Learning and Memory Exam 3

The mTORC2 complex regulates processes that contribute to the regulation of __________.

actin

C/EBPβ is critical to the ________ wave of protein synthesis

second

Memory traces can differ on at least three dimensions: __________

state, duration, and vulnerability to disruption

Memory consolidation can depend on multiple waves of _________ and _______

transcription and translation

A memory may be considered consolidated when it is no longer vulnerable to ___________ and __________ inhibitors.

transcription, translation

(T/F) If the first wave of BDNF protein synthesis is blocked retention at both the 1- and 7-day interval will be impaired.

true

The BDNF-TrkB pathway is critical to _______ waves of protein synthesis.

two

To determine the role of a molecule in memory consolidation the experiment should use at least _______ retention intervals. what are they?

two short interval (1-2 hours) longer interval (around 24 hours)

Fear Learning Induces _______ Receptor Trafficking

AMPA

_____ it is critical to both the first and second waves of protein synthesis.

BDNF

C/EBPβ is targeted by _______ for transcription

CREB

stereotaxic surgery

brain surgery using a stereotaxic apparatus to position an electrode or cannula in a specified position of the brain

If mTOR is inhibited by rapamycin 5 minutes after avoidance conditioning, what will happen? Why?

memory retention would not be impaired at any retention interval local protein synthesis actions don't last/are not used longer than 5 minutes

The existence of a ___________ is inferred when the training experience influences __________ Thus, _____________ can be thought of as the window to the memory trace

memory trace behavior test behavior

When trying to assess the effect of a gene or drug on short-term memory, the retention interval is __________. for long term memory, the retention interval is _________.

4 hours or less about 24 hours

Memories can be disrupted for two reasons: Is the amnesia permanent or temporary?

Storage failure: amnesia is permanent (cannot be recovered) Retrieval failure: amnesia is temporary

When the response measure is at its maximum, researchers should be wary of the __________.

ceiling effect

The ECS methodology ________ advance our understanding of memory because it was already known that newly acquired memories are vulnerable to disruption

did not

(T/F) Blocking CREB translation impairs STM.

false

The _______ is varied to test for STM or LTM

retention interval

Fear Learning Induces AMPA Receptor Trafficking (Malinow) used _______ strategies to prove that ______ drives AMPA receptors into amygdala neuron synapses. part 1: Genetically engineered ______ AMPAs that fluoresced a green fluorescent protein when brought to the membrane surface Used a ________ system to deliver these receptors into neurons located in the amygdala Exposed the mice to a fear conditioning experience of _______ and _______ tone & shock Association learning: _________ group No association learning: _______ group result = After the training, rats in the paired condition had _______ GluA1 receptors in the plasma membrane than rats in the unpaired condition.

two, fear conditioning GluA1 viral vector paired and unpaired paired, unpaired more

Consolidation refers to the process of converting _______ memories in to ______ ones.

weak strong

What is the evidence that the UPS is involved in memory consolidation?

1) Behavioral experiences that induce lasting memories increase ubiquitination and proteasome activity 2) drugs that block proteasome activity also prevent long-term memory formation.

The TOP protein ______ normally interferes with the initiation of local protein synthesis

4E-BP

NMDA receptors and memory formation: GluN1 deletion (Tonegawa) Main idea: They deleted the gene for this receptor in the ______ region in mice and found that it ________ performance in the ________ task.

CA1 impaired hidden platform

Electroconvulsive Shock _________ (1949) was the first person to use ECS to experimentally induce amnesia in animals. He found that when ECS was administered within ________ after the training it produced _______ But it did not produce ________ when given an hour or so after training. Thus, as the memory aged it became resistant to disruption, suggesting that the memory requires time to _________

Carl Duncan a minute, amnesia amnesia consolidate

Some methods for altering brain function: genetic engineering ______ is injected into a pronucleus from a _________ This _____ can be designed to ______, ________ or _______ particular gene or it can _______ for another gene more ________ than applying drugs in manipulating molecules involved in memory

