Tag: Learning

Synchronization of Memory Cells Critical For Learning and Forming Memories

Credit: UNH

On the left is an enlarged image showing many hippocampal neurons, most of which are silent and only a few are active. On the right are close ups of three highly active neurons, or memory cells, which become synchronized after memory formation

The phrase “Pavlov’s dogs” has long evoked images of bells, food and salivating dogs. Even though this tried-and-true model of repetitive patterns mimics a variety of learning processes, what happens on a cellular level in the brain isn’t clear. Researchers at the University of New Hampshire took a closer look at the hippocampus, the part of the brain critical for long-term memory formation, and found that the neurons involved in so-called Pavlovian learning shift their behavior during the process and become more synchronized when a memory is being formed – a finding that helps better understand memory mechanisms and provides clues for the development of future therapies for memory-related diseases like dementia, autism and post-traumatic stress disorder (PTSD).

“There are tens of millions of neurons in the hippocampus but only a small fraction of them are involved in this learning process” said Xuanmao (Mao) Chen, assistant professor of neurobiology. “Before engaging in Pavlovian conditioning, these neurons are highly active, almost chaotic, without much coordination with each other, but during memory formation they change their pattern from random to synchronized, likely forging new connecting circuits in the brain to bridge two unrelated events.

In the study, recently published in The FASEB Journal, researchers looked at Pavlovian learning patterns, or respondent conditioning, in mice. In the beginning, before any repetitive learning exercises, the mice did not know what to expect and using special imaging with an endomicroscope the researchers saw that the neural activity was disorderly. But after repeating different tasks associated with a conditional stimulus, like a tone or bell, the mice began to recognize the pattern and the highly active neurons became more synchronized. The researchers hypothesize that without forming synchronization, animals cannot form or retrieve this type of memory.

In the 1890’s, Russian psychologist, Ivan Pavlov discovered classical conditioning through repetitive patterns of bell ringing which signaled to his dogs that food was on its way and stimulated salivation. This same learned behavior is important for episodic knowledge which is the basis for such things as learning vocabulary, textbook knowledge, and memorizing account passwords. Abnormal learning processing and memory formation are associated with a number of diseases like dementia, autism, and PTSD. People who struggle with these cognitive dysfunction-related disorders may have trouble retaining memories or can even form too strong a memory, as with PTSD patients. The UNH researchers believe that understanding the fundamentals of how classical conditioning shape neural connections in the brain could speed up the development of treatments for these disorders in the future.

Contributing to these findings are Yuxin Zhou, doctoral candidate; Liyan Qiu, research scientist; both at UNH, and Haiying Wang, assistant professor at the University of Connecticut.

This work was supported by the National Institutes of Health (NIH) and the Cole Neuroscience and Behavioral Faculty Research Awards.

The University of New Hampshire inspires innovation and transforms lives in our state, nation and world. More than 16,000 students from all 50 states and 71 countries engage with an award-winning faculty in top-ranked programs in business, engineering, law, health and human services, liberal arts and the sciences across more than 200 programs of study. As one of the nation’s highest-performing research universities, UNH partners with NASA, NOAA, NSF and NIH, and receives more than $110 million in competitive external funding every year to further explore and define the frontiers of land, sea and space. 

Some Learning is A Whole-Brain Affair

Credit: Richard Roth and Richard Huganir

AMPA receptors in green on neurons in magenta at one time point in a live mouse.

Researchers at Johns Hopkins Medicine have successfully used a laser-assisted imaging tool to “see” what happens in brain cells of mice learning to reach out and grab a pellet of food. Their experiments, they say, add to evidence that such motor-based learning can occur in multiple areas of the brain, even ones not typically associated with motor control.

“Scientists should be looking at the entire brain to understand specific types of learning,” says Richard Huganir, Ph.D., Bloomberg Distinguished Professor and Director of the Solomon H. Snyder Department of Neuroscience at the Johns Hopkins University School of Medicine. “Different parts of the brain contribute to learning in different ways, and studying brain cell receptors can help us decipher how this works.”

The work, say the researchers, may ultimately inform efforts to develop treatments for learning-based and neurocognitive disorders.

