This paper illustrates the Science Practices standards (SP.1-SP.4).

The authors take observed phenomena, note that they have yet to be fully explored, and carefully form testable hypotheses about their role in the development of Alzheimer’s disease.

In their study, the researchers combine knowledge from earlier research using mouse models to study the molecular basis of the disease with two main observations:

(1) Tau is known to build up in Alzheimer’s disease patients, and

(2) a higher than normal level of tau protein results in a higher risk for developing the disease.

They hypothesize that changing the level of tau will result in less severe disease symptoms, which they carefully test in well-designed experiments, choosing powerful methods to collect and analyze data and to control for as many variables as possible.

Finally, they incorporate their findings into a general model for tau working together with amyloid-β to cause the symptoms of Alzheimer’s disease.

http://apcentral.collegeboard.com/apc/public/repository/cbscs-science-standards-2009.pdf (Page iii)

A set of genes inherited together.

In this case, the authors discuss the idea that several genes related to the tau protein seem to affect the probability that a person will develop Alzheimer’s disease later in life.

This means that molecular changes are made to tau proteins after they are being made.

Some types of abnormal tau appear in cases of Alzheimer’s disease.

Although the sequence of molecular events that causes Alzheimer's disease was and still is unclear, it is generally believed that, as a first step, amyloid-β proteins build up into plaques; then, abnormal tau proteins kill neurons and build up into tangles.

Targeting plaques as a treatment therefore made sense, because, if successful, it would affect the disease earlier in the process of neural destruction.

When this paper was published in 2007, virtually all experimental treatments for Alzheimer’s disease targeted the amyloid-β proteins, either to stop their production, to help the brain get rid of them better, or to stop them from building up into plaques.

The plaques formed from built-up amyloid-β were easy to see in tissue samples from Alzheimer’s patients and it seemed like an obvious target.

Alzheimer's disease is the most common type of dementia. It's a disease of aging in which the proteins amyloid-β and tau build up or aggregate in the brain, causing neurons to die.

Amyloid-β proteins build up into clumps called plaques, and abnormal tau proteins fall off of their microtubules, which kills the neurons. These tau proteins later aggregate into clumps called tangles.

Symptoms of Alzheimer’s disease include memory and cognitive problems, and patients eventually die from the disorder.

This peptide consists of a strand of up to about 40 amino acids that are the main component of the amyloid plaques found in the brains of Alzheimer's patients.

Evidence from this study and following studies showing the importance of lowering tau has led researchers to target tau with their experimental new treatments, including vaccines that use the body’s own immune system to fight off the problematic tau proteins.

http://www.medicaldaily.com/alzheimers-disease-tau-protein-vaccine-391883

Almost 10 years after this paper was published, no good treatments for Alzheimer’s disease exist, but more and more of the new drugs in clinical trials are targeting the tau protein, as a result of early laboratory research such as this.

http://www.bloomberg.com/news/articles/2016-06-27/after-190-tries-are-we-any-closer-to-a-cure-for-alzheimer-s

A process in which neurons are damaged or die as a result of too much stimulation (or excitation, hence "excito-toxicity").

For example, excitotoxicity can occur from a seizure.

Mice that have been genetically engineered to produce the amyloid precursor protein, which is thought to give rise to amyloid-β.

Originating from within the body. In this case, "endogenous" refers to the tau proteins that occur naturally in the body of the mice.

A protein that is bound to microtubules.

Microtubules are part of a neuron’s inner cytoskeleton that maintains the structure and stability of the cell.

Tau proteins are primarily found in neurons of the central nervous system.

They stabilize the neuron's microtubules, which are components of the cell's cytoskeleton, the inner stabilizing network of filaments and tubules.

A small protein.

Chapter 10: Empathy, sympathy, and prosocial preferences in primates.

There are several potential lines of evidence for the existence of empathy in nonhuman primates. Because of the subjectivity in interpretation of animals' intentions as well as no defined assay for empathy or sympathy, "we cannot be certain whether any given interpretation is right or wrong."

"To transform singular observations of behavior into more robust findings we need to develop theoretically grounded hypotheses that we can subject to empirical testing."

http://www.amazon.com/Oxford-Handbook-Evolutionary-Psychology-Handbooks/dp/0199561788

"Current claims for the existence of empathy, sympathy, and moral sentiments and other-regarding preferences in other primates rest on an insecure empirical foundation.

The anecdotal accounts have limited value because they rely on subjective interpretation of animals' intentions and motivations and they are not systematically collected or analysed.

This means we cannot be certain whether any given interpretation is right or wrong and we have no means of discriminating against competing claims."

The chapter covering this controversial view of whether nonhuman animals display empathy may be found here:

http://www.amazon.com/Oxford-Handbook-Evolutionary-Psychology-Handbooks/dp/0199561788

Type the word empathy into the "search inside this book" window.

From materials and methods: In addition, audio samples (n=272, 5-minute duration) were randomly chosen from all 12 days of the trapped, object, and empty conditions and were similarly analyzed.

http://www.sciencemag.org/content/suppl/2011/12/07/334.6061.1427.DC1/Bartal.SOM.pdf

A piece of equipment used to record and identify high frequency calls beyond the range of human hearing.

These detectors have a frequency dial. Once a frequency is chosen, the detector only detects sounds at that frequency. Because the dial was set at 23 kHz, sounds far above or below that frequency would not be detected.

http://www.batbox.com

From materials and methods:

Audio files were collected from all sessions where only one condition was tested (26 rats in the trapped condition, 16 rats in the empty condition, and eight rats in the object condition).

All audio files collected on days 1–3 of male rats in the trapped condition were analyzed for the presence of alarm calls.

Judges blind to the experimental condition used the freeware Audacity 1.3 to locate potential alarm calls (about 23 kHz), and listened to each candidate segment to verify which of these segments indeed contained alarm calls.

Each file was then categorized as either containing alarm calls or not containing alarm calls.

The proportion of samples from each experimental condition that contained alarm calls was then calculated.

Used to describe sounds at a frequency above the human hearing range.

From materials and methods: Measuring opening style: Each door opening was classified to indicate how the door was opened.

Three types of opening were observed:

1) Rats opened the door by nudging it up with their head from the front of the restrainer (“head”),

2) rats opened the door by leaning on the heavy side of the door (“side”), or

3) rats opened the door by standing on top of the door (“top”).

Empathic concern (identifying with the emotions of another person) in humans is thought to be hard-wired into our brains. It becomes evident as early as age 2 and is dependent on our social interactions.

