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What role do AMPARs play in memory processes?

  • They primarily contribute to sensory perception.
  • They are involved only in the acquisition of memories.
  • They facilitate the retrieval of memories but not the acquisition.
  • They are essential for both memory acquisition and retrieval. (correct)

    • What happens when NMDARs are blocked during learning?

  • Learning is enhanced through alternative pathways.
  • There may still be learning due to other mechanisms. (correct)
  • Memory formation is completely eliminated.
  • Only sensory deficits are observed.

    • How does fear conditioning affect AMPAR trafficking?

  • It has no impact on AMPAR levels in the brain.
  • It prevents AMPARs from being inserted into the synapse.
  • It promotes the trafficking of GluA1-containing AMPARs into spines. (correct)
  • It selectively affects NMDAR functioning.

    • What effect does blocking AMPAR trafficking have on fear memory?

    <p>It decreases fear memory and LTP.</p> Signup and view all the answers

    What is the role of AMPAkines in cognitive processes?

    <p>They enhance the rate of fear conditioning.</p> Signup and view all the answers

    Which statement is true regarding NMDARs in memory processes?

    <p>They are necessary for memory acquisition but not for retrieval.</p> Signup and view all the answers

    What is a potential consequence of using a nonfunctional version of the GluA1 subunit in an experiment?

    <p>Weakened fear memory due to interference.</p> Signup and view all the answers

    What mechanisms may support memory in the absence of NMDARs?

    <p>Redundant mechanisms, including other Ca2+ sources.</p> Signup and view all the answers

    What is the significance of the phrase 'cells that fire together wire together' in memory formation?

    <p>It highlights the connection between neurons in response to shared experiences.</p> Signup and view all the answers

    Which receptors are specifically mentioned as crucial for long-term potentiation (LTP) and memory formation?

    <p>NMDA and AMPA receptors</p> Signup and view all the answers

    What effect does the overexpression of GluN2B subunits in NMDA receptors have on learning?

    <p>It enhances the induction of LTP and improves memory.</p> Signup and view all the answers

    What molecule is essential for the generation of LTP and memory formation according to pharmacological studies?

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

    Which subunit is present in all functional NMDA receptors?

    <p>GluN1</p> Signup and view all the answers

    What experimental approach was used to study the necessity of NMDARs for memory formation?

    <p>Pharmacological manipulation with NMDAR antagonists.</p> Signup and view all the answers

    What does the term 'memory trace' refer to in neuronal terms?

    <p>The changes in connectivity between neurons after an experience.</p> Signup and view all the answers

    What can be concluded about CA1 knockout mice from the genetic studies discussed?

    <p>They exhibit normal learning abilities in visible platform tasks.</p> Signup and view all the answers

    Which of the following is NOT a contributor to early memory formation as mentioned?

    <p>Serotonin receptors</p> Signup and view all the answers

    What is indicated by the findings regarding the GluN2B subunits of NMDARs?

    <p>Their presence enhances the effectiveness of learning.</p> Signup and view all the answers

    What type of memory disruption occurs when a memory is stored but cannot be accessed?

    <p>Retrieval failure</p> Signup and view all the answers

    In the Inhibitory Avoidance conditioning test, what is measured to assess learning?

    <p>Time taken to cross to the dark side</p> Signup and view all the answers

    What effect occurs when performance measures are at their maximum in a behavioral test?

    <p>Ceiling effect</p> Signup and view all the answers

    Which type of fear conditioning involves an auditory cue predicting an electrical shock?

    <p>Auditory-cue fear conditioning</p> Signup and view all the answers

    In the Water-escape task, what indicates that a rodent has learned the location of the hidden platform?

    <p>Decreased escape latency</p> Signup and view all the answers

    What behavior is expected during testing in the fear conditioning procedure?

    <p>Freezing behavior</p> Signup and view all the answers

    What is the primary goal of the Recognition Memory tasks in animal models?

    <p>To assess recognition capacity</p> Signup and view all the answers

    Which type of transgenic mice allows for precise modification of a gene in specific cells?

    <p>Conditional knockout</p> Signup and view all the answers

    Which receptors are necessary for memory acquisition according to the findings?

    <p>NMDARs and AMPARs</p> Signup and view all the answers

    What does an increased response latency in the Inhibitory Avoidance task suggest?

    <p>Stronger memory trace</p> Signup and view all the answers

    What behavioral task showed that CaMKII knockout mice are deficient in learning?

