Nav: Home

Mood neurons mature during adolescence

June 24, 2019

Researchers have discovered a mysterious group of neurons in the amygdala -- a key center for emotional processing in the brain -- that stay in an immature, prenatal developmental state throughout childhood. Most of these cells mature rapidly during adolescence, suggesting a key role in the brain's emotional development, but some stay immature throughout life, suggesting new ideas about how the brain keeps its emotional responses flexible throughout life.

"Most brain cells have matured far beyond this stage by the time you are born," said study lead author Shawn Sorrells, PhD, a former UCSF researcher who is now assistant professor of neuroscience at the University of Pittsburgh. "It's fascinating that these are some of the very last cells to mature in the human brain, and most do so during puberty, precisely when huge developments in emotional intelligence are going on."

The amygdala is an almond-shaped brain structure located deep in the brain's temporal lobes (you actually have two, one on each side of the brain) that plays a key role in learning appropriate emotional responses to our environment. During childhood and adolescence -- long after most of the rest of the human brain is finished growing -- the amygdala continues to expand by as many as two million neurons, a late growth spurt that researchers believe is likely to play a key role in human emotional development, and which may go awry in neurodevelopmental disorders. For example, this expansion is absent in children with autism, and mood disorders that frequently emerge in adolescence, such as depression, anxiety, bipolar disorder, and post-traumatic stress disorder (PTSD), have also been linked to problems with amygdala development.

Recent studies had detected a unique group of immature neurons in a region of the amygdala called the paralaminar nuclei (PL), which could help explain the amygdala's rapid growth, but researchers had little idea where these cells came from or what role they play in mature brain circuits -- even whether they are excitatory or inhibitory, the two main functional classes of neurons.

In the new study, published June 21, 2019, in Nature Communications, researchers from the lab of Arturo Alvarez-Buylla, PhD, the Heather and Melanie Muss Endowed Chair and Professor of Neurological Surgery and a member of the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research at UCSF, set out to understand the identity of these cells and their role in the amygdala's rapid growth during childhood.

The researchers examined postmortem human amygdala tissue from 49 human brains -- ranging in age from 20 gestational weeks to 78 years of age. Using both anatomical and molecular techniques to classify individual neurons' maturity and function within neural circults, they found that the percentage of immature cells in the PL region of the amygdala remains high throughout childhood, but declines rapidly during adolescence: from birth to age 13, the number of immature cells declines from approximately 90 percent to just under 70 percent, but by the end of adolescence, only about 20 percent of PL cells remain immature.

Based on quantification of neurons in different stages of development coupled with analysis of gene expression patterns in individual neurons extracted from PL, the researchers showed that as the immature cells disappear, they are replaced by mature excitatory neurons -- suggesting that the cells have taken their place in the amygdala's maturing emotion processing circuitry. Since this is the first time these neurons have been clearly studied, scientists don't know exactly what function the neurons serve, but the timing of their maturation suggests they may play a role in the rapid emotional development that occurs during human adolescence.

"Anyone who's met a teenager knows that they are going through a rapid and sometimes tumultuous process of emotional learning about how to respond to stress, how to form positive social bonds, and so on," Sorrells said. "At the same time, adolescence is when many psychiatric disorders known to involve the amygdala first manifest, suggesting that perhaps something has gone wrong with the normal process of emotional and cognitive development -- though whether these cells are involved is a matter for future study."

Notably, the researchers also found that some immature neurons appear to remain in the amygdala throughout life, and were even found in one 77-year-old brain. These results were in stark contrast to the hippocampus -- a nearby structure in which the authors recently found that newborn and immature neurons completely decline to undetectable levels by adolescence.

"This is consistent with what we have seen before: that immature neurons are vanishingly rare in the adult hippocampus, but they do appear to persist in the amygdala," Alvarez-Buylla said. "As far as we can tell, these cells aren't being born throughout life, but seem to be maintained in an immature state from birth, though we can't say this for sure given the techniques we've used here."

