Chapter 10 - Memory Formation: Early Stages
In a CA1KO mouse, GluN1 subunits are absent in the (*CA1 region | dentate gyrus*)
(*T/F*) In a CA1KO mouse, GluN1 subunits are absent in the CA1 region
In a CA1KO mouse, LTP cannot be induced in (*CA1 region | dentate gyrus*) slices
(*T/F*) In a CA1KO mouse, LTP cannot be induced in CA1 in slices
Describe how the radial arm maze can be used to study both working and reference memory.
(1) Working memory requires the animal to remember which arm was already visited; and (2) Reference memory requires the animal to discriminate between the arms always baited and the arms never baited.
(*T/F*) Early in development the ratio of GluN1/GluN2B to GluN1/GluN2A containing NMDA receptors favors the GluN1/GluN2A complex
*FALSE*
(*T/F*) NMDA receptors composed of the GluN1/GluN2A subunits remain open longer than those composed of GluN1/GluN2B subunits
*FALSE*
(*T/F*) GluN1 subunits are absent in the dentate gyrus
*FALSE* GluN1 subunits are absent in the CA1 region. *Are we talking just about the CA1KO?*
(*T/F*) In the radial methodology maze task, rats make both types of errors equally
*FALSE* In the radial methodology maze task, rats rarely make reference or working memory errors
(*T/F*) In the radial methodology maze task, rats make reference memory errors but not working memory errors
*FALSE* In the radial methodology maze task, rats rarely make reference or working memory errors
(*T/F*) In the radial methodology maze task, rats make working memory errors but not reference memory errors
*FALSE* In the radial methodology maze task, rats rarely make reference or working memory errors
(*T/F*) LTP cannot be induced in the dentate gyrus
*FALSE* LTP cannot be induced in CA1 in slices
(*T/F*) NMDA receptors are activated by calcium
*FALSE* NMDA receptor channels allow calcium to enter the cell
Every functional NMDA receptor has _______ subunits.
*GluN1* - remember Tonegawa made CA1KO mice that lacked GluN1 subunit.
Roberto Malinow used two strategies to prove that fear conditioning drives AMPA receptors into amygdala neuron synapses. What were they?
1. In one case he created *identifiable GluA1 receptors* and infected neurons in the *amygdala* with these receptors to show that fear conditioning would drive them into synapses. 2. He created *dummy receptors* to compete with endogenous receptors and showed that their presence impaired fear conditioning.
In Malinow's AMPA receptor trafficking experiment, what was the difference between the rats in the paired condition (tone with fear) and the rats in the unpaired (tone only) condition?
After the training, rats in the paired condition (tone with fear) had more *GluA1* receptors trafficked into the plasma membrane of amygdala than rats in the unpaired (tone only) condition.
What are ampakines?
Ampakines bind to a site on AMPA receptors and *increase the duration of the channel opening* when glutamate also binds to the receptor. (not an agonist or antagonist - PAM?)
What is cerebral spinal fluid?
Cerebral spinal fluid is the substance that covers the brain and spinal cord and cushions them against impact. It also provides them with oxygen and nutrients and removes waste products.
Describe the composition of the NMDA receptor.
Each receptor has four subunits, and they are some combination of the two classes GluN1 and GluN2.
(*T/F*) AMPA receptors are needed only for memory acquisition, but NMDA receptors are required for both acquisition and retrieval.
FALSE
(*T/F*) AMPA receptors have been shown to be important in the induction but not the expression of LTP
FALSE
(*T/F*) Early in development the ratio of GluN1/GluN2B to GluN1/GluN2A containing NMDA receptors favors the GluN1/Glun2A complex
FALSE
(*T/F*) GluN1 subunits are not required to form functional NMDA receptors.
FALSE
(*T/F*) NMDA composed of the GluN1/GluN2A subunits remain open longer than those composed of GluN1/GluN2B subunits.
FALSE
(*T/F*) NMDA receptors are activated by calcium
FALSE
(*T/F*) NMDA receptors have been shown to be important in both the induction and expression of LTP
FALSE
(*T/F*) Remembering the plot of a book you read a few months ago is an example of working memory.
FALSE
(*T/F*) The CA1KO mouse was able to display LTP in the CA1 regions but not in the dentate gyrus.
FALSE
(*T/F*) Working memory cannot be studied in animals, because they cannot communicate what problems they are trying to solve.
FALSE
What genetic engineering methods were used to study the role of NMDA receptors in memory formation?
Genetic engineering methods have been used to selectively delete (*CA1KO*) or overexpress (*Doogie GluN2B*) one of the NMDA subunits in mice.
GluA1 KO mice display (*short lasting | long-lasting*) LTP
GluA1 KO mice display long-lasting LTP
GluA1 KO mice have impaired (*reference | working*) memory
GluA1 KO mice have impaired working memory
Which NMDA receptor subunit is required to form a functional receptor?
GluN1
The Doogie mouse is genetically engineered to overexpress (*GluN2A | GluN2B | GluN2C | GluN1*) subunits.
GluN2B subunits
When _______ subunits dominate, it is easier to induce LTP than when _______ subunits dominate.
GluN2B; GluN2A
What was Richard Morris' experiment? What was he trying to study?
He implanted a cannula to deliver the NMDA receptor antagonist APV into the ventricular system of a rat's brain where it would enter the cerebral spinal fluid. He was testing the hypothesis that the initial formation of a memory trace depends on the activation of NMDA receptors.
If there are more GluN1-GluN2B receptor complexes present in a tissue sample than GluN1-GluN2A receptor complexes, what was the likely age of the mouse?
It is likely a sample from a very young animal, because with maturation, the composition of NMDA receptors changes, and GluN1-GluN2B receptor complexes are replaced by GluN1-GluN2A receptor complexes.
