____
The initial wave also occurred
mTORC1 is _____ to rapamycin, while mTORC2 is _____ to rapamycin
- sensitive
- insensitive
What do mTORC1 and mTORC2 do?
- mTORC1 regulates signaling cascades that increase local protein synthesis
- mTORC2 regulates processes that contribute to the regulation of actin
What component of mTORC2 was knocked out to study mTORC2’s contribution to memory?
Rictor
mTORC2 only contributes to ____
LTM
What happens to BDNF levels after training?
Levels peak 1 hour and 12 hours after, but don’t return to baseline until 30 hours
Interfering with BDNF function 30 minutes before training _____
Reduced fear conditioning for both 1 day 7 days
Interfering with BDNF function 9 hours after training _____
Reduced fear conditioning only for 7 days
A behavioural experience that initiates local protein synthesis also initiates _____
Genomic signaling
CREB may be critical for
LTM formation
What happens when antisense ODNs are administered to brain memory storage sites prior to training?
There will be less CREB protein available to target transcription of the new mRNA needed to produce the enduring memory
What does C-EBPB do?
Targets BDNF for transcription, and is critical for the second wave of protein synthesis
A behaviour that can produce a LTM rapidly activates ______
Post-translation processes that establish a STM which can endure for a few hours
The activation of the ______ cascade initiates local protein synthesis
BDNF-TrkB-mTOR-TOP
What is the positive feedback loop in the second wave?
BDNF-CREB-C/EBPB-BDNF
What is the interference theory of forgetting?
Forgetting results from learning new information that interferes with/overwrites the old memory traces
What happens to memory during sleep?
Neural activity that results in the reactivation or replay of neuronal ensembles recently established during learning
Drugs that block proteasome ______
Prevent LTM formation
Protein degradation mediated by _____ is critical for establishing enduring memories
the ubiquitin proteasome system
What is UPS’s role in memory formation?
Degrades proteins that repress protein translation and transcription
BDNF leads to the ______ of CREB
phosphorylation
What are the two principles of memory consolidation?
- Enduring memories require that the behavioural experience initiate processes that generate new proteins
- The consolidation processes occur in waves that last 24-48 hours
Shortly after an experience, memory retrieval is supported by _____
An active short-term trace
What did Zola-Morgan & Squire do?
Lesioned the hippocampus of monkeys after learning multiple-object discrimination tasks at different intervals before the surgery
Contextual fear conditioning is dependent on the ____, while cue fear conditioning is dependent on the _____
- Hippocampus
- Amygdala
What did Kim & Fanselow do?
Lesioned the hippocampus of rats after learning multiple-object discrimination tasks at different intervals before the surgery
There is more activation in the _____ with recent memories compared to more distant memories
Medial temporal lobe
What are some challenges with studying consolidation in humans?
- Ethical concerns
- Lack of experimental control
- Can not separate encoding, consolidation, retrieval,
- Encoding may vary between participants
How many new hippocampal neurons die before becoming adult neurons?
-80-90%
What is Lewis’s active trace theory?
Memories exist in either a short-term active state or long-term inactive state