    <p>Place-learning water-escape task</p> Signup and view all the answers

    Which of the following is NOT a potential manipulation to study memory processes in animal models?

    <p>Replacing the animal with a human</p> Signup and view all the answers

    What effect does the T286A mutation in CaMKII have on memory formation?

    <p>Causes LTP deficiency</p> Signup and view all the answers

    What is a common outcome of the floor effect in a behavioral test?

    <p>Performance measures are too low</p> Signup and view all the answers

    Which drug was administered to assess the role of AMPARs in memory retrieval?

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

    In the fear conditioning procedure, what is the unconditioned stimulus (US)?

    <p>Electrical shock</p> Signup and view all the answers

    What happens to CaMKII when it is autophosphorylated at the Thr286 residue?

    <p>It becomes autonomously active</p> Signup and view all the answers

    What is the primary aim of the behavioral tests for studying memory in animal models?

    <p>To understand learning and memory formation</p> Signup and view all the answers

    Which molecule is crucial for the phosphorylation process that leads to increased actin polymerization?

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

    How do T286A mice perform on tasks after multiple training trials?

    <p>They learn associations with more trials</p> Signup and view all the answers

    What impact does pharmacological blockade of CaMKII phosphorylation have on fear conditioning?

    <p>It blocks acquisition of fear conditioning</p> Signup and view all the answers

    Which behavior is NOT associated with CaMKII knockout mice based on experiment findings?

    <p>Internet surfing tasks</p> Signup and view all the answers

    What is the main role of CaMKII in the context of memory formation?

    <p>Generating and stabilizing LTP</p> Signup and view all the answers

    What is the destabilization function in memory retrieval?

    <p>It makes a retrieved memory vulnerable to disruption.</p> Signup and view all the answers

    What did Cerletti and Bini observe in patients undergoing electroconvulsive shock therapy (ECS)?

    <p>They had impaired memories following the treatment.</p> Signup and view all the answers

    In the fear-conditioning experiment by Lewis, what was the effect of electroconvulsive shock (ECS) when the fear memory was reactivated?

    <p>It caused disruption of the reactivated fear memory.</p> Signup and view all the answers

    What can be inferred about the integrative function of memory retrieval?

    <p>It leads to the formation of a new engram with prior and new information.</p> Signup and view all the answers

    What theory explains the vulnerability of reactivated memories to disruption?

    <p>Reactivated memories enter a labile state due to the retrieval process.</p> Signup and view all the answers

    What is the role of K252a in BDNF signaling?

    <p>It acts as a TrkB receptor antagonist.</p> Signup and view all the answers

    What impact does blocking BDNF function 30 minutes before training have on learning?

    <p>It impairs both day 1 and day 7 retention.</p> Signup and view all the answers

    What characterizes the second wave of BDNF signaling?

    <p>It relies on the activation of transcription factors leading to new mRNA synthesis.</p> Signup and view all the answers

    What consequence occurs when CREB is inhibited before training?

    <p>It prevents the transcription of new mRNAs essential for memory.</p> Signup and view all the answers

    What is the relationship between C/EBP-beta and long-term memory?

    <p>C/EBP-beta is responsible for initiating the second peak of BDNF expression.</p> Signup and view all the answers

    What happens when BDNF is infused 12 hours post-training?

    <p>It has no effect on learning retention.</p> Signup and view all the answers

    How does inhibiting BDNF affect phosphorylated CREB levels?

    <p>It decreases the levels of phosphorylated CREB.</p> Signup and view all the answers

    What initiates the signaling pathway responsible for phosphorylating CREB?

    <p>The BDNF/TrkB/mTOR pathway.</p> Signup and view all the answers

    Study Notes

    LTP and Learning

    • LTP experiments are artificial, inducing changes via low-intensity, high-frequency electrical events bypassing sensory input.
    • Hippocampal slices model the brain, but are one step removed from the actual brain.
    • Long-term changes at individual synapses, associated with LTP, don't fully represent memory.
    • Memories are produced by organisms interacting with their environment.
    • Observing behavior to understand learning and memory requires training and testing.
    • Behavioral changes are influenced by more than just learning and memory—many processes impact behavior.
    • Experimental methods must account for other factors influencing behavior changes.

    Memory Processes

    • Memory traces (engrams) represent the physical basis of memory.
    • Mouse models are used to train mice to navigate mazes, assess post-training time to complete the task, lesion a brain area, then test.

