Neurobiology L&M Exam 3

List three differences between a short-term memory trace and a long-term memory trace.

1) Duration, 2) state, and 3) vulnerability to disruption/decay rate

Describe three methods for influencing brain function?

1) Experimentally damaging a particular region of the brain; 2) injecting drugs; 3) genetic engineering

Roberto Malinow's laboratory (Rumpel et al., 2006) 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

Describe how the radial arm maze can be used to study both working and reference memory.

1) Working memory requires that the animal remember which arm was already visited; and 2) reference memory requires that the animal discriminate between the arms always baited and the arms never baited.

CNQX

AMPAr antagonist. In perirhinal cortex, when applied before training it blocks memory formation, if applied before testing it blocks memory retrieval.

If _____ is inhibited BDNF will not be transcribed

C/EBPb

Which of the following statements about opsins is true?

Channelrhodopsin can excite neurons by depolarizing them. Halorhodopsin can inhibit neurons by hyperpolarizing them.

genetic engineering

DNA injected to knock out or knock in a gene. Viral vectors deliver genes through neurons infected by viruses.

What are the unconditioned stimulus, the conditioned stimulus, and the conditioned response in fear conditioning?

Electrical shock, auditory stimulus, freezing

GluN1-GluN2B receptors to GluN1-GluN2A ratio increases during development

False

In the object in context task animals memory is demonstrated if the animal explores the object in that was present in the training context.

False

Morris used genetically engineered mice in the first study that investigated the role of NMDA receptors in memory formation.

False

Place learning in the Morris water task uses a visible platform.

False

NMDA receptor subtypes

GluN1 - needed for receptor to function GluN2A GluN2B

Tonegawa deleted the __________ in __________ in the CA1 field of the mouse hippocampus.

GluN1 subunit; pyramidal cells

How is the visible-platform task used to evaluate results observed in the place-learning task? Explain why.

If a treatment has no effect on performance on the visible-platform task, then one would be more confident about concluding that the treatment influenced some aspect of memory. This is because the task makes no demand on spatial memory of the platform location.

mTORC1

Mechanistic target of rapamycin complex 1, kinase Increases translation -> increases protein synthesis. Rapamycin sensitive. 1st wave necessity 4E-BP -> TOP mRNAs -> LPS

fear conditioning

Rats are then tested for their fear of the context-place where shock occurred and later for their fear of the tone. Shocked (S) rats display more freezing than rats that were not shocked (NS).

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 targeted the NMDA receptors in CA1 pyramidal cells but not the dentate gyrus. The mouse's memory was impaired, and it could not learn to swim to the platform.

What is the retention interval?

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

Explain the floor effect.

When a treatment is hypothesized to impair the memory processes that produce avoidance behavior, but the performance measure was too low to be further reduced by the drug.

Fear conditioning increased the presence of phosphorylated CaMKII in dendritic spines. This result means that the conditioning experience __________ this __________.

activated; kinase

stereotaxic surgery

an electrode or cannula is used to determine electric current or chemical solution

GluA1 KO mice

display long-lasting LTP. have impaired working memory.

James McGaugh

found that memory can be improved by moderate postlearning injections into the amygdala of epinephrine. Implied there is a short time after induction of an experience where the strength of the trace can be modified.

Autophosphorylation of CaMKII

is critical for rapid formation of a fear memory but not essential for memories produced with multiple training trials

memory is a concept that:

links how our experience can effect our environment and behavior.

Which of the following is true?

reference memory and working memory both require glutamate receptor activation

GluN2A KO

required for working memory, not reference memory.

CA1 GluN1 KO

resulted in no LTP. Impaired space-learning. LTP could be observed in dentate gyrus. NMDAr in this region is essential for memory.

retrieval failure

the inability to recall long-term memories because of inadequate or missing retrieval cues. Memory is stored, cannot be accessed. Amnesia can disrupt the neural pathways of retrieval. Amnesia is temporary.

Why lesioning a specific area does not prove that region stores memory:

the lesion could have impaired sensory, attentional, or perceptual processes; motivational and emotional processes; or motor processes.

inhibitory avoidance conditioning

the time it takes for the rat to cross over to the dark side. An increase in shock will increase in response latency.

consolidation period

time it take to stabilize the memory trace. Memories are more vulnerable to disruption with less time than if it were a longer time period.

protein degradation processes in enduring memories

ubiquination and proteasome activity increase when consolidating memories. UPS operates in parallel with Ca2+ processes. Inhibiting proteasome activity will prevent degradation of repressor proteins for translation and transcription, which will inhibit LTM.

