title: Impairment of cortical GABAergic synaptic transmission in an environmental rat model of autism.
abstract: The biological mechanisms of autism spectrum disorders (ASDs) are largely unknown in spite of extensive research. ASD is characterized by altered function of multiple brain areas including the temporal cortex and by an increased synaptic excitation:inhibition ratio. While numerous studies searched for evidence of increased excitation in ASD, fewer have investigated the possibility of reduced inhibition. We characterized the cortical γ-amino butyric acid (GABA)ergic system in the rat temporal cortex of an ASD model [offspring of mothers prenatally injected with valproic acid (VPA)], by monitoring inhibitory post-synaptic currents (IPSCs) with patch-clamp. We found that numerous features of inhibition were severely altered in VPA animals compared to controls. Among them were the frequency of miniature IPSCs, the rise time and decay time of electrically-evoked IPSCs, the slope and saturation of their input/output curves, as well as their modulation by adrenergic and muscarinic agonists and by the synaptic GABAA receptor allosteric modulator zolpidem (but not by the extra-synaptic modulator gaboxadol). Our data suggest that both pre- and post-synaptic, but not extra-synaptic, inhibitory transmission is impaired in the offspring of VPA-injected mothers. We speculate that impairment in the GABAergic system critically contributes to an increase in the ratio between synaptic excitation and inhibition, which in genetically predisposed individuals may alter cortical circuits responsible for emotional, communication and social impairments at the core of ASD.
authors.affiliation: School of Behavioral and Brain Sciences, University of Texas at Dallas, Richardson, TX 75080, USA.
authors.forename: Anwesha
authors.initials: A
authors.lastname: Banerjee
authors.forename: Francisco
authors.initials: F
authors.lastname: García-Oscos
authors.forename: Swagata
authors.initials: S
authors.lastname: Roychowdhury
authors.forename: Luis C
authors.initials: LC
authors.lastname: Galindo
authors.forename: Shawn
authors.initials: S
authors.lastname: Hall
authors.forename: Michael P
authors.initials: MP
authors.lastname: Kilgard
authors.forename: Marco
authors.initials: M
authors.lastname: Atzori
mesh_terms: D000818:Animals; D018692:Antimanic Agents / Q000633:toxicity; D001321:Autistic Disorder / Q000209:etiology / Q000473:pathology*; D001703:Biophysics; D004195:Disease Models, Animal; D004558:Electric Stimulation; D004777:Environment; D005260:Female; D018682:GABA Agents / Q000494:pharmacology; D059330:GABAergic Neurons / Q000502:physiology*; D066298:In Vitro Techniques; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D008297:Male; D018408:Patch-Clamp Techniques; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D013702:Temporal Lobe / Q000187:drug effects / Q000473:pathology*; D014635:Valproic Acid / Q000633:toxicity
chemical_list: D018692:Antimanic Agents; D018682:GABA Agents; D014635:Valproic Acid