The genetic mutation that causes autism has been found to overstimulate brain cells

Scientists trying to understand the underlying brain mechanisms of autism spectrum disorder have discovered that a genetic mutation known to be associated with the disorder causes overstimulation of brain cells to a much greater extent than neuronal cells
that are not mutated.

The Rutgers-led study, which took seven years, employed some of the most advanced methods in the scientific toolbox, including growing human brain cells from stem cells and transplanting them into mouse brains
.

Scientists say the work illustrates the potential
of a new way to study brain diseases.

Describing the study in the journal Molecular Psychiatry, the researchers reported finding a mutation — R451C in the neural login-3 gene, which is known to cause autism in humans — that triggered higher levels of communication
in a network of human brain cells transplanted in mouse brains.
The scientists quantified this overexcitability in their experiments, manifesting itself as an explosion of electrical activity at levels more than
twice that seen in brain cells without mutations.

Pang Zhiping, associate professor in the Department of Neuroscience and Cell Biology at the New Jersey Institute of Child Health at the Robert Wood Johnson School of Medicine at Rutgers University and senior author of the study, said: "We were surprised to find that this was an enhancement, not a defect
.
" "Our study found that the increased function of these specific cells leads to an imbalance in the brain's neuronal network, disrupting the normal flow of
information.
"

The interconnected network of cells that make up the human brain contains special "excitatory" cells that stimulate electrical activity, balanced
with "inhibitory" brain cells that inhibit electrical impulses.
The scientists found that bursts of ultra-high electrical activity caused by genetic mutations threw the brains of mice out of balance
.

Autism spectrum disorder is a developmental disorder
caused by differences in the brain.
The Centers for Disease Control and Prevention estimates that about 1 in 44 children are diagnosed with the disease
.

Research by the National Institutes of Health's Institute of Neurological Disorders and Stroke suggests that autism may be the result of disruption of
normal brain growth early in development.
According to the National Institutes of Health, these disturbances may be the result of
genetic mutations that control brain development and regulate the way brain cells communicate with each other.

Professor Pang said: "Many of the underlying mechanisms of autism are unknown, which hinders the development of
effective therapies.
" "Using human neurons generated from human stem cells as a model system, we wanted to understand how and why specific mutations cause autism
in humans.
"

The researchers used CRISPR technology to alter the genetic material of human stem cells, creating a series of cells containing the mutations they wanted to study, and then deriving human neuronal cells
that carry the mutations.
CRISPR is a unique gene-editing technology
.

In this study, the resulting human neuronal cells, half with mutations and half without, were then implanted into the brains
of mice.
From there, researchers measure and compare the electrical activity of specific neurons using electrophysiology, a branch of physiology that studies the electrical properties
of biological cells.
Voltage changes or currents can be quantified on different scales, depending on the dimension
of the object of study.

Professor Pang said: "Our results suggest that the NLGN3 R451C mutation greatly affects excitatory synaptic transmission in human neurons, thereby triggering changes
in the overall network properties that may be related to mental disorders.
" "We think this is very important information
in this area.
"

Professor Pang said he hoped that many of the techniques developed to conduct the experiment could be used in future scientific research on other brain diseases, such as schizophrenia
.

"This study highlights the potential
to use human neurons as model systems to study mental disorders and develop new treatments," he said.