Unifying Views of Autism Spectrum Disorders: A Consideration of Autoregulatory Feedback Loops

Caitlin Mullins, Gord Fishell, Richard W. Tsien

Research output: Contribution to journalReview articlepeer-review

Abstract

Understanding the mechanisms underlying autism spectrum disorders (ASDs) is a challenging goal. Here we review recent progress on several fronts, including genetics, proteomics, biochemistry, and electrophysiology, that raise motivation for forming a viable pathophysiological hypothesis. In place of a traditionally unidirectional progression, we put forward a framework that extends homeostatic hypotheses by explicitly emphasizing autoregulatory feedback loops and known synaptic biology. The regulated biological feature can be neuronal electrical activity, the collective strength of synapses onto a dendritic branch, the local concentration of a signaling molecule, or the relative strengths of synaptic excitation and inhibition. The sensor of the biological variable (which we have termed the homeostat) engages mechanisms that operate as negative feedback elements to keep the biological variable tightly confined. We categorize known ASD-associated gene products according to their roles in such feedback loops and provide detailed commentary for exemplar genes within each module.

Original languageEnglish (US)
Pages (from-to)1131-1156
Number of pages26
JournalNeuron
Volume89
Issue number6
DOIs
StatePublished - Mar 16 2016

ASJC Scopus subject areas

  • Neuroscience(all)

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