New research identifies how the birth of new neurons can reshape the brain. 
Posted Feb 06, 2017


  • XStudio3D/Shutterstock

    Source: XStudio3D/Shutterstock

    For over a decade, neuroscientists have been trying to figure out how neurogenesis (the birth of new neurons) and neuroplasticity (the malleability of neural circuits) work together to reshape how we think, remember, and behave.

    This week, an eye-opening new study, “Adult-Born Neurons Modify Excitatory Synaptic Transmission to Existing Neurons (link is external)” reported how newborn neurons (created via neurogenesis) weave themselves into a “new and improved” neural tapestry. The January 2017 findings were published in the journal eLife.

    During this state-of-the-art study on mice, neuroscientists at the University of Alabama at Birmingham (UAB) found that the combination of neurogenesis and neuroplasticity caused less-fit older neurons to fade into oblivion and die off as the sprightly, young newborn neurons took over existing neural circuits by making more robust synaptic connections.

    For their latest UAB study, Linda Overstreet-Wadiche (link is external) and Jacques Wadiche (link is external)—who are both associate professors in the University of Alabama at Birmingham Department of Neurobiology—focused on neurogenesis in the dentate gyrus region of the hippocampus.

    The dentate gyrus is an epicenter of neurogenesis responsible for the formation of new episodic memories and the spontaneous exploration of novel environments, among other functions.

    More specifically, the researchers focused on newly born granule cell neurons (link is external) in the dentate gyrus that must become wired into a neural network by forming synapses via neuroplasticity in order to stay alive and participate in ongoing neural circuit function.

    There are only two major brain regions that are currently believed to have the ability to continually give birth to new neurons via neurogenesis in adults; one is the hippocampus (long-term and spatial memory hub) the second is the cerebellum (coordination and muscle memory hub). Notably, granule cells have the highest rate of neurogenesis. Both the hippocampus and cerebellum are packed, chock-full with granule cells.

    Interestingly, moderate to vigorous physical activity (MVPA) is one of the most effective ways to stimulate neurogenesis and the birth of new granule cells in the hippocampus and the cerebellum. (As a cornerstone of The Athlete's Way platform, I've been writing about the link between MVPA and neurogenesis for over a decade. To read a wide range of Psychology Today blog posts on the topic click on this link (link is external).)

    Instituto Santiago Ramón y Cajal, Madrid, Spain

    Drawing of Purkinje cells (A) and granule cells (B) from pigeon cerebellum by Santiago Ramón y Cajal, 1899.

    Source: Instituto Santiago Ramón y Cajal, Madrid, Spain

    Granule cells were first identified by Santiago Ramón y Cajal, who made beautiful sketches in 1899 that illustrate how granule cells create synaptic connections with Purkinje cells in the cerebellum. His breathtaking and Nobel Prize-winning illustrations are currently on a museum tour across the United States (on loan from the Instituto Santiago Ramón y Cajal in Madrid, Spain) as part of "The Beautiful Brain" traveling art exhibit.  

    (As a side note, the olfactory bulb is the only other subcortical brain area known to have high rates of neurogenesis. Speculatively, this could be one reason that scent plays such an indelible and ever-changing role in our memory formation and ‘remembrance of things past.’)

Neurogenesis and Neuroplasticity Work Together to Rewire Neural Circuitry

One of the key aspects of neural plasticity is called Neural Darwinism, or "neural pruning," which means that any neuron that isn’t ‘fired-and-wired’ together into a network is likely to be extinguished. The latest UAB research suggests that newborn neurons play a role in expediting this process by "winning out" in a survival of the fittest type of neuronal battle against their more elderly or worn out counterparts.

Long before there were neuroscientific studies on neuroplasticity and neurogenesis, Henry David Thoreau unwittingly described the process of how the paths that one's mind travels can become hardwired (when you get stuck in a rut) by describing a well-worn path through the woods. In Walden, Thoreau writes,

"The surface of the earth is soft and impressible by the feet of men; and so with the paths which the mind travels. How worn and dusty, then, must be the highways of the world, how deep the ruts of tradition and conformity!"

