New research of University of Maryland suggests that this burden of connections begins early in mammalian development, when key neurons in the brain section known as the cerebral cortex begin to form their first brain circuits. By pinpointing where and when autism-related neural defects start in mice studies, the study results could lead to a stronger understanding of autism in humans -- including possible early intervention methods.
Researchers Outlined Their Findings To Incorporate Early Intervention Methods
"Our work proposes the neural pathology of autism reveals in the earliest cortical circuits, formed by a cell type called subplate neurons," said UMD Biology Professor and the senior study author Patrick Kanold. "Nobody has looked at evolving circuits this early, in this detailed creation, in the context of autism before. This is truly a new discovery and potentially represents a new paradigm for autism research."
Subplate neurons form the first circuit connections in the developing cerebral cortex -- the outer portion of the mammalian brain that controls perception, memory and, in humans, higher functions such as language and intellectual reasoning. As the brain progresses, the interconnected subplate neurons build a network of framework thought to support other neurons that grow at a later stage of development.
"The cortex is a vital region in the adult human brain that undergoes a complex, multi-tasking development process," said Daniel Nagode, a former postdoctoral researcher at UMD and lead author of the study. "Because the findings implicate the earliest stages of cortex circuit formation in a mouse model, they propose that the pathological changes leading to autism might start before birth in humans."
To study the bond between autism and subplate neuron development in mice, Kanold, Nagode and their colleagues began with a mouse model of autism. The model involves inducing mouse embryos with valproic acid (VPA) on 12th day of their 20-day gestation period by injecting the drug into the mother mouse.
VPA has a connection to autism in humans and induces autism-like cerebral and interactive abnormalities in mice. For example, normal newborn mouse pups will emit frequent, high-pitched noises when they are separated from their companion, but VPA-treated pups do not.
The Study Developed A Technique That Could Somehow Detect Early Autism Indicators
They use a technique called laser scanning photo stimulation to map out the connections between individual subplate neuron cells in the brains of each mouse pups. The first week after birth, the VPA-dosed mice showed some coverings of "hyperconnected" subplate neurons. In contrast, control mouse pups dosed with plain saline solution showed normal connections all over their cortical tissue.
Ten days after birth, the patches of hyperconnected subplate neurons had grown widespread and homogeneous in the VPA-dosed pups likened with the control pups. Because subplate neurons help lay the basis for cortical development in all mammalian brains, a copse of hyperconnected subplate neurons in the evolving cortex could result in permanent hyperconnections.
"Subplate neurons form critical developmental assemblies. If their early progress is reduced, later development of the cortex is also reduced," Kanold explained. "In a developing human fetus, this stage is a critical doorway, when subplate neuron circuits are abundant."
If the same context plays out in human brains, hyperconnections in the developing cortex could result in the neural pathologies experiential in human autism, Kanold said. In mice as well as in humans, the critical gap of time when subplate neurons develop is very short.
"Our results suggest that we might have to inhibit quite early to address autism," Kanold said. "The fetal brain is not just a small adult brain, and these subplate neurons are the major variance. There may be other developmental disorders we can tackle using this evidence."