Brainwide Social Network in Mice Underlying Autism Spectrum Disorder
Abstract
Scientific Objective and Rationale for the Proposed Project: Social impairment is a devastating symptom of autism spectrum disorder (ASD). However, social impairment varies dramatically across individuals. This heterogeneity hinders our ability to understand the neuronal mechanisms underlying social interaction. We know our brain is social; each social interaction leads to activity of neurons in many brain areas; but how the social brain dysfunctions in ASD is still unknown. Here, we turn to the mouse model, which enables us to measure the social brain during natural social interactions. Using a novel technique, we will measure neuronal activity in dozens of areas from two mice during social interactions. Some of the mice will be normal, whereas some mice will have a genetic mutation that results in an autistic-like social impairment. We will put a strong emphasis on the personality and symptoms of each and each mouse. We expect that each autistic-like mouse will be different and therefore have a different social brain. Some autistic-like mice with a severe social deficit will have dysfunctional activity in certain areas, whereas other autistic-like mice will have a dysfunction in other areas. With this experimental design, we can attempt to mind-read: Can the mind of an autistic-like mouse predict which mouse is approaching it? After finding dysfunctional brain areas in a certain autistic-like mouse, we can use optogenetic tools to activate the neurons in those areas that may lead mice to gain back normal social behavior. Our rationale is that the social brain is highly dynamic and very personal. Describe the Ultimate Applicability of the Research: Who will it help and how will it help them? This research will aid the ASD scientific community in understanding the social brain and pinpointing crucial areas that may be involved in social impairment. In addition, our individual-based approach will widen our understanding of the heterogeneity in ASD and may help in settling debates regarding inconsistent results. What are the potential clinical applications, benefits, and risks? Although the past decades have yielded substantial advances in our understanding of the ASD pathology, little therapeutic progress has been made. Novel treatments such as non-invasive brain stimulation (BS) target specific areas associated with ASD. Several target areas have been proposed, but current studies have reported a variability in response to the treatment. Determination of which individuals with ASD are likely to respond to BS and which are not remains a crucial area of ongoing investigation. In this project, we will outline key areas that may be relevant to BS treatment at the individual level. Our aim is to provide a sub-network of brain areas aiding in the development of multi-area BS in ASD individuals. In addition, this project builds a platform to study other mental disorders such as schizophrenia, depression, and anxiety. What is the projected time anticipated to achieve a clinically relevant outcome? At year 3, we already anticipate initiating collaboration with clinical researchers. Our laboratory is situated within the Hadassah Medical Center, making future collaboration easier than ever. We expect a clinically relevant outcome of personalized brain stimulation to be made available within 4-5 years from the start of the project. What are the likely contributions of this study to advancing the field of ASD research and ultimately leading to improved outcomes for individuals living with ASD and the well-being of their families/caregivers? Optimizing non-invasive brain stimulation by providing personalized target areas may immediately increase the quality of life for millions of individuals and their families. How is the project relevant to military Service Members, Veterans, and their families? It is estimated that more than 20,000 military dependents have some form of autism. A typical
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210333
Entities
People
- Ariel Gilad
Organizations
- Hebrew University of Jerusalem
- United States Army