This project is developing and applying new spatial transcriptomic methods to simultaneously probe neuroanatomy and gene expression in the brains of mouse autism models providing an integrated, high-resolution picture of the impact that autism-associated genetic mutations have on gene regulation, cellular make-up of the brain and brain wiring.

Dysregulated levels of neuromodulators and other chemical signals may contribute to behavioral characteristics of ASD. Yet previous efforts have often focused on only one signal at a time, and typically provide a static description of signal levels in the brain. In the current project, Mark Andermann and colleagues plan to use novel optical methods to track and control dozens of neuromodulators and peptides in the brain of a genetic mouse model of ASD.

Infection or inflammation during critical windows of pregnancy, termed “maternal immune activation” (MIA), has been strongly associated with increased risk of neurodevelopmental and neuropsychiatric conditions in children, including autism spectrum disorder. In the current project, Brian Kalish and Yeong Shin Yim aim to discover how MIA elicits a sex-specific effect on RNA metabolism and to target these pathways to reduce MIA-associated behavioral alterations in mice.

Although some ASD risk genes have hardly been studied, for many others, a wealth of basic research data is already available. In the current project, August Smit and Matthijs Verhage aim to better disclose this available information, especially for synaptic genes, to support the translation of genetic findings into specific disease concepts.