Memory Consolidation and Engrams

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Questions and Answers

What role do engrams play during the learning process?

  • They stabilize neural connections without change.
  • They activate a specific type of neurotransmitter.
  • They undergo plasticity and are activated. (correct)
  • They inhibit memory recall.

What is the primary function of the FOS promoter in relation to engrams?

  • It regulates the activity of the Tta gene. (correct)
  • It enhances the permanent changes in neurons.
  • It prevents the activation of engram-related pathways.
  • It suppresses the expression of memory genes.

During the memory consolidation process, which structure directly receives output from the hippocampus?

  • Amygdala
  • Prefrontal cortex
  • Medial entorhinal cortex (correct)
  • Cortex

What happens when DOX is removed in the context of labeling engrams?

<p>It allows the identification of active engrams. (B)</p> Signup and view all the answers

What is the role of blue light in the fear expression experiment?

<p>To facilitate the expression of fear in new contexts. (C)</p> Signup and view all the answers

What did the results of Experiment 1 suggest regarding the role of the mPFC in recent memory recall?

<p>The mPFC has no significant role in the recall of recent memories. (A)</p> Signup and view all the answers

What does the c-FOS expression indicate in the context of memory processing?

<p>High c-FOS indicates active neural engagement during memory. (B)</p> Signup and view all the answers

What impact does inhibiting BLA projections to the mPFC have during contextual fear conditioning?

<p>It results in a reduction of c-FOS expression. (B)</p> Signup and view all the answers

What is necessary for the formation of the fear engram in the mPFC?

<p>Input from the entorhinal cortex (C)</p> Signup and view all the answers

Which observation supports the reactivation of engram cells on day 13?

<p>Same cells tagged on Day 1 are active on Day 13 (D)</p> Signup and view all the answers

What happens when the mEC inputs to the mPFC are inhibited on Day 1?

<p>Consolidation of the memory is disrupted (B)</p> Signup and view all the answers

What role does the mPFC play in the fear memory after 12 days of consolidation?

<p>It maintains the fear memory without additional inputs (A)</p> Signup and view all the answers

What did the inhibition of the engram on Day 2 indicate about fear expression?

<p>Little fear expression occurred (C)</p> Signup and view all the answers

What is the role of spine growth in tagged neurons following fear conditioning?

<p>Indication of memory retention and strengthening (B)</p> Signup and view all the answers

Which statement about c-Fos+ neurons is true regarding context-recall?

<p>Most active during context-induced recall after consolidation (C)</p> Signup and view all the answers

How does stimulating tagged c-Fos+ neurons affect memory retrieval?

<p>It enhances retrieval without reliance on mPFC (B)</p> Signup and view all the answers

What happens when the blue light is turned on in the fear expression experiment?

<p>Fear is induced (D)</p> Signup and view all the answers

The hippocampus is primarily involved in the recall of remote memories.

<p>False (B)</p> Signup and view all the answers

What is the effect of inhibiting mEC projections to the mPFC during learning?

<p>It results in a reduction of c-FOS expression in the mPFC during contextual fear conditioning.</p> Signup and view all the answers

The primary regions involved in the generation of memory circuits are the hippocampus, medial entorhinal cortex, ___, and ___.

<p>mPFC, BLA</p> Signup and view all the answers

Match the engram activation elements to their effects:

<p>ChR2 = Activates engrams ArchT = Inhibits engrams DOX = Prevents TRE expression c-FOS = Product of plasticity</p> Signup and view all the answers

During memory consolidation, which pathway is primarily involved when recalling memories after a long term?

<p>Hippocampus to mPFC (B)</p> Signup and view all the answers

Removal of DOX leads to the labeling of inactive engrams.

<p>False (B)</p> Signup and view all the answers

What does high c-FOS expression in the PFC following shock in a specific context indicate?

<p>It indicates that some cells in the PFC are still important at early stages of memory formation.</p> Signup and view all the answers

What is the main finding regarding the involvement of mEC inputs in the formation of the fear engram in the mPFC?

<p>mEC inputs are necessary for engram formation. (C)</p> Signup and view all the answers

The inhibition of mPFC on Day 12 results in a significant recall of fear memory.

<p>False (B)</p> Signup and view all the answers

What occurs in mPFC neurons when the fear engram is consolidated?

<p>Increased spine growth in tagged neurons.</p> Signup and view all the answers

The early consolidation of fear memory occurs in the _______ before it is completely stored in the mPFC.