In other animals, such as mice, new neurons continue to be born throughout life in the memory-forming hippocampus -- and possibly at low rates in the amygdala -- which researchers believe allows the brain to continuously rewire neural circuits to adapt to new experiences and environments. Following on the authors' 2018 study showing that the birth of new neurons declines in the human brain during childhood and is very rare or absent in adults, the new study suggests that the human brain may maintain reserves of immature neurons throughout life, using these "Peter Pan" cells in a similar manner to the neurogenesis seen in other species -- as new cells to be called on as needed to keep the brain's emotional responses flexible and adaptable into old age.

"You could imagine these immature cells let the brain continue to sculpt the structure of neural circuits and their growth once you are out in the world experiencing what it's like," Sorrells said. "Of course, that's just speculation at this point -- one of the fascinating questions these findings open up for future study."

Neurogenesis Sidebar:

Whether new neurons are born in the adult primate or human brain remains controversial. In 2018, Alvarez-Buylla, Sorrells and colleagues published results of the most rigorous search yet for new neurons in the human hippocampus, and they found that the birth of new neurons declined rapidly in childhood and was undetectable in adults.

Subsequently, other groups published data that appears to show newborn neurons in the adult human hippocampus, but Alvarez-Buylla and colleagues believe these studies rely too strongly on a small number of molecular markers for newborn neurons. They have shown that these markers can also be found in fully mature neurons and in non-neuronal cells called glia -- which are known to continue dividing throughout life.

"Identifying new neurons is technically very challenging," Alvarez-Buylla said. "It's easy to forget that the molecular markers we use to identify particular molecules are not produced for our benefit -- cells are using these molecules for their own biological needs, which are always going to be messy from the perspective of someone looking for simple classification. This is why we have endeavored to examine as many lines of evidence as possible -- not just molecular markers but also cells' shape and appearance -- to make sure we are confident in what types of cells we are actually looking at in these analyses."

The new study in the amygdala uses comprehensive single-cell gene expression techniques to sensitively detect immature neurons based on multiple lines of molecular evidence, and reinforces the group's earlier findings in the hippocampus -- showing that the precursors that divide to give birth to new neurons disappear within the first two years of life in the human amygdala, and that most immature neurons disappear during adolescence.

"Single-cell sequencing not only clearly identifies these long-lived immature neurons, but also shows that they express many developmental genes involved in axon development, synaptogenesis, dendrite morphogenesis, and even neuronal migration," Sorrells said. "These cells could be erroneously assumed to be newborn neurons, but based on our developmental perspective, and the fact that we see few dividing cells present nearby, it looks as though they are already present at birth and decline throughout life."
-end-
MEDIA AVAILABLE: Download images of immature amygdala neurons in the adolescent brain here

Authors: Additional authors on the paper were Mercedes F. Paredes, Dmitry Velmeshev, Kadellyn Sandoval, Simone Mayer, Edward F. Chang, Arnold R. Kriegstein, John R. Rubenstein, Eric J. Huang of UCSF; Jose Manuel Garcia-Verdugo of the University of Valencia, Spain; Vicente Herranz-Pérez of the University of Valencia and Universitat Jaume I, Spain; and Ricardo Insausti of the University of Castilla-La Mancha, Spain.

Funding: The researchers were supported by the US National Institutes of Health (NIH) (P01 NS083513, R01 NS028478, F32 MH103003, K08 NS091537), the German Research Foundation (DFG, MA 7374/1-1), and a gift from the John G. Bowes Research Fund.

