Reduced GABAergic Action in the Autistic Brain

Curr Biol. 2016 Jan 11;26(1):80-5. doi: 10.1016/j.cub.2015.11.019. Epub 2015 Dec 17.

Abstract

An imbalance between excitatory/inhibitory neurotransmission has been posited as a central characteristic of the neurobiology of autism [1], inspired in part by the striking prevalence of seizures among individuals with the disorder [2]. Evidence supporting this hypothesis has specifically implicated the signaling pathway of the inhibitory neurotransmitter, γ-aminobutyric acid (GABA), in this putative imbalance: GABA receptor genes have been associated with autism in linkage and copy number variation studies [3-7], fewer GABA receptor subunits have been observed in the post-mortem tissue of autistic individuals [8, 9], and GABAergic signaling is disrupted across heterogeneous mouse models of autism [10]. Yet, empirical evidence supporting this hypothesis in humans is lacking, leaving a gulf between animal and human studies of the condition. Here, we present a direct link between GABA signaling and autistic perceptual symptomatology. We first demonstrate a robust, replicated autistic deficit in binocular rivalry [11], a basic visual function that is thought to rely on the balance of excitation/inhibition in visual cortex [12-15]. Then, using magnetic resonance spectroscopy, we demonstrate a tight linkage between binocular rivalry dynamics in typical participants and both GABA and glutamate levels in the visual cortex. Finally, we show that the link between GABA and binocular rivalry dynamics is completely and specifically absent in autism. These results suggest a disruption in inhibitory signaling in the autistic brain and forge a translational path between animal and human models of the condition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Autistic Disorder / metabolism*
  • Biomarkers / metabolism
  • Brain / metabolism*
  • Case-Control Studies
  • Female
  • Glutamic Acid / metabolism*
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Synaptic Transmission
  • Vision, Binocular / physiology*
  • Visual Cortex / metabolism*
  • gamma-Aminobutyric Acid / metabolism*

Substances

  • Biomarkers
  • Glutamic Acid
  • gamma-Aminobutyric Acid