Basolateral amygdala (BLA)

used in fear conditioning, determines if training drives GluA1 into spines. It increases in response at the synapse when fluoresced.

The __________ is often used as a control task to evaluate alternative interpretations of the effect of brain manipulation on performance in the place-learning task.

visible-platform task

testing behavior:

window to memory tracing

Why we do not know how memories are made by understanding how synapses are modified:

1. induced LTP is low intensity, high frequency. Unknown how this regulates without being induced. 2. Modified synapses are usually from slice of brain tissue maintained in chemical cocktail, can easily be disturbed.

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

4 hours or less

Morris water maze

A common test of spatial memory. A rodent is placed in a small round pool filled with opaque-colored water and must remember the location of a submerged platform to escape. Escape latency decreases as a function of training trials.

In Malinow's AMPA receptor trafficking experiment, what was the difference between the rats in the paired condition and the rats in the unpaired condition?

After the training, rats in the paired condition had more GluA1 receptors in the plasma membrane than rats in the unpaired condition.

Why would infant mice display stronger LTP than older mice?

Because the ratio of GluN1-GluN2B to GluN1-GluN2A receptor complexes is higher in the infant mice, and GluN1-GluN2B receptor pass more calcium.

Which of the following statements about memory is FALSE?

Blocking CREB translation impairs STM. Neurons that over-express CREB do not compete successfully for selection in the neuronal ensemble

Explain why genetic engineering is believed to be more precise than applying drugs in manipulating the molecules involved in memory.

Drugs are said to be "dirty," meaning they are not highly selective 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 modify or delete the gene for a particular protein or to transfer new genes into the genome.

Morris was the first to find a possible role for NMDA receptors in memory formation. What was his essentially methodology?

He implanted a cannular into a ventricle to delivery an NMDA receptor antagonist. He assessed the effect by studying its effect on the hidden platform version of the water task.

Learning-performance distinction

If concluding memory was affected, which is unobservable, it has to be shown that other components are not affected

The Dummy Receptor Competition Strategy

If fear conditioning drives AMPA receptors into the synapse and they are necessary for memory, then cells that contain competing dummy AMPAs should display reduce LTP and Memory than normal controls

What is the significance of 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.

1st wave of PS

LPS with BDNF -> TrkB -> mTOR -> TOP mRNAs pathway. Rapamycin blocks mTOR and if applied before training it only effects LTM, both waves for LTM blocked. If applied after training both waves endure. Reveals that mTOR is essential for this.

Inject anisomycin into amygdala after training:

LTM present 2 days later, but not 7-9 days. LTM can happen for around 2 days, 1 day after training. LTM can happen for 3 days, not 8 with 2 days after training. LTM endures 1 week later.

Which of the following statements about inhibitory avoidance conditioning is true?

Longer latencies reflect a stronger memory trace. The dependent variable is crossover latency. As shock intensity increases, so does response latency.

Richard Morris was the first researcher to directly investigate the role of __________ in memory formation.

NMDA

STM and trauma

STM will be interrupted and not consolidate. One can only remember events beforehand that had STM consolidation.

What is the consolidation period?

The time it takes to increase the resistance or a newly formed memory to disruption

How did Tonegawa's laboratory discover a role for the GluN1 receptor?

They deleted the gene for this receptor in the CA1 region in mice and found that it impaired performance in the hidden platform task.

In the object recognition test memory is demonstrated if the animal spends more time exploring the new object.

True

What is the function of channelrhodopsin and halorhodopsins?

When activated by blue light, channelrhodopsins (channel proteins) could be stimulated to open and close with millisecond precision and conduct positive ions with the result of depolarizing the neuron. Halorhodopsins, when stimulated with green light, conduct negatively charged chloride ions and thereby hyperpolarize the neuron.

Is it reasonable to expect that behavioral experiences that produce memories would engage the LIMK signaling pathway? Why?

Yes, because actin polymerization is necessary for synaptic changes in LTP.

storage failure

a memory not stored can never be recovered. Amnesia and trauma interferes with storage. Amnesia is permanent.

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

Memories themselves are established by...

behavioral experience. This produces changes in synaptic activity.

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

behavioral experience; weakly connected

Blocking actin polymerization in hippocampus

blocks object-place memory formation. Can be affected by blocking the Rho-Rock/RAC-PAK pathways, or dephosphorylating cofilin

learning-performance distinction

brain manipulation must show that influencing unobservable memory did not affect other components in the process.