There are several contributors to empathy including:

(A) Shared neural representations (activity in the brain in response to an experience in your environment). For example, the neural networks that are active when you feel sad would also be active when you see someone else expressing sadness and feel empathy for them.

(B) Self-awareness (conscious knowledge of one's own character, feelings, motives, and desires).

(C) Mental flexibility, or the ability to shift a course of thought or action according to the changing demands of a situation. It allows an individual to abandon a previous response set or pattern in order to generate an alternative that is better suited to the requirements of the situation at hand.

(D) Emotion regulation, or the ability to respond to the ongoing demands of an emotional experience in a manner that is socially tolerable and sufficiently flexible to permit spontaneous reactions.

This paper describes the patterns rodents take while exploring their environment using a computational method of analysis. SEE allows for the distinction between stopping and progressing, spatial spread, dynamics of space occupancy, number of stops per excursion, and the maximal speeds attained.

[http://www.sciencedirect.com/science/article/pii/S0149763401000227]

The authors tested whether albino rats could display altruistic characteristics. They defined altruism as "behavior of one animal that relieves another animal's 'distress.'"

The distress-causing paradigm was using a harness to suspend one rat free from the floor. The second rat is free in a separate compartment and can see and hear the suspended rat.

The second rat can bring the suspended rat down to the floor by pressing a lever, and did so significantly more than if there was a styrofoam block being suspended.

These results do point toward rats being capable of altruistic behavior because the rats performed an action that was not beneficial to itself, but that benefits one of its species.

These authors tested whether the purpose of pain expression is to attract comfort or receive aid from conspecifics.

For this they assayed the likelihood of a free mouse to approach/contact a jailed mouse experiencing pain versus a jailed mouse unaffected by pain.

This hypothesis was true in the case of female mice but not male mice. However the observer female mice only approached mice that were "known" (i.e., had previous contact with the observer mouse). Thus there is sex specificity to the social approach to pain in laboratory mice.

The contact made by the free mouse with the mouse in pain resulted in less pain behavior.

The authors of this paper measure the reaction one group of rats has to the outward show of pain of another rat receiving an electric shock.

One group of rats had lever pushing for food associated with the electric shock of another rat and a shock to themselves (paired shock). A second group had lever pushing for food associated with only themselves receiving a shock (unpaired shock). The third group received no shock when they pushed the lever for food (no shock).

The authors then measured the frequency of lever pushing by spectator rats from all three groups (paired shock, unpaired shock, and no shock) in response to shock delivery to the tester rat.

Rats trained in the paired shock paradigm reacted by significantly less lever pushing compared with the no shock group.

This suggests that the responses given by the paired shock group may be a result of conditioning rather than that action being a show of sympathy.

In this review, the authors note that "Empathy involves not only any sentimentally commanded encounters with another person’s actual or inferred emotional state but also some minimal recognition and understanding of another’s emotional state."

They also highlight the main components of empathy: shared neural representations, self-awareness, mental flexibility, and emotion regulation.

These components are used together to form a model to predict empathy deficits in social and neurological disorders.

From the review: Putting together phylogenetic and ontogenetic perspectives on empathy

"The ability to perceive, share, and understand others’ affective states is crucial for successfully navigating the social world."

"Broadly defined as empathy-related responding (Eisenberg and Eggum, 2009), this set of socioemotional competences underlies some of the most meaningful human interactions, from bonding between mother and child to complex prosocial behaviors (Batson, 2009), all essential for survival."

[http://www.sciencedirect.com/science/article/pii/S187892931100048X]

The latency to door opening as well as the likelihood of door opening to free a trapped cagemate were used as readouts for empathy. Based on these criteria the authors conclude that rats are capable of feeling empathy and will act on those feelings.

de Waal et al.

The authors looked at consolation behavior in chimpanzees. Consolation is ranked under the same umbrella as empathy. In their paper it was defined as "an interaction in which an uninvolved bystander initiates friendly contact with a recent victim of aggression."

Main finding: The empathy hypothesis that states that consolation is more likely to occur among animals that are socially close was supported.

Behavior in different species that arose from a common ancestral gene.

Simplest.

See Figure 2E.

See Figure 2D.

See Figure 2B.

Go back to Figure 2 panel F. Alarm calls accounted for only 14% of the ultrasonic noises rats made in the trapped condition.

QUESTIONS: Do you agree with the statement that infrequency of alarm calls rules them out as the source of helping behavior?

What experiment would you design to make the authors' interpretation stronger?

Altruism or Arousal in the rat?

Previous work has shown that rats will press a bar to lower a fellow rat suspended in the air and showing signs of distress including squealing and wriggling (G.E. Rice and P. Gainer. J. Comp. Physiology and Psychol. 55, 123-125(1962).

However, subsequent work showed that rats will press a bar to stop the sound of white noise more frequently than to stop the noise of a squealing rat.

This suggests that any noise can elicit this bar pressing behavior. It also suggests that the motive behind the bar-pressing action of the rat is to stop the irritating noise and not to save its fellow rat.

Here is a nice summary video of the authors' work, narrated by one of the authors, Dr. Peggy Mason.

[https://www.youtube.com/watch?v=3jkOwYKBJEI]

Rats took about 6 days to learn to open the chocolate containing restrainer. In the earlier experiment with the trapped cagemate, the rats took about 7 days to open the restrainer.

The length of time it takes for the rats to master this door-opening maneuver indicates that this action took some effort and didn't come naturally.

Once rats learned to open the door, they were just as likely to open the door to the chocolate-containing restrainer as to the restrainer holding their cagemate.

Acceptable or agreeable to the taste.

The helper rats' motivation to set their trapped cagemates free does not depend on social contact with their freed cagemates.

This is evidenced by the fact that helper rats freed their trapped cagemates even when there was no possibility of interaction after freeing.

Here the authors investigate the motivation behind the helper rat opening the restrainer for their cagemate.

QUESTION: Is the opening action driven by empathy for the distressed cagemate, or by the expectation to interact socially with the freed rat?

By allowing the freeing of the trapped animal but preventing social interaction after freeing, the authors were able to determine the motivating factor behind the freeing action.

Rats that showed bolder traits may be more likely to act to help their fellow rat. The second panel of figure S1 shows this. However, although a trend is there, it did not reach statistical significance. http://www.sciencemag.org/content/suppl/2011/12/07/334.6061.1427.DC1/Bartal.SOM.pdf

The rats that displayed more boldness, (as measured by a shorter time to emerge from a half-opened cage) were the ones who freed their cagemates.

http://www.sciencemag.org/content/suppl/2011/12/07/334.6061.1427.DC1/Bartal.SOM.pdf

When their cagemate was trapped in the restrainer, female rats moved around the arena faster than males and also opened the door of their trapped cagemates quicker than males.