<p>hippocampus</p> Signup and view all the answers

Match the following days with the relevant findings regarding the fear engram activation:

<p>Day 1 = Cells are tagged and active during CFC. Day 2 = Little fear expression with mPFC inhibition. Day 12 = No fear expression with mPFC inhibition. Day 13 = Reactivation of tagged cells from Day 1.</p> Signup and view all the answers

What is suggested by the presence of active tagged c-Fos+ neurons during context-induced recall?

<p>They indicate consolidation and memory recall. (B)</p> Signup and view all the answers

Inhibition of the mEC to mPFC pathway during CFC enhances the consolidation of fear memory.

<p>False (B)</p> Signup and view all the answers

What technique is used to stimulate the tagged neurons in the engram study?

<p>Optogenetics</p> Signup and view all the answers

What happens to silent engrams in the mPFC during contextual fear conditioning?

<p>They are in a state of inactivity. (A)</p> Signup and view all the answers

The mPFC is involved in the recall of both recent and remote memories.

<p>False (B)</p> Signup and view all the answers

What does c-FOS indicate in the context of memory processing?

<p>c-FOS is a plasticity product that marks active neurons involved in memory processing.</p> Signup and view all the answers

Removal of _______ allows for the labeling and activation of active engrams.

<p>DOX</p> Signup and view all the answers

Match the following memory pathways with their corresponding functions:

<p>Hippocampus = Memory generation/formation Medial entorhinal cortex (MEC) = Contextual information processing mPFC = Long-term memory storage BLA = Emotional memory processing</p> Signup and view all the answers

Which action can inhibit freezing behavior during memory recall?

<p>Flashing yellow light (A)</p> Signup and view all the answers

Engrams are only active during memory recall and not during the learning process.

<p>False (B)</p> Signup and view all the answers

What can be concluded from the inhibition of the mEC to mPFC pathway during CFC?

<p>It disrupts the consolidation of the memory for later recall.</p> Signup and view all the answers

The majority of memory integration occurs in the _______ during consolidation.

<p>mPFC</p> Signup and view all the answers

Which of the following states describes the state of engrams in the mPFC shortly after contextual fear conditioning?

<p>Silent engrams (B)</p> Signup and view all the answers

Flashcards

Engram

A group of active neurons that are changed during learning and later reactivated for memory recall.

Engram activation

Turning on an engram using light and specific proteins (ChR2).

Memory consolidation circuit (generation)

The hippocampus, medial entorhinal cortex, mPFC, and BLA work together to create new memories.

Memory consolidation circuit (recall for recent memory)

The hippocampus and the BLA work together to recall recent memories.

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Memory consolidation circuit (maturation/consolidation)

Memory becomes strong and independent from the hippocampus.

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Memory consolidation circuit (recall for remote memory)

Memory retrieval that avoids the hippocampus; mPFC and BLA are primarily used.

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Hippocampal engram's role in fear

Activating the hippocampal engram triggers fear responses in new situations.

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mPFC role in early memory (inhibition)

Inhibiting the medial entorhinal cortex's (mEC) connection to the mPFC during learning impairs recent memory later.

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Fear EnGram Formation in mPFC

The formation of a fear memory trace (engram) in the medial prefrontal cortex (mPFC) depends on input from the basolateral amygdala (BLA) and medial entorhinal cortex (mEC).

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CFC Engram & Recall

The conditioned fear context (CFC) engram, while initially formed, may not be sufficient on its own for recall; activation of the mEC engram in mPFC is required.

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mEC Input & Engram Formation

The input from the medial entorhinal cortex (mEC) to the mPFC is crucial for the formation of the fear engram.

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mPFC Engram & Fear Expression

The engram in the mPFC is necessary for fear expression and recall.

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mPFC Activation Duration

mPFC neurons are most active during context-induced fear recall 12 days post-conditioning.

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Optogenetic Engram Activation

Stimulating tagged neurons in the mPFC (using optogenetics) directly elicits fear memories even before typical mPFC dependence.

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Early Hippocampal Role

A subset of hippocampal neurons plays a necessary role in early stages of fear conditioning, conveying information to the mEC & BLA.

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mPFC Engram Formation

The formation of a fear memory trace (engram) in the medial prefrontal cortex (mPFC) depends on inputs from the basolateral amygdala (BLA) and medial entorhinal cortex (mEC).

