Ohio State researcher receives Simons Foundation Autism Research Initiative pilot award
Autism affects an estimated one in 54 children in the United States today, according to the Centers for Disease Control and Prevention, yet little is known about the cause of the disease. A new study at The Ohio State University College of Medicine is examining the early neurological processes that occur as the cerebral cortex develops, leading to the development of autism spectrum disorders (ASDs).
Scientists know that healthy brain function depends on the proper development of neurological circuitry during the embryonic period in human development. Certain mutations occurring within the chromosomes can disrupt the normal process of prenatal neuronal differentiation and proliferation, resulting in abnormal postnatal cortical development and ASDs. They also know that ARID1B haploinsufficiency, an insufficiency of one of the ARID1B proteins that associate to remodel the way DNA is packaged, is involved in the development of ASDs. This interferes with proper development of both excitatory projection neurons and inhibitory interneurons. However, scientists don’t yet understand the mechanisms involved in producing the specific changes to synaptic connectivity and physiology that result in the aberrant circuit configurations that lead to ASDs.
To better understand these processes, the Ohio State College of Medicine team led by Jason Wester, PhD, assistant professor of Neuroscience, will study a mouse model of ARID1B haploinsufficiency and conditionally “knock out” one copy of ARID1B from either projection neurons or interneurons during embryonic development. They’ll then use paired whole-cell recordings to study the formation of synaptic connections between neighboring neurons that are either mutants or genetically normal during postnatal development.
Spanning from early postnatal development to adulthood, the study will reveal how and when the trajectory of circuit formation is disrupted. During the first postnatal week, the team will investigate early patterns of synaptic connectivity and the emergence of intrinsic network activity generated by the immature cortex. In mature mice, they will then test circuit motifs observed among different classes of excitatory projection neurons and distinct subtypes of inhibitory interneurons.
The study will provide important insight into the relative contributions of these neurons to the development of microcircuit-level ASD pathology, paving the way for further research into the prevention and treatment of ASDs.
The study is funded by a grant from the Simons Foundation Autism Research Initiative, a division of the Simons Foundation supporting innovative research to advance the understanding, diagnosis and treatment of autism.