(7) Previous work has shown that female mice will frequently approach another familiar female mouse in pain, whereas male mice rarely approached another familiar male mouse in pain.

(12) This study examined consolation through physical contact in chimpanzees and found "female chimpanzees offered more consolation to recent victims of aggression than males, suggesting that females were particularly responsive to the distress of others."

The trapped rats emitted ultrasonic alarm calls, which is a measure of stress in rats.

The amount of time between the free rat being placed in the arena and the door opening.

Rats in an arena with a trapped cagemate:

A. moved more frequently around the arena

B. moved faster around the arena

C. spent a longer time in the arena center near the<br> restrainer

D. moved more after the restrainer was opened and the previously confined rat was freed

All these findings point toward the movement and activity of the free rat being linked to the presence of a rat in the restrainer.

Only in the scenario where the helper rat is an arena with a trapped rat was the movement of the free rat concentrated around the restrainer. The pattern of blue dots (rat's head) is denser closer to the red rectangle (restrainer).

Rats do not like to be in the middle of an open space and usually concentrate their movement close to the sides, as seen in the empty and object containing conditions. This tendency to hug the sides of a space is called thigmotaxis.

QUESTION: Why does the rat in the 2+ empty condition only move along the perforated divide?

Measuring location and movement in the arena The free tracking software ImageJ (v1.44e, NIH, USA) was used to convert the black marker on the rats' head into x,y coordinates denoting the rats' location at each frame at a rate of 0.5 frames per second (FPS).

These data were then used to calculate movement velocity (termed activity). Other indices (time away from wall and persistence ratio) were calculated using the free SEE software (28), developed specifically for the analysis of rodent movement in an arena. [http://www.sciencedirect.com/science/article/pii/S0149763401000227]

To free.

These rat pairs are referred to as "cagemates" throughout the study. This 2-week period of housing in the same cage established familiarity between the rats.

In previous studies, rodents showed evidence of emotional contagion by demonstrating emotional behavior that is caught or shared from another individual.

For example, emotional contagion for fear may lead one mouse to freeze upon seeing another mouse that is frozen in fear. In another example, rats react to a conspecific receiving a painful stimulus when they have experienced the same stimulus before.

In a human study, heart rate deceleration was an indicator of increased willingness to help someone in distress.

However, if the person's heart rate accelerated when they saw someone in trouble, they were less likely to help the person, and more likely to try to remove themselves from the situation.

Thus, identifying with someone's distress without yourself feeling in danger is a precedent for acting to alleviate that person's distress.

In agreement.

The opposite of selfish. Thinking or acting in the interest of someone else. Putting the well-being of another above your own.

This is a very interesting paper showing that a single-nucleotide polymorphism in the BDNF gene can impair the extinction of a conditioned fear response in both humans and mice. This polymorphism is also associated with anxiety-related behavior and atypical frontoamygdala activity in humans.

This is important because it suggests that the variant allele may affect the efficacy of exposure therapy, which relies on the process of extinction.

The goal of this study was to examine the effects of chronic mild stress on hippocampal and medial prefrontal cortex potentiation and extinction memory in rats.

The authors found that chronic mild stress did not interfere with the extinction of fear, but did impair the recall of extinction.

They found that chronic mild stress interfered with the development of extinction-related potentiation in the hippocampal/medial prefrontal cortex pathway.

In this study, the BDNF gene was deleted from the hippocampi of mice. This impaired the animals' ability to recognize new objects, learn spatial orientation, and extinguish conditioned fear.

These cognitive impairments are also found in anxiety disorders, suggesting that BDNF in the hippocampus may play a role in anxiety and depression.

This is a very interesting article showing that BDNF, acting through the tyrosine kinase B receptor, is required for the consolidation of stable extinction memories.

This is an older paper that was one of the first to show that fear extinction may be an NMDA-dependent process by infusion an NMDA antagonist (AP5) into the amygdala and measuring fear potentiated startle.

This paper shows that infusion of CPP, which is an NMDA receptor antagonist, into the ventromedial prefrontal cortex can impair extinction recall.

Here, the authors review current research describing the role of BDNF in long-term potentiation, and its known molecular mechanisms.

In this paper, the authors examine how epigentic gene expression regulation of BDNF enables fear extinction.

This paper investigates the role of NR2-containing N-methyl-D-aspartate receptors in the ventromedial prefrontal cortex and lateral amygdala in the consolidation of fear extinction memories.

In this paper, the authors examine research that has led to the notion that the medial prefrontal cortex is a critical component in both emotional regulation and fear extinction.

Next Generation Science Standards

ETS2.B: Influence of engineering, technology, and science on society and the natural world.

This is good example of how basic research can translate into real-world applications.

http://www.nap.edu/openbook.php?record_id=13165&page=212

One of the goals of fear learning research is to be able to improve therapies for people suffering from fear and anxiety disorders.

The fear extinction process is impaired in many of these patients, so identifying molecular targets may aid in drug development.

A single-nucleotide polymorphism is a variation in a single nucleotide at a particular location in the genome.

The authors are referring to a position in the human BDNF gene. Variation in the DNA sequence at this position is associated with a reduced ability to recall extinction.

Changes that occur following fear conditioning, such as a reduction in hippocampal BDNF, may be corrected by BDNF treatment.

The effects that infused BDNF has on extinction are mediated by NMDA receptors in the IL mPFC.

Activation of these receptors may stimulate neurons in this region, and this could explain why infusion of BDNF results in reduced freezing even when the animals do not go through extinction training.

This research furthers our understanding of fear learning by describing extinction using both a systems level approach (hippocampus to IL-mPFC pathway) and a molecular mechanism (BDNF-mediated NMDA activation).

When infused into the hippocampus, BDNF can induce extinction in the absence of extinction training.

This suggests that activation of this pathway is a key component of the fear extinction process.

Blocking BDNF activity in the IL mPFC inhibits the effects of BDNF infused into the hippocampus.

The fact that BDNF infusion into the hippocampus results in similar fear reduction to infusion into the IL mPFC supports the hypothesis that the hippocampus supplies BDNF to the IL mPFC.

Now that the authors believe the hippocampus is the source of BDNF, they want to test their hypothesis by injecting BDNF into the hippocampus and seeing whether they can block the effects of increased BDNF levels with an antibody in the IL mPFC. If they can, it means that hippocampal BDNF is acting at the IL mPFC.

