Lectures 16, 17, 18, & 19 Flashcards
Behavioral experiences that result in a memory also traffic additional WHAT AMPA receptors into the spines?
GluA1
Describe manilow’s experiment that found GluA1s role in LTP?
Genetically engineered GluR1 AMPAs were encoded and given to mice using viruses and after mice were exposed to fear conditioning they tested to see if their brain had evidence of trafficking the engineered receptors
Where were the AMPA GluA1 receptors inserted in the mice in Manilow’s experiment?
Lateral Amygdala
How did Manilow label the GluA1 AMPA receptors?
With a fluorescent molecule
Describe the fear conditioning in manilow’s experiment
Rats were tested for fear of a tone paired with a shock or tested with a fear of a tone unpaired with shock
What did Manilow’s paired vs unpaired mice reveal?
The paired mice had lots of GluA1 AMPA receptors in the spines
What happens if you block AMPA receptor trafficking?
Impairs fear conditioning
What happened to fear conditioning in Manilow’s mice to tone paired shocks at 3 and 24 hours with the dummy AMPA GluA1?
Impaired
Can slices with virally modified receptors sustain LTP in the lateral amygdala?
No
What are two levels that consolidation is studied at?
Cellular synaptic and systems
What is the cellular synaptic level of analysis of consolidation?
- requires an experience induced activation of intracellular signaling cascades resulting in postranslational modifications, modulation of gene expression and the synthesis of gene products
- presumed to draw to a close hours to days after the experience
What is the systems level of analysis of consolidation?
- post-encoding time-dependent reorganization of LTM representation over distributed brain circuits
- last days to months and even years
How does something become an LTM trace?
A STM trace can evolve into a LTM trace
- requires generation of new proteins
- requires changes to the synapse and to the connections between widespread circuits
- consolidation process occurs in multiple waves that involve multiple cell signaling processes
What are the intervals for STM and LTM?
1-2 hours STM
24 hrs LTM
What are the two possible outcomes of an experiment looking at the effects of impairing molecule X on LTM formation?
- effects LTM but not STM
- effects both LTM and STM
How was testing the effect of inhibiting protein synthesis on memory retention done? (What kind of task)
Inhibitory avoidance task
What did the inhibitory avoidance task reveal about waves of consolidation?
Two waves
Does STM require new protein?
No
How long must protein synthesis occur to let LTM form?
24 hours
What does BDNF bind to?
TrkB receptors
What does Rapamycin do?
Inhibits mTOR
What is mTOR?
The complex kinase that is activated by TrkB
What effect does delivering anisomycin 1 day following training have on retention 3 days after? How about 8 days?
- 3 days later no problem
- 8 days its gone
What effect does delivering anisomycin 2 day following training have on retention 3 days after? How about 8 days?
Both are retained, suggests second wave of consolidation occurs after 24 hrs
What happens if you introduce rapamycin in the hippocampus before training?
STM fine, LTM cooked
What happens if you introduce rapamycin after training in the hippocampus?
No effect on consolidation (suggesting allowing local protein synthesis to occur allows not only for the first but also the second wave)
What happens to Rictor KO Mice’s LTM? How about when JPK is introduced as well (an actin polymerization promoter)?
Fried
LTM is sorta saved
What happens to Rictor KO mice? (What does the KO do?)
Actin dynamics and signaling is disrupted
Ratio of f-actin and g-actin is the measure
Rictor KO is ok for STM but LTM is fried
What are mTORs two distinct protein complexes?
MROC1 and mTORC2
Which mTORC is rapamycin sensitive?
MTORC1
What does mTORC1 deactivate?
4E-BP
What does mTORC2 activate?
PCofilin (allows for actin polymerization)
When does BDNF protein peak after fear conditioning?
1 hour and 12 hours after
What happens to fear response at day 1 and day 7 if you impair BDNF function 1 hour after training?
Impairs for both
What does the second peak of BDNF support?
Memory expressed on the 7 day retention test
What is antisense?
RNA that blocks mRNA by forming a kinda DNA structure to stop translation
What did infusing an antisense that blocks CREB translation lead to following a Morris water escape task?
LTM impaired, STM fine
How long was the antisense in the brain?
20 hours after training
Describe the trend of phosphorylated CREB in the hippocampus after training?
Increases levels of pCREB shortly after training for at least 20 hours
Describe the trend of C/EBPbeta mRNA in the hippocampus after training
Only observed 9 hours after training
What did infusing C/EBPbeta antisense into the hippocampus 5 and 24 hours after training reveal?
Impaired retention of the inhibitory avoidance memory
C/EBPbeta protein dependent processes operate at least 24 hours following training
What does inhibiting BDNF signaling do to phosphorylated CREB associated with in avoidance training?
Dramatically reduces it
What happens if you infuse BDNF into the hippocampus 5 hours following training in those with inhibited C/EBPbeta?
Restores memory impairment
This suggests that C/EBPbeta not only targets BDNF but its expression is critical to the second wave of consolidation
Is BDNF signaling a critical player in CREB activation?
Yah and dont forget it
What is C/EBPbeta?
A protein important to LTM formation
A transcription factor that targets the BDNF gene for transcription