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

ceiling effect

Malinow's experiments

changed conductance of GluA2 receptors. showed fear learning induces AMPAr trafficking. Trafficking GluA1s are necessary for the expression of conditioned fear.

GluA1 AMPAr

critical for fear memory. Using a nonfunctional version of GluA1 receptor would drive into the spine but could not respond to glutamate release-dummy receptor.

Methods to influence brain function:

damage region of brain, injecting drugs to influence neural function, and genetic engineering to alter expression of memory molecules.

memory modulators

effects storage of memory but themselves do not store the memory. It is time-limited in that it influences recently acquired memories and will operate during consolidation. Not apart of retrieval system.

Cerletti and Bini

electrical current across the brain to treat severe psychiatric disorders à called electroconvulsive shock therapy (ECS).

Carl Duncan

first person to use ECS to experimentally induce amnesia in animals. He found that when ECS was administered within a minute after the training it produced amnesia But it did not produce amnesia 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 consolidate.

Malinow's experiments showed that 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

In fear conditioning, the duration of the __________ is an indicator of the __________ of the memory.

freezing; strength

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

genomic signaling hypoth.

sleep deprivation

impairs mTOR functioning.

control experiments are used

in order to make sure other components are not influencing memory. However, trauma can still effect results on memory experiments.

Memories are the product of organisms __________ with their __________.

interacting; environments

working memory

involves inserting AMPA GluA1r into spine. This relies on GluN1 + Glun2A subunits of NMDAr.

ampakines

keep AMPAr channel open for longer so more ions can flow in, enhanced synaptic response. Enhances rate of auditory fear conditioning. It is not an agonist nor antagonist. Enhances cognitive functions and it crosses BBB. May help in memory with aging.

reference memory

may depend on GluA2 subunits, does not depends on GluA1.

If mTOR is inhibited by rapamycin 5 minutes after avoidance conditioning

memory retention would not be impaired at any retention interval memory retention would not be impaired if the retention interval is 1 hour or less.

electroconvulsive shock (ECS)

might be useful to produce amnesia as it was earlier used to treat psychiatric disorders and induce time-limited retrograde amnesia. This technique did not advance our understanding of memory consolidation.

2nd wave of PS

need transcription and translation. Genomic signaling, involves CREB autoregulation loop - targets mRNAS for transcription. BDNF is essential to phosphorylate CREB.

interference theory of forgetting

new memories can interfere and write over old memories, which can lead to forgetting. Sleep can help postpone the interference of forgetting.

The ECS methodology did not advance our understanding of memory because it was already known that

newly acquired memories are vulnerable to disruption

If CaMKII is unable to phosphorylate...

no LTP induction in CA1 region via schaffer collateral stimulation. LTP will be induced in DG via perforant path. No fear conditioning. KN-62 is a molecule that will do this by blocking acquisition of contextual and auditory fear conditioning and prevent LTP.

If the GluA1 is deleted reference memory in the radial maze will be _______?`

normal

mTORC2

not sensitive to rapamycin as it has RICTOR. If KO, memory stabilized but not consolidated. No memory at 24 hrs, not effect STM. pcofilin -> actin polym.

JPK

promotes actin polym. so if applied to mTORC2, LTM can slightly endure.

Inject anisomycin into amygdala before training:

protein synthesis blocked, STM intact as STM does not rely on PS.

sleep in memory consolidation

reactivation/replay in same order will initiate a round of LPS -> more likely for memory to endure. Those allowed to sleep after learning showed less forgetting. Disrupting sleep will impair learning.

GluN2B

receptor channels stay open for longer than 2A channels. Will ultimately increase in Ca2+ -> LTP and memory formation enhanced. Experiment done by Tsien.

In the radial arm maze methodology, if a rat revisits an arm that was never baited, it is making an __________ error.

reference memory

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

retention interval

Amnesia for events experienced prior to the blow to the head that caused it is an example of __________.

retrograde amnesia

measurable behavior is the final product of different processes including:

sensory, attentional, and perceptual processes that determine what the subject experiences at the time of training and testing; motivational processes that determine the subject's willingness to initiate a response; emotional processes that interfere with accessibility of stored information; motor systems that provide the behavioral response to be expressed; and a memory system that sores the experience.

CA3 GluN1 KO

spatial learning occurs with the same platform over a number of trials. This does not occur if the platform is at different locations.

insular cortex

taste aversion memories. Cytochalasin D interferes with actin polymerization and prevents lengthening in PSD which prevent memory.

Müeller and Pilzecker

the first experimentally controlled observation that new memories are more easily disrupted than old memories.