DNA, fertilized egg DNA, replace, knock-in, or knockout, substitute precise

To study memory, neurobiologists can: •_______ a particular region of the brain •Inject ________ into the brain that are designed to influence some aspect of neural function •Modify the ______ to increase or decrease the expression of some molecule •Increase or decrease the activity of certain ______ Any of these treatments could influence behavior by affecting some component process other than ________. Thus, this possibility must be ruled out by other ______ experiments

Damage Drugs DNA cells memory control

DREADDS what does it stand for? takes _______ time to activate or inhibit neurons than optogenetics. DREADDS operate on a much ______ time frame than optogenetics both DREADDs and optogenetic methods depend on ________

Designer receptor exclusively activated by designer drug more, longer viral vector delivery systems

How might sleep contribute to consolidation. (hint: replay)

During sleep intrinsic neural processes might reactive the additional rounds of local proteins synthesis that use the mRNA and proteins provided by the autoregulatory loop.

NMDA receptors and memory formation: GluN1 deletion (Tonegawa) Tonegawa's group deleted the ________ in ______ in __________ LTP could not be induced in the ______ , but could be induced in the _______ These regions are located in the ________

GluN1 subunit, CA1 pyramidal cells CA1 region, dentate gyrus hippocampus

Working and Reference Memory Depend on ___________

Glutamate Receptors

How did John Guzowski examine the importance of CREB for memory retention?

He used an antisense to CREB and tested rats at both a short and long retention interval.

What is the evidence that proteins translated in response to the mTORC1 signaling are important for the consolidation of long-term memory but not for producing a short-term memory?

Inhibitory avoidance procedure revealed that rapamycin selectively impaired performance when the retention interval was 24 hours but not when it was only 3 hours.

Why is the rictor KO mouse useful? The study found that: mTORC2 contributes to _________ but does not influence ________

It allows researchers to study the contribution of mTORC2 to consolidation. long term memory, short term memory

What is the learning-performance distinction?

It recognizes the challenge the researcher has in being sure that the treatment exerted its effect by its influence on the memory component rather than some other component process that could also influence performance.

Why what is the role of C/EBPβ in the autoregulatory loop?

It targets BNDF for transcription.

CREB deletion impairs _______

LTM

CREB overexpression can improve ________ under certain conditions.

LTM

Preventing Autophosphorylation of CaMKII Impairs _______

Learning

Time limited retrograde amnesia is more likely to affect _______ when produced by a concussion, it likely affects memories in the ______

Long term memory active state

Behavior Is the Window to the ___________

Memory Trace

What is the importance of the two distinct peak levels of BDNF expression?

One peak of BDNF occurs 1 hour after training and is critical for fear response memory on 1-day and 7-day retention intervals. The second occurs 12 hours later and supports the memory on the 7-day retention test.

NMDA Receptors and Memory Formation: GluN2B Overexpression (Tsien) Which tasks were enhanced in GluN2B overexpression mice? (4)

Place learning in morris water maze Cued fear conditioning Novel object learning Enhanced contextual fear learning

An organism's behavioral response is determined by the interaction of many different component processes. Thus, before one can conclude that some biological manipulation influenced some aspect of memory, one has to be sure that it did not influence some other component that influences behavior. Examples of this? (motivational, emotional, motor, etc)

SAP - What the subject experiences at the time of training and testing Motivational - willingness to respond Emotion - interfere with accessing stored information Motor - can the subject move appropriately? Memory that stores the experience

Dimensions of memory traces 2 dimensions: Active or inactive state? Speed of decay? Vulnerable to disruption?

Short-term memory: active state, rapid decay, vulnerable to disruption Long-term memory: inactive state, slow decay, less vulnerable to disruption

What were the results and implications from systematically injecting the protein-synthesis inhibitor anisomycin prior to fear conditioning?