From a psychological standpoint, the latest UAB discovery presents the exciting possibility that when adult-born neurons weave into existing neural networks that new memories are created and older memories may be modified.

Through neurogenesis and neuroplasticity, it may be possible to carve out a fresh and unworn path for your thoughts to travel upon. One could speculate that this process opens up the possibility to reinvent yourself and move away from the status quo or to overcome past traumatic events that evoke anxiety and stress. Hardwired fear-based memories often lead to avoidance behaviors that can hold you back from living your life to the fullest. 


Future Research on Neurogenesis Could Lead to New PTSD Treatments

Granule cells in the dentate gyrus are part of a neural circuit that processes sensory and spatial input from other areas of the brain. By integrating sensory and spatial information, the dentate gyrus has the ability to generate unique and detailed memories of an experience.

Before this study, Overstreet-Wadiche and her UAB colleagues had a few basic questions about how the newly born granule cells in the dentate gyrus function. They asked themselves two specific questions:

  1. Since the number of neurons in the dentate gyrus increases by neurogenesis while the number of neurons in the cortex remains the same, does the brain create additional synapses from the cortical neurons to the new granule cells?
  2. Or do some cortical neurons transfer their connections from mature granule cells to the new granule cells?
Through a series of complex experiments with mice, Overstreet-Wadiche et al. found that some of the cortical neurons in the cerebral cortex transferred all of their former connections with older granule cells (that may have been worn out or past their prime) to the freshly born granule cells that were raring to go.

This revolutionary discovery opens the door to examine how the redistribution of synapses between old and new neurons helps the dentate gyrus stay up to date by forming new connections. 

One of the key questions the researchers want to dive deeper into during upcoming experiments is: “How does this redistribution relate to the beneficial effects of exercise, which is a natural way to increase neurogenesis?”

In the future, it's possible that cutting-edge research on neurogenesis and neuroplasticity could lead to finely-tuned neurobiological treatments for ailments such as post-traumatic stress disorder (PTSD) and dementia. In a statement to UAB (link is external), Overstreet-Wadiche said,

"Over the last 10 years there has been evidence supporting a redistribution of synapses between old and new neurons, possibly by a competitive process that the new cells tend to 'win.’ Our findings are important because they directly demonstrate that, in order for new cells to win connections, the old cells lose connections.

So, the process of adult neurogenesis not only adds new cells to the network, it promotes plasticity of the existing network. It will be interesting to explore how neurogenesis-induced plasticity contributes to the function of this brain region.

Neurogenesis is typically associated with improved acquisition of new information, but some studies have also suggested that neurogenesis promotes 'forgetting' of existing memories."

Aerobic Exercise Is the Most Effective Way to Stimulate Neurogenesis and Create Adult-Born Neurons

For the past 10 years, the actionable advice I've given in The Athlete's Way has been rooted in the belief that through the daily process of working out anyone can stimulate neurogenesis and optimize his or her mindset and outlook on life via neuroplasticity.

"The Athlete's Way" program is designed to reshape neural networks and optimize your mindset. Since the beginning, this program has been based on the discovery that aerobic activity produces brain-derived neurotrophic factor (BDNF) and stimulates the birth of new neurons through neurogenesis. I describe my philosophy in the Introduction to The Athlete's Way,

"Shifting the focus from thinner thighs to stronger minds makes this exercise book unique. The Athlete's Way does not focus just on sculpting six-pack abs or molding buns of steel. We are more interested in bulking up your neurons and reshaping your synapses to create an optimistic, resilient, and determined mindset. The goal is transformation from the inside out.

My mission is to get this message to you so that you can use neurobiology and behavioral models to help improve your life through exercise. I am a zealot about the power of sweat to transform people’s lives by transforming their minds. My conviction is strong and authentic because I have lived it."