In a report on the work, appearing online Dec. 31 in Neuron, Huganir and his research team say they focused on AMPA-type glutamate receptors, or AMPARs, key molecules that help send messages between brain cells called neurons. AMPARs function like antennas that form along the surface of a particular spot on neurons called a synapse, where it receives molecular signals from other neurons.

To monitor and measure AMPAR levels in mouse brains, scientists previously had to dissect the organ before and after a learning experiment and compare differences. Now, scientists have ways to directly view the brain during learning, recording thousands of synapses at a time.

In the new experiments, scientists injected DNA-encoding AMPARs carrying a fluorescent tag into the brains of mice, and used an electrical pulse to get neurons to absorb the AMPAR DNA. Next, with a tool called two-photon microscopy, the scientists used a laser — essentially an intensely focused beam of light — to detect and measure the amount of fluorescence coming from the tagged AMPARs.

More fluorescence is an indication of increased AMPAR activity and messaging between neurons, a good sign that learning and memory building is taking place in those neurons, Huganir says.

To “see” what learning looked like in the test animals’ neurons, Huganir’s team trained mice to reach for and grab a food pellet placed just outside their cage using their paws. Normally, mice get pellets with their mouths.

While the mice were learning how to reach for the pellet, the scientists found an approximately 20% increase in the activity of AMPARs in an area of the brain known as the motor cortex, which is known for controlling and precisely moving muscles. On neurons, the AMPARs look like lights on a Christmas tree and glow brighter with increasing activity.

But the experiments also showed the same increase in AMPAR activity levels in the visual cortex too.

“This made sense because vision is very important for motor control,” says Richard Roth, Ph.D., currently a postdoctoral fellow at Stanford University, but who performed experiments for this study as a graduate student in Huganir’s laboratory.

“So, we did the same experiment again, but with the lights switched off,” says Roth.

Using infrared light, which the mice couldn’t see, the mice eventually learned to successfully grab the food, but there was a smaller increase (10%) in the activity of AMPARs in the visual cortex.

“We believe the mice brains are using different sets of sensory cues in the dark to learn the motor task, including touch and smell, enabling these other senses to take over,” says Roth.

Next, the research team repeated the experiments using specialized light-activated modulators to shut down neurons in either the motor or visual cortex.

If the mice were trained to get the pellet with the room lights on, the mice could not complete the task if their visual cortex was shut down. “Clearly, these mice relied on learning centralized in their visual cortex to reach the pellet,” says Roth.

However, mice initially trained to grab the pellet in the dark could still complete the task, even if their visual cortex was shut down.

“We’ve traditionally thought that motor-based learning happens solely in the motor part of the brain, but our studies and others now show that it’s not as specific as we had thought. There is more of a brainwide effect in learning,” says Roth.

Huganir notes that among the genes that control neuronal receptors involved in learning is SYNGAP. His and others’ research has shown that when the gene is mutated, it contributes to conditions including intellectual disability, autism and schizophrenia — all conditions marked in part by disrupted thinking and learning.

This research was supported by the National Institutes of Health (R01NS036715 and P50MH100024).

Other scientists who contributed to this research include Robert H. Cudmore from the University of California School of Medicine, Davis; Han Tan and Ingie Hong from Johns Hopkins; and Yong Zhang from Peking University, Beijing.

DOI: 10.1016/j.neuron.2019.12.005

iPads and Teens with Autism

As adults, individuals with autism spectrum disorder (ASD) can be highly dependent on family members or assistance programs for their day-to-day living needs. It has been reported that following high school and up to eight years after, only 17 percent of adults with ASD live independently. Developing skills like cooking, getting dressed and cleaning are essential to promoting autonomy and self-determination and improving quality of life. For some individuals with ASD, completing daily tasks can be challenging because they often involve sequential steps.

Research has shown that people with ASD are strong visual learners. With technological advances, devices such as smartphones and tablets have become more portable and ultimately, accessible to caregivers. However, few studies have examined whether parents can learn to effectively deliver evidence-based practices using portable, mainstream devices like an iPad.