The drug had no effect at the 1-hour retention interval but impaired retention at the longer 6- and 24-hour tests. These results are consistent with the idea that a short-term memory trace can be formed that does not depend on protein synthesis, whereas a long-term memory trace requires new proteins.

What is the retention interval?

The time between the training experience that establishes the memory and the test used to retrieve the memory.

What can be said about the contribution of molecule X to memory?

These results indicate that molecule X contributes to the consolidation of the long-term memory trace but is not required for short-term memory.

LIMK pathway and object-place learning It is reasonable to expect that behavioral experiences that produce memories would engage in the LIMK signaling pathway because _________ is necessary for synaptic changes in LTP Phosphorylated cofilin _________ in hippocampus following object-place learning Blocking actin polymerization in hippocampus _______ object-place memory formation A behavioral experience that produces a memory is likely to result in more ____________ and more ___________. Fear conditioning increased the presence of ____________ in dendritic spines. This result means that the conditioning experience ___________ this __________.

actin polymerization increases blocks phosphorylated cofilin, autophosphorylated CaMKII phosphorylated CaMKII, acitivated, kinase

GluN1-GluN2A vs GluN1-GluN2B More GluN1-GluN2A during ________ More GluN1-GluN2B during _________ Which can stay open longer? It's easier to induce LTP when _________ subunits dominate

after development development (childhood) GluN1-GluN2B GluN1-GluN2B

Working and Reference Memory Depend on Glutamate Receptors = Insights from the radial arm maze 1) Working memory requires that the animal remember which arm was _________ 2) reference memory requires that the animal discriminate between the arms _________ and the arms ________

already visited always baited, never baited

CaMKII and Memory Formation: CaMKII KO mouse With CAMKII KO: - LTP cannot _______ - The CaMKII KO mouse can learn to ___________ but cannot learn the _________. Control mice ________ the target quadrant on a probe trial while CaMKII KO _____.

be induced swim to the visible platform, location of the hidden platform search, don't

LTP electrically induced in tissue slices or in the brain does not represent a _________________

behavioral experience

The formation of a memory trace begins when a _________ activates a ________ ensemble that represents the experience.

behavioral experience neuronal

The formation of a memory trace begins when a __________ activates a set of __________ neurons.

behavioral experience; weakly connected

Summary of Malinow's Experiments In the first experiment he established that a ________ experience could traffic ________ into the spine. In the second experiment he asked if trafficking of GluA1s was _________ for the expression of ________. The rationale was that if they were necessary and the dummy receptors competed with the endogenous ones then the animals should display reduced ______. They ______.

behavioral fear conditioning, GluA1 receptors necessary, conditioned fear fear, did

AMPA receptors in the novel object test CNQX in PRC before training ________ novel object memory formation CNQX before testing _______ novel object memory retrieval Result = AMPA receptors are necessary for _______

blocks blocks learning

Channelrhodopsins When activated by _______ light, could be stimulated to ______ and _____ with millisecond precision and conduct _________ ions with the result of _________ the neuron. = _____ the neuron

blue open close positive sodium depolarizing excites

AMPAkines and Cognitive Enhancement AMPA receptor normally rapidly ______ AMPAkines keep the channel ________, allowing ______ ________ ions to enter and the synaptic response is _________ to promote learning AMPAkines are not an _______ or ________ They bind __________ Can cross the ________ They facilitate memory ________, but doesn't effect the actual ________

closes open longer, more calcium, enhanced agonist, antagonist non-competitively (different area) blood brain barrier formation, memory

Short-term memories are more vulnerable to _______ than long-term memories.