About UCSF: UC San Francisco (UCSF) is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care. It includes top-ranked graduate schools of dentistry, medicine, nursing and pharmacy; a graduate division with nationally renowned programs in basic, biomedical, translational and population sciences; and a preeminent biomedical research enterprise. It also includes UCSF Health, which comprises three top-ranked hospitals - UCSF Medical Center and UCSF Benioff Children's Hospitals in San Francisco and Oakland - as well as Langley Porter Psychiatric Hospital and Clinics, UCSF Benioff Children's Physicians and the UCSF Faculty Practice. UCSF Health has affiliations with hospitals and health organizations throughout the Bay Area. UCSF faculty also provide all physician care at the public Zuckerberg San Francisco General Hospital and Trauma Center, and the SF VA Medical Center. The UCSF Fresno Medical Education Program is a major branch of the University of California, San Francisco's School of Medicine. Please visit http://www.ucsf.edu/news.

Follow UCSF
ucsf.edu | Facebook.com/ucsf | YouTube.com/ucsf

University of California - San Francisco

Related Neurons Articles:

How do we get so many different types of neurons in our brain?
SMU (Southern Methodist University) researchers have discovered another layer of complexity in gene expression, which could help explain how we're able to have so many billions of neurons in our brain.
These neurons affect how much you do, or don't, want to eat
University of Arizona researchers have identified a network of neurons that coordinate with other brain regions to influence eating behaviors.
Mood neurons mature during adolescence
Researchers have discovered a mysterious group of neurons in the amygdala -- a key center for emotional processing in the brain -- that stay in an immature, prenatal developmental state throughout childhood.
Astrocytes protect neurons from toxic buildup
Neurons off-load toxic by-products to astrocytes, which process and recycle them.
Connecting neurons in the brain
Leuven researchers uncover new mechanisms of brain development that determine when, where and how strongly distinct brain cells interconnect.
The salt-craving neurons
Pass the potato chips, please! New research discovers neural circuits that regulate craving and satiation for salty tastes.
When neurons are out of shape, antidepressants may not work
Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed medication for major depressive disorder (MDD), yet scientists still do not understand why the treatment does not work in nearly thirty percent of patients with MDD.
Losing neurons can sometimes not be that bad
Current thinking about Alzheimer's disease is that neuronal cell death in the brain is to blame for the cognitive havoc caused by the disease.
Neurons that fire together, don't always wire together
As the adage goes 'neurons that fire together, wire together,' but a new paper published today in Neuron demonstrates that, in addition to response similarity, projection target also constrains local connectivity.
Scientists accidentally reprogram mature mouse GABA neurons into dopaminergic-like neurons
Attempting to make dopamine-producing neurons out of glial cells in mouse brains, a group of researchers instead converted mature inhibitory neurons into dopaminergic cells.
More Neurons News and Neurons Current Events

Top Science Podcasts

We have hand picked the top science podcasts of 2019.
Now Playing: TED Radio Hour

Risk
Why do we revere risk-takers, even when their actions terrify us? Why are some better at taking risks than others? This hour, TED speakers explore the alluring, dangerous, and calculated sides of risk. Guests include professional rock climber Alex Honnold, economist Mariana Mazzucato, psychology researcher Kashfia Rahman, structural engineer and bridge designer Ian Firth, and risk intelligence expert Dylan Evans.
Now Playing: Science for the People

#541 Wayfinding
These days when we want to know where we are or how to get where we want to go, most of us will pull out a smart phone with a built-in GPS and map app. Some of us old timers might still use an old school paper map from time to time. But we didn't always used to lean so heavily on maps and technology, and in some remote places of the world some people still navigate and wayfind their way without the aid of these tools... and in some cases do better without them. This week, host Rachelle Saunders...
Now Playing: Radiolab

Dolly Parton's America: Neon Moss
Today on Radiolab, we're bringing you the fourth episode of Jad's special series, Dolly Parton's America. In this episode, Jad goes back up the mountain to visit Dolly's actual Tennessee mountain home, where she tells stories about her first trips out of the holler. Back on the mountaintop, standing under the rain by the Little Pigeon River, the trip triggers memories of Jad's first visit to his father's childhood home, and opens the gateway to dizzying stories of music and migration. Support Radiolab today at Radiolab.org/donate.