HUMAN CORTICAL AND THALAMOCORTICAL SYNAPTIC DYSCONNECTIVITY IN ASD

A major challenge in human neuroscience is understanding the biophysical mechanisms of the dynamic processes underlying neural function. We examined the intrinsic and synaptic properties of human neurons from patients diagnosed with or without autism spectrum disorder (ASD) via patch clamp electrophysiology in acute brain slices, followed by post-hoc immunohistochemistry and functional magnetic resonance imaging data analysis. In ASD, local excitatory cortical connectivity was decreased, along with changes in the unitary synaptic properties including decreased N-methyl-D-aspartate (NMDA) receptor conductance and shifted short-term synaptic plasticity exhibiting early facilitation and reduced depression. Conversely, thalamocortical connectivity was increased in ASD, suggesting input-dependent modifications in cortical processing. We did not find any difference in the passive membrane properties of pyramidal neurons or fast-spiking interneurons, nor cortical excitation-inhibition balance, regardless of association with ASD. These findings represent the first documentation of electrophysiological phenotypes at single-cell resolution obtained directly from human patients clinically diagnosed with ASD.