Researchers from Florida Atlantic University and collaborators conducted a small, novel study to examine whether video prompting interventions using an iPad could be effective in increasing parents’ competence and confidence to use mobile devices to interact with their adolescent children with ASD. The objective was to evaluate the effects of behavior skills training with follow-along coaching to instruct parents to deliver video prompting with an iPad to teach daily living skills to their children. What makes this study unique is that parents of adolescents were coached and learned to use an iPad in their own homes. While other studies have been successful in teaching parents to implement evidence-based practices, they largely targeted parents of young children.

For the study, published in the Journal of Autism and Developmental Disorders, researchers targeted parents of adolescents with ASD who would be transitioning into adulthood in the near future and who needed to cultivate independent living skills to decrease dependency on others, while improving self-esteem and confidence. Each child, between the ages of 12 and 17 years old, had to complete a skill selected by the parents: make a bed, cook pasta or tie shoelaces. Parents received guidance on using an iPad and implementing the intervention. They learned how to guide their child to watch the instructional video, imitate what they viewed, and then provide appropriate feedback.

Depending on the outcome, parents were asked to provide praise, correct the errors or demonstrate the step themselves if the child made two or more consecutive errors on the same task step. Lead researcher of the study Elisa Cruz-Torres, Ed.D., in the Department of Exceptional Student Education in FAU’s College of Education, visited families’ homes three times a week for one hour for each family’s intervention, which lasted between five to seven weeks.

Results of the study showed that all of the children substantially improved correct and independent completion of their daily living skills, which validates that video prompting procedures are effective in ameliorating skill deficits.

While parents were successful in implementing the video prompting preparation and procedures, they were inconsistent with the consequence strategies such as social praise and error correction. None-the-less, the children still mastered their skills and maintained the skill three weeks after the end of the intervention.

“Our findings show that video prompting interventions produced both immediate and lasting effects for children with autism spectrum disorder and that parents can be powerful delivery agents to increase independence in their children,” said Cruz-Torres. “While it is desirable that parents follow steps exactly, we learned that even with slight variations in parent delivery, the teens still mastered the intended skills.”

Data from this study also revealed that none of the children required more than 17 interventions to reach mastery criteria. In addition, this study draws attention to the importance of evidence-based practices for families of older children with ASD.

“Now, when I’m working with my son to learn a new skill or even talk about a new skill, because of this study I have learned to break it down into smaller pieces rather than asking him to do the whole thing. We use this concept for other things like doing laundry. I’ve also learned that he is very responsive to praise,” said Susan Freeman, a parent in the study. “John is a very visual learner so being able to see what each step should look like enables him to complete the task. He’s still making his bed and we’re working on changing the sheets, which is a new skill. I don’t have to make his bed anymore.”

Freeman’s son Johnathon “John” DiFusco also is pleased with this instructional method, which makes him feel good about himself as well as proud.

“Now, I can be on time for school and I also know how to vacuum,” said DiFusco.  

Co-authors of the study are Mary Louise Duffy, Ph.D., a retired professor; Michael P. Brady, Ph.D., a professor and chair; and Peggy Goldstein, Ed.D.; an associate professor, all within FAU’s Department of Exceptional Student Education; and Kyle D. Bennett, Ed.D., associate professor, Department of Teaching and Learning, Florida International University.  

– FAU – 

About Florida Atlantic University:

Florida Atlantic University, established in 1961, officially opened its doors in 1964 as the fifth public university in Florida. Today, the University, with an annual economic impact of $6.3 billion, serves more than 30,000 undergraduate and graduate students at sites throughout its six-county service region in southeast Florida. FAU’s world-class teaching and research faculty serves students through 10 colleges: the Dorothy F. Schmidt College of Arts and Letters, the College of Business, the College for Design and Social Inquiry, the College of Education, the College of Engineering and Computer Science, the Graduate College, the Harriet L. Wilkes Honors College, the Charles E. Schmidt College of Medicine, the Christine E. Lynn College of Nursing and the Charles E. Schmidt College of Science. FAU is ranked as a High Research Activity institution by the Carnegie Foundation for the Advancement of Teaching. The University is placing special focus on the rapid development of critical areas that form the basis of its strategic plan: Healthy aging, biotech, coastal and marine issues, neuroscience, regenerative medicine, informatics, lifespan and the environment. These areas provide opportunities for faculty and students to build upon FAU’s existing strengths in research and scholarship. For more information, visit www.fau.edu.