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What is memory consolidation?
The process by which a memory becomes more stable and less vulnerable to disruption over time.
When is a memory trace most vulnerable to disruption?
Immediately after a learning experience.
How does a memory trace change as time passes after learning?
It becomes more stable and more resistant to disruption.
What is the consolidation period?
The time it takes for a memory to become more stable and less vulnerable to disruption.
What does the graph show about resistance to disruption over time?
Resistance increases as time passes after the learning experience (LE).
Why is protein synthesis necessary for a memory to endure?
The learning experience must trigger the production of new proteins that support lasting memory.
What processes are involved in producing new proteins for memory consolidation?
Transcription and translation.
Do memory consolidation processes occur all at once?
No, they occur in multiple waves.
How long can these waves of consolidation be sustained?
For at least 24 hours.
What happens when protein synthesis is inhibited before training?
Short-term memory (STM) remains intact, but consolidation into long-term memory (LTM) is prevented.
What happens when protein synthesis is inhibited shortly after training?
Long-term memory develops but is unstable and decays over time.
What happens when protein synthesis inhibition is delayed until one day after training?
Memory retention lasts longer but eventually declines.
What happens when protein synthesis inhibition is delayed until two days after training?
Memory remains stable, indicating that consolidation endures.
What do these experiments show about when protein synthesis is needed?
Protein synthesis is required during a critical window after learning to stabilize memories.
How does delaying protein synthesis inhibition affect memory retention across these experiments?
Longer delays lead to more lasting retention because consolidation has more time to occur.
What does intact STM but impaired LTM show about protein synthesis?
New protein synthesis is necessary for lasting memory consolidation, but not for short-term retention.
According to active trace theory, what characterizes short-term memory?
It is active, unstable, and quick to decay.
According to active trace theory, what characterizes long-term memory?
It is inactive, stable, and slow to decay.
What happens to a long-term memory trace during retrieval?
It is reactivated, returning to an active and unstable state.
What is the destabilizing function of memory retrieval?
Retrieving a memory makes it labile (changeable) and vulnerable to disruption.
What is the integrative function of memory retrieval?
During retrieval, the brain incorporates new information and re-establishes an updated memory trace, or engram.
What happens to the reactivated memory after it is stabilized again?
It returns to an inactive, stable long-term state.
Why can recalling a memory change it?
Retrieval makes the memory changeable, allowing new information to be incorporated.
What is memory reconsolidation?
The process of stabilizing a memory again after it has been reactivated and destabilized.
How was reconsolidation tested in the fear-conditioning experiment?
Researchers created a fear memory, reactivated it 24 hours later, then administered anisomycin or a control solution and tested STM and LTM.
What does anisomycin do?
It inhibits protein synthesis.
How did inhibiting protein synthesis after reactivation affect fear memory?
It impaired long-term memory but left short-term memory intact.
What does this finding suggest about reactivated memories?
They must undergo protein-dependent reconsolidation to endure.
Are all memories destabilized when retrieved?
No. Stronger and older memories are less likely to destabilize.
What is the prediction error hypothesis of destabilization?
A memory destabilizes when the current experience differs from what the memory predicts.
How was the fear memory initially created in the prediction error experiment?
A tone was paired with a shock delivered after a 30-second interval.
How did researchers create a prediction error 24 hours later?
They delivered the shock after 10 seconds instead of the expected 30 seconds.
Which shock timing matched the existing memory?
The shock delivered after 30 seconds.
What treatment did the prediction error group receive?
Anisomycin to inhibit protein synthesis.
What happened when fear memory was tested 24 hours after prediction error and anisomycin treatment?
The animals showed less freezing, indicating reduced fear memory.
What does the prediction error experiment suggest?
Prediction error destabilizes the memory, making it vulnerable to disruption when protein synthesis needed for reconsolidation is blocked.
What is an engram?
The physical representation of a memory in the brain.
What makes up an engram?
Populations of neurons whose connections are modified through learning.
How do engram neurons contribute to memory retrieval?
Reactivation of these neuronal populations contributes to recalling the memory.
What four findings identify neurons as engram cells?
They are activated during learning, some reactivate during retrieval, directly activating them produces the memory-related behavior, and disrupting them prevents it.
What does overlap between neurons active during learning and retrieval show?
Some of the same neurons participate in both forming and retrieving the memory.
What does directly activating engram cells demonstrate?
Their activation is sufficient to produce the memory-related behavior.
What does disrupting engram cells demonstrate?
Their activity is necessary for the memory-related behavior.
What is a TetTag mouse used for?
Labeling neurons active during a specific time window so they can be identified later.
What is the role of Fos in the TetTag system?
It is activated in recently active neurons.
What is the role of tTA in the TetTag system?
It controls expression of the reporter gene, LAC.
What is the role of doxycycline (DOX) in the TetTag system?
It determines when labeling can occur.
What happens when DOX is present?
No new neurons are labeled.
What happens when DOX is absent?
Active neurons express LAC and become labeled.
What happens when DOX is restored?
New labeling stops, but previously labeled neurons remain identifiable.
How does fear conditioning in TetTag mice help identify candidate engram cells?
It allows researchers to identify neurons active during both learning and memory retrieval.
What happens during fear conditioning when DOX is absent?
Active neurons are labeled with LacZ.
What identifies reactivated neurons during memory retrieval when DOX is present?
Expression of ZIF, an immediate early gene.
What does expression of both LacZ and ZIF indicate?
The neuron was active during both learning and retrieval.
How did fear-conditioned mice behave compared with controls?
They showed greater freezing.
What happens during the “build” step of creating a viral vector?
A gene of interest is combined with a promoter that controls its expression.
What happens during the “package” step?
The genetic material is inserted into a modified virus.
What are viral vectors used for in neuroscience?
Delivering specific genes into neurons so researchers can control or monitor neuronal activity.
What happens during the “deliver” step?
The virus is injected into the brain, where infected neurons can express the new gene.
What is optogenetics?
A technique that uses light-sensitive proteins to activate or inhibit genetically modified neurons.
What do opsin genes encode?
Light-sensitive proteins that regulate the flow of ions across neuronal membranes.
How does light control neurons in optogenetics?
Light activates opsin proteins expressed in neuronal membranes, changing ion flow to excite or inhibit the neurons.
Which opsin and light color are used to excite neurons in these notes?
Channelrhodopsin, activated by blue light.
Which opsin and light color are used to inhibit neurons in these notes?
Halorhodopsin, activated by green light.
How does optogenetics help researchers study memory?
It tests whether activating or inhibiting specific neurons influences memory.
What question does activating engram cells test?
Whether activating neurons recruited during learning can trigger memory retrieval.
What happens to freezing when blue light is ON?
Freezing increases as the tagged neurons are activated.
What happens to freezing when blue light is OFF?
freezing is minimal
What does increased freezing during engram cell activation demonstrate?
Activating a specific neuronal population can trigger a learned fear response.
What does optogenetic activation show about the sufficiency of engram cells?
Reactivating these cells can be sufficient to produce memory-related behavior.
What question does inhibiting engram cells test?
Whether neurons recruited during learning are necessary for memory retrieval.
How do researchers test whether engram cells are necessary?
They label neurons activated during fear conditioning, then inhibit those neurons during memory retrieval.
What happens when the light is ON and engram cells are inhibited?
Freezing decreases.
What happens when the light is turned OFF and engram cells are inhibited?
Freezing returns.
What does the context-specific effect of inhibition suggest?
The inhibited neurons contribute to the fear memory associated with a particular context.
What does inhibiting engram cells demonstrate?
Neuronal populations recruited during learning are necessary for the normal expression of that memory.