The authors infuse BDNF into the hippocampus to demonstrate that this is the source of BDNF in the IL mPFC.

Previous studies have shown that BDNF infusion in regions of the brain such as the prefrontal cortex results in increased BDNF levels in prefrontal cortical targets.

Genetic knockdown is a technique that researchers use to reduce the expression of specific genes in order to study their function.

The authors want to know what brain region is supplying BDNF to the medial prefrontal cortex, so they separate animals based on their natural variation in extinction ability.

Animals that extinguish well have elevated levels of BDNF in the hippocampus relative to animals that extinguish poorly. These results suggest that the hippocampus may be the source of BDNF.

Based on previous research (see references 14–16), the authors chose to test the amygdala and hippocampus because they were the most likely contributors of BDNF to the IL mPFC.

In order to understand fear extinction, it is important to consider the underlying neural circuitry. Which regions of the brain are involved, and in what capacity? References 1 and 2 address these questions.

Some rats are naturally bad at extinguishing fearful associations. The authors take advantage of this fact to see whether there is a correlation between BDNF levels in various brain regions and extinction ability.

They used an ELISA assay (Sample methods: http://www.thermofisher.com/us/en/home/references/protocols/cell-and-tissue-analysis/elisa-protocol/general-elisa-protocol.html) to quantify protein levels in the hippocampus, mPFC, and amygdala.

The naturally poor extinquishers had lower BDNF levels in the hippocampal region.

Next Generation Science Standards Practice 1: Asking Questions and Defining Problems

The authors clearly state the question that they want to answer, followed by a description of the experiments used to answer it.

http://www.nap.edu/openbook.php?record_id=13165&page=54

The role of NMDA receptors in fear acquisition has been previously established.

By showing that rats receiving an NMDA antagonist do not respond to BDNF, the authors show that these receptors are also required for BDNF-induced fear reduction.

The authors think that BDNF may be working through NMDA receptors. They test this by treating rats with an NMDA antagonist (injected peripherally), to see whether it blocks the effects of BDNF infusion (directly into brain).

Rats that received the NMDA antagonist have freezing behavior similar to that of controls, suggesting that BDNF is indeed acting through NMDA receptors in this situation.

When something is said to occur "in vitro," it means that it has been tested or observed in parts of an organism that have been removed from their original biological surroundings.

Examples include most studies done in test tubes or petri dishes, where some tissues or cells are isolated so they can be studied more carefully.

When something is said to occur "in vivo," it means that it has been tested or observed in whole, living organisms.

A receptor antagonist is a drug or compound that can bind a receptor and inhibit its activation.

NMDA receptors interact with glutamate and glycine in nerve cells. These receptors are found all over the central nervous system, and are involved in the processes of learning, synaptic plasticity, and memory formation.

Fear extinction is an active learning process, and blockade of NMDA receptors (with the antagonist CPP) could interfere with fear extinction.

See references 4, 8, and 9 for more information about the role of NMDA receptors in acquisition and extinction of fear memories.

Based on the fact that unsignaled footshocks can reinstate freezing after extinction, the authors conclude that BDNF does not degrade the original memory.

The authors want to see whether the original memory is still intact. After extinction, rats are given footshocks without a preceding tone.

The re-emergence of a fearful association between the tone and shock indicates that the memory has not been degraded.

There are two ways in which BDNF could reduce freezing behavior on day 3: It could degrade the original memory, or it could just reduce the expression of fear, without having any effect on the initial fear memory. This is an important distinction to make!

A type of learning where repeated presentation of a stimulus leads to a decrease in response. If you put an animal into a new environment for behavioral testing, the animal may become agitated or fearful.

However, if you expose the animal to that environment a few times before the experiment begins, the animal will not be as nervous because it has been “habituated” to the testing environment.

Pre-exposure to a stimulus can make it difficult to form new associations with that stimulus. In other words, it takes longer for a familiar stimulus to acquire meaning than a new stimulus.

In this case, the authors wanted to see whether BDNF was changing freezing behavior by enhancing the effects of habituation trials.

BDNF does not appear to enhance the process of latent inhibition.

When testing the behavioral effects of a treatment, it is important to rule out nonspecific interaction with other regions of the brain that may similarly affect behavior through an alternative route.

The amygdala is known to be involved in fear acquisition, so if the BDNF was nonspecifically acting on the amygdala it would be apparent during conditioning or open-field anxiety testing.

The authors performed additional behavioral tests in order to rule out nonspecific behavioral effects of the BDNF injection.

This experiment shows that an infusion of BDNF reduces freezing only if given after fear conditioning. By showing that the effects of BDNF require, but do not alter, fear conditioning, the authors show that BDNF is acting specifically on the extinction process.

Extinction training was removed in order to see whether the effects of BDNF were extinction-dependent.

The purpose of extinction training is to subject the animals to the tone enough times to allow them to form a new memory. They realize that the tone is not followed by a shock and therefore is not associated with a threat. This concept forms the basis of exposure therapy, which is used to treat humans with anxiety disorders by progressively re-exposing them to a traumatic memory while in a safe environment.

In this experiment, the BDNF animals show reduced freezing prior to extinction training. This allows the authors to conclude that at least some of the effects that BDNF infusion has on fear expression occur regardless of whether the animals receive extinction training.

Extinction memory is tested on the third day, when the animals are subjected to another round of tones without footshocks. If the animals freeze less in response to the tones, it means that they have successfully extinguished their perceived association between the conditioned stimulus (tone) and unconditioned stimulus (footshock).

BDNF infusions reduced freezing relative to controls, indicating that the extinction memory in these animals was strengthened.

Freezing is a behavioral response that many animals exhibit when scared. This is a measurable response that researchers use to study the fear learning process in rodents. If an animal is conditioned to fear a high-pitched sound, for instance, it will freeze when the sound is played.

During fear extinction, as the animal learns to no longer fear the sound, less freezing will be observed.

The authors are interested in the function of the IL mPFC, and how it is affected by the injection of BDNF.

The targeted injection is achieved by using a stereotaxic setup, which is a highly precise, 3D guiding system that allows researchers to place a canula into specific regions of the brain. The canula is just a hollow tube that allows for the delivery of drugs or other fluids to that brain region.

Once the canula is in place, BDNF can be directly injected into the region of interest at any time.

This is a 3-day process that allows the researcher to study the formation and extinction of associative fear memories in an animal model.

