title: The Number of Parvalbumin-Expressing Interneurons Is Decreased in the Prefrontal Cortex in Autism.
abstract: The cognitive phenotype of autism has been correlated with an altered balance of excitation to inhibition in the cerebral cortex, which could result from a change in the number, function, or morphology of GABA-expressing interneurons. The number of GABAergic interneuron subtypes has not been quantified in the autistic cerebral cortex. We classified interneurons into 3 subpopulations based on expression of the calcium-binding proteins parvalbumin, calbindin, or calretinin. We quantified the number of each interneuron subtype in postmortem neocortical tissue from 11 autistic cases and 10 control cases. Prefrontal Brodmann Areas (BA) BA46, BA47, and BA9 in autism and age-matched controls were analyzed by blinded researchers. We show that the number of parvalbumin+ interneurons in these 3 cortical areas-BA46, BA47, and BA9-is significantly reduced in autism compared with controls. The number of calbindin+ and calretinin+ interneurons did not differ in the cortical areas examined. Parvalbumin+ interneurons are fast-spiking cells that synchronize the activity of pyramidal cells through perisomatic and axo-axonic inhibition. The reduced number of parvalbumin+ interneurons could disrupt the balance of excitation/inhibition and alter gamma wave oscillations in the cerebral cortex of autistic subjects. These data will allow development of novel treatments specifically targeting parvalbumin interneurons.
authors.affiliation: Department of Pathology and Laboratory Medicine.|Institute for Pediatric Regenerative Medicine and Shriners Hospitals for Children Northern California, Sacramento, CA, USA.
authors.forename: Ezzat
authors.initials: E
authors.lastname: Hashemi
authors.affiliation: Department of Pathology and Laboratory Medicine.|Institute for Pediatric Regenerative Medicine and Shriners Hospitals for Children Northern California, Sacramento, CA, USA.
authors.forename: Jeanelle
authors.initials: J
authors.lastname: Ariza
authors.affiliation: Department of Pathology and Laboratory Medicine.|Institute for Pediatric Regenerative Medicine and Shriners Hospitals for Children Northern California, Sacramento, CA, USA.
authors.forename: Haille
authors.initials: H
authors.lastname: Rogers
authors.affiliation: Department of Psychiatry and Behavioral Sciences, UC Davis, Sacramento, CA, USA.|MIND Institute, UC Davis School of Medicine, Sacramento, CA, USA.
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Noctor
authors.affiliation: Department of Pathology and Laboratory Medicine.|Institute for Pediatric Regenerative Medicine and Shriners Hospitals for Children Northern California, Sacramento, CA, USA.|MIND Institute, UC Davis School of Medicine, Sacramento, CA, USA.
authors.forename: Verónica
authors.initials: V
authors.lastname: Martínez-Cerdeño
mesh_terms: D000293:Adolescent; D000328:Adult; D001321:Autistic Disorder / Q000378:metabolism* / Q000473:pathology*; D064032:Calbindin 2 / Q000378:metabolism; D064026:Calbindins / Q000378:metabolism; D002452:Cell Count; D002648:Child; D005260:Female; D006801:Humans; D007395:Interneurons / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D010320:Parvalbumins / Q000378:metabolism*
chemical_list: D064032:Calbindin 2; D064026:Calbindins; D010320:Parvalbumins
keywords: autism; basket cells; chandelier cells; interneurons; parvalbumin; prefrontal cortex