John Allman Ph.D.

Abstract

• Neuronal populations related to deficits in social emotions and cognition in autism: A neurobiological and genomics approach

  Autism is a complex behavioral disorder caused by perturbations in the development and functioning of cellular circuitry that governs human social emotions. Neuroanatomy and brain imaging point to a set of increasingly well-defined sites in the human brain that are linked in circuits that are responsible for social emotions. Among these are the cingulate and fronto-insular cortex, septum, amygdala and fusiform face area. These cellular circuits develop and function under the control of molecular genetic circuits, and genetic data argue that genetic and epigenetic disruptions in the structure and output from these genetic circuits are crucially involved in the etiopathogenesis of autism. The challenge this program project proposal addresses is to bring together genetics, neuroanatomy, and neuropathology to identify specific gene circuits that define cells at these crucial brain sites. Specifically, we propose to focus on molecular genetic differences between brains from autistic patients and normal controls in vulnerable cell populations identified with high-precision design-based stereology, so that they can ultimately be targeted with specific pharmaceutical or genetic interventions. Very recent technological developments in functional genomics give us a good way to define these brain sites in comprehensive genomic terms. These experiments will sift among all known and unknown human genes, aiming to identify a much smaller group that defines the specific pathways and molecular complexes at these brain sites that differ in autism. Resulting molecular information can then be used to drive computational modeling and functional tests to establish how normal and autistic social circuits work and shed light on how to ameliorate the destructive differences.

Institution

• California Institute of Technology