I created The Athlete's Way along with the indispensable help of my late father, Richard Bergland, who was a visionary neuroscientist, neurosurgeon, and author of The Fabric of Mind (Viking).

A decade ago, when I published The Athlete’s Way: Sweat and the Biology of Bliss (link is external) (St. Martin's Press) I put neurogenesis and neuroplasticity in the spotlight. At the time, the discovery of neurogenesis was brand new, and still a radical notion in mainstream neuroscience.

In the early 21st century, most experts still believed that human beings were born with all the neurons they would have for their entire lifespan. If anything, it was believed that people could only lose neurons or "kill brain cells" as we got older.

Understandably, when I published The Athlete's Way in 2007 there were lots of skeptics and naysayers who thought my ideas about reshaping mindset using a combination of neurogenesis and neuroplasticity through moderate to vigorous physical activity were ludicrous.

For the past 10 years, I've kept my antennae up and my finger on the pulse of all the latest research on neurogenesis and neuroplasticity hoping to find additional empirical evidence that gives more scientific credibility to my system of belief and The Athlete’s Way methodology. 

Needless to say, I was over the moon and ecstatic this morning when I read about the new research by Linda Overstreet-Wadiche and Jacques Wadiche that pinpoints the specifics of how adult-born neurons modify existing neural circuits. This is fascinating stuff!

These are exciting times in neuroscience. Modern day neuroscientific techniques are poised to solve many more riddles regarding the complex mechanism by which neurogenesis and neuroplasticity work together as a dynamic duo to reshape our neural networks and functional connectivity between brain regions. Stay tuned for future empirical evidence and scientific research on neurogenesis and neuroplasticity in the months and years ahead. 

In the meantime, if you'd like to read a free excerpt from The Athlete’s Way that provides some simple actionable advice and practical ways for you to stimulate neurogenesis and rewire your brain via neuroplasticity and moderate to vigorous physical activity—check out these pages from a section of my book titled: "Neuroplasticity and Neurogenesis: Combining Neuroscience and Sport (link is external)." 





References

Elena W Adlaf, Ryan J Vaden, Anastasia J Niver, Allison F Manuel, Vincent C Onyilo, Matheus T Araujo, Cristina V Dieni, Hai T Vo, Gwendalyn D King, Jacques I Wadiche, Linda Overstreet-Wadiche. Adult-born neurons modify excitatory synaptic transmission to existing neurons. eLife, 2017; 6 DOI: 10.7554/eLife.19886 (link is external)



UAB summer neuroscience program expands with NSF funding

- February 06, 2017  

The expanded UAB Summer Program in Neuroscience, with renewed funding from the National Science Foundation, is looking for underserved undergrads for science mentoring.

spin 2017 2Krista Hoevemeyer, class of 2013, at a lab bench. UAB's SPIN program fosters career development for underrepresented minority college students and/or students from non-research-intensive universities.The University of Alabama at Birmingham Summer Program in Neuroscience, a program designed to promote careers in science to deserving undergraduate college students, has regained funding from the National Science Foundation. The new grant, $120,000 per year for three years, will allow for significant expansion of the program, which aims to foster career development and provide research training for underrepresented minority students and/or students from non-research-intensive universities.

“The SPIN program focuses on students with demonstrated scientific aptitude who have interest in pursuing a career in scientific research but have not been exposed to that environment,” said Gwendalyn King, Ph.D., assistant professor in the Department of Neurobiology and the SPIN program director. “SPIN is a 10-week research-intensive program in which students are mentored in UAB neuroscience labs to get a firsthand look at whether research is a good career option for them.”

The program enrolls 10 students each summer, usually juniors and seniors, who get hands-on experience in a laboratory, as well as career counseling. Students are paired with a UAB neuroscience faculty member and are also mentored by senior graduate students in the lab.

“The program is a real opportunity for learning what a career in science is all about,” said Lucas Pozzo-Miller, Ph.D., professor of neurobiology and SPIN co-director. “They don’t sit and watch — they are actively involved in the lab’s work. The goal of the program is that students accomplish enough to qualify for co-author status on research papers that originate in the lab.”