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mEC Input & Engram

The input from the medial entorhinal cortex (mEC) to the mPFC is crucial for the formation of the fear engram.

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mPFC Engram & Memory

The engram in the mPFC is necessary for fear expression and recall.

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Memory Consolidation

During consolidation, silent engrams in the mPFC are being reactivated, strengthening the association between the fear memory and the context it occurred in.

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Silent Engram

An engram that is not activated by natural cues but can be artificially stimulated.

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c-FOS

A protein produced during neuronal plasticity that helps mark active engrams.

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Optogenetics

Using light to control the activity of specific neurons containing light-sensitive proteins.

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What happens during memory consolidation?

Memories become stronger and more permanent as different brain regions interact, transferring information from the hippocampus to the cortex.

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mPFC's role in memory recall

The medial prefrontal cortex (mPFC) plays a crucial role in retrieving memories, especially for remote memories.

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Hippocampus' role in memory

The hippocampus initially forms new memories and then passes them along for long-term storage in other brain areas.

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How does the mPFC engram develop in fear conditioning?

The mPFC engram develops through the transfer of information from the hippocampus and amygdala, particularly through the medial entorhinal cortex (mEC).

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Inhibition of mEC to mPFC pathway during CFC

Blocking the connection from the mEC to the mPFC during fear conditioning disrupts the ability to recall the memory later.

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Why is the mPFC engram important for memory recall?

The mPFC engram is crucial for retrieving the memory, particularly for more distant memories. Activating these neurons can evoke the memory directly without reliance on the hippocampus.

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Study Notes

Engrams

  • Engrams are neuron populations activated during learning.
  • They exhibit enduring cellular changes (plasticity).
  • Engrams are reactivated by the original learning stimulus.

Turning Engrams On/Off

  • Transcription factor c-FOS is a product of plasticity and is induced when neurons are activated to bing to Transcriptional Response Elements (TREs).
  • The expression of the protein ChR2 results in activation while ArcheT inhibits the activation.
  • DOX inhibits TREs, so by removing DOX, active engrams can be labelled.
  • Light can be used to turn engrams on or off. Blue light turns engrams on, while yellow light inhibits them.
  • Removal of DOX labels active engrams.

Memory Consolidation Circuits

  • Engrams form in a circuit from the hippocampus to the medial entorhinal cortex (MEC) to the mPFC and BLA.
  • Memories are consolidated, shifting from the hippocampus to cerebral cortex.
  • Recent memories rely on the hippocampus, while remote memories do not. Consolidation occurs, involving transfer of the engram to cortex for permanent storage.

Recall

  • Recent memory recall involves a hippocampus to BLA pathway.
  • Remote memory recall bypasses the hippocampus using the mPFC and BLA. Early memory relies on the hippocampus, but later memory is stored in the cortex.

Fear Conditioning

  • Hippocampal engrams are sufficient for fear expression.
  • Methods include: context A with DOX, a second fear-conditioning context with DOX, and returning to the first context with light.
  • Light activation of the hippocampus engram leads to fear reactivation in new contexts. The hippocampus is necessary for the initial fear conditioning.

Inactivation of Entorhinal Cortex Projections

  • Injecting a virus with ChR2 into the MEC, inhibiting mEC terminals in the mPFC, while implanting optical fibers in the mPFC impacts recent memory recall.
  • Disrupting the mEC projections to the mPFC affects recall of recent memory, but not remote memory. The mEC pathway is important for forming recent memories.

mPFC Activity

  • Some mPFC cells play a role in early memory, but are not sufficient to support subsequent memories as memories move to the cortex.
  • mPFC activity increases when a context includes shock.
  • Inactivation of BLA projections to mPFC during learning reduces c-FOS in contextual fear-conditioning situations. The BLA is necessary for some early activity in the mPFC.

Engram Sufficiency

  • A subset of c-FOS-positive mPFC neurons experience plasticity during learning depending on inputs from the BLA and mEC to form an engram.
  • Injecting ChR2 to activate engrams in the mEC leads to increased fear reaction.
  • Activation of mPFC engrams is crucial for fear conditioning memory consolidation. The mPFC is critical for the long-term storage of the fear engram

Silent Engrams

  • Engrams can be in a "silent" state initially.
  • Engrams are not activated by natural cues, but only artificially.
  • Engrams in the mPFC are silent after contextual fear conditioning, and can be reactivated by light. Memory reactivation, or reconsolidation, can occur. Repeated activation strengthens these engrams.

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