disruption

NMDA Receptors and Memory Formation: GluN2B Overexpression (Tsien) overexpressed ___________ in hippocampus & cortex Called the _______ mouse these receptors can ________ longer and allow more _______ influx

doogie GluN2B subunits stay open, calcium

The concept of consolidation exists to explain the observation that newly formed memories are more _________ compared to older ones Thus memory researchers believe after its initial formation additional post acquisition processes __________

easily disrupted consolidate the trace

The Concept of Consolidation: Electroconvulsive Shock Therapy applied ________ across the brain to treat severe psychiatric disorders there were clinical reports that the patients who received ECS had _________

electrical current impaired memories

Some methods for altering brain function: stereotaxic surgery the advantage of using this is that the experimenter can precisely place the _________ or ________ in the desired location

electrode cannular

Glutamate Receptor Composition Is Critical to Working Memory: GluA1 receptors GluA1 KO mice can display an __________ but not the ________. These mice can learn and remember the ________ memory component of the task. However, they are impaired on the ________ memory component. This results suggest that GluA1 receptors are critical for _______ memory

enduring LTP, rapidly formed early phase reference working, working

Training phase to _________ a memory Test phase to ________ the memory.

establish detect

(T/F) If a molecule is critical for long-term memory, it should also be critical for short-term memory.

false

NMDA and AMPA Receptors: One trial Acquisition and Retrieval Acquisition: ______ two different flavored foods Retrieval test: Locations uncovered and fed one of two foods, decide which well _______ the food When given before acquisition, ______which antagonist(s)?________ interfered with establishing the food-location memory. However, only ______, the _______ receptor antagonist, interfered with the retrieval of the memory. Results mirror the necessity of these receptors for LTP ______ and ________

find contained APV and CNQX CNQX, AMPA induction, expression

NMDA receptor subtypes: Each receptor has ______ subunits Functional NMDA receptors require a _____ subunit Other subunits can be some combination of ________

four GluN1 GluN2As and GluN2Bs

The idea that a behavioral experience can generate the transcription of new genetic material is called the __________.

genomic signaling hypothesis

reference memory and working memory both require _________

glutamate receptor activation

Halorhodopsins: when stimulated with _______ light they conduct _______ charged ________ ions and thereby _________ the neuron = ______ the neuron

green negatively chloride hyperpolarize inhibits

Why use genetic engineering? Drugs are said to be "dirty," meaning they are not _________ to the intended target, and it is hard to control for the spread of the drug to other regions. Moreover, by using biotechnology to directly influence the genome, it is possible to ______ or ______ the gene for a particular protein or to _______ new genes into the genome.

highly selective modify, delete, transfer

Overexpressing CREB in the amygdala rescues an ___________ Neurons in the lateral amygdala compete to participate in the neuronal ensemble that supports the __________ Neurons that overexpress CREB at the time of fear conditioning _________

impaired long-term fear memory fear memory win the competition

NMDA receptors and memory formation: GluN1 deletion (Tonegawa) CA1-GluN1 KO mice are _______ in ________ the Morris water maze CA1-GluN1 KO mice do not _________ the training quadrant aka they could not ________ but can perform the ______ platform version

impaired, learning (and memory) selectively search, learn to swim to the platform visible

CaMKII and Fear Memories: Fear learning produces __________ in dendritic spines in the amygdala. KN-62, which inhibits the phosphorylation of CaMKII, impairs both _________ and ________ conditioning.

increased phosphorylated CaMKII contextual, tone-fear

AMPA receptors are important in the ___________ of LTP NMDA receptors are important in the ___________ of LTP

induction and expression induction

Rapamycin ______ the function of the mTORC1 complex. Rapamycin ______ the function of the mTORC2 complex. RICTOR ______ the function of the mTORC2 complex.

inhibits does not inhibit inhibits

CA3 differences: CA3 NMDA Receptors and Memory Formation: GluN1 Deletion CA3-GluN1 KO mice do _______ the maze keeping the platform the _____ over trials CA3-GluN1 KO mice do not ______ with new _______ each day (four trials) Normal mice learn the task in _____ trial.

learn, same learn, locations (can't rapidly learn) one

The mTORC1 complex regulates __________.

local protein synthesis

Inhibiting the mTORC1 complex interferes with __________ and could interfere with _________

local protein synthesis, consolidation

The de novo protein synthesis hypothesis states that

long-term memory depends on behavior initiating the synthesis of new protein.

when investigating a drug or some other manipulation that is hypothesized to strengthen a memory trace, researches should use a ________ intensity shock to avoid the ______ effect

lower ceiling

What are the differences between mTORC1 and mTORC2? (what are the sensitive to and what they regulate)

mTORC1 is sensitive to rapamycin and regulates protein synthesis; mTORC2 is insensitive to rapamycin and regulates actin polymerization.

