Nav: Home

Fragile X finding shows normal neurons that interact poorly

January 18, 2018

Neurons in mice afflicted with the genetic defect that causes Fragile X syndrome (FXS) appear similar to those in healthy mice, but these neurons fail to interact normally, resulting in the long-known cognitive impairments, shows a new study by a team of neuroscientists.

The results point to a new approach to address FXS: targeting neuronal interactions rather than the immediate molecular abnormalities of genetic mutations.

"The genetic defect that causes the most widespread form of intellectual disability and autism is surprisingly characterized by normally functioning memory and cognition-encoding neurons," explains André Fenton, a professor in New York University's Center for Neural Science and the senior author of the paper, which appears in the journal Neuron. "But despite being individually normal, these neurons are abnormal in their interactions, which results in cognitive impairments.

"The good news, however, is we now have a better place to look for remedies: we can pursue a therapeutic strategy that targets neuronal interactions rather than the proximal molecular effects of a genetic mutation."

The study also included Dino Dvorak, a post-doctoral fellow in NYU's Center for Neural Science, Zoe Talbot, an NYU graduate student at the time of the study, Fraser Sparks, an NYU postdoctoral fellow at the time of the study and now at Columbia University, and researchers from SUNY Downstate Medical Center.

It's long been known that FXS is caused by a mutation that shuts down a particular gene--FMR1--so the protein product it normally produces, FMRP, cannot be made. In their study, the scientists mimicked the genetic defect in FXS by mutating the FMR1 gene in mice so that it could not produce the protein FMRP, which is vital for learning and memory.

In a series of active place avoidance tests, the FXS mice could learn and remember a location they should avoid, but as expected, were unable to efficiently adapt to environmental changes that contradicted their prior experience; so, when the place to avoid was relocated, the FXS mice could not avoid the new location, unlike control mice that rapidly adapted to the new information.

When the researchers looked into what explained these cognitive flexibility deficits, they found that the neurons of the FXS mice appeared normal.

However, their examination also showed a lack of coordination among neurons--organized interaction that is crucial in processing information from contradictory sources. Specifically, the mutated FMR1 gene disrupted the functioning of the neurons in the hippocampus--a brain structure known to play a significant role in memory in general and for the place avoidance task in particular. The disruption prevented the neurons from appropriately forming and disbanding in groups--"neural coalitions" that work to perform cognitive tasks by transiently discharging together in time.
-end-
The research was supported, in part, by a grant from the National Institutes of Health (R01MH099128) and by a Simons Foundation Autism Research Initiative grant (SFARI 294388).

DOI: 10.1016/j.neuron.2017.12.043

New York University

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

#540 Specialize? Or Generalize?
Ever been called a "jack of all trades, master of none"? The world loves to elevate specialists, people who drill deep into a single topic. Those people are great. But there's a place for generalists too, argues David Epstein. Jacks of all trades are often more successful than specialists. And he's got science to back it up. We talk with Epstein about his latest book, "Range: Why Generalists Triumph in a Specialized World".
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.