Toward a developmental neurobiology of autism.
Autism is a complex, behaviorally defined, developmental brain disorder with an estimated prevalence of 1 in 1,000. It is now clear that autism is not a disease, but a syndrome with a strong genetic component. The etiology of autism is poorly defined both at the cellular and the molecular levels. Based on the fact that seizure activity is frequently associated with autism and that abnormal evoked potentials have been observed in autistic individuals in response to tasks that require attention, several investigators have recently proposed that autism might be caused by an imbalance between excitation and inhibition in key neural systems including the cortex. Despite considerable ongoing effort toward the identification of chromosome regions affected in autism and the characterization of many potential gene candidates, only a few genes have been reproducibly shown to display specific mutations that segregate with autism, likely because of the complex polygenic nature of this syndrome. Among those, several candidate genes have been shown to control the early patterning and/or the late synaptic maturation of specific neuronal subpopulations controlling the balance between excitation and inhibition in the developing cortex and cerebellum. In the present article, we review our current understanding of the developmental mechanisms patterning the balance between excitation and inhibition in the context of the neurobiology of autism.
Polleux
Franck
F
Department of Pharmacology-Neuroscience Center, School of Medicine, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina, USA. polleux@med.unc.edu
Lauder
Jean M
JM
D001321:Autistic Disorder / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D001921:Brain / Q000002:abnormalities / Q000378:metabolism / Q000503:physiopathology*; D001933:Brain Stem / Q000002:abnormalities / Q000378:metabolism / Q000503:physiopathology; D002531:Cerebellum / Q000002:abnormalities / Q000378:metabolism / Q000503:physiopathology; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics; D002890:Chromosomes, Human, Pair 20 / Q000235:genetics; D015870:Gene Expression / Q000235:genetics; D005819:Genetic Markers; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D008279:Magnetic Resonance Imaging; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D005819:Genetic Markers; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid