Summary: According to researchers, people with Fragile X have ‘noisier’ brains, which can impair information flow and make social interactions more difficult.
Source: VIB Flanders.
In neurotypical brains, 20% of neurons are inhibitory, meaning that they send signals that limit communication between other neurons to make sure that signals exchanged within the brain are finely tuned and confined to specific areas, depending on what the person or animal is doing or perceiving. Fragile X syndrome, which is caused by a fault on the X chromosome, leads to defects in how brain neurons communicate with each other. In this study, scientists observed that fruit flies that lack the Fragile X protein have much less inhibition among their brain neurons, possibly leading to “noise” during information processing.
The impacts of “noisier” brains
Even though the research was performed on fruit flies, there are many analogues between flies and humans that lead to insights into human brain diseases.
Prof. Emre Yaksi (Kavli Institute for Systems Neuroscience at NTNU): “The Fragile X protein in fruit flies is very similar to the Fragile X protein in humans. Our research indicates that patients with Fragile X syndrome have ‘noisier’ brains, impairing their ability to manage and understand the flow of information and making it more difficult to interact with the world. This may explain why many patients show anxiety, have learning and communication difficulties and may fall on the autism spectrum.”
Building research tech from scratch
To achieve the research goals of the project, new approaches to working with model organisms were built from the ground up at KU Leuven, including the technology to perform electrophysiological recordings and process images of individual fruit fly neurons. Now that they have been established, these technologies are now available to the broader scientific research community.
Dr. Luis Franco (VIB-KU Leuven): “These new tools helped us test our hypotheses much more rapidly, as they allowed us to collect and process large datasets more efficiently.”
Toward therapies that boost inhibition
Based on the results of their research, the scientists propose that pharmacological treatment of Fragile X sufferers that enhances inhibition might reduce anxiety and epileptic seizures that are observed in a subset of Fragile X patients. It may also improve how Fragile X patients process sensory information, alleviating patients’ autistic symptoms.
Prof. Bassam Hassan (Brain & Spine Institute, Paris, France): “Future research could include testing whether sensory discrimination tasks such as discriminating odors, auditory tones or colors/visual patterns could be used for early diagnosis of Fragile X syndrome. Our next steps are to test drugs that enhance inhibition that are already approved for use in humans, such as benzodiazepines and barbiturates — first in models, and then in the clinic.”
Source: Sooike Stoops – VIB Flanders
Image Source: NeuroscienceNews.com image is in the public domain.
Original Research: Full open access research for “Reduced Lateral Inhibition Impairs Olfactory Computations and Behaviors in a Drosophila Model of Fragile X Syndrome” by Luis M. Franco, Zeynep Okray, Gerit A. Linneweber, Bassem A. Hassan, and Emre Yaksi in Current Biology. Published online March 30 2017 doi:10.1016/j.cub.2017.02.065
Reduced Lateral Inhibition Impairs Olfactory Computations and Behaviors in a Drosophila Model of Fragile X Syndrome
•Lack of dFMRP leads to reduced olfactory attraction and aversion in fruit flies
•Odor selectivity of antennal lobe projection neurons is impaired in dfmr1− flies
•GABAergic lateral inhibition within the antennal lobe is weaker in dfmr1− flies
•Deficient lateral inhibition impairs sensory computations and animal behavior
Fragile X syndrome (FXS) patients present neuronal alterations that lead to severe intellectual disability, but the underlying neuronal circuit mechanisms are poorly understood. An emerging hypothesis postulates that reduced GABAergic inhibition of excitatory neurons is a key component in the pathophysiology of FXS. Here, we directly test this idea in a FXS Drosophila model. We show that FXS flies exhibit strongly impaired olfactory behaviors. In line with this, olfactory representations are less odor specific due to broader response tuning of excitatory projection neurons. We find that impaired inhibitory interactions underlie reduced specificity in olfactory computations. Finally, we show that defective lateral inhibition across projection neurons is caused by weaker inhibition from GABAergic interneurons. We provide direct evidence that deficient inhibition impairs sensory computations and behavior in an in vivo model of FXS. Together with evidence of impaired inhibition in autism and Rett syndrome, these findings suggest a potentially general mechanism for intellectual disability.
“Reduced Lateral Inhibition Impairs Olfactory Computations and Behaviors in a Drosophila Model of Fragile X Syndrome” by Luis M. Franco, Zeynep Okray, Gerit A. Linneweber, Bassem A. Hassan, and Emre Yaksi in Current Biology. Published online March 30 2017 doi:10.1016/j.cub.2017.02.065