SPIN was originally funded by NSF for three years beginning in 2005. Following a loss of external funding in 2008, the program continued on a reduced scale through generous contributions from UAB internal organizations, including the Department of Neurobiology, the Comprehensive Neuroscience Center, the Civitan International Research Center and the Office of the Provost.

spin 2017 3SPIN participants such as Jinwoo Hur, class of 2013, spend ten weeks in UAB neuroscience research labs.The reinstatement of NSF funding will allow the program to expand the number of students enrolled, provide stipends and help cover the cost of housing and meals. Since inception in 2005, SPIN has trained 106 undergraduates hailing from 29 states and two foreign countries.

Several former participants are now graduate students at UAB.

“I went to a small, liberal arts university in Minnesota for my undergraduate degree where there was little opportunity for doing research,” said Angie Nietz, now a fifth-year graduate student in the lab of Jacques Wadiche, Ph.D., associate professor of neurobiology. “The program gave me one of my only experiences of what it is like to do research outside of a classroom setting before entering graduate school. The research experience and excellent mentorship I received prepared me for applying to and being successful in graduate school.”

Nancy Gallus did her undergraduate work in molecular medicine at the University of Tübingen, Germany, before attending the UAB Spin program. She is now a graduate student in the laboratory of Jeremy Day, Ph.D., assistant professor of neurobiology.

“SPIN was very important for me, as it was one of my first real research experiences,” she said. “It also helped me decide where I wanted to go for graduate school and how to apply.”

Shelly Nason, now a second-year graduate student in the lab of Kirk Habegger, Ph.D., assistant professor, Department of Medicine, says her Michigan liberal arts college did not offer opportunities for neuroscience research.

“SPIN was most beneficial to me in professional development, beyond the benefits of understanding what it meant to participate in actual research,” she said. “I entered the program feeling less than confident in my ability to get into graduate school, and I left with the tools and confidence that helped me receive multiple acceptance letters. I highlight the SPIN program as the best opportunity in my undergraduate studies that propelled me forward in my career as a scientist.”

Pozzo-Miller says the program has benefit even for those attendees who ultimately decide against a career in science.

“These are people who will have a voice in the future of science,” he said. “They are voters, decision-makers and potential leaders of our country, and it is incumbent on us to teach them critical thinking skills, to help them understand the importance of scientific thought, and to understand and believe in the value of science.”

“Diversity in science is extremely important, as it is in all fields,” King said. “We need investigators with different backgrounds and different experiences. This program, we hope, will foster and instill a love of science in these students.”

The deadline for applying for a position in the 2017 SPIN program in March 1. Information on applying is available online. The program runs from June 5 to Aug. 11.
The University of Alabama System Board of Trustees met at UAB and the program included an annual highlight of the institution. This year, President Watts decided to do something a bit different than other years. In highlighting the accomplishments as a University to the Board, he decided to draw attention to a small handful of outstanding faculty. He invited 5 faculty who represent excellence in their respective areas: Outstanding Nurse, Physician, Educator, Researcher and Investigator. He chose Dr. Jeremy Day to highlight as an example of an outstanding research scientist! When President Watt’s gave the short backstory of the faculty's accomplishments, he asked them to stand in the audience - then President Pro Tempore Karen Brooks asked them to come forward. Although this may not be an official award, this is a huge honor! Congratulations, Jeremy!!
Day Annual event
Brain plasticity: How adult-born neurons get wired-in
- February 2, 2017  

It appears that new cells compete to ‘win’ synapse connections away from old cells, which promotes network plasticity.

linda wadicheLinda Overstreet-Wadiche, Ph.D.

One goal in neurobiology is to understand how the flow of electrical signals through brain circuits gives rise to perception, action, thought, learning and memories.

Linda Overstreet-Wadiche, Ph.D., and Jacques Wadiche, Ph.D., both associate professors in the University of Alabama at Birmingham Department of Neurobiology, have published their latest contribution in this effort, focused on a part of the brain that helps form memories — the dentate gyrus of the hippocampus.

The dentate gyrus is one of just two areas in the brain where new neurons are continuously formed in adults. When a new granule cell neuron is made in the dentate gyrus, it needs to get ‘wired in,’ by forming synapses, or connections, in order to contribute to circuit function. Dentate granule cells are part of a circuit that receive electrical signals from the entorhinal cortex, a cortical brain region that processes sensory and spatial input from other areas of the brain. By combining this sensory and spatial information, the dentate gyrus can generate a unique memory of an experience.

Overstreet-Wadiche and UAB colleagues posed a basic question: Since the number of neurons in the dentate gyrus increases by neurogenesis while the number of neurons in the cortex remains the same, does the brain create additional synapses from the cortical neurons to the new granule cells, or do some cortical neurons transfer their connections from mature granule cells to the new granule cells?

Their answer, garnered through a series of electrophysiology, dendritic spine density and immunohistochemistry experiments with mice that were genetically altered to produce either more new neurons or kill off newborn neurons, supports the second model — some of the cortical neurons transfer their connections from mature granule cells to the new granule cells.

This opens the door to look at how this redistribution of synapses between the old and new neurons helps the dentate gyrus function. And it opens up tantalizing questions. Does this redistribution disrupt existing memories? How does this redistribution relate to the beneficial effects of exercise, which is a natural way to increase neurogenesis?

“Over the last 10 years there has been evidence supporting a redistribution of synapses between old and new neurons, possibly by a competitive process that the new cells tend to ‘win,’” Overstreet-Wadiche said. “Our findings are important because they directly demonstrate that, in order for new cells to win connections, the old cells lose connections. So, the process of adult neurogenesis not only adds new cells to the network, it promotes plasticity of the existing network.”

“It will be interesting to explore how neurogenesis-induced plasticity contributes to the function of this brain region,” she continued. “Neurogenesis is typically associated with improved acquisition of new information, but some studies have also suggested that neurogenesis promotes ‘forgetting’ of existing memories.”

The researchers also unexpectedly found that the Bax gene, known for its role in apoptosis, appears to also play a role in synaptic pruning in the dentate gyrus.

“There is mounting evidence that the cellular machinery that controls cell death also controls the strength and number of synaptic connections”

—Linda Overstreet-Wadiche

“There is mounting evidence that the cellular machinery that controls cell death also controls the strength and number of synaptic connections,” Overstreet-Wadiche said. “The appropriate balance of synapses strengthening and weakening, collectively termed synaptic plasticity, is critical for appropriate brain function. Hence, understanding how synaptic pruning occurs may shed light on neurodevelopmental disorders and on neurodegenerative diseases in which a synaptic pruning gone awry may contribute to pathological synapse loss.”

All of the work was performed in the Department of Neurobiology at UAB. In addition to Overstreet-Wadiche and Wadiche, co-authors of the paper, “Adult born neurons modify excitatory synaptic transmission to existing neurons,” published in eLife, are Elena W. Adlaf, Ryan J. Vaden, Anastasia J. Niver, Allison F. Manuel, Vincent C. Onyilo, Matheus T. Araujo, Cristina V. Dieni, Hai T. Vo and Gwendalyn D. King.

Much of the data came from the doctoral thesis research of Adlaf, a former UAB Neuroscience graduate student who is now a postdoctoral fellow at Duke University.

Funding for this research came from Civitan International Emerging Scholars awards, and National Institutes of Health awards or grants NS098553, NS064025, NS065920 and NS047466.


Selwyn M. Vickers, M.D., senior vice president for Medicine and dean of the UAB School of Medicine delivered the annual State of the School address to a packed crowd at the Margaret Cameron Spain Auditorium.  He highlighted some of the many accomplishments during the last year and talked about the vision for the future.  Research continues to be one of the many keys to the UAB community.

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