Lecture 2 – Introduction to autism research

Ilan Dinstein

What is the cause of autism?

Dendrites

Axon

Cell body

Neural activity

Modularity

Developmental disorder

Brain development movie

Nature versus nurture

Genes or Environment?

Genetics

Control > ASD

DNA sequencing

Control > ASD

Identify meaningful mutation

Control > ASDSubstitution

Deletion

Insertion

Determine the function of the gene

What is the function of the protein that the gene encodes?

Is it involved in neural transmission?

Neural development?

Synaptic development?

Bourgeron 2009

Create a genetically modified animal model

Control > ASD

Compare animals with extremely similar genetics except for a specific modification.

Perform behavioral experiments

Control > ASD

Testing social behavior in mice

In vitro electrophysiology

Control > ASD

In vivo electrophysiology

Control > ASD

Electrical properties of cells & networks

Control > ASD

Electrode location

Control > ASD

Cellular morphology and connectivity

Control > ASD

What about humans?

Human genetics – SFARI, Autism Speaks

Neuroimaging – MRI, fMRI, DTI

Electrophysiology – EEG

Post mortem

Human genetics

Magnetic resonance imaging (MRI)

Anatomy - Separating tissues

1T 2T

Anatomy – Cortical thickness

Anatomy – Cortical folding

Anatomy – white matter

TractographyFiber volumeFiber length

Electroencephalogram - EEG

Control > ASD

EEG and epilepsy

Spence, Pediatrics Res 2009

Control > ASD

Epileptiform activity

Epileptic seizure

Post mortem studies

Brain slices:

Control > ASD

Post mortem studies

Cellular morphology

Control > ASD

Post mortem studies

Neural numbers and organization

Control > ASD