- Awarded: 2014
- Award Type: Research
- Award #: 306796
Autism is most likely caused by changes in the development of the cerebral cortex, particularly in neural circuits that process social and cognitive information. Under- or over-connectivity in these circuits has been found in the brains of children and adults with autism. It remains unknown how altered development might lead to these disrupted connections. This knowledge is crucial for new diagnostic, preventive and therapeutic approaches in autism.
Anthony-Samuel LaMantia and his colleagues plan to investigate whether disrupted development of a key subset of nerve cells in the cerebral cortex leads to altered connectivity and disrupted circuit function. This subset comprises projection neurons in the superficial layers, whose long axons make connections between association areas of the cortex that process cognitive and social information.
The researchers plan to study this issue in a mouse model of the human 22q11 deletion syndrome, a paradigmatic genetic disease that results in autism. They plan to use genetic techniques that allow them to trace the developmental history of neurons, anatomical methods that allow them to define the number of connections made by these neurons, and electrophysiological techniques that allow the capacity of these neurons to receive, process and relay information.
The teams plan to undertake these studies in animals that have been thoroughly characterized for cognitive and social behavioral deficits. This will make it possible to determine whether developmental disruption of connections in cortical circuits that mediate social and cognitive behaviors are key determinants for essential autism-related behavioral changes.