Sample methods: http://www.jove.com/video/50871/contextual-cued-fear-conditioning-test-using-video-analyzing-system

Fear conditioning (day1) - The rats are exposed to tones followed by footshocks.

Fear extinction (day 2) - The rats are exposed to the same tones multiple times, without a footshock.

Testing (day 3) - The animals are tested to see whether they are still fearful of the tone.

Next Generation Science Standards Practice 2: Developing and using models

This is something that cannot be directly tested in humans, so the authors must develop a model to test their hypothesis.

http://www.nap.edu/read/13165/chapter/7#56

Consolidation is a series of events following the initial acquisition of a memory trace that leads to its retention.

Extinction memories are long-lasting, and therefore require regulated gene expression. Epigenetic mechanisms are important to enduring changes in gene expression, so the authors examine the role of these mechanisms in fear extinction.

In this study, Bredy et al. show that fear conditioning is accompanied by certain epigenetic changes such as an increase in H4 acetylation around the BDNF P4 promoter and an increase in prefrontal cortical mRNA expression of BDNF exons I and IV.

Epigenetic regulation is the process of altering gene expression levels without mutating the DNA itself.

For instance, if a cell needs to increase the expression of a specific gene, it can change the microstructure of the DNA in the area of that gene, making it more accessible for transcription into RNA.

Rodents aren't the only animals that show similar stress responses to humans. Check out this interesting story about how crayfish are also being used study anxiety:

http://www.aaas.org/news/science-crayfish-can-be-calmed-anti-anxiety-medication

A good summary of this article and its potential implications for the development of drugs to help patients suffering from anxiety disorders:

http://brainblogger.com/2010/09/19/fear-reducing-drugs-an-emerging-science/

Decades of research have been devoted to understanding the neural mechanisms involved in fear conditioning. This work has led to a better understanding of extinction.

In reference (2), the authors review new research on the neural mechanisms of the extinction learning process. They examine research describing the acquisition, consolidation, and retrieval of extinction memories, as well as the specific brain structures associated with these processes.

Extinction occurs when a conditioned stimulus (tone) is presented repeatedly without a footshock, and the conditioned fear responses to the tone diminish.

Observations of spontaneous re-emergence of extinguished fear support the hypothesis that extinction does not erase the original fear memory, but instead forms a new memory that competes with the original memory and inhibits its expression.

In this study, the authors show a relationship between infralimbic activity and extinction recall, which suggests that infralimbic neurons are involved in the process of recalling extinction memories.

There is a great need for effective treatments of fear and anxiety disorders.

http://www.cbsnews.com/news/the-war-within-treating-ptsd-2/

NMDA receptors are found in nerve cells and are activated by the excitatory neurotransmitter glutamate. These receptors are involved in memory function in the brain.

After the animal has formed an association between the tone and the shock, it will freeze when it hears the tone. However, if the tone is presented enough times in the absence of the shock, the mouse will eventually stop showing a fear response to the tone through a process known as fear extinction.

A rodent model in which a neutral auditory cue (high-pitched beep) is paired with an aversive stimulus (footshock), resulting in the formation of an associative fear memory.

After repeated presentations of the paired stimuli, the animal will experience fear in response to the tone alone.

A term used to describe the ability of neuronal synapses to change their strength, becoming stronger or weaker in response to changes in their activity levels.

BDNF is a protein in the brain (and peripheral nervous system) that supports the survival, growth, and differentiation of neurons involved in memory.

The medial prefrontal cortex is a region of the brain that is associated with cognitive and executive processes such as working memory and decision-making.

The infralimbic subregion of the medial prefrontal cortex is necessary for the inhibition of conditioned fear after extinction.

The authors rule out the alarm calls as an indicator of stress and the source for door opening.

QUESTION: What other criteria could the trapped rat use to communicate its distress to the helper rat?

A group used in a study that have something in common.

The authors pitted freeing a trapped cagemate against opening a restrainer containing chocolate chips. This tests how the helper rat values freeing their friend versus accessing a tasty treat.

The amount of time the helper rat remained frozen after door opening significantly decreased by day 6.

This suggests the helper rat expected the door to fall as a result of its action.

Meaningful, noteworthy, important.

The free rat moved around much more quickly after the door opening that freed the trapped rat. The authors interpret this increase in activity as an indication of the importance of the freeing event in the mind of the rescuing rat.

Pierced with holes.

Conditioned behavior in which an individual gives up trying to escape a painful situation after repeatedly failing to escape. http://dictionary.reference.com/browse/learned+helplessness

Learned helplessness occurs when an animal is repeatedly subjected to an aversive stimulus that it cannot escape. Eventually, the animal will stop trying to avoid the stimulus and behave as if it is utterly helpless to change the situation.

Even when opportunities to escape are presented, this learned helplessness will prevent any action http://psychology.about.com/od/lindex/f/earned-helplessness.htm

Learned helplessness is also a model for depression in rodents.

Reduced or suppressed.

Voluntarily helping others.

Actions that help others caused by a feeling of empathy.

Condition of the mind that drives a behavior

How does the author estimate the number of elephants killed based on the weight of seized ivory?

It's known that only about 10% of all smuggled goods, such as ivory, drugs, or weapons, are caught by customs. So if 51 tons of seized ivory is only 10% of all poached ivory, the actual amount of all smuggled ivory should be 10 times as high, or about 510 tons (510,000 kilograms).

510,000 kg of ivory corresponds to about 51,000 elephants.

In this study the authors used improved methods to identify the geographic origin of the largest ivory seizure since the 1989 ivory trade ban. They showed that the ivory was from savanna elephants from a narrow east-to-west band of southern Africa, centered on Zambia.

The findings enabled law enforcement to focus their investigation to a smaller area and fewer trade routes. They also led the Zambian government to improve antipoaching efforts.

This earlier paper by the first author describes in greater detail how the genetic reference map was constructed. It also explains the statistical smoothing method that the authors used to assign a geographic location to seized ivory.

This paper shows that African elephants that live in forests are actually a different species than African elephants that dwell in the savanna. Until this paper, all African elephants had been grouped together as a single species.

The authors proposed two species names: Loxodonta africana for the savanna elephants and L. cyclotis for the forest elephants.

This document is produced by the United Nations Office on Drugs and Crime. It analyzes a range of key transnational crime threats and offers a view of its global dimensions.

The Convention on International Trade in Endangered Species Decision 16.83 refers to the "Monitoring of illegal trade in ivory and other elephant specimens (Elephantidae spp.)."