LTP Is Not ________

memory

Inhibiting protein synthesis should _________ short-term memory.

not effect

Genetic engineering: viral vectors part of the _________ methodology inserts genes in a ________ specific manner viral vector systems deliver _______ used to deliver _________ to specific regions in the brain.

optogenetics cell-type genetic material mRNA constructs

Memories are the product of ___________ interacting with their ___________

organisms environments

NMDA receptors and memory formation To do this, morris used a: _____________ approach Infused ________ into the brain (which is a....) Implanted a _______ into a ________ Which task was used?

pharmacological APV (NMDA receptor antagonist) cannula, cerebral ventricle hidden platform test

BDNF positive feedback loop A memory-producing behavioral experience such as inhibitory avoidance training immediately activates a set of _________ in the dendritic spine compartment that produces a __________. It also activates _______ signaling to initiate _____________ that can support a ______ memory that can last about ______. BDNF signaling also leads to the __________ in the nucleus, which targets the transcription of mRNAs for ________ as well as the transcription factor ______. ________ targets BDNF for transcription. Synaptic protein mRNAs and BDNF are transported back to the dendritic spine to replenish the supply of __________. This positive autoregulatory BDNF → CREB → C/EBPβ → BDNF feedback loop lasts ________ and is responsible for the _________ of consolidation, which supports memories that can endure for _________.

post-translation modifications, short-term memory BDNF, local protein synthesis, long-term, 2 days (first wave) phosphorylation of CREB, synaptic protein, C/EBPβ C/EBPβ synaptic proteins (SP) over a day, second wave, over a week.

Preventing Autophosphorylation of CaMKII Impairs Learning Autophosphorylation is critical for ___________ of a fear memory but not essential for memories produced with ___________ aka, without autophosphorylation, the mice will still _________

rapid formation, multiple training trials learn eventually, just not as quickly

Consolidation refers to the process of increasing the memory trace's ____________. When memories are consolidated they decay at a ________ rate

resistance to disruption slower

Two related implications to dimensions of memory traces: Memories become ________ as they age. Memories in the active state are more _______________ than memories that have become inactive.

resistant to disruption vulnerable to disruption

What is the key independent variable manipulated to determine if a molecule is selectively involved in LTM but not STM?

retention interval

Fear Learning Induces AMPA Receptor Trafficking (Malinow) used _______ strategies to prove that ______ drives AMPA receptors into amygdala neuron synapses. part 2: he used a _______ to delivery _______ AMPA receptors to the amygdala result = Dummy AMPA receptors competed with endogenous receptors for for _______ to synapses and impair _______ and ______

two, fear conditioning virus, dummy/artificial delivery, fear conditioning, LTP (cannot learn cued-fear test)

Genetic engineering: optogenetics allows scientists to control one ________ without altering _______ which two neurons are used? After ________ genes have been expressed on membranes, they can be activated by _______ to ______ neurons or to ______ neurons

type of cell, other types Channelrhodopsins and Halorhodopsins rhodopsin, light, excite, inhibit

The formation of a memory trace begins when a behavioral experience activates a set of __________

weakly connected neurons

Brain region-specific actin dynamics and memory Insular cortex & Conditioned Taste Aversion example: PSD size (actin polymerization) ________ in insular cortex after conditioned taste aversion PSD size does not change in _______ or _______ Blocking actin polymerization in insular cortex blocks ________

when you eat something and get sick, so you don't want to eat it again increases amygdala, Prelimbic cortex CTA formation

NMDA GluN1-GluN2A subunits are required for __________ but not for __________.

working memory (rapid learning) reference memory