    Types of Memory

    • Short-term memory (STM) rapidly decays, while long-term memory (LTM) decays more slowly and is inactive.
    • STM traces are active; LTM traces are inactive.
    • Memory traces can transition from active to inactive states.

    Memory Consolidation

    • Memory consolidation is the process of stabilizing memory traces, making them resistant to disruption.
    • Key factors, possibly, are CREB phosphorylation, protein degradation, and mTOR activation
    • Three main principles are needed: Translation and transcription of the initial behavioral experience
    • Consolidation processes can continue for at least 24 hours; this is regulated by autoregulatory positive feedback loops.
    • Variables of memory, that can be manipulated
    • Pharmacological or genetic manipulation can influence molecules considered to be important to memory.
    • The retention interval is the time between training and testing.

    Memory Tasks

    • Recognition memory tasks test for recognition of novel objects. Rats typically spend more time exploring a novel object.
    • Inhibitory avoidance task. Procedure: rodents are stimulated. Expected results: increased latency (a longer time taken) to cross to the other side of the box if they had learned.
    • Fear conditioning. Procedure: rodents in a box are stimulated with a tone or a shock. Expected results): increased freezing behavior with a shock. Thus, more freezing behavior demonstrated the strengthening of the memory trace.
    • Water escape task. Procedure: rats placed in a pool of water. Rats need to locate a hidden platform. Expected results: Decreased latency(faster time) if they had learned..

    Transgenic Mice

    • Transgenic mice are modified to have a specific gene for Cre recombinase attached to the promoter region. Other genes with interest are surrounded by loxP sites, the Cre recombinase interacts with loxP sites and cuts out the target gene.
    • A full knockout is where a specific gene has been removed entirely.
    • Conditional knockdown is where a specific gene is removed in specific cells or at specific times in the animal.

    Optogenetics

    • Optogenetics uses light to control neurons with high temporal precision.
    • Opsins (proteins) respond to light. Channels (e.g. channelrhodopsin, halorhodopsin) change the ion permeability, activating or inhibiting neurons
    • Genetic engineering creates designer receptors (DREADDs) activated only by particular synthetic drugs.
    • Viral vectors allow delivery of these receptors into specific neurons

    Neurotransmitters and Memory Formation

    • Sensory input creates connections between neurons; the strength of these connections changes from experience.
    • Cell assemblies (neurons) that fire together wire together. This is the basis of memory.
    • Multiple neurotransmitters are involved (e.g., glutamate binding to AMPA and NMDA receptors).

    NMDARs and Memory

    • Functional NMDA receptors have GluN1, GluN2A, and GluN2B subunits—all functional receptors have GluN1, and some have GluN2A and/or GluN2B subunits.
    • NMDARs are necessary for generating LTP, a mechanism believed to be necessary for some forms of memory.

    Consolidation Principles - Time-Dependence

    • Consolidation is a process that stabilizes memories, making them resistant to disruption.
    • Short-term memories may not require new protein synthesis.
    • Long-term memories usually depend on new protein synthesis (in multiple waves).
    • Consolidation involves both local protein synthesis and genomic signaling (transcription and translation).
    • This includes the BDNF-TrkB-mTOR pathway for the first wave of protein synthesis , allowing for memory retention for 2 days and C/EBP for the second, lasting up to 7 days

    Epinephrine and Memory

    • Epinephrine can modulate memory by influencing glucose release from the liver.
    • Adrenergic receptors (ARs) on the liver mediate this effect.
    • Arousal increases epinephrine release, which can enhance memory consolidation by providing energy for protein synthesis.
    • Age-related memory declines might be linked to reduced liver responsiveness to epinephrine, leading to lower glucose availability to support brain function.

    Freezing Response in Arousal and Memory

    • The freezing response, which represents an animal's innate reaction to a perceived threat or danger, can be connected to memory modulation.
    • Pharmacological blockade of the CaMKII pathway can inhibit memory acquisition in both contextual and auditory-cued fear conditioning.
    • Factors like the retention interval (time between training and testing) affect memory consolidation. Short-term memories might only persist a few hours, while long-term memories last for days or weeks.

    Other Key Concepts

    • Memory for a taste aversion is mediated by the insular cortex.
    • Injecting ZIP into the insular cortex can erase taste aversion memory.
    • PKM-zeta can prevent endocytosis of AMPA receptors, thereby preserving memories.
    • Blocking NMDA receptors can affect memory consolidation and/or retrieval depending on the timing of the block.

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