It states that any party involved in large scale ivory seizures (of 500 kg or more) has to collect samples from the ivory within 90 days of the seizure and, if possible, from all large seizures from the past 24 months. The samples are supposed to be handed in to the appropriate forensic analysis facilities that can reliably determine the origin of the ivory samples so that the crime can be immediately addressed.

The Convention on International Trade in Endangered Species (CITES) of Wild Fauna and Flora is an international United Nations agreement between governments.

The goal is to ensure that international trade with specimens of wild animals and plants does not threaten their survival. CITES implements controls in the international trade with specimens of selected species.

This paper examined the long-term impact of poaching on elephant family structure, stress levels, and reproductive output approximately 15 years after the 1989 ivory ban was implemented. Before the ban, widespread poaching drastically altered the demographic structure of the African elephant family groups by decreasing the number of old adult female elephants.

The authors specifically examined 218 adult female African elephants from 109 groups that differed in size, age structure, and average genetic relatedness.

Females from groups that lacked an old matriarch, first-order relatives, and strong social bonds had significantly higher stress hormone levels than females from groups where these features existed. Female elephants from groups disrupted by poaching had significantly lower reproductive output.

The negative impact of poaching persisted 15 years after the 1989 ivory ban was implemented.

Since 2006, most ivory poaching occurred in just two key areas.

The author’s suggest that the actual accuracy of their assignment method is very high because they used all the reference samples to assign seized ivory.

Poaching activity is highest in a few key regions.

To test how accurately the reference map predicts geographic origins, the authors treated some of the reference map samples as unknown samples. They then determined how well the reference map predicts the origin of that sample.

Voronoi diagrams or polygons divide a plane into regions based on distance to certain points of interest. They have distance information that can help answer questions like “which object is closest to point P?” and “where is the nearest hospital from point Q?”

Table S2 has a complete list of the countries, location names, regions, sample sizes, and longitudes and latitudes for the all 1350 reference samples.

The method relies on noninvasive techniques that acquire DNA from elephant scat.

The "spatial smoothing" method assumes that populations close to one another are genetically more similar than populations that are more distant.

The scientists used this method separately for reference samples from savanna and forest elephants to create maps that spanned all of Africa. This way, they could assign tusks without known origin to any location in Africa, not just to those few areas where reference samples are available.

A Markov chain refers to a sequence of random events or variables, where each event is dependent on the previous event.

In biology, Markov chain algorithms are often used to model population processes or to describe gene frequencies in populations.

Here, the researchers used a statistical method to model complicated allele distributions and assign geographic locations to seized ivory.

An accumulating body of work published in references 9-12 set the stage and enabled the current study.

For example, a study in 2001 revealed that African elephants that dwell in the forest are actually a different species than African elephants that live in the savanna. Until this study, these groups were lumped together as one species.

A stretch of repetitive DNA in which sequences of base pairs are repeated, typically two to seven times.

Example: GATC GATC GATC GATC GATC

Allele frequency is the relative frequency of a particular allele (or gene variant) in a population. Allele frequencies are shown as fractions or percentages.

An allele is one of two or more alternative forms of a gene that are located at the same position (genetic locus) on a chromosome.

The genotype is the genetic makeup of an organism. It can also refer to the two inherited alleles of a particular gene.

Forensics experts have traditionally been unable to determine the geographic origin of poached ivory. That's because the illegal ivory is usually caught while in transit, and ivory isn't necessarily exported from the same country in which it was poached.

A species that is crucial to how an ecosystem functions. If the keystone species were removed, the ecosystem would dramatically change or cease to exist.

Ivory is a hard, creamy white material that is derived from tusks and incisor teeth of animals, including elephants.

There are two subspecies of African elephants, the African forest elephant and the African savanna elephant.

Transnational organized crime involves associations or groups of individuals that profit from the sale of illegal goods across national borders, creating international illegal markets.

Activities of transnational organized crime include drug trafficking, human trafficking, money laundering, sale of counterfeit goods, and illegal wildlife trade.

A place of significant activity or danger.

Illegal hunting, killing, or capturing of wild animals.

Author's Hypothesis: 1

To assess whether the hypothesis is correct, the authors stated that first and foremost the incidence (amount of) non-measles death each year should correlate (increase or decrease with) the levels of measles infections that occurred in that same year. In other words, when there are high levels of measles disease this should result in high levels of non-measles infections and mortality, and vise versa.

It is common for a paper to contain an "Acknowledgments" section to thank the people and organizations without whom the study could not have occurred, but who were not sufficiently involved in the study to be included as authors on the paper.

Commonly included in this section are funding agencies that provided the money for the study, core facilities that (in exchange for a fee) provided services or instruments to perform assays included in the study, and collaborators who provided reagents or materials for the study.

The authors offered sugar solutions containing increasing amounts of caffeine to honeybees. They found that the honeybees preferred not to drink the sugar solutions containing higher amounts of caffeine. At caffeine concentrations greater than 1 mM, the sugar solutions were too bitter for the honeybees.

As shown in Figure 1, the amounts of caffeine in the nectar of the plants tested were lower than this amount, indicating that the honeybees would have had no problem drinking their nectar.

A technique that first separates individual chemicals present in a sample (via liquid chromatography) and then identifies what those chemicals are by measuring the masses of the particles in those separated chemicals (via mass spectrometry).

Liquid chromatography separates out the different chemicals in the sample by forcing a liquid containing the sample at a very high pressure through a column. This column contains a solid material that the particles in the sample will cling to.

Different chemicals in the sample will interact slightly differently with that solid material, and so they will flow through the column at different rates. This causes them to separate out so the investigators can look at each of these chemicals individually in the next step and try to figure out what they are.

Mass spectrometry allows investigators to identify what the now-separated chemicals are by measuring the mass-charge ratio of the particles that make up the chemicals.

In order to do this, the chemicals are bombarded with electrons, causing some of their molecules to break apart into charged fragments. Those charged fragments are then run through an electromagnetic field, and naturally separate according to their mass-charge ratio.

The pattern of separation that results is called a "mass spectrum." By looking at the masses of the individual particles that make up a chemical, we can guess what that chemical is.

For example, if the mass spectrum told us that we had 2 particles the mass of a hydrogen atom and 1 particle the mass of an oxygen atom, we would deduce that we had a water molecule on our hands.

An organism that moves pollen from the male reproductive organs of a flower to the female reproductive organs of flower, resulting in fertilization.

Without pollinators, many types of flowers would not be able to reproduce. Types of pollinators include honey bees, butterflies, and hummingbirds.