Provide an example of working memory.
Memorizing a list of groceries and discarding it from your memory
Richard Morris was the first researcher to directly investigate the role of _______ on memory formation.
NMDA receptors
(*T/F*) A behavioral experience that produces a memory is likely to result in more phosphorylated cofilin and more autophosphorylated CaMKII.
TRUE
(*T/F*) AMPA receptors have been shown to be important in both the induction and expression of LTP
TRUE
(*T/F*) Ampakines are neither agonists nor antagonists.
TRUE
(*T/F*) GluN1 subunits are absent in the CA1 region
TRUE
(*T/F*) In the radial methodology maze task, rats rarely make reference or working memory errors
TRUE
(*T/F*) NMDA receptor channels allow calcium to enter the cell
TRUE
(*T/F*) NMDA receptors have been shown to be important in the induction but not the expression of LTP
TRUE
(*T/F*) The formation of a memory trace begins when a behavioral experience activates a neuronal ensemble that represents the experience.
TRUE
(*T/F*) To influence NMDA function, Morris implanted a cannula into a cerebral ventricle
TRUE
(*T/F*) To influence NMDA function, Morris infused APV into the brain
TRUE
(*T/F*) Tonegawa used genetically engineered mice in the first study investigating the role of NMDA receptors in memory formation.
TRUE
(*T/F*) Memory formation can take place without the contribution of NMDA receptors.
TRUE (*How?* 10B.11)
(*T/F*) To influence NMDA function, Morris tested rats in the space-learning swim task
TRUE (*after first dosing them with APV - NMDA antagonist - through ventricle system*)
(*T/F*) An enduring LTP can be established independent of any contribution from GluA1 receptors, but it requires GluA2 AMPA receptors.
TRUE (*explain this - because GluA2 substituted for GluA1?*)
(*T/F*) LTP cannot be induced in CA1 in slices
TRUE *In CA1KO?*
(*T/F*) To influence NMDA function, Morris used a pharmacological approach
TRUE Implanted candula into ventrical and hooked it to osmotic mini-pump that would diffuse APV (NMDA antagonist) over many hours, then did LTP experiment - could not sustain LTP
What is the Doogie mouse?
The Doogie mouse was genetically engineered to *overexpress GluN2B* subunits in the *cortex and the hippocampus*. Doogie mice displayed *enhanced LTP*, *enhanced memory formation*, and *superior performance in behavioral tests*.
What is a reasonable conclusion that can be made based on Saucier and Cain's observations? Did they disprove the role of NMDA receptors as crucial to memory formation?
The brain has redundant mechanisms that might substitute for each other and there are such mechanisms that can produce memories when NMDA receptors are not functional. No, it is possible that functioning NMDA receptors normally contribute to creating place memories. (p. 183-184)
Explain why it is possible to induce LTP in the dentate gyrus of the CA1KO mouse, but not in the CA1 region of the brain. How does this affect the mouse's performance in the place-learning task?
The genetically engineered deletion *of GluN1* targeted the NMDA receptors in CA1 pyramidal cell and not the dentate gyrus. Its memory was impaired and it could not learn to swim to the platform.
What evidence suggest that actin regulation is critical for memory formation?
The training procedure used to produce object-place recognition memory increases phosphorylated cofilin. *what training procedure?*
Defend or refute the following statement citing experimental evidence to support your argument: "GluA1 subunits are required for the initial early phase of LTP but not for the later developing phase."
This is true because, when stimulated by a stronger theta-burst protocol, slices from the GluA1 of KO mice display an enduring LTP equivalent to control mice, even though they do not display the early, short-lasting phase. *See Figure 10.15* This tested working memory (revisiting arm where they'd already taken pellet) vs reference memory (visiting arms that never had pellet). Did not impact reference.
Is it reasonable to expect that behavioral experiences that produce memories would engage the LIMK signaling pathway?
Yes, because actin polymerization is necessary for synaptic changes in LTP
As the nervous system develops, would you expect to see any changes in LTP induction? Explain why or why not.
Yes. because GluN2B subunits are replaced by GluN2A subunits, and they have different channel-opening properties. NMDA receptor complexes that contain *GluN2B subunits remain open longer* than those that contain GluN2A subunits and presumably permit more Ca2+ to enter the spine. When the GluN2B subunits dominate, it is easier to induce LTP than when GluN2A subunits dominate.
Fear conditioning increased the presence of phosphorylated CaMKII in dendritic spines. This result means that the conditioning experience ________ this __________.
activated; kinase
The _______ of _______ may be critical for the rapid formation of a memory but other processes can compensate for this contribution when multiple training trials occur.
autophosphorylation; CaMKII
The formation of a memory trace begins when a _______ activates a set of _____________ neurons.
behavioral experience; weakly connected
Malinow's experiments showed that the memory for the fear experience, as measured by the rat's _______ depends on trafficking AMPA receptors with ________ into the membrane.
freezing response; functional GluA1 subunits
When glutamate and ampakines both bind to the AMPA receptor the channel stays open _________.
longer
In the radial arm maze methodology, if a rat revisits an arm that was never baited, it is making a/an ____________ error.
reference memory
_______ of AMPA and NMDA receptors determines whether or not rodents are successful on working memory and reference memory tasks.
subunit composition *think about what NMDA units and AMPA units needed for working vs reference*
Tonegawa deleted _______ in _______ in the CA1 field of the mouse hippocampus.
the GluN1 subunit; pyramidal cells
As the nervous system develops, _______ subunits tend to be replaced by _______ subunits.
the GluN2B; GluN2A
Ampakines cross _______ and bind to a site on the ______ receptor.
the blood-brain barrier; AMPA
In the radial arm maze methodology, if a rat revisits an arm, it is making a _______ error.
working memory
