title: Altering the trajectory of early postnatal cortical development can lead to structural and behavioural features of autism.
abstract: BACKGROUND
  Autism is a behaviourally defined neurodevelopmental disorder with unknown etiology. Recent studies in autistic children consistently point to neuropathological and functional abnormalities in the temporal association cortex (TeA) and its associated structures. It has been proposed that the trajectory of postnatal development in these regions may undergo accelerated maturational alterations that predominantly affect sensory recognition and social interaction. Indeed, the temporal association regions that are important for sensory recognition and social interaction are one of the last regions to mature suggesting a potential vulnerability to early maturation. However, direct evaluation of the emerging hypothesis that an altered time course of early postnatal development can lead to an ASD phenotype remains lacking.
  
  
  RESULTS
  We used electrophysiological, histological, and behavioural techniques to investigate if the known neuronal maturational promoter valproate, similar to that in culture systems, can influence the normal developmental trajectory of TeA in vivo. Brain sections obtained from postnatal rat pups treated with VPA in vivo revealed that almost 40% of cortical cells in TeA prematurely exhibited adult-like intrinsic electrophysiological properties and that this was often associated with gross cortical hypertrophy and a reduced predisposition for social play behaviour.
  
  
  CONCLUSIONS
  The co-manifestation of these functional, structural and behavioural features suggests that alteration of the developmental time course in certain high-order cortical networks may play an important role in the neurophysiological basis of autism.
authors: Department of Clinical Neurosciences, Hotchkiss Brain Institute, Faculty of Medicine, University of Calgary, Calgary, Alberta, T2N 4N1, Canada. tgchomia@ucalgary.ca
authors: Taylor
authors: T
authors: Chomiak
authors: Vikram
authors: V
authors: Karnik
authors: Edward
authors: E
authors: Block
authors: Bin
authors: B
authors: Hu
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000633:toxicity; D001321:Autistic Disorder / Q000139:chemically induced / Q000473:pathology* / Q000523:psychology; D001522:Behavior, Animal; D002540:Cerebral Cortex / Q000254:growth & development* / Q000473:pathology*; D003463:Cues; D004594:Electrophysiology; D005260:Female; D005456:Fluorescent Dyes; D007211:Indoles; D008297:Male; D010988:Play and Playthings; D011827:Radiation; D051381:Rats; D012919:Social Behavior; D014635:Valproic Acid / Q000633:toxicity
chemical_list: D000927:Anticonvulsants; D005456:Fluorescent Dyes; D007211:Indoles; C007293:DAPI; D014635:Valproic Acid