See more about pollinators in this video from National Geographic: People, Plants, and Pollinators

Myosin is the motor protein for the cytoskeletal protein actin. These two proteins make up much of the cytoskeleton in muscle cells and thus myosin is good marker for skeletal muscle.

The authors can not possibly show a picture of every single animal they performed this experiment on so they show two "representative" animals.

That is, two animals that best show what they saw in the rest of the animals.

From the information provided by Singer and Craven (1948), whatever role the nerves are playing with blastema, it is happening early in regeneration.

When they remove the nerve later in regeneration there is no effect.

Sidman and Singer (1951) and Drachman and Singer (1971) demonstrated that neither activation of the neurons nor the release of neurotransmitters play a role in limb regeneration.

There is likely something else about these nerves that give them their status in limb regeneration.

Prevented.

The grouping of all anterior gradient proteins (see below).

The axis extending from the shoulder (proximal) to the tips of the fingers (distal).

In other words, "proximal or distal identity." Proximal meaning near the point of attachment versus distal meaning away from the point of attachment.

A cell surface protein studied for its roles in salamander limb regeneration. To date, the Prod 1 gene is only present in salamander species.

Findings from this study suggest that when juveniles are not engaged in supervised activities they are more likely to engage in certain anti-social behaviors; at the same time, the increase in interactions associated with school attendance leads to more interpersonal conflict and violence.

Using Census and FBI data, this study finds that schooling significantly reduces the probability of incarceration and arrest.

Controlling Crime considers alternative ways to reduce crime that do not sacrifice public safety. Among the topics considered here are criminal justice system reform, social policy, and government policies affecting alcohol abuse, drugs, and private crime prevention.

In this book, W. J. Wilson persuasively argues that problems endemic to America's inner cities--from fatherless households to drugs and violent crime--stem directly from the disappearance of blue-collar jobs in the wake of a globalized economy

This paper concludes that the most efficient strategy for strengthening the future workforce, both economically and neurobiologically, and improving its quality of life is to invest in the environments of disadvantaged children during the early childhood years.

A brief overview of research on the relationship between work and crime.

This study showed that unemployment and crime mutually influence one another over the individual's life span.

Social-emotional learning is a particular approach to teaching people how to manage and process their emotions.

This study is randomly assigning half of the treatment group to social-emotional learning to see if this kind of curriculum has any effect on rates of violent activity.

The link below provides more detail on what social-emotional learning entails and can help you consider why this would be an important part of this kind of study:

http://greatergood.berkeley.edu/article/item/how_social_emotional_learning_transforms_classrooms

Professor Wilson has been a pioneering researcher on issues of poverty. His website shows examples of his past research.

https://www.hks.harvard.edu/about/faculty-staff-directory/william-julius-wilson

From their PCR genotyping experiment, the authors confirmed that F1 male MCR flies only had DNA bands from the PCR reactions that amplify the MCR insertion. F1 females had bands in all reactions, indicating that some females had one wildtype copy of the y+ allele and one MCR target copy.

From this result, the authors concluded that these females were mosaic.

The authors' goal was to develop a novel way to create homozygous mutations without the need to interbreed heterozygotes. They turned to CRISPR-Cas9 technology to accomplish this. The idea was to insert genes encoding Cas9 and the gRNA into the genome precisely at the gRNA cut site.

First, they created a genetic construct containing the Cas9 protein coding sequence, a Cas9 guide RNA targeting their locus of interest, and flanking homology arms with sequence homology to their sequence of interest. They used this construct to create transgenic flies to test out their method.

CRE Integrases/recombinases (causes recombination) are a family of enzymes which catalyze recombination, i.e., exchange of genetic material either between multiple chromosomes or between different regions of the same chromosome.

They delete segments of DNA flanked by LoxP sites (floxed) in experimental animals, and can generate animals with mutations limited to certain cell types (tissue-specific knockouts) or animals with chemically inducible mutations (time-specific inducible knockouts).

Author's Hypothesis: 3

The mathematically calculated prevalence of immune-amnesia in the population (i.e. the number of people with the adverse immune-suppressive sequelae of measles) will increase for any given point in time. The calculated prevalence of immune-amnesia for each particular hypothesized duration of immune-amnesia tested can be correlated to the number of non-measles infectious disease deaths from year to year. Thus, each different duration of immune-amnesia that is tested will correlated differently (better or worse) with the number of non-measles deaths.

This third part of the hypothesis simply states that, as the hypothesized duration of immune-amnesia is changed, the 'best guess' for the true duration of immune-amnesia will be that duration which leads to a calculated prevalence of immune-amnesia that best correlates with the amount of non-measles infectious disease deaths.

Essentially, the who commissioned a group of expert scientists to take an objective look at all of the research that has been published in order to assess the evidence that there is truly a reduction in all-cause childhood mortality following measles vaccination.

They found that there is in fact very strong evidence that all-cause mortality is reduced following vaccination.

However, when they looked at all of the published studies they could not conclude that there is strong evidence as to why this happens because there are very few reports that successfully describe a mechanism for the reduced mortality.

Other researchers have attempted to explain the beneficial effect of measles vaccination by suggesting that the vaccination against measles may also protect from pathogens that have similar features as the measles virus.

This type of protection, often conferred by T-cells, is called 'cross-reactive' because the same T-cells that might fight against the measles virus could also 'cross' over and fight against, or 'react' to an infection that is similar to measles. Hence the term cross-reactive T-cell response.

The articles referenced (14-17) are works by other basic researchers who have tried to better understand the cellular cause of this immunosuppression after measles infections.

Researchers have identified types of cells and chemicals released by cells during measles infection that may help to explain this phenomenon.

Herd immunity is a key principle in infectious disease vaccination. Epidemiologists, scientists who study patterns in disease, have discovered that if you vaccinate the majority of people in a population even those who are not vaccinated don't catch the infectious disease. This effect is because the likelihood of coming into contact with anyone else who could also get sick is so small (because everyone else is vaccinated).

Further thoughts: Does herd immunity apply to NON-infectious disease vaccines, like a hypothetical vaccine that could prevent heart disease?

Hint: does your risk for heart disease depend on if your close contacts have heart disease?

Still confused or want to learn more? VIsit http://www.vaccines.gov/basics/protection (vaccines.gov) for a more detailed explanation and pictures.

High-Income countries are those countries whose residents make good living wages. Examples include the US, England, Japan, and many others. This is in contrast to low-income countries where there is more poverty and thus more disease and higher mortality rates (more death) for many diseases.

It is important to know that this study is considering high-income countries because the outcomes of many of the nonmeasles infectious diseases are worse, and more children die in low-income countries. This makes the ability to study how measles effects these outcomes more difficult.

This topic will be discussed more later in the paper in a Previous Work annotation.

Infectious diseases are illnesses that can be passed from one person to another, like the flu. These are the diseases whose outcomes are examined in this paper.

Non-infectious diseases are like heart disease or diabetes which you cannot catch from someone else. Non-infectious diseases are NOT important for this paper and have not been shown to be effected by measles.

Importantly, these nonmeasles infectious diseases include opportunistic infections mentioned previously.

Immunosuppression is when the body's defense mechanism against disease, called the immune system no longer works as well as it should

In 2015, an outbreak of measles at Disneyland resulted in 147 unvaccinated children getting sick. Fortunately, no one died of the disease.

Read more about the outbreak and the threat of not vaccinating children here: [Measles Outbreak Traced to Disneyland Declared Over.]

http://www.nbcnews.com/storyline/measles-outbreak/measles-outbreak-traced-disneyland-declared-over-n343686

When all conclusions are put together the authors found that the immune-amnesia resulting from measles virus infections could be indirectly responsible for up to half of all childhood deaths from infectious disease.

The authors determined this using statistics and found that when all of the deaths associated with the measles immune-amnesia lasting for 2-3 years were removed, then the overall rate of non-measles infectious disease deaths was calculated to be only half the rate of deaths measured without 'controlling' for the effects of measles.

Gamma Transformation

The number of immunomodulated individuals (after measles infection) was diveded by the total population of interest. This means that the data is presented as a percent of the whole rather than absolute numbers.

It is important to look at data such as this as a percent of the whole and not just total numbers so that the numbers can be compared across time and across populations. For example, if a total of 50 people out of 100 people get sick and die from some illness, that is a very high number or rate of death (50%). However, if 50 people die out of 1 million who got sick, then even though it is the same number of people who died, it is a much much lower rate of death per person (0.005%). When the number of people who are ill is divided by the total population at risk for the illness, the answer to the division problem is essentially rate or the prevalence of the illness in the population.

Once the 'baseline prevalence' of measles immune-amnesia was calculated, the authors used a tool from statistics, called a gamma function, to make theoretical calculations of how many people from this 'baseline prevalence' would truly still have immune amnesia, at a certain point in time since the measles infection.

The purpose of using the gamma function was to create a distribution of immune-amnesia with time following measles. For example, if the immune amnesia would last for 3 years, it wouldn't make sense, biologically, to assume that 100% of children have immune-amnesia at the end of three years since getting measles and then 0% have immune-amnesia 1 day later, at the beginning of the fourth year since getting measles. The gamma function allowed a smooth gradient where 100% of children had immune amnesia directly following measles infection and this gradually dropped over time to 0% of children with immune amnesia by, for example, four years following measles. In the study, how long it took to reach 0% was what was defined by the gamma function.

Author's Hypothesis: 2

If the long-term immune-amnesia predicted by the authors is true, there should be a measurable difference, detectable in the population-level data, to prove this hypothesis. The authors' will show this by accounting for the length of time that the immune system remains impaired due to the immune-amnesia or immuno-modulation as they also refer to it. They suggest that this immuno-amnesia is like a measles "Shadow" that remains even after the measles epidemic has ended. At a population level, it can be accounted for as an accumulation of past measles cases or epidemics.

For example, if there is a very large amount of measles (a high incidence of measles) in year 1, and the immune-amnesia following measles lasts for 3 years, then for up to three years after this large measles epidemic there might be a noticeable increase in other infectious diseases due to the impaired immune resistance from the immune-amnesia.

So, if the amnesia lasts for 3 years, then during year 2, for example, the amount of other infectious diseases during that year will be proportional not only to the amount of measles that happened during year 2, but rather to the amount of measles that happened during both years 1 and 2. Similarly, during year three, the amount of non-measles infections will be a reflection of the amount of measles that happened in that year, year 3, as well as years 2 and 1. However, because we said that the immune-amnesia in this example lasts for 3 years only, then if we look at the amount of non-measles infections in year 4, it will be a reflection of the amount of measles that happened in that year, year 4, plus year 3 and year 2. It will not however reflect the large measles epidemic that happened in year 1 anymore, because those children would no longer have immune amnesia by year 4.

This is the authors' main hypothesis for the paper.

The authors' hypothesize that if impaired host resistance (immune memory loss, also known as immune-amnesia, or, as they describe it in the text, immunomodulation) exists after measles infection, that they will be able to observe this phenomenon by examining population-level or epidemiological data. As discussed above, this sort of data is collected for each country by government health agencies (like the U.S. Centers for disease control and prevention) in order to monitor disease incidence and prevalence over time. It includes the age of patients, why they are sick, when they are sick, and if they die, along with lots of other data not used in this study.

As previously discussed, they will be examining epidemiological data from high-income countries where the general incidence of childhood disease is lower.

This main hypothesis is divided into 4 sub-level hypothesis examined in this paper and annotated in the next paragraph.

Researchers used a measles virus that glows green and can infect monkeys to study where the virus goes in the body and what happens after infection that can explain what is going on. They observed that the virus infects and kills T- and B-cells, the important cell types required for the adaptive memory immune response.

Destruction of these cell thus causes a loss of the memory that these T cells had regarding previous pathogens they had encountered, and it leaves the patient susceptible to infections that they were previously resistant to. This type of immune memory loss is termed immune-amnesia, similar to the type of memory loss that a person may have after getting hit very hard in the head, only immune-amnesia is due to loss of immune cells while amnesia after getting hit in the head might be due to the loss of some brain cells.

Thus, it is possible that by vaccinating children against measles, the children would never get the measles infection and would therefore not lose their B- and T-cell memory, thus allowing them to remain resistant to all the pathogens against which they had spent the first years of their life building up immune memory.

Other researchers have attempted to explain the beneficial effect of measles vaccination by showing some evidence that vaccination may allow the innate immune system to take on some ability to remember particular pathogens, and thus be more effective at reducing other infectious diseases.

Recall that innate immunity is the first line of defense. It is the generic immunity that is not usually assumed to have any memory and therefore doesn't usually totally cure one from an infection.

In this case, there is some evidence that by vaccinating an individual, the individual's innate immune response may be 'trained' to be more like a memory or adaptive immune response. This could be beneficial because it means that the innate response, which is usually weak but has the advantage of being able to act against almost any infection, could actually, by taking on adaptive immune response type qualities, become stronger and cure from infections.